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Shirinezhad A, Azarboo A, Mafhoumi A, Islampanah M, Mohammadi S, Ghaseminejad-Raeini A, Hoveidaei AH. Urinary pentosidine as a potential biomarker of impaired bone health: a systematic review and meta-analysis. J Diabetes Metab Disord 2025; 24:6. [PMID: 39697860 PMCID: PMC11649614 DOI: 10.1007/s40200-024-01515-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 11/17/2024] [Indexed: 12/20/2024]
Abstract
Background Urinary pentosidine, an advanced glycation end product (AGE), has been proposed as a potential biomarker for impaired bone health, especially in older adults and those with diabetes. This study aimed to systematically review and meta-analyze the association of urinary pentosidine with bone mineral density (BMD) and fracture risk. Methods A comprehensive search of Embase, PubMed, Scopus, and Web of Science databases was conducted and records were gathered from 1960 to February 2024. Relevant papers were screened and data were extracted by two independent reviewers. Hedges' g standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated to compare urinary pentosidine levels between patients with and without fractures. Results A total of 12 studies comprising 5,878 participants were included in the systematic review. The meta-analysis revealed that patients with fractures had significantly higher urinary pentosidine levels compared to those without fractures (SMD [95% CI] = 0.53 [0.39-0.68]; I² = 54%; P < 0.01). In patients with vertebral fractures, pentosidine levels were also elevated (SMD [95% CI] = 0.51 [0.32-0.70]; I² = 64%; P < 0.01). Additionally, some studies demonstrated that an increase in urinary pentosidine was significantly associated with fracture risk (aHR = 1.20 [95% CI = 1.07-1.33]; P = 0.001) and BMD reduction (β = -0.125 [95% CI = -0.248, -0.002]; P = 0.047). However, other studies showed inconsistent results, particularly regarding the association between pentosidine and BMD or fracture risk in non-diabetic populations (aRR [95%CI] = 1.08 [0.79-1.49]; P = 0.6). Diagnostic accuracy analyses revealed a sensitivity of 71.9% and specificity of 61.2% for urinary pentosidine in predicting vertebral fracture in patients with type 2 diabetes mellitus. Conclusion This systematic review and meta-analysis demonstrate that elevated urinary pentosidine levels are associated with an increased risk of fractures and, to a lesser extent, reduced bone mineral density. Its diagnostic accuracy improves when integrated with other clinical markers, such as BMD and bone turnover indices. However, due to the variability in results, further research is needed to standardize pentosidine's use as a reliable biomarker for impaired bone health in clinical practice.
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Affiliation(s)
- Amirhossein Shirinezhad
- School of Medicine, Tehran University of Medical Sciences, District 6, Pour Sina St, P94V+8MF, Tehran, Tehran Province Iran
| | - Alireza Azarboo
- School of Medicine, Tehran University of Medical Sciences, District 6, Pour Sina St, P94V+8MF, Tehran, Tehran Province Iran
| | - Asma Mafhoumi
- School of Medicine, Tehran University of Medical Sciences, District 6, Pour Sina St, P94V+8MF, Tehran, Tehran Province Iran
| | - Muhammad Islampanah
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sara Mohammadi
- School of Medicine, Tehran University of Medical Sciences, District 6, Pour Sina St, P94V+8MF, Tehran, Tehran Province Iran
| | | | - Amir Human Hoveidaei
- Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
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Giaze TR, Mohamed N, Syed Hashim SA, Shuid AN, Soelaiman IN, Muhammad N, Jafar Sidik FZ, Jamal JA. Marantodes pumilum var. alata Enhances Fracture Healing Through Gene Regulation in a Postmenopausal Rat Model. Pharmaceuticals (Basel) 2025; 18:736. [PMID: 40430554 DOI: 10.3390/ph18050736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 05/09/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
Background:Marantodes pumilum var. alata (MPva) has been reported to promote fracture repair. This study investigates the role of MPva leaf extract on biochemical markers and bone-repair genes in a postmenopausal rat model to understand its fracture-healing properties. Methods: Thirty female Sprague Dawley rats were grouped into sham-operated (Sham), ovariectomized control (OVXC), estrogen treatment (ERT), and plant treatment (MPv20 and MPv100) groups. After ovariectomy, the right tibiae of rats were fractured. The ERT group was treated with 64.5 μg/kg/day of estrogen, while the MPv20 and MPv100 groups received 20 and 100 mg/kg/day doses of MPva leaf extract, respectively, for 8 weeks. Sham and OVXC acted as untreated controls. Blood samples collected before and after treatment were assayed for pro-inflammatory cytokines (IL-6 and TNF-α), while bone samples were assayed for bone-turnover markers: osteocalcin and pyridinoline, oxidative-status markers (GPx, SOD, and MDA), and bone-repair genes (Bglap, Spp1, Dkk1, Igf1, Tnfsf11, and Fgf23). Results: IL-6, GPx, and SOD levels were significantly increased in both MPv groups (p < 0.05). IGF1 was significantly upregulated in both MPv groups, while Tnfsf11 was downregulated in the MPv20 group (p < 0.05). Conclusions: MPva leaf extract may promote bone repair by stimulating pro-inflammatory and antioxidant responses, which are associated with its regulation of Igf1 and Tnfsf11 genes.
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Affiliation(s)
- Tijjani Rabiu Giaze
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Selangor, Malaysia
- Department of Pharmacology and Toxicology, Usmanu Danfodiyo University, Sokoto 2346, Nigeria
| | - Norazlina Mohamed
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Selangor, Malaysia
| | - Syed Alhafiz Syed Hashim
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Selangor, Malaysia
- Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK
| | - Ahmad Nazrun Shuid
- Department of Pharmacology, Faculty of Medicine, Universiti Teknologi Mara, Sungai Buloh 47000, Selangor, Malaysia
| | - Ima Nirwana Soelaiman
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Selangor, Malaysia
| | - Norliza Muhammad
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Selangor, Malaysia
| | | | - Jamia Azdina Jamal
- Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Selangor, Malaysia
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Ghasemi N, Rokhshad R, Zare Q, Shobeiri P, Schwendicke F. Artificial intelligence for osteoporosis detection on panoramic radiography: A systematic review and meta analysis. J Dent 2025; 156:105650. [PMID: 40010536 DOI: 10.1016/j.jdent.2025.105650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 02/13/2025] [Accepted: 02/23/2025] [Indexed: 02/28/2025] Open
Abstract
INTRODUCTION Osteoporosis is a disease characterized by low bone mineral density and an increased risk of fractures. In dentistry, mandibular bone morphology, assessed for example on panoramic images, has been employed to detect osteoporosis. Artificial intelligence (AI) can aid in diagnosing bone diseases from radiographs. We aimed to systematically review, synthesize and appraise the available evidence supporting AI in detecting osteoporosis on panoramic radiographs. DATA Studies that used AI to detect osteoporosis on dental panoramic images were included. SOURCES On April 8, 2023, a first comprehensive search of electronic databases was conducted, including PubMed, Scopus, Embase, IEEE, arXiv, and Google Scholar (grey literature). This search was subsequently updated on October 6, 2024. STUDY SELECTION The Quality Assessment and Diagnostic Accuracy Tool-2 was employed to determine the risk of bias in the studies. Quantitative analyses involved meta-analyses of diagnostic accuracy measures, including sensitivity and specificity, yielding Diagnostic Odds Ratios (DOR) and synthesized positive likelihood ratios (LR+). The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS A total of 24 studies were included. Accuracy ranged from 50% to 99%, sensitivity from 50% to 100%, and specificity from 38% to 100%. A minority of studies (n=10) had a low risk of bias in all domains, while the majority (n=18) showed low risk of applicability concerns. Pooled sensitivity was 87.92% and specificity 81.93%. DOR was 32.99, and L+ 4.87. Meta-regression analysis indicated that sample size had only a marginal impact on heterogeneity (R² = 0.078, p = 0.052), suggesting other study-level factors may contribute to variability. Egger's test suggested potential small-study effects (p < 0.001), indicating a risk of publication bias. CONCLUSION AI, particularly deep learning, showed high diagnostic accuracy in detecting osteoporosis on panoramic radiographs. The results indicate a strong potential for AI to enhance osteoporosis screening in dental settings. However, significant heterogeneity across studies and potential small-study effects highlight the need for further validation, standardization, and larger, well-powered studies to improve model generalizability. CLINICAL SIGNIFICANCE The application of AI in analyzing panoramic radiographs could transform osteoporosis screening in routine dental practice by providing early and accurate diagnosis. This has the potential to integrate osteoporosis detection seamlessly into dental workflows, improving patient outcomes and enabling timely referrals for medical intervention. Addressing issues of model validation and comparability is critical to translating these findings into widespread clinical use.
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Affiliation(s)
- Nikoo Ghasemi
- Department of Orthodontics and Dentofacial Orthopedics, School of Dentistry, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Rata Rokhshad
- Topic Group Dental Diagnostics and Digital Dentistry, WHO Focus Group AI on Health, Berlin, Germany.
| | - Qonche Zare
- Department of oral and maxillofacial radiology, School of Dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Parnian Shobeiri
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, United States
| | - Falk Schwendicke
- Clinic for Conservative Dentistry and Periodontology, LMU Klinikum, Munich, Germany
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Bailly AR, Hester GM, Alesi MG, Buresh RJ, Feito Y, Mermier CM, Ducharme JB, VanDusseldorp TA. Quercetins efficacy on bone and inflammatory markers, body composition, and physical function in postmenopausal women. J Bone Miner Metab 2025; 43:304-314. [PMID: 40053115 DOI: 10.1007/s00774-025-01592-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 02/09/2025] [Indexed: 05/21/2025]
Abstract
INTRODUCTION This study aimed to investigate the effects of quercetin (a plant-based flavonoid) supplementation over 90 days on prominent bone turnover markers (BTMs), inflammatory markers, bone mineral density (BMD), body composition, and physical function in postmenopausal women. MATERIALS AND METHODS Thirty-three healthy postmenopausal women were recruited to participate in a double-blind, placebo-controlled investigation. Participants were randomized into one of two supplement groups: (1) 500 mg of quercetin (QUE) once daily or (2) 500 mg of methylcellulose (placebo; PLB) once daily. Pre- and post-testing visits included assessments of BTMs (i.e., osteocalcin [OC], procollagen type I N-terminal propeptide [PINP], and type I collagen cross-linked C-terminal telopeptide [CTX]), inflammatory markers (i.e., interleukin [IL]-6, tumor necrosis factor-alpha [TNF-α], and C-reactive protein [CRP]), BMD measurements, body composition measurements, and physical function including timed up and go and handgrip strength. RESULTS The QUE group increased OC (p = 0.016; d = 0.89), PINP (p = 0.030; d = 0.64), and CTX (p = 0.023; d = 0.91) levels and decreased IL-6 (p = 0.045; d = 0.73) and TNF-α (p = 0.021; d = 0.90) levels compared to PLB. CRP (p = 0.448; d = 0.34), body composition (p > 0.05), and physical function (p > 0.05) remained unchanged. CONCLUSION The results suggest that QUE may better assist in controlling a normal bone turnover cycle by mediating bone formation and decreasing pro-inflammatory cytokines. However, although within the accepted range, there was an increase in the bone resorption marker and therefore, it is unclear if QUE will protect against future bone loss. Nonetheless, additional research is necessary to evaluate the bone-conserving properties of QUE among postmenopausal women. CLINICAL TRAIL REGISTRATION The ClinicalTrials.gov ID number: NCT05371340.
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Affiliation(s)
- Alyssa R Bailly
- Department of Exercise Science and Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, Kennesaw, Georgia, 30144, United States of America.
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, 200 Cornell Dr, Albuquerque, NM, 87131, United States of America.
| | - Garrett M Hester
- Department of Exercise Science and Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, Kennesaw, Georgia, 30144, United States of America
| | - Michaela G Alesi
- Department of Exercise Science and Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, Kennesaw, Georgia, 30144, United States of America
- Bonafide Health, 500 Mamaroneck Avenue, Suite 510, Harrison, NY, 10528, United States of America
| | - Robert J Buresh
- Department of Exercise Science and Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, Kennesaw, Georgia, 30144, United States of America
| | - Yuri Feito
- Department of Exercise Science and Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, Kennesaw, Georgia, 30144, United States of America
| | - Christine M Mermier
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, 200 Cornell Dr, Albuquerque, NM, 87131, United States of America
| | - Jeremy B Ducharme
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, 200 Cornell Dr, Albuquerque, NM, 87131, United States of America
| | - Trisha A VanDusseldorp
- Department of Exercise Science and Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, Kennesaw, Georgia, 30144, United States of America
- Bonafide Health, 500 Mamaroneck Avenue, Suite 510, Harrison, NY, 10528, United States of America
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Daljeet M, Warunek S, Covell DA, Monegro A, Giangreco T, Al-Jewair T. Association between obstructive sleep apnea syndrome and bone mineral density in adult orthodontic populations. Cranio 2025; 43:390-400. [PMID: 36368042 DOI: 10.1080/08869634.2022.2142724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To determine the association between obstructive sleep apnea syndrome (OSAS) and predicted bone mineral density (BMD) in adults presenting for orthodontic treatment. METHODS This retrospective cross-sectional study included 38 adults divided into OSAS and non-OSAS groups. Using pre-treatment CBCT images, radiographic density (RD) of left and right lateral regions of the 1st cervical vertebrae and dens of the 2nd cervical vertebrae were measured as an indicator for BMD. RESULTS When controlling for age, sex, and BMI, the mean RD was significantly lower in the OSAS group compared to the non-OSAS group (left CV1: 36.69 ± 84.50 vs. 81.67 ± 93.25 Hounsfield Units [HU], respectively, p = 0.031; right CV1: 30.59 ± 81.18 vs. 74.26 ± 91.81 HU, p = 0.045; dens: 159.25 ± 115.96 vs. 223.94 ± 106.09 HU, p = 0.038). CONCLUSION Adults with OSAS have lower values for predicted BMD than those without OSAS.
