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Elkhouli E, Nagy E, Santos CGS, Barreto FC, Chaer J, Jorgetti V, El-Husseini A. Mixed uremic osteodystrophy: an ill-described common bone pathology in patients with chronic kidney disease. Osteoporos Int 2023; 34:2003-2012. [PMID: 37658999 DOI: 10.1007/s00198-023-06886-5] [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: 06/17/2023] [Accepted: 08/07/2023] [Indexed: 09/05/2023]
Abstract
Renal osteodystrophy (ROD) starts early and progresses with further loss of kidney function in patients with chronic kidney disease (CKD). There are four distinct types of ROD based on undecalcified bone biopsy results. Adynamic bone disease and osteomalacia are the predominant forms of low bone turnover, while hyperparathyroid bone disease and mixed uremic osteodystrophy (MUO) are typically associated with high bone turnover. MUO is a prevalent but poorly described pathology that demonstrates evidence of osteomalacia on top of the high bone formation/resorption. The prevalence of MUO ranges from 5 to 63% among different studies. The pathogenesis of MUO is multi-factorial. Altered phosphate homeostasis, hypocalcemia, vitamin D deficiency, increased FGF-23, interleukins 1 and 6, TNF-α, amyloid, and heavy metal accumulation are the main inducers of MUO. The clinical findings of MUO are usually non-specific. The use of non-invasive testing such as bone turnover markers and imaging techniques might help to suspect MUO. However, it is usually impossible to precisely diagnose this condition without performing bone biopsy. The principal management of MUO is to control the maladaptive hyperparathyroidism along with correcting any nutritional mineral deficiencies that may induce mineralization defect. MUO is a common but still poorly understood bone pathology category; it demonstrates the complexity and difficulty in understanding ROD. A large prospective bone biopsy-based studies are needed for better identification as proper diagnosis and management would improve the outcome of patients with MUO.
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Affiliation(s)
- Ekbal Elkhouli
- Mansoura pathology department, Mansoura University, Mansoura, Egypt
| | - Eman Nagy
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Cassia Gomes S Santos
- Division of Nephrology, Department of Internal Medicine, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Fellype Carvalho Barreto
- Division of Nephrology, Department of Internal Medicine, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Juliana Chaer
- University of São Paulo, Department of Internal Medicine, São Paulo, Brazil
| | - Vanda Jorgetti
- University of São Paulo, Department of Internal Medicine, São Paulo, Brazil
| | - Amr El-Husseini
- Division of Nephrology & Bone and Mineral Metabolism, University of Kentucky, Lexington, USA.
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Ye Y, Yi X, Zhang Y, Xu G, Yu M, Qu X. Association between renal function and bone mineral density in patients with type 2 diabetes mellitus. Heliyon 2023; 9:e15967. [PMID: 37215877 PMCID: PMC10195895 DOI: 10.1016/j.heliyon.2023.e15967] [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: 06/07/2022] [Revised: 04/25/2023] [Accepted: 04/27/2023] [Indexed: 05/24/2023] Open
Abstract
Background This study evaluated the association between renal function, assessed by serum creatinine and estimated glomerular filtration rate (eGFR) according to the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations, and bone mineral density (BMD) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods 1322 patients with T2DM were included, and their basic clinical information, serum biochemical tests, and BMD at the total hip and femur neck were collected. Multivariate adjusted linear regression, smooth curve fitting and a piecewise linear regression model were used to analyze linear and nonlinear associations. Age, BMI, drinking, smoking, systolic blood pressure and diastolic blood pressure, FBG, HbA1C, course of diabetes, hsCRP, TC, TG, HDL-C, LDL-C, Ca, P, PTH, ALP, OC, P1NP, β-CTX and 25(OH)D were adjusted. Results After adjusting the variables, no correlation between eGFR CG and eGFR MDRD and femur neck BMD was observed in women, men, or the total population. The eGFR CG and eGFR MDRD had a significant positive association with total hip BMD in men and the total population with T2DM. With a 10-unit decrease in eGFR CG, total hip BMD reduced by 0.012 g/cm2 in men and 0.010 g/cm2 the total population. Total hip BMD reduced by 0.014 g/cm2 in men and 0.022 g/cm2 in the total population with a 10-unit decrease in eGFR MDRD. There was no correlation between eGFR CG or eGFR MDRD and total hip BMD in female participants. Conclusion Impaired renal function was associated with decreased total hip BMD in men and the total population with T2DM. No associated between renal function with femur neck BMD was observed.
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Affiliation(s)
- Yangli Ye
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xilu Yi
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Endocrinology and Metabolism, Central Hospital of Songjiang District, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Infectious Disease, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guiping Xu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
- VIP Clinical Department, Fujian Provincial Hospital, Fuzhou, China
| | - Mingxiang Yu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinhua Qu
- Department of Bone and Joint Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Tsuji K, Kitamura M, Chiba K, Muta K, Yokota K, Okazaki N, Osaki M, Mukae H, Nishino T. Comparison of bone microstructures via high-resolution peripheral quantitative computed tomography in patients with different stages of chronic kidney disease before and after starting hemodialysis. Ren Fail 2022; 44:381-391. [PMID: 35220856 PMCID: PMC8890516 DOI: 10.1080/0886022x.2022.2043375] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 11/17/2022] Open
Abstract
Chronic kidney disease (CKD) negatively affects bone strength; however, the osteoporotic conditions in patients with CKD are not fully understood. Moreover, the changes in bone microstructure between pre-dialysis and dialysis are unknown. High-resolution peripheral quantitative computed tomography (HR-pQCT) reveals the three-dimensional microstructures of the bone. We aimed to evaluate bone microstructures in patients with different stages of CKD. This study included 119 healthy men and 40 men admitted to Nagasaki University Hospital for inpatient education or the initiation of hemodialysis. The distal radius and tibia were scanned with HR-pQCT. Patient clinical characteristics and bone microstructures were evaluated within 3 months of initiation of hemodialysis (in patients with CKD stage 5 D), patients with CKD stage 4-5, and healthy volunteers. Cortical bone parameters were lower in the CKD group than in healthy controls. Tibial cortical and trabecular bone parameters (cortical thickness, cortical area, trabecular volumetric bone mineral density, trabecular-bone volume fraction, and trabecular thickness) differed between patients with CKD stage 5 D and those with CKD stage 4-5 (p < 0.01). These differences were also observed between patients with CKD stage 5 and those with CKD stage 5 D (p < 0.017), but not between patients with CKD stage 4 and those with CKD stage 5, suggesting that the bone microstructure rapidly changed at the start of hemodialysis. Patients with CKD stage 5 D exhibited tibial microstructural impairment compared with those with CKD stage 4-5. HR-pQCT is useful for elucidation of the pathology of bone microstructures in patients with renal failure.