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Affiliation(s)
| | - Stephen Warunek
- Department of Orthodontics, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA
| | - David A Covell
- Department of Orthodontics, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA
| | - Alberto Monegro
- Pediatric Sleep Center, School of Medicine, University at Buffalo, Buffalo, NY, USA
| | | | - Thikriat Al-Jewair
- Department of Orthodontics, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA
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Li S, Zhang Y, Ding S, Chang J, Liu G, Hu S. Curcumin Ameliorated Glucocorticoid-Induced Osteoporosis While Modulating the Gut Microbiota and Serum Metabolome. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:8254-8276. [PMID: 40139762 DOI: 10.1021/acs.jafc.4c06689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Glucocorticoid-induced osteoporosis (GIOP) is the leading cause of secondary osteoporosis. Recently, the "bone-gut axis" theory has linked bone development with gut microbial diversity, community composition, and metabolites. Curcumin, a well-studied polyphenol, shows potential in mitigating bone loss and osteoporosis. Alendronate, a standard therapeutic agent for osteoporosis, serves as a positive control in this investigation. The study demonstrates the potency of curcumin in reducing bone loss and restoring bone mineral density, enhancing trabecular parameters notably through increased trabecular number, volume, and thickness and reduced bone marrow cavity size. Gut microbiome sequencing revealed that both curcumin and alendronate treatments similarly enhanced gut microbial diversity and altered microbiota composition, increasing beneficial bacteria (Akkermansia_muciniphila, Dubosiella_sp910585105, and Ruminococcus_sp910584195) while reducing harmful bacteria (Treponema_D_sp910584475 and Duncaniella_sp910584825). Furthermore, significant changes in serum levels of metabolites including raffinose, ursolic acid, spermidine, inosine, hypoxanthine, thiamine, and pantothenic acid were observed post-treatment with curcumin or alendronate. Importantly, these beneficial metabolites and microorganisms were negatively correlated with inflammatory cytokines. In conclusion, curcumin holds promise for use against GIOP by modulating the gut microbiome and serum metabolome as well as reducing systemic inflammation.
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Affiliation(s)
- Siying Li
- The Orthopaedic Center, The First People' s Hospital of Wenling, Wenling Hospital of Wenzhou Medical University, Wenling 317500, Zhejiang Province, China
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China
| | - Yating Zhang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China
| | - Sujuan Ding
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Jiang Chang
- The Orthopaedic Center, The First People' s Hospital of Wenling, Wenling Hospital of Wenzhou Medical University, Wenling 317500, Zhejiang Province, China
| | - Gang Liu
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Siwang Hu
- The Orthopaedic Center, The First People' s Hospital of Wenling, Wenling Hospital of Wenzhou Medical University, Wenling 317500, Zhejiang Province, China
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Ambrosio MR, Cattaneo CA, Gagliardi I, Carnevale A, Zatelli MC. Aetiology, diagnosis and treatment of thalassemia-associated osteoporosis of the adult. J Endocrinol Invest 2025; 48:799-815. [PMID: 39760968 DOI: 10.1007/s40618-024-02503-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/14/2024] [Indexed: 01/07/2025]
Abstract
AIM This review aims to overview factors contributing to TAO development and addresses the targeted diagnostic work-up and treatment management in adult thalassemic patients. RESULTS Osteoporosis management in Thalassemia is challenging because several factors contributing to its pathogenesis should be considered and controlled starting from child- hood. A multidisciplinary approach is crucial. Evidence concerning the efficacy of available anti-osteoporosis drugs in thalassemic patients is scarce. In this scenario, clinical experience and center resources often guide the treatment choice. More efforts should be made to share knowledge in this field in order to indicate specific treatment strategies for TAO management. METHODS We performed a literature search in Pubmed from 1992 to March 2024 using the words Thalassemia and: osteoporosis, Bisphosphonates, Denosumab, Teriparatide, Romosozumab, hormone replacement therapy, growth hormone, hypogonadism, calcium, vitamin D, bone disease, sarcopenia. The search was limited to English literature including original studies, reviews, meta-analyses, case reports.
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Affiliation(s)
- Maria Rosaria Ambrosio
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
| | - Camilla Alice Cattaneo
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Irene Gagliardi
- Service d'Endocrinologie, Diabétologie et Nutrition, Nantes Université, CHU Nantes, l'institut du thorax, Nantes, F-44000, France
| | - Aldo Carnevale
- Department of Translational Medicine - Section of Radiology, University of Ferrara, Ferrara, Italy
| | - Maria Chiara Zatelli
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
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Jacques LS, Pereira JPC, Santos BM, Barrioni BR, Del Bianco Borges B. Flaxseed and mulberry extract improve trabecular bone quality in estrogen-deficient rats. Climacteric 2025; 28:175-183. [PMID: 39937165 DOI: 10.1080/13697137.2025.2457988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/31/2024] [Accepted: 01/14/2025] [Indexed: 02/13/2025]
Abstract
Many hormones, including estrogens, modulate bone metabolism, which plays a crucial role in maintaining bone health. Estrogen depletion, as occurs in menopause, leads to increased bone resorption and decreased formation, resulting in osteopenia/osteoporosis. This study investigates the effects of flaxseed (Linum usitatissimum) and mulberry (Morus nigra L.) extracts, known for their phenolic compounds and antioxidant properties, against estrogen deficiency-induced bone loss in female Wistar rats. These extracts were administered to ovariectomized rats for 60 days. High-performance liquid chromatography analysis revealed the presence of some phenolic compounds in the extracts, including trigonelline, gallic acid, theobromine, chlorogenic acid, syringic acid and p-coumaric acid. The extracts improved bone microstructure with higher trabecular bone, bone mineral density, calcium, phosphorus and magnesium levels, and lower porosity and intertrabecular space in bone tissue. Furthermore, plasma alkaline phosphatase activity was elevated in extract-treated animals, indicating enhanced bone tissue formation. Although serum carboxy-terminal fragment levels showed no significant change, the data suggest that flaxseed and mulberry extracts may protect against trabecular bone loss and support bone formation in estrogen-deficient conditions. These results suggest that supplementing these natural extracts holds promise in preventing or alleviating the signs and symptoms associated with estrogenic deficiency.
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Affiliation(s)
- Larissa Sampaio Jacques
- Medicine Department, Health Science Faculty, Lavras Federal University - UFLA, Lavras, Brazil
| | | | - Beatriz Menegate Santos
- Medicine Department, Health Science Faculty, Lavras Federal University - UFLA, Lavras, Brazil
| | - Breno Rocha Barrioni
- Postgraduate Program in Metallurgical Engineering, Mines and Materials, Minas Gerais Federal University- UFMG, Belo Horizonte, Brazil
| | - Bruno Del Bianco Borges
- Medicine Department, Health Science Faculty, Lavras Federal University - UFLA, Lavras, Brazil
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Li S, Qiu J, Zhang X, Wang F, Yang X, Chen X, Guo X, Li Z, Lin M, Li X, He J, Lyu G, Zhang J. Comparison of microwave ablation and parathyroidectomy for treating severe secondary hyperparathyroidism. Front Endocrinol (Lausanne) 2025; 16:1424248. [PMID: 40130166 PMCID: PMC11931417 DOI: 10.3389/fendo.2025.1424248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 02/24/2025] [Indexed: 03/26/2025] Open
Abstract
Objective This study compared the efficacy of microwave ablation (MWA) and parathyroidectomy (PTX) in the treatment of secondary hyperparathyroidism (SHPT) and evaluated the improvement of bone metabolic markers (BMMs) and bone mineral density (BMD). Materials and methods Eligible patients with SHPT treated between January 2019 and August 2022 were enrolled in the study and were divided into two groups: MWA and PTX. Outcome measures included the treatment success rate, percentage of patients whose intact parathyroid hormone (iPTH) concentration was within the target range, serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (β-CXT), and BMD. Data on the procedure time, intraoperative blood loss volume, length and cost of hospitalization, incidence of postoperative complications, and recurrence rates were analyzed. Results A total of 107 patients with SHPT-48 in the MWA group and 59 in the PTX group- were included in the study. There were no significant differences in baseline data between the two groups (p>0.05). At the final follow-up, both therapies decreased iPTH, Ca, P, ALP, OC, and β-CXT levels and increased BMD (p<0.05). Nonetheless, the decrease in iPTH, ALP, OC, and β-CXT was more pronounced 6 and 12 months after PTX (p<0.05). The percentage of patients whose iPTH level was within the target range was significantly higher in the MWA group (p<0.05). The incidence of severe hypocalcemia was significantly lower in the MWA group (p<0.05). Conclusion MWA can improve BMMs and BMD, and is a minimally invasive approach with great potential for treating patients with SHPT who cannot tolerate PTX.
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Affiliation(s)
- Shuiping Li
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Jincheng Qiu
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xiaoguang Zhang
- Department of Interventional Ultrasound, The Fifth Clinical Medical College of Henan University of Traditional Chinese Medicine, Zhengzhou People’s Hospital, Zhengzhou, China
| | - Fuzhen Wang
- Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xianrong Yang
- Department of Thyroid and Breast Surgery, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xiaoyan Chen
- Department of Nuclear Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xiaofang Guo
- Department of Ophthalmology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Zuolin Li
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Min Lin
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xiaolian Li
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Jinghua He
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Guorong Lyu
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jiantang Zhang
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
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Kang TH, Chung ST, Seo IW, Cho M, Lee JH. Bone turnover markers are risk factors for endplate injuries during lumbar interbody fusion: a retrospective case-control study. J Orthop Surg Res 2025; 20:192. [PMID: 39987433 PMCID: PMC11847339 DOI: 10.1186/s13018-025-05585-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 02/06/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Intraoperative endplate injury (IEI) is a type of fracture and a potential complication during lumbar interbody fusion (LIF). Osteoporosis diagnosed by bone mineral density (BMD) is a well-known risk factor for fracture itself and IEI also. The bone turnover markers (BTMs) are parameters of bone qualities and have some correlations with fractures, but there is no study about the BTMs and intraoperative fractures especially IEI. This study aims to identify the correlation between IEI and BTMs, especially in misTLIF. METHODS We retrospectively reviewed 184 patients (230 spine levels). The IEI was diagnosed as the breakage of the endplate observed on postoperative 1 mm thin-cut CT scans. All surgical and endogenous risk factors of IEI were also checked including the bone resorption marker (serum CTX) and bone formation marker (serum P1NP) of BTMs. Additionally, the ratio (P1NP/CTX) and the subtype groups of BTMs were analyzed. RESULTS The rate of total IEI was 38%. The sex, osteoporosis, spine BMD, femur BMD, CTX, P1NP/CTX, preoperative disc height, and the discrepancy between preoperative disc height and cage size were risk factors in multivariate logistic regression analyses. The subtypes according to BTMs showed a different rate of IEI, resulting in subtype 2 A (low CTX and P1NP and high P1NP/CTX ratio) having the lowest incidence and statistically significant odds ratios compared to other subtype groups. CONCLUSION This study demonstrated that the IEI is related to BTMs regardless of BMD in misTLIF. In addition, the P1NP/CTX ratio or subtypes could be helpful in predicting the risk of IEI due to the parallel dynamics of BTMs.
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Affiliation(s)
- Tae Hoon Kang
- Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, 20, Boramae-ro 5-gil, Seoul, South Korea
- Department of Orthopedic Surgery, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, Republic of Korea
| | - Sung Taek Chung
- Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, 20, Boramae-ro 5-gil, Seoul, South Korea
- Department of Orthopedic Surgery, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, Republic of Korea
| | - In-Wook Seo
- Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, 20, Boramae-ro 5-gil, Seoul, South Korea
- Department of Orthopedic Surgery, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, Republic of Korea
| | - Minjoon Cho
- Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, 20, Boramae-ro 5-gil, Seoul, South Korea
- Department of Orthopedic Surgery, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, Republic of Korea
| | - Jae Hyup Lee
- Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, 20, Boramae-ro 5-gil, Seoul, South Korea.
- Department of Orthopedic Surgery, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
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11
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Bladt F, Varaeva YR, Retter GJ, Courtney A, Holloway PAH, Frost G, Garcia-Perez I, Birtwisle J, Beasley IFR, McGregor AH, Abel RL. Pilot Study of Bone Turnover Biomarkers, Diet, and Exercise in Elite Female Ballet Dancers. J Dance Med Sci 2025:1089313X251315812. [PMID: 39968943 DOI: 10.1177/1089313x251315812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
Introduction: Elite ballet is one of the most demanding physical activities for the skeleton, making dancers susceptible to bone stress injuries. This pilot study compared bone remodeling in professional female ballet dancers from the Royal Ballet Company with controls from Imperial College London. Methods: The study included dancers (n = 5, median age 29 ± 16 years) and controls (n = 6, median age 24 ± 8.5 years). The main outcome measure was bone turnover, assessed by measuring the ratio of resorption (NTX) and formation (P1NP) markers in urine and serum. Estrogen metabolism was evaluated through 2OH/16OH metabolite ratios. Both markers were measured using ELISA kits. Diet was tracked using 72-hour diaries, and weekly exercise hours were recorded through 2-week diaries and cross referenced with training logs. Results: Results showed significantly higher bone resorption to formation ratio (NTX/P1NP) in dancers versus controls (P < .050), and elevated estrogen metabolite ratios (2OH/16OH) (P < .010). These findings occurred despite similar dietary profiles between groups including fat (P = .874) carbohydrate (P = .501) and protein (P = .099). Dancers showed significantly higher weekly exercise hours (46.50 ± 38.75 vs 14.75 ± 11.75 hours/week, P < .001) and lower BMI (18.36 ± 1.35 vs 20.77 ± 3.66, P = .020). Conclusions: The pilot data suggest elite ballet dancers may exhibit an imbalance in bone remodeling with high resorption and low formation relative to controls. This imbalance in bone turnover markers could serve as a screening tool for identifying dancers at increased risk of bone stress injuries. The NTX/P1NP ratio could potentially offer a low-cost, non-invasive approach to identify at-risk dancers early and implement preventative measures. Further research and longitudinal trials are needed to test whether these markers can predict bone stress injury risk.