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Affiliation(s)
- Kiyokazu Tsuji
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mineaki Kitamura
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Ko Chiba
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kumiko Muta
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuaki Yokota
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Narihiro Okazaki
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Makoto Osaki
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Milan KL, Jayasuriya R, Harithpriya K, Anuradha M, Sarada DVL, Siti Rahayu N, Ramkumar KM. Vitamin D resistant genes - promising therapeutic targets of chronic diseases. Food Funct 2022; 13:7984-7998. [PMID: 35856462 DOI: 10.1039/d2fo00822j] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Vitamin D is an essential vitamin indispensable for calcium and phosphate metabolism, and its deficiency has been implicated in several extra-skeletal pathologies, including cancer and chronic kidney disease. Synthesized endogenously in the layers of the skin by the action of UV-B radiation, the vitamin maintains the integrity of the bones, teeth, and muscles and is involved in cell proliferation, differentiation, and immunity. The deficiency of Vit-D is increasing at an alarming rate, with nearly 32% of children and adults being either deficient or having insufficient levels. This has been attributed to Vit-D resistant genes that cause a reduction in circulatory Vit-D levels through a set of signaling pathways. CYP24A1, SMRT, and SNAIL are three genes responsible for Vit-D resistance as their activity either lowers the circulatory levels of Vit-D or reduces its availability in target tissues. The hydroxylase CYP24A1 inactivates analogs and prohormonal and/or hormonal forms of calcitriol. Elevation of the expression of CYP24A1 is the major cause of exacerbation of several diseases. CYP24A1 is rate-limiting, and its induction has been correlated with increased prognosis of diseases, while loss of function mutations cause hypersensitivity to Vit-D. The silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and its corepressor are involved in the transcriptional repression of VDR-target genes. SNAIL1 (SNAIL), SNAIL2 (Slug), and SNAIL3 (Smuc) are involved in transcriptional repression and binding to histone deacetylases and methyltransferases in addition to recruiting polycomb repressive complexes to the target gene promoters. An inverse relationship between the levels of calcitriol and the epithelial-to-mesenchymal transition is reported. Studies have demonstrated a strong association between Vit-D deficiency and chronic diseases, including cardiovascular diseases, diabetes, cancers, autoimmune diseases, infectious diseases, etc. Vit-D resistant genes associated with the aforementioned chronic diseases could serve as potential therapeutic targets. This review focuses on the basic structures and mechanisms of the repression of Vit-D regulated genes and highlights the role of Vit-D resistant genes in chronic diseases.
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Affiliation(s)
- Kunnath Lakshmanan Milan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
| | - Ravichandran Jayasuriya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
| | - Kannan Harithpriya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
| | - Murugesan Anuradha
- Department of Obstetrics & Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur 603 203, Tamil Nadu, India
| | - Dronamraju V L Sarada
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
| | - Nadhiroh Siti Rahayu
- Department of Nutrition, Faculty of Public Health, Universitas Airlangga, Indonesia
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
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Alshabrawy AK, Cui Y, Sylvester C, Yang D, Petito ES, Barratt KR, Sawyer RK, Heatlie JK, Polara R, Sykes MJ, Atkins GJ, Hickey SM, Wiese MD, Stringer AM, Liu Z, Anderson PH. Therapeutic Potential of a Novel Vitamin D3 Oxime Analogue, VD1-6, with CYP24A1 Enzyme Inhibitory Activity and Negligible Vitamin D Receptor Binding. Biomolecules 2022; 12:biom12070960. [PMID: 35883516 PMCID: PMC9312876 DOI: 10.3390/biom12070960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 06/29/2022] [Accepted: 06/30/2022] [Indexed: 02/04/2023] Open
Abstract
The regulation of vitamin D3 actions in humans occurs mainly through the Cytochrome P450 24-hydroxylase (CYP24A1) enzyme activity. CYP24A1 hydroxylates both 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), which is the first step of vitamin D catabolism. An abnormal status of the upregulation of CYP24A1 occurs in many diseases, including chronic kidney disease (CKD). CYP24A1 upregulation in CKD and diminished activation of vitamin D3 contribute to secondary hyperparathyroidism (SHPT), progressive bone deterioration, and soft tissue and cardiovascular calcification. Previous studies have indicated that CYP24A1 inhibition may be an effective strategy to increase endogenous vitamin D activity and decrease SHPT. This study has designed and synthesized a novel C-24 O-methyloxime analogue of vitamin D3 (VD1-6) to have specific CYP24A1 inhibitory properties. VD1-6 did not bind to the vitamin D receptor (VDR) in concentrations up to 10−7 M, assessed by a VDR binding assay. The absence of VDR binding by VD1-6 was confirmed in human embryonic kidney HEK293T cultures through the lack of CYP24A1 induction. However, in silico docking experiments demonstrated that VD1-6 was predicted to have superior binding to CYP24A1, when compared to that of 1,25(OH)2D3. The inhibition of CYP24A1 by VD1-6 was also evident by the synergistic potentiation of 1,25(OH)2D3-mediated transcription and reduced 1,25(OH)2D3 catabolism over 24 h. A further indication of CYP24A1 inhibition by VD1-6 was the reduced accumulation of the 24,25(OH)D3 , the first metabolite of 25(OH)D catabolism by CYP24A1. Our findings suggest the potent CYP24A1 inhibitory properties of VD1-6 and its potential for testing as an alternative therapeutic candidate for treating SHPT.
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Affiliation(s)
- Ali K. Alshabrawy
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt
| | - Yingjie Cui
- Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; (Y.C.); (Z.L.)
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Cyan Sylvester
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Dongqing Yang
- Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; (D.Y.); (G.J.A.)
| | - Emilio S. Petito
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Kate R. Barratt
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Rebecca K. Sawyer
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Jessica K. Heatlie
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Ruhi Polara
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Matthew J. Sykes
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Gerald J. Atkins
- Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; (D.Y.); (G.J.A.)
| | - Shane M. Hickey
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Michael D. Wiese
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Andrea M. Stringer
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
| | - Zhaopeng Liu
- Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; (Y.C.); (Z.L.)
| | - Paul H. Anderson
- UniSA Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5001, Australia; (A.K.A.); (C.S.); (E.S.P.); (K.R.B.); (R.K.S.); (J.K.H.); (R.P.); (M.J.S.); (S.M.H.); (M.D.W.); (A.M.S.)
- Correspondence:
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Renal impairment and time to fracture healing following surgical fixation of distal radius fracture. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 2022; 33:1329-1334. [PMID: 35643949 DOI: 10.1007/s00590-022-03300-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/20/2022] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Despite the prevalence of renal impairments, the existing literature examining fracture healing in the upper limb in patients with renal impairment is sparse. This study hence aims to investigate the effect of renal impairment on time to fracture healing after distal radius fracture fixation surgery. MATERIALS AND METHODS Patients above 50 years old who underwent distal radius fracture fixation via volar plating were included. Time to fracture healing was defined as duration between day of surgery and presence of radiographic union as evidence by bridging of callus or osseous bone. To assess for renal impairment, estimated glomerular filtration rate (eGFR) was calculated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Pre-existing comorbidities were also collected and analysed. RESULTS Ninety-nine consecutive patients took mean 65.5 ± 8.0 days to fracture healing post-operatively. Patients with renal impairment had longer time to fracture healing than patients without (67.1 ± 50.4 days versus 50.4 ± 31.8 days, p = 0.044). Patients ≥ 65 years also had a longer duration to fracture healing compared to patients < 65 years (mean 63.7 ± 53.0 days versus 50.2 ± 27.2 days, p = 0.033). Similarly, patients with ASA Class I had a shorter mean time to fracture healing than patients with ASA Class II and above (mean 42.5 ± 22.8 days versus 62.8 ± 47.6 days, p = 0.028). CONCLUSIONS Time to fracture healing post-distal radius fracture fixation was significantly related to renal impairment, age and ASA classification.
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Zengin A, Shore-Lorenti C, Sim M, Maple-Brown L, Brennan-Olsen SL, Lewis JR, Ockwell J, Walker T, Scott D, Ebeling P. Why Aboriginal and Torres Strait Islander Australians fall and fracture: the codesigned Study of Indigenous Muscle and Bone Ageing (SIMBA) protocol. BMJ Open 2022; 12:e056589. [PMID: 35379631 PMCID: PMC8981296 DOI: 10.1136/bmjopen-2021-056589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 03/08/2022] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVES Aboriginal and Torres Strait Islander Australians have a substantially greater fracture risk, where men are 50% and women are 26% more likely to experience a hip fracture compared with non-Indigenous Australians. Fall-related injuries in this population have also increased by 10%/year compared with 4.3%/year in non-Indigenous Australians. This study aims to determine why falls and fracture risk are higher in Aboriginal and Torres Strait Islander Australians. SETTING All clinical assessments will be performed at one centre in Melbourne, Australia. At baseline, participants will have clinical assessments, including questionnaires, anthropometry, bone structure, body composition and physical performance tests. These assessments will be repeated at follow-up 1 and follow-up 2, with an interval of 12 months between each clinical visit. PARTICIPANTS This codesigned prospective observational study aims to recruit a total of 298 adults who identify as Aboriginal and Torres Strait Islander and reside within Victoria, Australia. Stratified sampling by age and sex will be used to ensure equitable distribution of men and women across four age-bands (35-44, 45-54, 55-64 and 65+ years). PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome is within-individual yearly change in areal bone mineral density at the total hip, femoral neck and lumbar spine assessed by dual energy X-ray absorptiometry. Within-individual change in cortical and trabecular volumetric bone mineral density at the radius and tibia using high-resolution peripheral quantitative computed tomography will be determined. Secondary outcomes include yearly differences in physical performance and body composition. ETHICAL APPROVAL Ethics approval for this study has been granted by the Monash Health Human Research Ethics Committee (project number: RES-19-0000374A). TRIAL REGISTRATION NUMBER ACTRN12620000161921.