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Affiliation(s)
- Francesca Bladt
- Faculty of Medicine, MSk Lab, Department of Surgery and Cancer, Imperial College, London, UK
| | | | | | - Alan Courtney
- Clinical Biochemistry, North West London Pathology, Charing Cross Hospital, Imperial College NHS Healthcare, London, UK
| | | | - Gary Frost
- Faculty of Medicine, Department of Metabolism, Digestion, and Reproduction, Nutrition and Dietetic Research Group, Imperial College, London, UK
| | - Isabel Garcia-Perez
- Faculty of Medicine, Department of Metabolism, Digestion, and Reproduction, Nutrition and Dietetic Research Group, Imperial College, London, UK
| | | | | | - Alison Hazel McGregor
- Faculty of Medicine, MSk Lab, Department of Surgery and Cancer, Imperial College, London, UK
| | - Richard Leslie Abel
- Faculty of Medicine, MSk Lab, Department of Surgery and Cancer, Imperial College, London, UK
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12
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Houtenbos SP, He Y, Cazzanelli P, Soultoukis G, Wuertz-Kozak K, Schulz TJ, Wippert PM. The underlying mechanisms of the association of bone health with depression - an experimental study. Mol Biol Rep 2025; 52:163. [PMID: 39869252 PMCID: PMC11772516 DOI: 10.1007/s11033-025-10230-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 01/06/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND Depression constitutes a risk factor for osteoporosis, but underlying molecular and cellular mechanisms are not fully understood. MiRNAs influence gene expression and are carried by extracellular vesicles (EV), affecting cell-cell communication. AIMS (1) Identify the difference in miRNA expression between depressed patients and healthy controls; (2) Analyze associations of these miRNAs with bone turnover markers; (3) Analyze target genes of differentially regulated miRNAs and predict associated pathways regarding depression and bone metabolism. METHODS AND RESULTS Blood samples from depressed patients (n = 11) were obtained from a previous study and healthy controls (n = 9) were recruited. Sociodemographic, depression diagnosis and depressive symptom (BDI-II) data were collected through questionnaires. Blood plasma was collected from each participant and real-time-quantitative PCR was performed on isolated plasma EVs; differences in miRNA expression between groups were analyzed using qbase+. Regression models assessed the associations of differentially regulated miRNAs with bone turnover markers procollagen-1 N-terminal-peptide, osteocalcin, and crosslaps; enriched pathways and miRNA target gene networks were analyzed. 19 miRNAs were differentially expressed between groups (p < 0.05). MiR-26b-5p and miR-106a-5p showed an association with procollagen-1 N-terminal-peptide; miR-330-5p and miR-377-3p were associated with osteocalcin, and miR-26b-5p, miR-34c-3p and miR-145 with crosslaps. Pathway analysis including the differentially expressed miRNAs predicted enriched pathways, including the FoxO signaling and p53 signaling pathway. Seven target genes were identified. CONCLUSIONS MiRNAs (e.g. miR-26b-5p, miR-377-3p), genes (TNRC6B, HSPA8), and pathways (FoxO- and Hippo-signaling pathway) are identified which could be mediators between the influence of depression on bone health and could possibly serve as biomarkers in the treatment of bone diseases among people with mental disorders.
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Affiliation(s)
- Sanne Paulien Houtenbos
- Medical Sociology and Psychobiology, Department of Health and Physical Activity, University of Potsdam, 14469, Potsdam, Germany.
- Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, The Brandenburg, Medical School Theodor Fontane and The Brandenburg University of Technology Cottbus-Senftenberg, 14469, Potsdam, Germany.
| | - Yangyang He
- Medical Sociology and Psychobiology, Department of Health and Physical Activity, University of Potsdam, 14469, Potsdam, Germany
- Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, The Brandenburg, Medical School Theodor Fontane and The Brandenburg University of Technology Cottbus-Senftenberg, 14469, Potsdam, Germany
| | - Petra Cazzanelli
- Department of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY, 14623, USA
| | - George Soultoukis
- Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, 14458, Nuthetal, Germany
- German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany
| | - Karin Wuertz-Kozak
- Department of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY, 14623, USA
- Spine Center, Schön Klinik München Harlaching, Academic Teaching Hospital and Spine Research Institute of The Paracelsus Private Medical University Salzburg (Austria), 81547, Munich, Germany
| | - Tim J Schulz
- Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, 14458, Nuthetal, Germany
- German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany
- Institute of Nutritional Science, University of Potsdam, 14558, Nuthetal, Germany
| | - Pia-Maria Wippert
- Medical Sociology and Psychobiology, Department of Health and Physical Activity, University of Potsdam, 14469, Potsdam, Germany
- Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, The Brandenburg, Medical School Theodor Fontane and The Brandenburg University of Technology Cottbus-Senftenberg, 14469, Potsdam, Germany
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13
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Patel N, Ganti L. The Treatment and Monitoring of Osteoporosis using Bone Turnover Markers. Orthop Rev (Pavia) 2025; 17:127772. [PMID: 39790440 PMCID: PMC11710883 DOI: 10.52965/001c.127772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 11/26/2024] [Indexed: 01/12/2025] Open
Abstract
Osteoporosis is a degenerative bone disease that causes the weakening of bone structure. Since bone structure is dynamic throughout a person's lifespan, bones are under constant growth and destruction in a process known as bone turnover or bone remodeling. Osteoporosis involves the disruption of this growth/destruction equilibrium towards the destructive side. An increase in bone turnover leads to a lower bone density and therefore a greater risk of fracture or injury of higher severity. Bone turnover markers serve as indicators of the process of bone turnover. These markers are split into two groups: formation (building up) markers and resorption (breaking down) markers. Using biochemical techniques and assays, these markers can be measured to monitor the activity of the markers as well as determine treatment options and efficacy based on this activity. The use of biomarkers in osteoporosis can pave the way for their use in other diseases such as cancer.
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Affiliation(s)
| | - Latha Ganti
- Orlando College of Osteopathic Medicine
- Brown University
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14
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Persia S, Holmlund-Suila E, Valkama S, Enlund-Cerullo M, Rosendahl J, Andersson S, Mäkitie O, Hauta-alus H. Bone turnover markers, and growth and bone parameters in infants participating in a vitamin D intervention study. Endocr Connect 2025; 14:e240482. [PMID: 39555588 PMCID: PMC11728877 DOI: 10.1530/ec-24-0482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 11/08/2024] [Accepted: 11/18/2024] [Indexed: 11/19/2024]
Abstract
Amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-I) are markers of bone metabolism. We examined the effect of vitamin D3 supplementation on these markers and their relationship with growth and bone parameters in 12-month-old infants. In a randomized, double-blinded, vitamin D intervention in infants (VIDI) study, 987 infants received daily vitamin D3 supplementation of 10 μg (group-10) or 30 μg (group-30) from age 2 weeks to 24 months. We conducted a secondary analysis of the original VIDI trial. At 12 months of age, P1NP (n = 812) and CTX-I (n = 786) concentrations were analyzed, and anthropometrics and total bone mineral content, volumetric bone mineral density, cross-sectional area and polar moment of inertia of tibia were measured by peripheral quantitative computed tomography. The growth rate in weight and length was calculated from birth to 12 months. The vitamin D dose did not influence mean (SD) levels of CTX-I (group-10: 0.90 (0.31); group-30: 0.89 (0.31) (P > 0.53)). The mean difference of P1NP (CI 95%) comparing group-10 with group-30 was 35 (-103, 33) ng/mL (P = 0.31) in boys and -63 (-4, 130) ng/mL (P = 0.064) in girls. In group-10, girls had higher mean (SD) value of P1NP (1509 (362) ng/mL) than boys (1407 (297) ng/mL) (P = 0.003); no sex differences were observed in group-30 (girls: 1446 (359); boys: 1442 (359), P = 0.91) or CTX-I. P1NP associated positively with the growth rate in length (B (CI 95%) 0.0003 (0.0001, 0.001), P = 0.022) in the whole cohort but not in subgroups divided by the intervention group or sex, adjusted for birth size and parental heights and corrected for multiple testing. P1NP associated positively with the growth rate in weight (0.01 (0.0003, 0.01), P < 0.001). An inverse association was observed between CTX-I and length (cm) in the whole cohort (-0.90 (-1.40, -0.40), P = 0.005) and in group-30 (-1.05 (-1.72, -0.39), P = 0.011). Furthermore, CTX-I associated negatively with weight (SDS) in the whole cohort (-0.33 (-0.55, -0.12), P = 0.015) and the growth rate in weight (-0.43 (-0.66, -0.20), P = 0.005), persisting in group-30 and in boys but not in group-10 or in girls. Neither marker was associated with bone parameters. The observed sex difference in P1NP might suggest that a higher vitamin D dose resulted in a small decrease in bone collagen matrix formation in girls but not in boys. P1NP and CTX-I associate with growth and body size but not with bone mineralization in infancy.
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Affiliation(s)
- Sabrina Persia
- Children’s Hospital Bambino Gesù, Tor Vergata University, Rome, Italy
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Elisa Holmlund-Suila
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Saara Valkama
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Maria Enlund-Cerullo
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Folkhälsan Institute of Genetics, Helsinki, Finland
| | - Jenni Rosendahl
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Sture Andersson
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Outi Mäkitie
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Folkhälsan Institute of Genetics, Helsinki, Finland
- Department of Moecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden
| | - Helena Hauta-alus
- Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Population Health Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
- Clinical Medicine Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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15
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Muollo V, Hvid LG, Shanbhogue VV, Steinhauser V, Caporossi D, Dimauro I, Andersen MS, Fantini C, Grazioli E, Strotmeyer ES, Caserotti P. Effects of 12-week power training on bone in mobility-limited older adults: randomised controlled trial. Arch Osteoporos 2024; 20:5. [PMID: 39729186 DOI: 10.1007/s11657-024-01487-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 12/13/2024] [Indexed: 12/28/2024]
Abstract
This study examines how power training affects estimated bone strength, revealing that females benefit more than males, especially in the upper limbs (radius). These findings highlight the importance of designing sex-specific exercise programs to enhance bone health. Further research is needed to optimize training duration and address site-specific differences. PURPOSE This study aimed to compare the effects of 12-week of power training (PWT), an explosive form of strength training, on bone microarchitecture, estimated bone strength, and markers in mobility-limited (gait speed < 0.9 m/s) older adults. METHODS Fifty-seven older adults (83 ± 5 years) were randomly assigned to either a training group (TRAIN, n = 28, 15 females, 13 males) performing high-intensity PWT or a control group (CTRL, n = 29, 22 females, 7 males) maintaining their usual lifestyle. High-resolution peripheral quantitative computed tomography (HR-pQCT) assessed bone geometry, densities, microarchitecture (e.g. trabecular number (Tb.N) and thickness (Tb.Th)), and estimated bone strength (stiffness and failure load) at the tibia and radius. Blood markers for bone metabolism (PINP and CTX-1) and muscle strength (handgrip and leg press) were also measured. RESULTS Baseline sex differences showed females having lower stiffness (- 37.5%) and failure load (- 38%) at the radius compared with males. After PWT, females in the TRAIN group exhibited declines in Tb.N (- 4.4%) and improvements in Tb.Th (+ 6.0%), stiffness (+ 2.7%), and failure load (+ 2.4%) at the radius (p < 0.05). A time x group interaction indicated increases in leg press strength for the whole TRAIN group (+ 23%), and within females (+ 29%) and males (+ 19%) (p < 0.001). Baseline handgrip strength correlated with stiffness (r = 0.577) and failure load (r = 0.612) at the radius (p < 0.001). Females in the TRAIN group showed a reduction in PINP (- 25%), while males showed an increase in CTX-1 (+ 18%). CONCLUSION A 12-week PWT may enhance estimated bone strength in mobility-limited older adults, especially at sites less accustomed to daily loading (i.e. radius). CLINICAL TRIAL REGISTRATION NCT02051725.
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Affiliation(s)
- Valentina Muollo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
| | - Lars G Hvid
- Department of Public Health, Exercise Biology, Aarhus University, Aarhus C, Denmark
- The Danish MS Hospitals, Ry and Haslev, Denmark
| | | | - Viktoria Steinhauser
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
| | - Daniela Caporossi
- Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | - Ivan Dimauro
- Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | | | - Cristina Fantini
- Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | - Elisa Grazioli
- Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | - Elsa S Strotmeyer
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Paolo Caserotti
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
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16
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Hammad M, Oktarina A, Suhardi VJ, Thomson A, Li Q, Döring K, Augustin EJ, Ivashkiv LB, Carli AV, Bostrom MPG, Yang X. Effects of antiseptic irrigation solutions on osseointegration in a cementless tibial implantation mouse model. J Orthop Res 2024; 42:2852-2862. [PMID: 39017392 DOI: 10.1002/jor.25937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 06/29/2024] [Indexed: 07/18/2024]
Abstract
Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H2O2) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H2O2, or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications.
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Affiliation(s)
- Mohammed Hammad
- Research Institute, Hospital for Special Surgery, New York, New York, USA
| | - Anastasia Oktarina
- Research Institute, Hospital for Special Surgery, New York, New York, USA
| | - Vincentius J Suhardi
- Research Institute, Hospital for Special Surgery, New York, New York, USA
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, USA
| | - Andrew Thomson
- Research Institute, Hospital for Special Surgery, New York, New York, USA
| | - Qingdian Li
- Research Institute, Hospital for Special Surgery, New York, New York, USA
- Department of Orthopaedic Surgery, Weill Cornell Medicine, New York, USA
| | - Kevin Döring
- Research Institute, Hospital for Special Surgery, New York, New York, USA
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria
| | - Edouard J Augustin
- Research Institute, Hospital for Special Surgery, New York, New York, USA
| | - Lionel B Ivashkiv
- Research Institute, Hospital for Special Surgery, New York, New York, USA
| | - Alberto V Carli
- Research Institute, Hospital for Special Surgery, New York, New York, USA
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, USA
- Department of Orthopedics, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China
| | - Mathias P G Bostrom
- Research Institute, Hospital for Special Surgery, New York, New York, USA
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, USA
- Department of Orthopedics, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China
| | - Xu Yang
- Research Institute, Hospital for Special Surgery, New York, New York, USA
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, USA
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17
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Lin PID, Cardenas A, Rokoff LB, Rifas-Shiman SL, Zhang M, Botelho J, Calafat AM, Gold DR, Zota AR, James-Todd T, Hauser R, Webster TF, Oken E, Fleisch AF. Associations of PFAS concentrations during pregnancy and midlife with bone health in midlife: Cross-sectional and prospective findings from Project Viva. ENVIRONMENT INTERNATIONAL 2024; 194:109177. [PMID: 39667063 DOI: 10.1016/j.envint.2024.109177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 10/12/2024] [Accepted: 11/29/2024] [Indexed: 12/14/2024]
Abstract
BACKGROUND PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown. METHODS We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife. RESULTS Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g. , PFOA 1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women. DISCUSSION Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.
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Affiliation(s)
- Pi-I Debby Lin
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Andres Cardenas
- Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA
| | - Lisa B Rokoff
- Center for Interdisciplinary Population & Health Research, MaineHealth Institute for Research, Westbrook, ME, USA
| | - Sheryl L Rifas-Shiman
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Mingyu Zhang
- Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Julianne Botelho
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Antonia M Calafat
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Diane R Gold
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Ami R Zota
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA
| | - Tamarra James-Todd
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Russ Hauser
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Thomas F Webster
- Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA
| | - Emily Oken
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Abby F Fleisch
- Center for Interdisciplinary Population & Health Research, MaineHealth Institute for Research, Westbrook, ME, USA; Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA.
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18
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Demir SA, Seyrantepe V. Abnormally accumulated GM2 ganglioside contributes to skeletal deformity in Tay-Sachs mice. J Mol Med (Berl) 2024; 102:1517-1526. [PMID: 39514043 DOI: 10.1007/s00109-024-02498-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 10/03/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
Tay-Sachs Disease is a rare lysosomal storage disorder caused by mutations in the HEXA gene, responsible for the degradation of ganglioside GM2. In addition to progressive neurodegeneration, Tay-Sachs patients display bone anomalies, including kyphosis. Tay-Sachs disease mouse model (Hexa-/-Neu3-/-) shows both neuropathological and clinical abnormalities of the infantile-onset disease phenotype. In this study, we investigated the effects of GM2 accumulation on bone remodeling activity. Here, we evaluated the bone phenotype of 5-month-old Hexa-/-Neu3-/- mice with age-matched control groups using gene expression analysis, bone plasma biomarker analysis, and micro-computed tomography. We demonstrated lower plasma alkaline phosphatase activity and calcium levels with increased tartrate-resistant acid phosphatase levels, indicating reduced bone remodeling activity in mice. Consistently, gene expression analysis confirmed osteoblast reduction and osteoclast induction in the femur of mice. Micro-computed tomography and analysis show reduced trabecular bone volume, mineral density, number, and thickness in Hexa-/-Neu3-/- mice. In conclusion, we demonstrated that abnormal GM2 ganglioside accumulation significantly triggers skeletal abnormality in Tay-Sachs mice. We suggest that further investigation of the molecular basis of bone structure anomalies is necessary to elucidate new therapeutic targets that prevent the progression of bone symptoms and improve the life standards of Tay-Sachs patients. KEY MESSAGES: We detected the markers of bone loss-associated disorders such as osteopenia and osteoporosis in the Tay-Sachs disease mice model Hexa-/-Neu3-/-. We also demonstrated for the first time there is an increase in trabecular spacing and a reduction in trabecular thickness and number indicating skeletal abnormalities in mice model using micro-CT analysis.
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Affiliation(s)
| | - Volkan Seyrantepe
- Izmir Institute of Technology, IYTEDEHAM, Urla, Izmir, Turkey.
- Department of Molecular Biology and Genetics, Izmir Institute of Technology, Urla, Izmir, Turkey.
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19
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Indarwulan N, Savitri M, Ashariati A, Bintoro SUY, Diansyah MN, Amrita PNA, Romadhon PZ. Bone Mineral Density, C-Terminal Telopeptide of Type I Collagen, and Osteocalcin as Monitoring Parameters of Bone Remodeling in CML Patients Undergoing Imatinib Therapy: A Basic Science and Clinical Review. Diseases 2024; 12:275. [PMID: 39589949 PMCID: PMC11592756 DOI: 10.3390/diseases12110275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/17/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Chronic myeloid leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a tyrosine kinase inhibitor (TKI), can be effectively used as therapy for CML. However, Imatinib can affect bone turnover thus having clinical implications on the bones of CML patients undergoing long-term Imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving Imatinib still need further study. A combination of imaging techniques such as bone mineral density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving Imatinib. OBJECTIVES This article explains the rationale for using BMD, CTX-1, and osteocalcin as monitoring parameters of bone remodeling in CML patients receiving Imatinib. RESULTS First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of Imatinib on BMD, CTX-1, and osteocalcin will be explained. CONCLUSION The assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and osteocalcin.
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Affiliation(s)
- Nurita Indarwulan
- Subspeciality Program in Hematology and Medical Oncology Division, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia;
- Subspeciality Program in Hematology and Medical Oncology Division, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Merlyna Savitri
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia; (A.A.); (S.U.Y.B.); (M.N.D.); (P.N.A.A.); (P.Z.R.)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Ami Ashariati
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia; (A.A.); (S.U.Y.B.); (M.N.D.); (P.N.A.A.); (P.Z.R.)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Siprianus Ugroseno Yudho Bintoro
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia; (A.A.); (S.U.Y.B.); (M.N.D.); (P.N.A.A.); (P.Z.R.)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Muhammad Noor Diansyah
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia; (A.A.); (S.U.Y.B.); (M.N.D.); (P.N.A.A.); (P.Z.R.)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Putu Niken Ayu Amrita
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia; (A.A.); (S.U.Y.B.); (M.N.D.); (P.N.A.A.); (P.Z.R.)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Pradana Zaky Romadhon
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia; (A.A.); (S.U.Y.B.); (M.N.D.); (P.N.A.A.); (P.Z.R.)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
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20
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Li Q, Wang J, Zhao C. From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches. Biomedicines 2024; 12:2389. [PMID: 39457701 PMCID: PMC11505085 DOI: 10.3390/biomedicines12102389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/16/2024] [Accepted: 10/17/2024] [Indexed: 10/28/2024] Open
Abstract
Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies-genomics, transcriptomics, proteomics, and metabolomics-have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions.
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Affiliation(s)
- Qingmei Li
- Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, China
| | - Jihan Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, China
| | - Congzhe Zhao
- Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, China
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21
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Octarina O, Munadziroh E, Razak FA, Handharyani E, Surboyo MDC. The Role of Bovine Amniotic Membrane and Hydroxyapatite for the Ridge Preservation. Int J Biomater 2024; 2024:4053527. [PMID: 39376510 PMCID: PMC11458299 DOI: 10.1155/2024/4053527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 08/19/2024] [Accepted: 08/27/2024] [Indexed: 10/09/2024] Open
Abstract
Ridge preservation is an important technique for maintaining the dimensions of the alveolar bone following tooth extraction, which is crucial for successful tooth rehabilitation. The combination of bovine amniotic membrane and hydroxyapatite has shown promise as a scaffold material containing growth factors that can stimulate osteogenic-related factors such as bone morphogenetic protein 2 (BMP2), Runt-related transcription factor 2 (RUNX2), and osteocalcin. This stimulation leads to collagen production and osteoblast proliferation, resulting in new bone formation. In this study, bovine amniotic membrane-hydroxyapatite (BAM-HA) composites were prepared using three different ratios of bovine amniotic membrane and hydroxyapatite (2 : 3, 3 : 7, 7 : 13). Thirty Sprague-Dawley rats had their first incisors extracted, and different types of BAM-HA were applied for ridge preservation. The control group received no treatment, while the positive control group was given xenograft. After 14 and 28 days, the animals were sacrificed, and immunohistochemical analysis was performed to evaluate the expression of BMP2, RUNX2, and osteocalcin. Additionally, a histological examination was conducted to analyse collagen thickness and osteoblast cell proliferation. The results demonstrated that the application of BAM-HA significantly increased collagen density, osteoblast cell proliferation, and the expression of BMP2, RUNX2, and osteoclacin compared to the control group (p < 0.05) on both days 14 and 28. Furthermore, increasing the hydroxyapatite content in the composite was found to enhance collagen thickness, osteoblast cell proliferation, and the expression of osteogenic-related factors. These preliminary findings suggest that the combination of BAM-HA can be used for ridge preservation to prevent further bone resorption following tooth extraction.
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Affiliation(s)
- Octarina Octarina
- Department of Dental Material, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia
- Doctoral Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
| | - Elly Munadziroh
- Department of Dental Material, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
| | - Fathilah Abdul Razak
- Department of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Ekowati Handharyani
- Division of Pathology, School of Veterinary Medicine and Biomedical, Institute Pertanian Bogor University, Bogor 16680, Indonesia
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22
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Hutson MJ, Varley I. An Opinion on the Interpretation of Bone Turnover Markers Following Acute Exercise or Nutrition Intervention and Considerations for Applied Research. Int J Sport Nutr Exerc Metab 2024; 34:315-321. [PMID: 38925537 DOI: 10.1123/ijsnem.2024-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 05/24/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024]
Abstract
It is important for athlete and public health that we continue to develop our understanding of the effects of exercise and nutrition on bone health. Bone turnover markers (BTMs) offer an opportunity to accelerate the progression of bone research by revealing a bone response to exercise and nutrition stimuli far more rapidly than current bone imaging techniques. However, the association between short-term change in the concentration of BTMs and long-term bone health remains ambiguous. Several other limitations also complicate the translation of acute BTM data to applied practice. Importantly, several incongruencies exist between the effects of exercise and nutrition stimuli on short-term change in BTM concentration compared with long-term bone structural outcomes to similar stimuli. There are many potential explanations for these inconsistencies, including that short-term study designs fail to encompass a full remodeling cycle. The current article presents the opinion that data from relatively acute studies measuring BTMs may not be able to reliably inform applied practice aiming to optimize bone health. There are important factors to consider when interpreting or translating BTM data and these are discussed.
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Affiliation(s)
- Mark J Hutson
- School of Sport, Faculty of Life and Health Sciences, Ulster University, Coleraine, United Kingdom
| | - Ian Varley
- School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom
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23
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Shankar R, Saha A, Dhull RS, Shroff R, Nangia A, Sharma S. Activin A: a marker of mineral bone disorder in children with chronic kidney disease? Pediatr Nephrol 2024; 39:2773-2777. [PMID: 38744714 DOI: 10.1007/s00467-024-06400-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/26/2024] [Accepted: 04/26/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.
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Affiliation(s)
- Raagul Shankar
- Division of Pediatric Nephrology, Department of Pediatrics, Lady Hardinge Medical College & Kalawati Saran Children's Hospital, New Delhi, India
| | - Abhijeet Saha
- Division of Pediatric Nephrology, Department of Pediatrics, Lady Hardinge Medical College & Kalawati Saran Children's Hospital, New Delhi, India.
| | - Rachita Singh Dhull
- Renal Unit, UCL Great Ormond Street Hospital and Institute of Child Health, London, UK
| | - Rukshana Shroff
- Renal Unit, UCL Great Ormond Street Hospital and Institute of Child Health, London, UK
| | - Anita Nangia
- Department of Pathology, Lady Hardinge Medical College & Sucheta Kriplani Hospital, New Delhi, India
| | - Sunita Sharma
- Department of Pathology, Lady Hardinge Medical College & Sucheta Kriplani Hospital, New Delhi, India
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24
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Deng D, Liu X, Huang W, Yuan S, Liu G, Ai S, Fu Y, Xu H, Zhang X, Li S, Xu S, Bai X, Zhang Y. Osteoclasts control endochondral ossification via regulating acetyl-CoA availability. Bone Res 2024; 12:49. [PMID: 39198395 PMCID: PMC11358419 DOI: 10.1038/s41413-024-00360-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 06/27/2024] [Accepted: 07/21/2024] [Indexed: 09/01/2024] Open
Abstract
Osteoclast is critical in skeletal development and fracture healing, yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear. Here, by using osteoclast-specific small GTPase Rheb1-knockout mice, we reveal that mitochondrial respiration, rather than glycolysis, is essential for cathepsin K (CTSK) production in osteoclasts and is regulated by Rheb1 in a mechanistic target of rapamycin complex 1 (mTORC1)-independent manner. Mechanistically, we find that Rheb1 coordinates with mitochondrial acetyl-CoA generation to fuel CTSK, and acetyl-CoA availability in osteoclasts is the central to elevating CTSK. Importantly, our findings demonstrate that the regulation of CTSK by acetyl-CoA availability is critical and may confer a risk for abnormal endochondral ossification, which may be the main cause of poor fracture healing on alcohol consumption, targeting Rheb1 could successfully against the process. These findings uncover a pivotal role of mitochondria in osteoclasts and provide a potent therapeutic opportunity in bone disorders.
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Affiliation(s)
- Daizhao Deng
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Xianming Liu
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Wenlan Huang
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Sirui Yuan
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Genming Liu
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Shanshan Ai
- Department of Physiology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Yijie Fu
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Haokun Xu
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Xinyi Zhang
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Shihai Li
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Song Xu
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
| | - Xiaochun Bai
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China.
| | - Yue Zhang
- Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong, China.
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25
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Thuong LHH, Hsu CJ, Chen HT, Kuo YH, Tang CH. Caffeic acid derivative MPMCA suppresses osteoclastogenesis and facilitates osteoclast apoptosis: implications for the treatment of bone loss disorders. Aging (Albany NY) 2024; 16:11926-11938. [PMID: 39189924 PMCID: PMC11386915 DOI: 10.18632/aging.206067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 07/18/2024] [Indexed: 08/28/2024]
Abstract
Osteoclast activity plays a crucial role in the pathological mechanisms of osteoporosis and bone remodeling. The treatment of these disorders involves the use of pharmacological medicines that work by inhibiting the activity of osteoclasts. Nevertheless, the prevalent and infrequent negative consequences of current antiresorptive and bone anabolic treatments pose significant drawbacks, hence restricting their prolonged administration in patients, particularly those who are elderly and/or suffer from many medical conditions. We are currently in the process of creating a new molecule called N-(4-methoxyphen) methyl caffeamide (MPMCA), which is a derivative of caffeic acid. This compound has shown potential in preventing the production of osteoclasts and causing existing osteoclasts to undergo cell apoptosis. Our investigation discovered that MPMCA hinders osteoclast function via suppressing the MAPK pathways. The expectation is that the findings of this study will stimulate the advancement of a novel approach to treating anti-resorption.
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Affiliation(s)
- Le Huynh Hoai Thuong
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Chin-Jung Hsu
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
- Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Hsien-Te Chen
- Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- Department of Sports Medicine, China Medical University, Taichung, Taiwan
| | - Yueh-Hsiung Kuo
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan
- Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
| | - Chih-Hsin Tang
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
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26
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Oni E, Boakye E, Pressman GS, Dardari Z, Jha K, Szklo M, Budoff M, Nasir K, Hughes TM, Blaha MJ. The Association of Mitral Annular Calcification With Cardiovascular and Noncardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis. Am J Cardiol 2024; 225:75-83. [PMID: 38914415 DOI: 10.1016/j.amjcard.2024.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 05/28/2024] [Accepted: 06/12/2024] [Indexed: 06/26/2024]
Abstract
Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). In addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes.