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Affiliation(s)
- Ayse Zengin
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- School of Health and Social Development, Faculty of Health, Deakin University, Geelong, Victoria, Australia
| | - Cat Shore-Lorenti
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Marc Sim
- Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, Western Australia, Australia
| | - Louise Maple-Brown
- Charles Darwin University, Menzies School of Health Research, Darwin, Northern Territory, Australia
- Endocrinology Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia
| | - Sharon Lee Brennan-Olsen
- School of Health and Social Development, Faculty of Health, Deakin University, Geelong, Victoria, Australia
- Institute for Health Transformation, Deakin University, Geelong, Victoria, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St Albans, Victoria, Australia
- Department of Medicine-Western Health, University of Melbourne, St Albans, Victoria, Australia
| | - Joshua R Lewis
- Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
- Medical School, Royal Perth Hospital Unit, The University of Western Australia, Perth, Western Australia, Australia
- Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, University of Sydney, Sydney, New South Wales, Australia
| | - Jennifer Ockwell
- Bunurong Health Service, Dandenong & District Aborigines Co-operative Ltd (DDACL), Dandenong, Victoria, Australia
| | - Troy Walker
- Health & Wellbeing, A2B Personnel, Echuca, Victoria, Australia
| | - David Scott
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Peter Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
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Raj JJ, Kow RY, Ramalingam S, Low CL. Neck of Femur Fracture in Young Patients With End-Stage Renal Disease and Hyperparathyroidism: A Report of Three Cases and Proposed Treatment Algorithm. Cureus 2021; 13:e16155. [PMID: 34367767 PMCID: PMC8338123 DOI: 10.7759/cureus.16155] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2021] [Indexed: 11/05/2022] Open
Abstract
Secondary hyperparathyroidism is a complication arising from untreated end-stage renal disease (ESRD). It can invariably lead to osteoporosis and subsequently cause pathological neck of femur (NOF) fracture. Despite being young, osteosynthesis in neck of femur fractures of these patients often leads to nonunion and implant failure due to severely osteoporotic bone. We present our experience in managing three young patients with ESRD and secondary hyperthyroidism who sustained NOF fractures. All three patients were successfully treated and showed no complication at one year post-operation. Based on our experience and literature review, we propose a simple algorithm to guide the management of these patients.
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Affiliation(s)
- Jeffrey J Raj
- Department of Orthopaedics, Hospital Tengku Ampuan Afzan, Kuantan, MYS
| | - Ren Yi Kow
- Department of Orthopaedics, Traumatology & Rehabilitation, International Islamic University Malaysia, Kuantan, MYS.,Department of Orthopaedics, Hospital Tengku Ampuan Afzan, Kuantan, MYS
| | | | - Chooi Leng Low
- Department of Radiology, International Islamic University Malaysia, Kuantan, MYS
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Nazzal Z, Khader S, Zawyani H, Abdallah M, Sawalmeh O, Hamdan Z. Bone mineral density in Palestinian patients with end-stage renal disease and the related clinical and biochemical factors: Cross-sectional study. PLoS One 2020; 15:e0241201. [PMID: 33180791 PMCID: PMC7661051 DOI: 10.1371/journal.pone.0241201] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 10/10/2020] [Indexed: 12/31/2022] Open
Abstract
Introduction End-Stage Renal Disease (ESRD) is the ultimate result of chronic kidney disease (CKD). In Palestine, the prevalence of ESRD was 240.3 PMP which is comparable with the nearby countries. Accelerated bone loss among ESRD patients is attributed to abnormal bone turn over that leads to osteoporosis and osteopenia. The risk of fractures is increased four-fold in men and women on hemodialysis, which explains the importance of assessing the bone mineral density among these population. The goals of this study were to find the prevalence of osteoporosis in ESRD patients as determined by bone mineral density (BMD) at different sites and to determine whether BMD correlates with many other clinical parameters. Methods A cross-sectional study of 194 ESRD patients were recruited from the dialysis unit in An-Najah National University Hospital, Nablus, Palestine. The patients were on regular hemodialysis or peritoneal dialysis. BMD was measured at the lumbar spine and the hip using the dual-energy X-Ray absorptiometry (DEXA) and the value is expressed as T-score. The data were analyzed using SPSS, version 26. The relationship between BMD and the clinical and biochemical parameters among the ESRD patients was assessed. Results We found that 42.8% of ESRD patient had osteoporosis and 40.2% had osteopenia. There were significantly higher proportions of osteoporosis and osteopenia among patients >60 years of age (p<0.005). Patients with osteoporosis and osteopenia had significantly higher serum levels of PTH (792.9 and 469.7) (p<0.05). BMD decreases as the duration of dialysis (39.0 months Vs. 56.8 months), (p<0.05). We found no significant difference between patients on hemodialysis or peritoneal dialysis. Conclusion This study showed that Palestinian patients with ESRD have low BMD at the hip and spine. The observed high serum level of PTH was associated with low BMD. Those patients should be closely monitored especially those with more than one risk factor. Moreover, more attention should be paid for these category of patients to decrease the incidence of falling down and the resulting fractures that might lead to mortality and morbidity.
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Affiliation(s)
- Zaher Nazzal
- Family and Community Medicine Department, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Shahd Khader
- Medicine Department, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Hiba Zawyani
- Medicine Department, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mazen Abdallah
- Orthopedic Surgery Department, An-Najah National University Hospital, An-Najah National University, Nablus, Palestine
| | - Osama Sawalmeh
- Internal Medicine Department, An-Najah National University Hospital, An-Najah National University, Nablus, Palestine
| | - Zakaria Hamdan
- Nephrology Consultant, Nephrology Department, An-Najah National University Hospital, An-Najah National University, Nablus, Palestine
- * E-mail:
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Kovvuru K, Kanduri SR, Vaitla P, Marathi R, Gosi S, Anton DFG, Rivera FHC, Garla V. Risk Factors and Management of Osteoporosis Post-Transplant. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E302. [PMID: 32575603 PMCID: PMC7353876 DOI: 10.3390/medicina56060302] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/11/2020] [Accepted: 06/17/2020] [Indexed: 02/06/2023]
Abstract
Bone and mineral disorders are common after organ transplantation. Osteoporosis post transplantation is associated with increased morbidity and mortality. Pathogenesis of bone disorders in this particular sub set of the population is complicated by multiple co-existing factors like preexisting bone disease, Vitamin D deficiency and parathyroid dysfunction. Risk factors include post-transplant immobilization, steroid usage, diabetes mellitus, low body mass index, older age, female sex, smoking, alcohol consumption and a sedentary lifestyle. Immunosuppressive medications post-transplant have a negative impact on outcomes, and further aggravate osteoporotic risk. Management is complex and challenging due to the sub-optimal sensitivity and specificity of non-invasive diagnostic tests, and the underutilization of bone biopsy. In this review, we summarize the prevalence, pathophysiology, diagnostic tests and management of osteoporosis in solid organ and hematopoietic stem cell transplant recipients.