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Affiliation(s)
- Ebenezer Oni
- Division of Cardiology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania.
| | - Ellen Boakye
- Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Gregg S Pressman
- Division of Cardiology, Einstein Medical Center, Philadelphia, Pennsylvania
| | - Zeina Dardari
- Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kunal Jha
- Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky
| | - Moyses Szklo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Matthew Budoff
- Lundquist Institute, Harbor-UCLA Medical Center, Torrance, California
| | - Khurram Nasir
- Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas
| | - Timothy M Hughes
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Michael J Blaha
- Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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27
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Cazzolla AP, Brescia V, Lovero R, Fontana A, Giustino A, Dioguardi M, Di Comite MS, Di Serio F, Ciavarella D, Crincoli V. Evaluation of Biomarkers of Bone Metabolism on Salivary Matrix in the Remodeling of Periodontal Tissue during Orthodontic Treatment. Dent J (Basel) 2024; 12:209. [PMID: 39056996 PMCID: PMC11276302 DOI: 10.3390/dj12070209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 05/23/2024] [Accepted: 06/27/2024] [Indexed: 07/28/2024] Open
Abstract
The aim of this study was to evaluate changes in the concentration of N-terminal type I collagen extension pro-peptide (PINP), tartrate-resistant acid phosphatase (TRAcP), and parathyroid hormone-related protein (PTHrP) in saliva during orthodontic treatment in order to evaluate whether changes in bone turnover marker (BTM) concentration can help highlight the effects of orthodontic mechanical loading in the absence of clinical evidence of tooth movement in terms of tooth movement. Saliva samples from 25 apparently healthy young subjects (10 females and 15 males) were collected using Salivette® (Sarstedt) with cotton swabs and the concentrations of PTHrP, TRAcP 5b, and PINP were analyzed at time 0 (T1), 25 days (T2), and at 45 days (T3). Differences in the median value of biomarker levels between baseline T1 and follow-up of the different groups (T2 and T3) were assessed using the non-parametric Mann-Whitney U test. Trough concentrations of P1NP, PTHrP, and TRAcP were 0.80 µg/L, 0.21 ng/mL, and 0.90 U/L above the method LOD. The non-parametric Mann-Whitney U test confirmed a statistically significant difference in T1 versus concentrations of T2 and T3. All subjects evaluated had a statistically significant difference between T1 vs. T3. when compared with the specific critical difference (RCV) for the analyte The results obtained demonstrate that the evaluation of BTM changes in saliva can help the evaluation of orthodontic procedures and the monitoring of biomechanical therapy.
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Affiliation(s)
- Angela Pia Cazzolla
- Department of Clinical and Experimental Medicine, Università degli Studi di Foggia, 71100 Foggia, Italy; (M.D.); (D.C.)
| | - Vincenzo Brescia
- Clinical Pathology Unit, AOU Policlinico Consorziale di Bari—Ospedale Giovanni XXIII, 70124 Bari, Italy; (V.B.); (R.L.); (A.F.); (F.D.S.)
| | - Roberto Lovero
- Clinical Pathology Unit, AOU Policlinico Consorziale di Bari—Ospedale Giovanni XXIII, 70124 Bari, Italy; (V.B.); (R.L.); (A.F.); (F.D.S.)
| | - Antonietta Fontana
- Clinical Pathology Unit, AOU Policlinico Consorziale di Bari—Ospedale Giovanni XXIII, 70124 Bari, Italy; (V.B.); (R.L.); (A.F.); (F.D.S.)
| | - Arcangela Giustino
- Department of Biomedical Sciences and Human Oncology, Aldo Moro, University of Bari, 70121 Bari, Italy;
| | - Mario Dioguardi
- Department of Clinical and Experimental Medicine, Università degli Studi di Foggia, 71100 Foggia, Italy; (M.D.); (D.C.)
| | - Maria Severa Di Comite
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Human Anatomy Section, Aldo Moro, University of Bari, 70121 Bari, Italy;
| | - Francesca Di Serio
- Clinical Pathology Unit, AOU Policlinico Consorziale di Bari—Ospedale Giovanni XXIII, 70124 Bari, Italy; (V.B.); (R.L.); (A.F.); (F.D.S.)
| | - Domenico Ciavarella
- Department of Clinical and Experimental Medicine, Università degli Studi di Foggia, 71100 Foggia, Italy; (M.D.); (D.C.)
| | - Vito Crincoli
- Interdisciplinary Department of Medicine, Aldo Moro, University of Bari, 70121 Bari, Italy
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Dutta D, Nagendra L, Chandran M, Sharma M, Bhattacharya S, Mukhopadhyay S. Impact of Pheochromocytoma or Paraganglioma on Bone Metabolism: A Systemic Review and Meta-analysis. J Clin Densitom 2024; 27:101501. [PMID: 38796986 DOI: 10.1016/j.jocd.2024.101501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 04/29/2024] [Accepted: 04/30/2024] [Indexed: 05/29/2024]
Abstract
INTRODUCTION Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. METHODS Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). RESULTS Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. CONCLUSION Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.
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Affiliation(s)
- Deep Dutta
- Department of Endocrinology, Centre for Endocrinology, Arthritis, and Rheumatism (CEDAR), Superspeciality Healthcare, Dwarka, New Delhi, India
| | - Lakshmi Nagendra
- Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, Karnataka, India.
| | - Manju Chandran
- Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore; DUKE-NUS Medical School, Singapore, Singapore
| | - Meha Sharma
- Department of Rheumatology, Centre for Endocrinology, Arthritis, and Rheumatism (CEDAR), Superspeciality Healthcare, Dwarka, New Delhi, India
| | | | - Satinath Mukhopadhyay
- Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research (IPGME&R) and Seth Sukhlal Karnani Memorial (SSKM) Hospital, Kolkata, India
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Dou J, Liang Z, Liu J, Liu N, Hu X, Tao S, Zhen X, Yang L, Zhang J, Jiang G. Quinoa alleviates osteoporosis in ovariectomized rats by regulating gut microbiota imbalance. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:5052-5063. [PMID: 38284744 DOI: 10.1002/jsfa.13339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 01/04/2024] [Accepted: 01/23/2024] [Indexed: 01/30/2024]
Abstract
BACKGROUND Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota. RESULTS Quinoa significantly improved osteoporosis-related biochemical parameters of OVX rats and ameliorated ovariectomy-induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD-like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis. CONCLUSION Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Jinfang Dou
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Zhengting Liang
- School of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China
| | - Jiaxian Liu
- Zhong Li Science and Technology Limited Company, Beijing, China
| | - Nannan Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xuehong Hu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Siyu Tao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xianjie Zhen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Lihua Yang
- Tangshan Maternal and Child Health Care Hospital, Tangshan, China
| | - Jinghua Zhang
- Tangshan Maternal and Child Health Care Hospital, Tangshan, China
| | - Guangjian Jiang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Sari GM, Kusumawati I, Arifandi YA, Swannjo JB. Effects of cosmos caudatus (Kenikir) antioxidant properties on bone metabolism marker in rat. Curr Res Physiol 2024; 7:100128. [PMID: 38841653 PMCID: PMC11150957 DOI: 10.1016/j.crphys.2024.100128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 04/26/2024] [Accepted: 05/14/2024] [Indexed: 06/07/2024] Open
Abstract
Cosmos caudatus leaves are one of around 7500 types of plants that are known to have herbal or medicinal plant properties in Indonesia. This research determines the effectiveness of Cosmos caudatus as an antioxidant agent against cells, biomolecules, and bone density. Forty-three male rat aged 3-4 months were divided into four groups.Group P0 was only given distilled water. Group P1 was given kenikir leaf extract at a dose of 0.91 mg/kg. Group P2 was given kenikir leaf extract at a dose of 1.82 mg/kg. And group P3 was given kenikir leaf extract at 3.64 mg/kg ad libitum once a day for 28 days. The highest average SOD level was in the 1.82 mg/bb P2 conversion dose group (1.09 ± 1.76). The lowest mean CTX level was in the P2 group (8.30 ± 1.10). There was a significant increase in mean trabecular bone in the P2 group (43.33 ± 5.32). The number of osteoblast cells increased significantly at P2 (103.94 (SD 38.14)). The number of osteoclasts decreased from the control group (P0) to 0.60 (SD 0.43) at P2. Indicate that the Cosmos caudatus extract may have advantages as an antioxidant support agent for bone metabolism.
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Affiliation(s)
- Gadis Meinar Sari
- Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Idha Kusumawati
- Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia
| | - Yoga Akbar Arifandi
- Medical Profession Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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Łapiński M, Żarnovsky K, Czarzasta K, Maciąg B, Maciąg G, Adamska O, Mamcarz A, Stolarczyk A. Bone turnover markers and muscle decay indicator in patients with proximal femur fracture - a case-control study. Reumatologia 2024; 62:121-127. [PMID: 38799774 PMCID: PMC11114133 DOI: 10.5114/reum/187096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/12/2024] [Indexed: 05/29/2024] Open
Abstract
Introduction Fracture of the proximal femur is common in elderly patients, in fact threatening their lives. Age-related sarcopenia may be involved in the imbalance resulting in the injury. Handy and readily accessible biochemical tests would be useful to assess the musculoskeletal system condition in daily practice. The aim of the study was to determine whether there is any relation between muscle decay and fracture of the proximal femur and to assess bone quality in elderly patients. Material and methods In the study 22 patients who represented the treatment group were hospitalized due to proximal femur fracture. Eighteen patients from the control group with no fracture in their history were admitted to the Internal Medicine Department. Anyone treated for osteoporosis, immune disease affecting protein balance, neoplasm, mental illness, heart failure, or myocardial infarction was excluded from the study. In every case a blood sample from an elbow vein was drawn, collected in EDTA-K2 tubes, and then centrifuged to separate plasma from the whole blood. Subsequently, the concentrations of C-terminal cross-linked telopeptide of type I collagen (CTX-I), sex hormone binding globulin (SHBG) and creatine kinase (CK) in plasma were determined using commercial enzyme-linked immunosorbent assays. Results The CK plasma concentration differed between the patient groups (p = 0.011). The SHBG plasma concentration was significantly higher in the treatment group (p = 0.006), whereas a slight difference in CTX-I plasma concentration between the groups was found (p = 0.038). No significant correlations between plasma CK, SHBG or CTX-I were found (p > 0.05). Conclusions Creatine kinase is actually not an appropriate marker for the clinical assessment of muscle tissue quality in patients with or at risk of proximal femur fracture. Analyzing the quality of bone tissue, we can conclude it was poorer in patients with proximal femur fracture than in the control group.
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Affiliation(s)
- Marcin Łapiński
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Poland
| | - Krystian Żarnovsky
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Poland
| | - Katarzyna Czarzasta
- Department of Experimental and Clinical Physiology, Medical University of Warsaw, Poland
| | - Bartosz Maciąg
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Poland
| | - Grzegorz Maciąg
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Poland
| | - Olga Adamska
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Poland
| | - Artur Mamcarz
- Department of Internal Medicine and Cardiology, Medical University of Warsaw, Poland
| | - Artur Stolarczyk
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Poland
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Baudin J, Hernandez-Baixauli J, Quesada-Vázquez S, Mulero F, Puiggròs F, Arola L, Caimari A. Combined supplementation with hesperidin, phytosterols and curcumin decreases adiposity and improves metabolic health in ovariectomized rats. Food Funct 2024; 15:4905-4924. [PMID: 38598180 DOI: 10.1039/d3fo05122f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
In recent years many women have looked for alternative therapies to address menopause. Hesperidin, phytosterols and curcumin are bioactive compounds that can ameliorate some cardiovascular risk factors associated with menopause, although there are no data concerning the effects of their combined supplementation. We used ovariectomized (OVX) rats, a postmenopausal model with oestrogen deficiency, to evaluate whether supplementation with a multi-ingredient (MI) including hesperidin, phytosterols and curcumin for 57 days would display beneficial effects against fat mass accretion and metabolic disturbances associated with menopause. Twenty OVX rats were orally supplemented with either MI (OVX-MI) or vehicle (OVX). Furthermore, 10 OVX rats orally received the vehicle along with subcutaneous injections of 17β-oestradiol biweekly (OVX-E2), whereas 10 rats were sham operated and received oral and injected vehicles (control group; SH). MI supplementation partly counteracted the fat mass accretion observed in OVX animals, which was evidenced by decreased total fat mass, adiposity index, the weight of retroperitoneal, inguinal and mesenteric white adipose tissue (MWAT) depots and MWAT adipocyte hypertrophy. These effects were accompanied by a significant decrease in the circulating levels of leptin and the mRNA levels of the fatty acid uptake-related genes Lpl and Cd36 in MWAT. These results were very similar to those observed in OVX-E2 animals. OVX-MI rats also displayed a higher lean body mass, lean/fat mass ratio, adiponectin-to-leptin ratio and insulin sensitivity than their OVX counterparts. Our findings can pave the way for using this MI formulation as an alternative therapy to manage obesity and to improve the cardiometabolic health of menopausal women.
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Affiliation(s)
- Julio Baudin
- Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Nutrition and Health, 43204 Reus, Spain
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain.
| | - Julia Hernandez-Baixauli
- Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Nutrition and Health, 43204 Reus, Spain
| | - Sergio Quesada-Vázquez
- Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Nutrition and Health, 43204 Reus, Spain
| | - Francisca Mulero
- Molecular Imaging Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
| | - Francesc Puiggròs
- Eurecat, Centre Tecnològic de Catalunya, Biotechnology Area, 43204 Reus, Spain.
| | - Lluís Arola
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain.
| | - Antoni Caimari
- Eurecat, Centre Tecnològic de Catalunya, Biotechnology Area, 43204 Reus, Spain.
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Wang J, Xue M, Hu Y, Li J, Li Z, Wang Y. Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease. Biomolecules 2024; 14:554. [PMID: 38785961 PMCID: PMC11118602 DOI: 10.3390/biom14050554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 04/25/2024] [Accepted: 05/01/2024] [Indexed: 05/25/2024] Open
Abstract
Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.
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Affiliation(s)
- Jihan Wang
- Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, China; (J.W.)
| | - Mengju Xue
- School of Medicine, Xi’an International University, Xi’an 710077, China
| | - Ya Hu
- Department of Medical College, Hunan Polytechnic of Environment and Biology, Hengyang 421000, China
| | - Jingwen Li
- Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, China; (J.W.)
- Research and Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China
| | - Zhenzhen Li
- Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, China; (J.W.)
- Research and Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China
| | - Yangyang Wang
- School of Electronics and Information, Northwestern Polytechnical University, Xi’an 710129, China
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Watanabe N, Ogawa T, Miyatake K, Takada R, Jinno T, Koga H, Yoshii T. Increased bone resorption that outpaces increased bone formation: An important pathology of rapidly destructive coxarthrosis. J Orthop Res 2024; 42:1066-1073. [PMID: 38044471 DOI: 10.1002/jor.25760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 11/24/2023] [Accepted: 11/28/2023] [Indexed: 12/05/2023]
Abstract
Rapid joint destruction caused by rapidly destructive coxarthrosis (RDC) can increase surgical complexity and intraoperative blood loss. This single-center retrospective study investigates osteoporosis-related biomarkers for early RDC diagnosis and explores new treatment targets. We included 398 hip joints from patients who underwent total hip arthroplasty, examining medical records for preoperative patient demographics, bone mineral density of the hip and lumbar spine from dual-energy X-ray absorptiometry scans, and osteoporosis-related biomarkers including TRACP-5b, total P1NP, intact parathyroid hormone, and homocysteine. We compared RDC and osteoarthritis (OA) patients, and univariate analysis showed that RDC patients were older (p < 0.001) and had lower serum levels of albumin (p < 0.001) and higher serum levels of TRACP-5b, total P1NP (p < 0.001), and homocysteine (p = 0.006). Multivariable analysis showed that the ratio of serum TRACP-5b to total P1NP had a more significant difference in RDC patients than in OA patients (p = 0.04). Serum TRACP-5b levels were negatively correlated with the time between RDC onset and blood collection, and Japanese Orthopedic Association pain score. Receiver operating characteristic curve analysis revealed that the ratio of serum TRACP-5b to total P1NP had the highest area under the curve value. This study is the first to demonstrate that the ratio of serum TRACP-5b to total P1NP-increased bone resorption that outpaces increased bone formation-is significantly elevated in patients with RDC and that TRACP-5b is higher in the early stages of RDC. Inhibiting serum levels of TRACP-5b, activated osteoclasts, during early RDC may suppress disease progression.
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Affiliation(s)
- Naoto Watanabe
- Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takahisa Ogawa
- Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazumasa Miyatake
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryohei Takada
- Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tetsuya Jinno
- Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hideyuki Koga
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshitaka Yoshii
- Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
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Mathold K, Nobin R, Brudin L, Carlsson M, Wanby P. Albumin-to-alkaline phosphatase ratio may be a better predictor of survival than sclerostin, dickkopf-1, osteopontin, osteoprotegerin and osteocalcin. Heliyon 2024; 10:e29639. [PMID: 38644839 PMCID: PMC11031828 DOI: 10.1016/j.heliyon.2024.e29639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 03/11/2024] [Accepted: 04/11/2024] [Indexed: 04/23/2024] Open
Abstract
Objectives The value of biochemical markers of bone turnover (BTMs) in predicting survival and disease remains unclear. In a prospective study we evaluated the novel biomarkers for bone turnover sclerostin, dickkopf-1 (DKK-1), osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC), as well as a traditional biomarker, alkaline phosphatase (ALP) in relation to risk of mortality, cardiovascular events and fractures. Participants and Methods:Routine blood tests and serum BTMs, including ALP, were analyzed in patients with hip fracture n = 97, stroke n = 71 and healthy volunteers n = 83 (mean age 86, 83 and 77, respectively), followed for 7 years. Hazard Ratios (HR) were calculated for mortality, cardiovascular events and fractures in relation to these biomarkers. After adding the albumin-to-ALP ratio (AAPR) a post hoc analysis was performed. Results 120 participants died during the study. In the entire group of patients and volunteers (n = 251) higher AAPR (HR 0.28, 95 % CI 0.14-0.59, p < 0.001) was associated with decreased mortality. OPN and OPG were associated with mortality risk only in the univariate statistical analysis. HR for high AAPR in relation to new cardiovascular events was borderline significant (HR 0.29, 95 % CI 0.08-1.06, p = 0.061). None of the examined biomarkers were associated with new fractures, nor with an increased risk of a new cardiovascular event. Conclusions AAPR may be a better predictor of mortality than the more novel BTMs, and higher AAPR could be associated with longer life expectancy. Further studies should determine the clinical usefulness of AAPR as a biomarker of mortality and cardiovascular disease.
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Affiliation(s)
- K. Mathold
- Department of Primary Care, Kalmar, Sweden
| | - R. Nobin
- Department of Orthopedics, Kalmar, Sweden
| | - L. Brudin
- Department of Clinical Physiology, Kalmar and Department of Medical and Health Sciences, University of Linköping, Sweden
| | - M. Carlsson
- Department of Clinical Chemistry, Kalmar and Department of Medicine and Optometry, Linnaeus University, Sweden
| | - P. Wanby
- Department of Internal Medicine, Section of Endocrinology, Kalmar, Department of Medical and Health Sciences, University of Linköping and Department of Medicine and Optometry, Linnaeus University, Sweden
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Padilla Apuntate N, Puerto Cabeza CG, Gallego Royo A, Goñi Ros N, Abadía Molina C, Acha Pérez J, Calmarza P. Estudio del efecto del tratamiento con fármacos antidiabéticos sobre el metabolismo óseo. ADVANCES IN LABORATORY MEDICINE 2024; 5:90-95. [PMID: 38634085 PMCID: PMC11019870 DOI: 10.1515/almed-2024-0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 02/27/2024] [Indexed: 04/19/2024]
Abstract
Objetivos La prevalencia de la diabetes mellitus tipo 2 (DMT2) está aumentando de forma exponencial en todo el mundo, habiéndose comprobado que estos pacientes tienen mayor riesgo de presentar fracturas óseas, con respecto a la población sana, por lo que resulta de gran relevancia el conocimiento del efecto de los fármacos antidiabéticos sobre el metabolismo óseo. Métodos Estudio estadístico descriptivo, retrospectivo, de 106 pacientes en tratamiento con seis grupos de fármacos antidiabéticos: insulina, inhibidores de dipeptidilpeptidasa 4 (iDPP4), agonistas del receptor del péptido similar al glucagón tipo 1 (arGLP1), sulfonilureas, inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) y pioglitazona, en los que se determinaron osteocalcina (OC), fosfatasa alcalina ósea (FAO) y telopéptido C-terminal del colágeno tipo 1 o beta-crosslaps (β-CTx). Resultados Se encontraron concentraciones más elevadas de β-CTx en los pacientes tratados con pioglitazona que en los tratados con iDPP4 (p=0,035), iSGLT2 (p=0,020) y con arGLP1 (p<0,001), siendo los pacientes tratados con arGLP1 los que presentaron las concentraciones más bajas de β-CTx. Conclusiones El tipo de tratamiento antidiabético recibido en pacientes que padecen DMT2 puede afectar el remodelado óseo. En nuestro estudio los pacientes que fueron tratados con pioglitazona mostraron las concentraciones más elevadas de β-CTx con respecto al resto de grupos de fármacos, lo cual parece indicar la conveniencia de evitar estos fármacos, sobre todo en mujeres postmenopáusicas con DMT2. Los fármacos arGLP1 presentaron los valores más bajos de β-CTx, por lo que podrían ejercer un efecto beneficioso sobre el metabolismo óseo.
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Affiliation(s)
| | | | - Alba Gallego Royo
- Servicio de Medicina Preventiva, Hospital Universitario Miguel Servet, Zaragoza, España
| | - Nuria Goñi Ros
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España
| | - Claudia Abadía Molina
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España
| | - Javier Acha Pérez
- Servicio de Endocrinología y Nutrición, Hospital Universitario Miguel Servet, Zaragoza, España
| | - Pilar Calmarza
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España
- Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, España
- Universidad de Zaragoza, Zaragoza, España
- Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto Salud Carlos III, Madrid, España
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Padilla Apuntate N, Puerto Cabeza CG, Gallego Royo A, Goñi Ros N, Abadía Molina C, Acha Pérez J, Calmarza P. Effects of antidiabetic drugs on bone metabolism. ADVANCES IN LABORATORY MEDICINE 2024; 5:85-89. [PMID: 38634079 PMCID: PMC11019883 DOI: 10.1515/almed-2024-0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 02/27/2024] [Indexed: 04/19/2024]
Abstract
Objectives The prevalence of diabetes mellitus type 2 (DMT2) is increasing exponentially worldwide. DMT2 patients have been found to be at a higher risk for bone fractures than the healthy population. Hence, improving our understanding of the impact of antidiabetic drugs on bone metabolism is crucial. Methods A descriptive, retrospective study involving 106 patients receiving six groups of antidiabetic drugs: insulin; dipeptidylpeptidase four inhibitors (DPP4i); glucagon-like peptide type 1 receptor agonists (GLP1ra); sulfonylureas; sodium-glucose cotransporter two inhibitors (SGLT2i); and pioglitazone, in which osteocalcin (OC), bone alkaline phosphatase (BAP) and C-terminal telopeptide of collagen type 1 or beta-crosslaps (β-CTx) were determined. Results β-CTx concentrations were higher in the patients treated with pioglitazone, as compared to patients treated with DPP4i (p=0.035), SGLT2i (p=0.020) or GLP1ra (p<0.001). The lowest β-CTx concentrations were observed in the patients treated with GLP1ra. Conclusions Bone remodeling is influenced by the type of antidiabetic drug administered to DMT2 patients. In our study, the patients who received pioglitazone showed higher β-CTx concentrations, as compared to patients treated with other types of antidiabetic drugs. This finding highlights the convenience of avoiding these drugs, especially in postmenopausal women with DMT2. GLP1ra drugs were associated with the lowest β-CTx concentrations, which suggests that these agents could exert beneficial effects on bone metabolism.
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Affiliation(s)
| | | | - Alba Gallego Royo
- Service of Preventive Medicine, Miguel Servet University Hospital, Zaragoza, Spain
| | - Nuria Goñi Ros
- Service of Clinical Biochemistry, Miguel Servet University Hospital, Zaragoza, Spain
| | - Claudia Abadía Molina
- Service of Clinical Biochemistry, Miguel Servet University Hospital, Zaragoza, Spain
| | - Javier Acha Pérez
- Service of Endocrinology and Nutrition, Miguel Servet University Hospital, Zaragoza, Spain
| | - Pilar Calmarza
- Service of Clinical Biochemistry, Miguel Servet University Hospital, Zaragoza, Spain
- Institute of Biomedical Research (IIS) of Aragón, Zaragoza, Spain
- University of Zaragoza, Zaragoza, Spain
- Spanish Network-Center for Cardiovascular Biomedical Research) (CIBERCV), Carlos III Health Institute, Madrid, Spain
- Member of SEQCML Oxidative Stress Commission and Lipoproteins and Vascular Diseases Commission, Madrid, Spain
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Jerban S, Ma Y, Jang H, Chang EY, Bukata S, Du J, Chung CB. Bone Biomarkers Based on Magnetic Resonance Imaging. Semin Musculoskelet Radiol 2024; 28:62-77. [PMID: 38330971 PMCID: PMC11786623 DOI: 10.1055/s-0043-1776431] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024]
Abstract
Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.
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Affiliation(s)
- Saeed Jerban
- Department of Radiology, University of California, San Diego, CA, USA
| | - Yajun Ma
- Department of Radiology, University of California, San Diego, CA, USA
| | - Hyungseok Jang
- Department of Radiology, University of California, San Diego, CA, USA
| | - Eric Y. Chang
- Department of Radiology, University of California, San Diego, CA, USA
- Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
| | - Susan Bukata
- Department of Orthopaedic Surgery, University of California, San Diego, CA, USA
| | - Jiang Du
- Department of Radiology, University of California, San Diego, CA, USA
- Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
- Department of Bioengineering, University of California, San Diego, CA, USA
| | - Christine B. Chung
- Department of Radiology, University of California, San Diego, CA, USA
- Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
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McGrail L, Vargas-Robles D, Correa MR, Merrill LC, Noel SE, Velez M, Maldonado-Contreras A, Mangano KM. Daily yogurt consumption does not affect bone turnover markers in men and postmenopausal women of Caribbean Latino descent: a randomized controlled trial. BMC Nutr 2024; 10:12. [PMID: 38212847 PMCID: PMC10785535 DOI: 10.1186/s40795-023-00800-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 11/16/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Caribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis. OBJECTIVE The primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation. METHODS Following a 4wk baseline period, participants were randomized to an 8wk whole fat yogurt intervention (n = 10) daily, containing only Streptococcus thermophilus and Lactobacillus bulgaricus, or to an untreated control group that did not consume yogurt (n = 10). Blood and stool samples collected at week-0 and week-8 were used to assess BTMs, inflammation, intestinal integrity biomarkers, and gut microbiota composition, short chain fatty acids (SCFAs), respectively. Data were evaluated for normality and statistical analyses were performed. RESULTS Participants were 55% women, with a mean age of 70 ± 9 years, BMI 30 ± 6 kg/m2, and serum C-reactive protein 4.8 ± 3.6 mg/L, indicating chronic low-grade inflammation. Following 8wks of yogurt intake, absolute change in BTMs did not differ significantly between groups (P = 0.06-0.78). Secondarily, absolute change in markers of inflammation, intestinal integrity, and fecal SCFAs did not differ significantly between groups (P range 0.13-1.00). Yogurt intake for 8wks was significantly associated with microbial compositional changes of rare taxa (P = 0.048); however, no significant alpha diversity changes were observed. CONCLUSIONS In this study, daily yogurt did not improve BTMs, inflammation, intestinal integrity, nor SCFAs. However, yogurt did influence beta diversity, or the abundance of rare taxa within the gut microbiota of the yogurt group, compared to controls. Additional research to identify dietary approaches to reduce osteoporosis risk among Caribbean Latino adults is needed. TRIAL REGISTRATION This study is registered to ClinicalTrials.gov, NCT05350579 (28/04/2022).
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Affiliation(s)
- Lindsay McGrail
- Department of Biomedical and Nutritional Sciences, University of Massachusetts, 3 Solomont Way, Lowell, MA, 01832, USA
- Center for Population Health, UMass Movement Research Center, University of Massachusetts, Lowell, MA, USA
| | - Daniela Vargas-Robles
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Mayra Rojas Correa
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Lisa C Merrill
- Department of Biomedical and Nutritional Sciences, University of Massachusetts, 3 Solomont Way, Lowell, MA, 01832, USA
- Center for Population Health, UMass Movement Research Center, University of Massachusetts, Lowell, MA, USA
| | - Sabrina E Noel
- Department of Biomedical and Nutritional Sciences, University of Massachusetts, 3 Solomont Way, Lowell, MA, 01832, USA
- Center for Population Health, UMass Movement Research Center, University of Massachusetts, Lowell, MA, USA
| | - Martha Velez
- Department of Health and Human Services, City of Lawrence, Lawrence, MA, USA
| | - Ana Maldonado-Contreras
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Kelsey M Mangano
- Department of Biomedical and Nutritional Sciences, University of Massachusetts, 3 Solomont Way, Lowell, MA, 01832, USA.