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Affiliation(s)
- Karthik Kovvuru
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA
| | - Swetha Rani Kanduri
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA; (S.R.K.); (P.V.); (D.F.G.A.); (F.H.C.R.)
| | - Pradeep Vaitla
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA; (S.R.K.); (P.V.); (D.F.G.A.); (F.H.C.R.)
| | - Rachana Marathi
- Division of Hospital Medicine, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA;
| | - Shiva Gosi
- Department of Hospital Medicine, Banner Thunderbird Medical Center, Glenadale, AZ 85306, USA;
| | - Desiree F. Garcia Anton
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA; (S.R.K.); (P.V.); (D.F.G.A.); (F.H.C.R.)
| | - Franco H. Cabeza Rivera
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA; (S.R.K.); (P.V.); (D.F.G.A.); (F.H.C.R.)
| | - Vishnu Garla
- Department of Internal Medicine and Mississippi Center for Clinical and Translational Research, University of Mississippi Medical Center, Jackson, MS 39156, USA;
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11
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Goto NA, Weststrate ACG, Oosterlaan FM, Verhaar MC, Willems HC, Emmelot-Vonk MH, Hamaker ME. The association between chronic kidney disease, falls, and fractures: a systematic review and meta-analysis. Osteoporos Int 2020; 31:13-29. [PMID: 31720721 PMCID: PMC6946749 DOI: 10.1007/s00198-019-05190-5] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 10/04/2019] [Indexed: 12/31/2022]
Abstract
Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. However, it is not well established how great the risk is for falls and fractures for the different stages of CKD compared to the general population. The objective of this systematic review and meta-analysis was to assess whether, and in which degree, CKD was associated with falls and fractures in adults. A systematic search in PubMed, Embase, CINAHL, and The Cochrane Library was performed on 7 September 2018. All retrospective, cross-sectional, and longitudinal studies of adults (18 years of older) that studied the association between CKD, fractures, and falls were included. Additional studies were identified by cross-referencing. A total of 39 publications were included, of which two publications assessed three types of outcome and four publications assessed two types of outcome. Ten studies focused on accidental falling; seventeen studies focused on hip, femur, and pelvis fractures; seven studies focused on vertebral fractures; and thirteen studies focused on any type of fracture without further specification. Generally, the risk of fractures increased when kidney function worsened, with the highest risks in the patients with stage 5 CKD or dialysis. This effect was most pronounced for hip fractures and any type of fractures. Furthermore, results on the association between CKD and accidental falling were contradictory. Compared to the general population, fractures are highly prevalent in patients with CKD. Besides more awareness of timely fracture risk assessment, there also should be more focus on fall prevention.
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Affiliation(s)
- N A Goto
- Dianet Dialysis Center, Utrecht, The Netherlands.
- Department of Geriatrics, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
| | - A C G Weststrate
- Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht, The Netherlands
| | - F M Oosterlaan
- Department of Geriatrics, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - M C Verhaar
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - H C Willems
- Department of Geriatrics, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - M H Emmelot-Vonk
- Department of Geriatrics, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - M E Hamaker
- Department of Geriatrics, Diakonessenhuis Utrecht, Utrecht, The Netherlands
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12
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Aleksova J, Ng KW, Jung C, Zeimer H, Dwyer KM, Milat F, MacIsaac RJ. Bone health in chronic kidney disease-mineral and bone disorder: a clinical case seminar and update. Intern Med J 2019; 48:1435-1446. [PMID: 30302919 DOI: 10.1111/imj.14129] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 08/15/2018] [Accepted: 08/25/2018] [Indexed: 12/14/2022]
Abstract
The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation. The Kidney Disease Improving Global Outcomes organisation describes these mineral metabolism derangements and skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this disorder have an increased risk of fracture, cardiovascular events and overall increased mortality. In light of the recently updated 2017 guidelines from the Kidney Disease Improving Global Outcomes, we present a clinical case-based discussion to highlight the complexities of investigating and managing the bone health of patients with CKD with a focus on these updates.
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Affiliation(s)
- Jasna Aleksova
- Hudson Institute for Medical Research, Melbourne, Victoria, Australia.,Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Kong W Ng
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Caroline Jung
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Howard Zeimer
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Karen M Dwyer
- School of Medicine, Faculty of Health, Deakin University, Melbourne, Victoria, Australia
| | - Frances Milat
- Hudson Institute for Medical Research, Melbourne, Victoria, Australia.,Department of Medicine, Monash University, Melbourne, Victoria, Australia.,Department of Endocrinology, Monash Health, Melbourne, Victoria, Australia
| | - Richard J MacIsaac
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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13
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Li C, Chen XM, Li Y, Zhou YL, Yan JN, Du XG. Factors and Outcome of Renal Osteodystrophy-Associated Initial Fragility Fracture in End-Stage Renal Disease Patients. KIDNEY DISEASES (BASEL, SWITZERLAND) 2019; 5:118-125. [PMID: 31019925 DOI: 10.1159/000494924] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 10/29/2018] [Indexed: 01/09/2023]
Abstract
Background Renal osteodystrophy has caused increased risk of fragility fracture in end-stage renal disease (ESRD) patients. However, risk factors and outcome of ESRD patients with fragility fracture remain uncharacterized. We aimed to assess these parameters in ESRD patients. Summary This retrospective case-control study analyzed 354 ESRD patients (initial fragility fracture [FF] group, n = 59; control group, n = 295). Pre-dialysis blood hemoglobin, serum albumin, lipid, calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were collected. All procedures performed involving human participants were in accordance with the ethical standards of the institutional committee of The First Affiliated Hospital of Chongqing Medical University (IRB approval number 216-82), and informed consent was obtained from all participants. There were higher prevalence rates of primary hypertension and diabetes, higher serum ALP, corrected calcium, and lower serum total cholesterol, low-density lipoprotein, lipoprotein-α, and iPTH in the FF group. Fractures were more likely to occur in the higher level of corrected calcium as well as in the lower iPTH group. High corrected calcium (p = 0.010, OR = 11.308, 95% CI: 1.770-72.242) and serum ALP (p = 0.000, OR = 1.007, 95% CI: 1.004-1.011) were independent risk factors of fragility fracture. The incidence of all-cause mortality and cardiovascular (CV) events in ESRD patients with fragility fracture was higher than in those without fracture. Key Messages Patients with hypertension, diabetes, excessive suppression of PTH, and poor nutritional status are more prone to fractures. Serum corrected calcium and ALP were independent risk factors of fragility fracture. Patients with initial fragility fracture had more CV events and higher mortality.
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Affiliation(s)
- Cai Li
- Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xue-Mei Chen
- Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yin Li
- Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Department of Nephrology and Endocrinology, The People's Hospital of Tongliang District, Chongqing, China
| | - Yan-Lin Zhou
- Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jia-Ni Yan
- Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Gang Du
- Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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14
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Damasiewicz MJ, Nickolas TL. Rethinking Bone Disease in Kidney Disease. JBMR Plus 2018; 2:309-322. [PMID: 30460334 PMCID: PMC6237213 DOI: 10.1002/jbm4.10117] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 09/05/2018] [Accepted: 10/03/2018] [Indexed: 12/17/2022] Open
Abstract
Renal osteodystrophy (ROD) is the bone component of chronic kidney disease mineral and bone disorder (CKD-MBD). ROD affects bone quality and strength through the numerous hormonal and metabolic disturbances that occur in patients with kidney disease. Collectively these disorders in bone quality increase fracture risk in CKD patients compared with the general population. Fractures are a serious complication of kidney disease and are associated with higher morbidity and mortality compared with the general population. Furthermore, at a population level, fractures are at historically high levels in patients with end-stage kidney disease (ESKD), whereas in contrast the general population has experienced a steady decline in fracture incidence rates. Based on these findings, it is clear that a paradigm shift is needed in our approach to diagnosing and managing ROD. In clinical practice, our ability to diagnose ROD and initiate antifracture treatments is impeded by the lack of accurate noninvasive methods that identify ROD type. The past decade has seen advances in the noninvasive measurement of bone quality and strength that have been studied in kidney disease patients. Below we review the current literature pertaining to the epidemiology, pathology, diagnosis, and management of ROD. We aim to highlight the pressing need for a greater awareness of this condition and the need for the implementation of strategies that prevent fractures in kidney disease patients. Research is needed for more accurate noninvasive assessment of ROD type, clinical studies of existing osteoporosis therapies in patients across the spectrum of kidney disease, and the development of CKD-specific treatments. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
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Affiliation(s)
- Matthew J Damasiewicz
- Department of NephrologyMonash HealthClaytonAustralia
- Department of MedicineMonash UniversityClaytonAustralia
| | - Thomas L Nickolas
- Columbia University Medical CenterDepartment of MedicineDivision of NephrologyNew YorkNYUSA
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15
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CKD, arterial calcification, atherosclerosis and bone health: Inter-relationships and controversies. Atherosclerosis 2018; 278:49-59. [DOI: 10.1016/j.atherosclerosis.2018.08.046] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 07/12/2018] [Accepted: 08/29/2018] [Indexed: 01/14/2023]
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Shigematsu T, Shimazaki R, Fukagawa M, Akizawa T. Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan. Clin Pharmacol 2018; 10:101-111. [PMID: 30254496 PMCID: PMC6141109 DOI: 10.2147/cpaa.s171044] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Purpose Cinacalcet is a positive allosteric modulator of calcium-sensing receptors in the parathyroid gland and an effective treatment for secondary hyperparathyroidism. However, this agent has considerable side effects and dosage limitations, which impair effective treatment. Therefore, we investigated the pharmacokinetics, pharmacodynamics, and safety of the novel calcimimetic, evocalcet. Patients and methods This was a multicenter, open-label study of single oral doses of 1, 4, and 12 mg evocalcet using an intrapatient dose escalation protocol in 29 Japanese secondary hyperparathyroidism patients receiving hemodialysis. Pharmacokinetics was assessed by plasma evocalcet concentrations. Pharmacodynamic evaluations consisted of measuring intact parathyroid hormone, serum corrected calcium, and fibroblast growth factor 23 concentrations. Safety and tolerability were evaluated by the analysis of adverse events (AEs). Results After a single 1-, 4-, or 12-mg dose, plasma evocalcet levels increased dose proportionally in a linear manner. Pharmacodynamic analyses showed that evocalcet effectively reduced intact parathyroid hormone and serum corrected calcium levels in a dose-dependent manner. AEs occurred in 31.0%, 28.6%, and 38.5% of patients receiving a single dose of 1, 4, or 12 mg, respectively. Most AEs were mild in severity. Conclusion Evocalcet is effective in the short term, has linear pharmacokinetics, and is well tolerated as observed by the low incidence of AEs.
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Affiliation(s)
| | | | - Masafumi Fukagawa
- Department of Internal Medicine, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Tadao Akizawa
- Department of Medicine, Division of Nephrology, Showa University School of Medicine, Minato-ku, Tokyo, Japan
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Shigematsu T, Shimazaki R, Fukagawa M, Akizawa T. Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients. Clin Exp Nephrol 2018; 23:258-267. [PMID: 30159688 PMCID: PMC6510802 DOI: 10.1007/s10157-018-1635-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 08/15/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND This study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis. METHODS In this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events. RESULTS Plasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE 'blood calcium decreased' occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased). CONCLUSION Multiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.