- Center for Population Health, UMass Movement Research Center, University of Massachusetts, Lowell, MA, USA.
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Hasan S, van Schie P, Kaptein BL, Schoones JW, Marang-van de Mheen PJ, Nelissen RGHH. Biomarkers to discriminate between aseptic loosened and stable total hip or knee arthroplasties: a systematic review. EFORT Open Rev 2024; 9:25-39. [PMID: 38193539 PMCID: PMC10823569 DOI: 10.1530/eor-22-0046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2024] Open
Abstract
Background Loosening is a major cause for failure of total hip and total knee arthroplasties (THAs/TKAs). Preemptive diagnostics of asymptomatic loosening could open strategies to prevent gross loosening. A multitude of biomarkers may discriminate between loosened and stable implants, but it is unknown which have the best performance. The present systematic review aimed to assess which biomarkers have shown the most promising results in discriminating between stable and aseptic loosened THAs and TKAs. Methods PubMed, Embase, Web of Science, Cochrane Library, and Academic Search Premier were systematically searched up to January 2020 for studies including THA/TKA and biomarkers to assess loosening. Two reviewers independently screened records, extracted data, and assessed the risk of bias using the ICROMS tool to classify the quality of the studies. Results Twenty-eight (three high-quality) studies were included, reporting on a median of 48 patients (interquartile range 28-69). Serum and urine markers were evaluated in 22 and 10 studies, respectively. Tumor necrosis factor α and osteocalcin were significantly higher in loosened compared with stable implants. Urinary N-terminal telopeptide had significantly elevated levels in loosened prostheses. Conclusion Several serum and urine markers were promising in discriminating between loosened and stable implants. We recommend future studies to evaluate these biomarkers in a longitudinal fashion to assess whether progression of loosening is associated with a change in these biomarkers. In particular, high-quality studies assessing the usability of these biomarkers are needed.
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Affiliation(s)
- Shaho Hasan
- Department of Orthopaedics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Peter van Schie
- Department of Orthopaedics, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands
| | - Bart L Kaptein
- Department of Orthopaedics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Jan W Schoones
- Walaeus Library, Leiden University Medical Centre, Leiden, The Netherlands
| | - Perla J Marang-van de Mheen
- Department of Orthopaedics, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Safety & Security Science, Delft University of Technology, Delft, The Netherlands
| | - Rob G H H Nelissen
- Department of Orthopaedics, Leiden University Medical Centre, Leiden, The Netherlands
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Chuu J, Lu J, Chang H, Chu Y, Peng Y, Ho Y, Shen P, Cheng Y, Cheng C, Liu Y, Wang C. Attenuative effects of collagen peptide from milkfish ( Chanos chanos) scales on ovariectomy-induced osteoporosis. Food Sci Nutr 2024; 12:116-130. [PMID: 38268910 PMCID: PMC10804110 DOI: 10.1002/fsn3.3746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 09/19/2023] [Accepted: 09/21/2023] [Indexed: 01/26/2024] Open
Abstract
Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.
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Affiliation(s)
- Jiunn‐Jye Chuu
- Department of Biotechnology and Food TechnologyCollege of Engineering, Southern Taiwan University of ScienceTainanTaiwan
| | - Jeng‐Wei Lu
- Biotech Research and Innovation CentreUniversity of CopenhagenCopenhagenDenmark
- The Finsen LaboratoryRigshospitalet/National University Hospital, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Hung‐Ju Chang
- Department of Biotechnology and Food TechnologyCollege of Engineering, Southern Taiwan University of ScienceTainanTaiwan
| | - You‐Hsiang Chu
- Department of PathologyTri‐Service General Hospital, National Defense Medical CenterTaipeiTaiwan
| | - Yi‐Jen Peng
- Department of PathologyTri‐Service General Hospital, National Defense Medical CenterTaipeiTaiwan
| | - Yi‐Jung Ho
- Graduate Institute of Life Sciences, National Defense Medical CenterTaipeiTaiwan
- School of Pharmacy, National Defense Medical CenterTaipeiTaiwan
| | - Pei‐Hung Shen
- Department of OrthopedicsTri‐Service General Hospital, National Defense Medical CenterTaipeiTaiwan
| | - Yu‐Shuan Cheng
- Department of Biotechnology and Food TechnologyCollege of Engineering, Southern Taiwan University of ScienceTainanTaiwan
| | - Chia‐Hui Cheng
- Department of Biotechnology and Food TechnologyCollege of Engineering, Southern Taiwan University of ScienceTainanTaiwan
| | - Yi‐Chien Liu
- Department of Biotechnology and Food TechnologyCollege of Engineering, Southern Taiwan University of ScienceTainanTaiwan
| | - Chih‐Chien Wang
- Department of OrthopedicsTri‐Service General Hospital, National Defense Medical CenterTaipeiTaiwan
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Panchagnula R, Amarnath SS. Osteoporosis: Investigations and Monitoring. Indian J Orthop 2023; 57:70-81. [PMID: 38107808 PMCID: PMC10721590 DOI: 10.1007/s43465-023-01019-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 10/07/2023] [Indexed: 12/19/2023]
Abstract
Background Osteoporosis is characterized by microarchitectural disruption of the bone, decrease in bone mineral density, and increased skeletal fragility and risk of fracture. Osteoporosis occurs due to the decoupling of bone formation and bone resorption, with a significant increase in resorption. This review article focuses on the role of laboratory investigations in the diagnosis and monitoring of treatment in patients with osteoporosis. Methods This review article collected literature from various databases using keywords such as 'Laboratory investigations', 'Osteoporosis', 'Diagnosis', 'Monitoring', and 'Bone turnover markers'. Results and Discussion Laboratory investigations, including serum calcium, alkaline phosphatase, vitamin D, and parathormone, are commonly performed tests to exclude secondary causes of osteoporosis and monitor the response to therapy. The biochemical markers of bone turnover are newly emerged tests for monitoring individual patients with osteoporosis. These markers are classified as bone formation and resorption markers, measurable in both serum and urine. The use of these markers is limited by biological and analytical variability. The International Federation of Clinical Chemistry and Laboratory Medicine and the International Osteoporosis Foundation recommend serum procollagen type 1 amino-terminal propeptide as the bone formation marker and β-form of C-terminal cross-linked telopeptide of type I collagen (β-CTx-1/β-CrossLaps) as the marker of choice, using standardized procedures. However, in specific cases, such as patients with chronic renal disease, CTx-1 is replaced by the resorption marker tartrate-resistant acid phosphatase 5b, as its levels are not affected by renal excretion. Conclusion Bone turnover markers have emerged as tools for the assessment of osteoporosis, using standardized procedures, and are useful in monitoring therapy and treatment compliance.
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Affiliation(s)
- Renuka Panchagnula
- ChanRe Diagnostic Laboratory, Margosa Road, Malleshwaram, Bengaluru, Karnataka 560003 India
| | - S. S. Amarnath
- Trinity Central Hospital, Swastik Circle, 139, SC Road, Seshadripuram, Bengaluru, Karnataka 560020 India
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Ong W, Liu RW, Makmur A, Low XZ, Sng WJ, Tan JH, Kumar N, Hallinan JTPD. Artificial Intelligence Applications for Osteoporosis Classification Using Computed Tomography. Bioengineering (Basel) 2023; 10:1364. [PMID: 38135954 PMCID: PMC10741220 DOI: 10.3390/bioengineering10121364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/24/2023] Open
Abstract
Osteoporosis, marked by low bone mineral density (BMD) and a high fracture risk, is a major health issue. Recent progress in medical imaging, especially CT scans, offers new ways of diagnosing and assessing osteoporosis. This review examines the use of AI analysis of CT scans to stratify BMD and diagnose osteoporosis. By summarizing the relevant studies, we aimed to assess the effectiveness, constraints, and potential impact of AI-based osteoporosis classification (severity) via CT. A systematic search of electronic databases (PubMed, MEDLINE, Web of Science, ClinicalTrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 39 articles were retrieved from the databases, and the key findings were compiled and summarized, including the regions analyzed, the type of CT imaging, and their efficacy in predicting BMD compared with conventional DXA studies. Important considerations and limitations are also discussed. The overall reported accuracy, sensitivity, and specificity of AI in classifying osteoporosis using CT images ranged from 61.8% to 99.4%, 41.0% to 100.0%, and 31.0% to 100.0% respectively, with areas under the curve (AUCs) ranging from 0.582 to 0.994. While additional research is necessary to validate the clinical efficacy and reproducibility of these AI tools before incorporating them into routine clinical practice, these studies demonstrate the promising potential of using CT to opportunistically predict and classify osteoporosis without the need for DEXA.
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Affiliation(s)
- Wilson Ong
- Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore (A.M.); (X.Z.L.); (W.J.S.); (J.T.P.D.H.)
| | - Ren Wei Liu
- Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore (A.M.); (X.Z.L.); (W.J.S.); (J.T.P.D.H.)
| | - Andrew Makmur
- Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore (A.M.); (X.Z.L.); (W.J.S.); (J.T.P.D.H.)
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore
| | - Xi Zhen Low
- Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore (A.M.); (X.Z.L.); (W.J.S.); (J.T.P.D.H.)
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore
| | - Weizhong Jonathan Sng
- Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore (A.M.); (X.Z.L.); (W.J.S.); (J.T.P.D.H.)
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore
| | - Jiong Hao Tan
- University Spine Centre, Department of Orthopaedic Surgery, National University Health System, 1E Lower Kent Ridge Road, Singapore 119228, Singapore; (J.H.T.); (N.K.)
| | - Naresh Kumar
- University Spine Centre, Department of Orthopaedic Surgery, National University Health System, 1E Lower Kent Ridge Road, Singapore 119228, Singapore; (J.H.T.); (N.K.)
| | - James Thomas Patrick Decourcy Hallinan
- Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore (A.M.); (X.Z.L.); (W.J.S.); (J.T.P.D.H.)
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore
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Patlataya NN, Bolshakov IN, Khorzhevskii VA, Levenets AA, Medvedeva NN, Cherkashina MA, Nikolaenko MM, Ryaboshapko EI, Dmitrienko AE. Morphological Reconstruction of a Critical-Sized Bone Defect in the Maxillofacial Region Using Modified Chitosan in Rats with Sub-Compensated Type I Diabetes Mellitus. Polymers (Basel) 2023; 15:4337. [PMID: 37960017 PMCID: PMC10647318 DOI: 10.3390/polym15214337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/20/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia leads to low bone regeneration and a chronic inflammatory response. The purpose of this study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high-molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on five groups of white female Wistar rats: group 1-regeneration of a bone defect in healthy animals under a blood clot; group 2-regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3-bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4-filling of a bone defect with a CH-SA-HA construct in healthy animals; group 5-filling of a bone defect with a CH-SA-HA construct in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.
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Affiliation(s)
- Nadezhda N. Patlataya
- Department of Fundamental Medical Disciplines, Institute of Medicine and Biology, Faculty of Medicine, State Educational Institution of Higher Education, Moscow State Regional University, Moscow 105005, Russia;
| | - Igor N. Bolshakov
- Department Operative Surgery and Topographic Anatomy, Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia
| | - Vladimir A. Khorzhevskii
- Department Pathological Anatomy, Voino-Yasenetsky Krasnoyarsk State Medical University, Pathological and Anatomical Department Krasnoyarsk Clinical Regional Hospital, Krasnoyarsk 660022, Russia;
| | - Anatoli A. Levenets
- Department Surgical Dentistry and Maxillofacial Surgery, Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia;
| | - Nadezhda N. Medvedeva
- Department of Human Anatomy, Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia;
| | - Mariya A. Cherkashina
- Pediatric Faculty, Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia; (M.A.C.); (E.I.R.); (A.E.D.)
| | - Matvey M. Nikolaenko
- Department of Maxillofacial and Plastic Surgery, Moscow State University of Medicine and Dentistry, Moscow 127473, Russia;
| | - Ekaterina I. Ryaboshapko
- Pediatric Faculty, Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia; (M.A.C.); (E.I.R.); (A.E.D.)
| | - Anna E. Dmitrienko
- Pediatric Faculty, Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia; (M.A.C.); (E.I.R.); (A.E.D.)
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Carneiro I, Krustrup P, Castagna C, Pereira R, Jørgensen NR, Coelho E, Póvoas S. Bone health, body composition and physical fitness dose-response effects of 16 weeks of recreational team handball for inactive middle-to-older-aged males - A randomised controlled trial. Eur J Sport Sci 2023; 23:2251-2263. [PMID: 37376804 DOI: 10.1080/17461391.2023.2222685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
In this study we aimed at analysing the effects of different weekly exercise volumes (1, 2 or 3 times 60-min) on bone health, body composition and physical fitness of inactive middle-to-older-aged males, after 16 weeks of recreational team handball (RTH). Fifty-four men (68 ± 4 years, stature 169 ± 6 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups (TH1, n = 13; TH2, n = 15; or TH3, n = 12, performing 1, 2 and 3 weekly 60-min training sessions, respectively), and a control group (CG, n = 14). The training sessions consisted mainly of RTH matches played as small-sided and formal game formats (4v4, 5v5, 6v6 or 7v7) with adapted rules. Matches' mean and peak heart rate (HR) ranged from 78-80% and 86-89%HRmax, respectively, and distance covered from 4676 to 5202 m. A time x group interaction was observed for procollagen type-1 amino-terminal propeptide (P1NP), osteocalcin (OC), carboxy-terminal type-1 collagen crosslinks (CTX), sclerostin, upper and lower body dynamic strength, right arm fat mass, left and right arm, right leg and android total mass (TM; p ≤ 0.047) with the greatest effects being shown for TH2 and TH3 groups. Post-intervention group differences were observed in CTX, left arm and right leg TM (TH3 > TH1), P1NP (TH2 > CG), OC, right arm TM (TH3 > CG), upper (CG < TH1, TH2 and TH3) and lower body dynamic strength (CG < TH1 and TH3) (p ≤ 0.047). RTH was effective in enhancing bone health, body composition and physical fitness in middle-to-older-aged males, especially for the intervention groups that performed 2-3 weekly training sessions.ClinicalTrials.gov ID: NCT05295511.Trial registration: ClinicalTrials.gov identifier: NCT05295511.HighlightsAfter 16 weeks of recreational team handball small-sided and formal matches, inactive middle-to-older-aged males improved bone health, body composition and physical fitness, by performing 1, 2 or 3 60-min weekly sessions, however, greater improvements were shown in the groups that performed 2 or 3 weekly training sessions.Training intensity was similar across the intervention groups that performed recreational team handball for 1, 2 or 3 60-min weekly sessions, which means that training volume is most likely to be the reason for the different health effects shown.The very high fun levels reported by all intervention groups shows that recreational team handball is a social and fun exercise modality for middle-to-older-aged males, with potential to intrinsically motivate the participants and assure long-term adherence to exercise.
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Affiliation(s)
- Ivone Carneiro
- Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University of Maia, Maia, Portugal
| | - Peter Krustrup
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, Odense, Denmark
- Danish Institute for Advanced Study (DIAS), University of Southern Denmark, Odense, Denmark
- Sport and Health Sciences, University of Exeter, Exeter, United Kingdom
| | - Carlo Castagna
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, Odense, Denmark
- Department of Biomolecular Sciences, School of Exercise and Health Sciences, Carlo Bo Urbino University, Urbino, Italy
| | - Rita Pereira
- Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, Porto, Portugal
- University of Maia, Maia, Portugal
| | - Niklas Rye Jørgensen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Eduardo Coelho
- Porto Sports Medicine Center (IPDJ, IP), Porto, Portugal
| | - Susana Póvoas
- Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University of Maia, Maia, Portugal
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, Odense, Denmark
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Navarro-Hortal MD, Romero-Márquez JM, Jiménez-Trigo V, Xiao J, Giampieri F, Forbes-Hernández TY, Grosso G, Battino M, Sánchez-González C, Quiles JL. Molecular bases for the use of functional foods in the management of healthy aging: Berries, curcumin, virgin olive oil and honey; three realities and a promise. Crit Rev Food Sci Nutr 2023; 63:11967-11986. [PMID: 35816321 DOI: 10.1080/10408398.2022.2098244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
As the number of older people has grown in recent decades, the search for new approaches to manage or delay aging is also growing. Among the modifiable factors, diet plays a crucial role in healthy aging and in the prevention of age-related diseases. Thus, the interest in the use of foods, which are rich in bioactive compounds such as functional foods with anti-aging effects is a growing market. This review summarizes the current knowledge about the molecular mechanisms of action of foods considered as functional foods in aging, namely berries, curcumin, and virgin olive oil. Moreover, honey is also analyzed as a food with well-known healthy benefits, but which has not been deeply evaluated from the point of view of aging. The effects of these foods on aging are analyzed from the point of view of molecular mechanisms including oxidative stress, mitochondrial dysfunction, inflammation, genomic stability, telomere attrition, cellular senescence, and deregulated nutrient-sensing. A comprehensive study of the scientific literature shows that the aforementioned foods have demonstrated positive effects on certain aspects of aging, which might justify their use as functional foods in elderly. However, more research is needed, especially in humans, designed to understand in depth the mechanisms of action through which they act.
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Affiliation(s)
- María D Navarro-Hortal
- Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, Department of Physiology, University of Granada, Granada, Spain
| | - Jose M Romero-Márquez
- Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, Department of Physiology, University of Granada, Granada, Spain
| | - Victoria Jiménez-Trigo
- Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, Department of Physiology, University of Granada, Granada, Spain
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, Ourense, Spain
| | - Francesca Giampieri
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
| | - Tamara Y Forbes-Hernández
- Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, Department of Physiology, University of Granada, Granada, Spain
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Maurizio Battino
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
- International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu University, Zhenjiang, China
- Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
| | - Cristina Sánchez-González
- Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, Department of Physiology, University of Granada, Granada, Spain
| | - José L Quiles
- Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, Department of Physiology, University of Granada, Granada, Spain
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
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47
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Kumar SE, Cherian KE, Paul TV, Goel A. Caring for the Bone Health Among Liver Transplant Recipients. J Clin Exp Hepatol 2023; 13:1130-1139. [PMID: 37975037 PMCID: PMC10643275 DOI: 10.1016/j.jceh.2023.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 05/04/2023] [Indexed: 11/19/2023] Open
Abstract
Liver transplant outcomes have improved over the years, and currently, the quality of life and long-term well-being of these patients needs to be improved. Improving bone health goes a long way toward achieving this objective. Poor bone health (osteopenia and osteoporosis) although prevalent, is often overlooked owing to its asymptomatic nature. It can be complicated by debilitating fracture affecting quality of life. It is recommended to assess and optimize bone health prior to liver transplant. Multiple factors contribute to poor bone health in a liver transplant recipient and it is vital to understand and ameliorate these. A careful and targeted approach with inputs from multidisciplinary team involving transplant physician, endocrinologist, occupational therapist, nutritionist, and nursing personnel may often be required. In this review, we aim to concisely discuss the various aspects related to prevalence, pathophysiology, evaluation, treatment, and follow-up of bone disease among liver transplant recipients.
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Affiliation(s)
- Santhosh E. Kumar
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Kripa E. Cherian
- Department of Endocrinology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Thomas V. Paul
- Department of Endocrinology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
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Tsuruda T, Funamoto T, Suzuki C, Yamamura Y, Nakai M, Chosa E, Kaikita K. Increasing baseline aortic valve peak flow velocity is associated with progression of aortic valve stenosis in osteoporosis patients-a possible link to low vitamin D status. Arch Osteoporos 2023; 18:129. [PMID: 37874407 PMCID: PMC10598115 DOI: 10.1007/s11657-023-01339-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 10/09/2023] [Indexed: 10/25/2023]
Abstract
PURPOSE The purpose of this study was to investigate the morphological characteristics of the aortic valve and identify factors associated with the progression of aortic valve stenosis (AS) in osteoporosis patients. METHODS In this single-center prospective cohort study, we recruited 10 patients (mean age: 75 ± 7 years, 90% female) who were taking anti-resorptive medicines at the outpatient clinic of University of Miyazaki Hospital, Japan. Baseline assessments, including transthoracic echocardiogram, blood sampling, and dual energy X-ray absorptiometry, were performed. Follow-up assessments were conducted at 6, 12, 18, and 24 months. RESULTS During the 2-year follow-up, three patients with aortic valve peak flow velocity (AV PFV) ≥2 m/s at baseline developed moderate AS, which is defined as AV PFV ≥3 m/s. However, seven patients with AV PFV <2 m/s did not exhibit any progression of AS. There were significant variations in terms of bone mineral density, T-score values, and biomarkers associated with bone turnover (i.e., bone alkaline phosphatase, tartrate-resistance acid phosphatase-5b) among the enrolled patients, but none of these factors were found to be associated with the progression of AS. All patients exhibited low vitamin D status, with a median level of 16.1 ng/mL (25th percentile, 9.7 ng/mL; 75th percentile, 23 ng/mL). The baseline levels of AV PFV values were negatively correlated with 25-hydroxyvitamin D levels, determined by univariate linear regression analysis (beta coefficient = -0.756, 95% confidence interval, -0.136 ̶ -0.023, p = 0.011). CONCLUSION Our data suggest that low vitamin D status might be a potential risk factor for the progression of AS in osteoporosis patients undergoing treatment with anti-resorptive medicines. Elderly patients with osteoporosis patients exhibited a subset of aortic valve stenosis. Our data suggest that the baseline aortic valve peak flow velocity predicts the progression of aortic valve stenosis, and there might be an association between the progression and the co-existing low vitamin D status in these patients.
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Affiliation(s)
- Toshihiro Tsuruda
- Cardiorenal Research Laboratory, Department of Vascular Advanced Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
- Division of Internal Medicine, Cardiovascular Medicine and Nephrology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
| | - Taro Funamoto
- Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Chiyoko Suzuki
- Clinical Laboratory, University of Miyazaki Hospital, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Yoshimasa Yamamura
- Division of Internal Medicine, Cardiovascular Medicine and Nephrology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Michikazu Nakai
- Clinical Research Support Center, University of Miyazaki Hospital, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Etsuo Chosa
- Division of Orthopaedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Koichi Kaikita
- Division of Internal Medicine, Cardiovascular Medicine and Nephrology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
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49
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Martone D, Vitucci D, Mancini A, Ermidis G, Panduro J, Cosco LF, Randers MB, Larsen MN, Mohr M, Buono P, Krustrup P. Bone Health, Body Composition and Physiological Demands in 70-85-Year-Old Lifelong Male Football Players. Sports (Basel) 2023; 11:205. [PMID: 37888532 PMCID: PMC10610943 DOI: 10.3390/sports11100205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/24/2023] [Accepted: 10/10/2023] [Indexed: 10/28/2023] Open
Abstract
The effects of lifelong football training on bone health, body composition and physiological demands were evaluated. A total of 20 veteran football players (VPG; 73.4 ± 3.7 years) and 18 untrained age-matched men (CG; 75.6 ± 4.2 years) were enrolled. Whole-body and regional dual-energy X-ray absorptiometry scans of arms, legs, proximal femur and lower spine (L1-L4) were recorded in all participants. We observerd higher bone mineral density (BMD) in the whole-body, arms and femoral regions and higher bone mineral content (BMC) in the legs and lower spine compared to the CG (p < 0.05), also higher total lean body mass (p < 0.05) and lower total body fat percentage (p < 0.05), were found. No differences in food habits were evidenced between the VPG and the CG, as evaluated using 3-day food records. Resting heart rate (RHR), blood pressure (BP) and activity profile during a football match were recorded using a global positioning system only in the VPG. The mean heart rate (HR)of theoretical maximal HR (ThHRmax), and peak of ThHRmax were 83.9 ± 8.6% and 98.6 ± 10.2%, respectively; the mean of total distance covered was 3666 ± 721 m, and the means of accelerations and decelerations were 419 ± 61 and 428 ± 65, respectively. Lifelong participation in football training improves regional BMD and BMC in legs, femur and lumbar spine compared to the CG. A high number of intense actions in term of HR and accelerations and decelerations suggests an elevated energy expenditure that in turn correlates to the healthier body composition observed in the VPG compared to the CG.
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Affiliation(s)
- Domenico Martone
- Department of Economics, Law, Cybersecurity and Sports Sciences, University Parthenope, 80035 Naples, Italy
- CEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l, 80131 Naples, Italy; (D.V.); (A.M.); (G.E.); (P.B.)
| | - Daniela Vitucci
- CEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l, 80131 Naples, Italy; (D.V.); (A.M.); (G.E.); (P.B.)
- Department of Movement Sciences and Wellbeing, University Parthenope, 80133 Naples, Italy;
| | - Annamaria Mancini
- CEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l, 80131 Naples, Italy; (D.V.); (A.M.); (G.E.); (P.B.)
- Department of Movement Sciences and Wellbeing, University Parthenope, 80133 Naples, Italy;
| | - Georgios Ermidis
- CEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l, 80131 Naples, Italy; (D.V.); (A.M.); (G.E.); (P.B.)
- Department of Movement Sciences and Wellbeing, University Parthenope, 80133 Naples, Italy;
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, 5230 Odense, Denmark; (J.P.); (M.B.R.); (M.N.L.); (M.M.); (P.K.)
| | - Jeppe Panduro
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, 5230 Odense, Denmark; (J.P.); (M.B.R.); (M.N.L.); (M.M.); (P.K.)
| | | | - Morten Bredsgaard Randers
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, 5230 Odense, Denmark; (J.P.); (M.B.R.); (M.N.L.); (M.M.); (P.K.)
| | - Malte Nejst Larsen
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, 5230 Odense, Denmark; (J.P.); (M.B.R.); (M.N.L.); (M.M.); (P.K.)
| | - Magni Mohr
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, 5230 Odense, Denmark; (J.P.); (M.B.R.); (M.N.L.); (M.M.); (P.K.)
- Centre of Health Sciences, Faculty of Health, University of Faroe Islands, FO-100 Tórshavn, Faroe Islands
| | - Pasqualina Buono
- CEINGE-Biotecnologie Avanzate Franco Salvatore S.c.a.r.l, 80131 Naples, Italy; (D.V.); (A.M.); (G.E.); (P.B.)
- Department of Movement Sciences and Wellbeing, University Parthenope, 80133 Naples, Italy;
| | - Peter Krustrup
- Department of Sports Science and Clinical Biomechanics, SDU Sport and Health Sciences Cluster (SHSC), University of Southern Denmark, 5230 Odense, Denmark; (J.P.); (M.B.R.); (M.N.L.); (M.M.); (P.K.)
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50
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Je M, Kang K, Yoo JI, Kim Y. The Influences of Macronutrients on Bone Mineral Density, Bone Turnover Markers, and Fracture Risk in Elderly People: A Review of Human Studies. Nutrients 2023; 15:4386. [PMID: 37892460 PMCID: PMC10610213 DOI: 10.3390/nu15204386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 09/24/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
Osteoporosis is a health condition that involves weak bone mass and a deteriorated microstructure, which consequently lead to an increased risk of bone fractures with age. In elderly people, a fracture attributable to osteoporosis elevates mortality. The objective of this review was to examine the effects of macronutrients on bone mineral density (BMD), bone turnover markers (BTMs), and bone fracture in elderly people based on human studies. A systematic search was conducted in the PubMed®/MEDLINE® database. We included human studies published up to April 2023 that investigated the association between macronutrient intake and bone health outcomes. A total of 11 meta-analyses and 127 individual human studies were included after screening the records. Carbohydrate consumption seemed to have neutral effects on bone fracture in limited studies, but human studies on carbohydrates' effects on BMD or/and BTMs are needed. The human studies analyzed herein did not clearly show whether the intake of animal, vegetable, soy, or milk basic proteins has beneficial effects on bone health due to inconsistent results. Moreover, several individual human studies indicated an association between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and osteocalcin. Further studies are required to draw a clear association between macronutrients and bone health in elderly people.
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Affiliation(s)
- Minkyung Je
- Department of Food and Nutrition, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea; (M.J.); (K.K.)
| | - Kyeonghoon Kang
- Department of Food and Nutrition, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea; (M.J.); (K.K.)
| | - Jun-Il Yoo
- Department of Orthopaedic Surgery, Inha University Hospital, 27 Inhang-Ro, Incheon 22332, Republic of Korea;
| | - Yoona Kim
- Department of Food and Nutrition, Institute of Agriculture and Life Science, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea
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