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Affiliation(s)
- Takashi Shigematsu
- Department of Nephrology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8509, Japan.
| | - Ryutaro Shimazaki
- R&D Division, Kyowa Hakko Kirin Co., Ltd., 1-9-2 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan
| | - Tadao Akizawa
- Division of Nephrology, Department of Medicine, Showa University School of Medicine, Namics 301, 4-24-51 Takanawa, Minato-ku, Tokyo, 108-0074, Japan
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18
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Hori Y, Takahashi S, Terai H, Hoshino M, Toyoda H, Suzuki A, Hayashi K, Tamai K, Ohyama S, Nakamura H. Impact of Hemodialysis on Surgical Outcomes and Mortality Rate after Lumbar Spine Surgery: A Matched Cohort Study. Spine Surg Relat Res 2018; 3:151-156. [PMID: 31435568 PMCID: PMC6690081 DOI: 10.22603/ssrr.2018-0025] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 08/06/2018] [Indexed: 01/05/2023] Open
Abstract
Introduction Despite ongoing improvements in both dialysis and surgical techniques, spinal surgery in patients undergoing hemodialysis (HD) is a challenge to surgeons because of the high mortality rate. However, no previous studies have examined clinical outcomes after lumbar surgery in HD patients. The purpose of this study is to compare clinical outcomes and complication rates after lumbar spinal surgery in patients with or without hemodialysis. Methods This retrospective, matched cohort study was conducted to compare surgical outcomes between HD vs non-HD patients who underwent lumbar surgery at our hospital. Controls were individually matched to cases at a ratio of 1:2. Clinical outcomes, complications, and mortality rates were compared between the two groups. Results Twenty-nine patients in the HD group and 57 in the non-HD group were included in the current study. Five patients in the HD group died during the follow-up period, whereas no patients died in the non-HD group (mortality rate, 17.2% vs. 0%, P = 0.003). Japanese Orthopaedic Association (JOA) scores were significantly less improved in the HD group than in the non-HD group (11.9 vs. 14.2 preoperatively, P = 0.001; 19.9 vs. 25.1 at final follow-up, P < 0.001). Five patients underwent repeat surgery in the HD group, which was significantly higher than the non-HD group (17.2% vs. 3.5%, P = 0.041). Conclusions The current study indicates that patients undergoing HD had poor outcomes after lumbar spinal surgery. Moreover, 5 of 29 patients died within a mean 2.4-years follow-up. The indications for lumbar spine surgery in HD patients must be carefully considered because of poor surgical outcomes and high mortality rate.
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Affiliation(s)
- Yusuke Hori
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shinji Takahashi
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hidetomi Terai
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masatoshi Hoshino
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiromitsu Toyoda
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akinobu Suzuki
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazunori Hayashi
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koji Tamai
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shoichiro Ohyama
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Nakamura
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Zengin A, Maple-Brown LJ, Brennan-Olsen S, Center JR, Eades S, Ebeling PR. Musculoskeletal health of Indigenous Australians. Arch Osteoporos 2018; 13:77. [PMID: 30008045 DOI: 10.1007/s11657-018-0493-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 06/29/2018] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Research on non-communicable diseases (NCD) in Indigenous Australians has mostly focused on diabetes mellitus and chronic kidney or cardiovascular disease. Osteoporosis, characterised by low bone mass and structural deterioration of bone tissue, and sarcopenia, the age-related loss of muscle mass and strength, often co-exist with these common NCDs-the combination of which will disproportionately increase bone fragility and fracture risk and negatively influence cortical and trabecular bone. Furthermore, the social gradient of NCDs, including osteoporosis and fracture, is well-documented, meaning that specific population groups are likely to be at greater risk of poorer health outcomes: Indigenous Australians are one such group. PURPOSE This review summarises the findings reported in the literature regarding the muscle and bone health of Indigenous Australians. FINDINGS There are limited data regarding the musculoskeletal health of Indigenous Australians; however, areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) is reported to be greater at the hip compared to non-Indigenous Australians. Falls are the leading cause of injury-related hospitalisations in older Australians, particularly Indigenous Australians, with a great proportion suffering from fall-related fractures. Despite sparse data, it appears that Indigenous men and women have a substantially higher risk of hip fracture at a much younger age compared to non-Indigenous Australians. CONCLUSION Data on more detailed musculoskeletal health outcomes are required in Indigenous Australians to better understand fracture risk and to formulate evidence-based strategies for fracture prevention and to minimise the risk of falls.
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Affiliation(s)
- Ayse Zengin
- Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash Medical Centre, Monash University, Level 5/Block E, 246 Clayton Road, Clayton, VIC, 3168, Australia.
| | - Louise J Maple-Brown
- Menzies School of Health Research, Darwin, Australia
- Division of Medicine, Royal Darwin Hospital, Darwin, Australia
| | - Sharon Brennan-Olsen
- Department of Medicine-Western Health, University of Melbourne, Melbourne, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, Melbourne, Australia
- Australian Health Policy Collaboration, Melbourne, Australia
| | - Jacqueline R Center
- Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia
- Department of Endocrinology, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Sandra Eades
- Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia
- Aboriginal Health Domain, Baker Heart and Diabetes Institute, Melbourne, Australia
| | - Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash Medical Centre, Monash University, Level 5/Block E, 246 Clayton Road, Clayton, VIC, 3168, Australia
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Lo LWT, Yanling X, Chou ACC, Howe TS, Allen JC, Koh JSB. End-Stage Renal Failure Is an Independent Risk Factor for 1-Year Mortality After Hip Fracture Surgery. Geriatr Orthop Surg Rehabil 2018; 9:2151459318770561. [PMID: 29707413 PMCID: PMC5912265 DOI: 10.1177/2151459318770561] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Revised: 02/15/2018] [Accepted: 02/15/2018] [Indexed: 11/16/2022] Open
Abstract
Introduction End-stage renal failure (ESRF) with its associated comorbidities increase postoperative mortality in hip fracture patients. This study investigated the association of ESRF with various comorbidities in patients on dialysis and assessed rates ESRF as an independent risk factor for all-cause postoperative 1- year mortality rates. Methods This was a retrospective cohort study on patients aged 55 years and older who underwent their first nonpathological, low-energy hip fracture surgery at an Asian tertiary hospital from June 2007 to 2012. Patients were identified as cases with ESRF on dialysis (study group) or non-ESRF patients (controls). Various comorbidity factors and postoperative 1-year mortality status were obtained from institutional electronic medical records. Univariate and multivariate logistic regression were used to identify significant risk factors for all-cause, 1-year mortality. Results With no loss to follow-up, the 1-year postoperative mortality rate was 19.6% for the 46 patients with ESRF on dialysis and 8.4% for non-ESRF controls (P = .028). Fisher exact test showed that hypertension, ischemic heart disease (IHD), diabetes mellitus (DM), anemia, cerebrovascular disease, and vascular disease were significantly associated with ESRF (P < .05). Multivariable logistic regression analysis identified ESRF (adjusted odds ratio[AOR] = 2.85, P = .021), cancer (AOR = 3.04, P = .003), IHD (AOR = 2.07, P = .020), DM (AOR = 2.03, P = .022), and age (AOR = 1.08, P <.0001) as independent risk factors for 1-year mortality following hip fracture surgery. The area under the receiver-operating characteristic curve (95% confidence interval) for the multivariable predictor of 1-year mortality was 0.75 (0.60-0.82). Conclusions Although associated with multiple comorbidities, ESRF was found to be independently predictive of 1-year mortality in patients undergoing hip fracture surgery, second to cancer in terms of magnitude of risk posed. As ESRF is a negative prognostic factor for 1-year mortality after hip fracture surgery, its importance should be recognized with implications on preoperative counseling to patients about the increased risk and implications on fracture prevention.
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Affiliation(s)
| | - Xu Yanling
- Department of Orthopaedic Surgery, Singapore General Hospital, Singapore
| | | | - Tet Sen Howe
- Department of Orthopaedic Surgery, Singapore General Hospital, Singapore
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Wu L, Luthringer BJC, Feyerabend F, Zhang Z, Machens HG, Maeda M, Taipaleenmäki H, Hesse E, Willumeit-Römer R, Schilling AF. Increased levels of sodium chloride directly increase osteoclastic differentiation and resorption in mice and men. Osteoporos Int 2017; 28:3215-3228. [PMID: 28849275 PMCID: PMC5635092 DOI: 10.1007/s00198-017-4163-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 07/13/2017] [Indexed: 01/30/2023]
Abstract
UNLABELLED To better understand the association between high salt intake and osteoporosis, we investigated the effect of sodium chloride (NaCl) on mice and human osteoclastogenesis. The results suggest a direct, activating role of NaCl supplementation on bone resorption. INTRODUCTION High NaCl intake is associated with increased urinary calcium elimination and parathyroid hormone (PTH) secretion which in turn stimulates the release of calcium from the bone, resulting in increased bone resorption. However, while calciuria after NaCl loading could be shown repeatedly, several studies failed to reveal a significant increase in PTH in response to a high-sodium diet. Another possible explanation that we investigated here could be a direct effect of high-sodium concentration on bone resorption. METHODS Mouse bone marrow macrophage and human peripheral blood mononuclear cells (PBMC) driven towards an osteoclastogenesis pathway were cultivated under culture conditions mimicking hypernatremia environments. RESULTS In this study, a direct effect of increased NaCl concentrations on mouse osteoclast differentiation and function was observed. Surprisingly, in a human osteoclast culture system, significant increases in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, calcitonin receptor (CTR)-positive osteoclasts, nuclear factor-activated T cells c1 (NFATc1) gene expression, and areal and volumetric resorptions were observed for increasing concentrations of NaCl. This suggests a direct, activating, cell-mediated effect of increased concentrations of NaCl on osteoclasts. CONCLUSIONS The reported that enhanced bone resorption after high-sodium diets may not only be secondary to the urinary calcium loss but may also be a direct, cell-mediated effect on osteoclastic resorption. These findings allow us to suggest an explanation for the clinical findings independent of a PTH-mediated regulation.
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Affiliation(s)
- L Wu
- Department of Biological Characterisation, Institute for Materials Research, Helmholtz-Zentrum Geesthacht, Geesthacht, Germany
- Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - B J C Luthringer
- Department of Biological Characterisation, Institute for Materials Research, Helmholtz-Zentrum Geesthacht, Geesthacht, Germany
| | - F Feyerabend
- Department of Biological Characterisation, Institute for Materials Research, Helmholtz-Zentrum Geesthacht, Geesthacht, Germany
| | - Z Zhang
- Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
- Department of Orthopedics, Hand Surgery Division, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - H G Machens
- Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - M Maeda
- Heisenberg Group for Molecular Skeletal Biology, Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - H Taipaleenmäki
- Heisenberg Group for Molecular Skeletal Biology, Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - E Hesse
- Heisenberg Group for Molecular Skeletal Biology, Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - R Willumeit-Römer
- Department of Biological Characterisation, Institute for Materials Research, Helmholtz-Zentrum Geesthacht, Geesthacht, Germany
| | - A F Schilling
- Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
- Clinic for Trauma Surgery, Orthopedic Surgery, and Plastic Surgery, University Medical Center Göttingen, Göttingen, Germany.
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Carvalho C, Magalhães J, Neto R, Pereira L, Branco P, Adragão T, Frazão JM. Cortical bone analysis in a predialysis population: a comparison with a dialysis population. J Bone Miner Metab 2017; 35:513-521. [PMID: 27830383 DOI: 10.1007/s00774-016-0781-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 08/29/2016] [Indexed: 01/16/2023]
Abstract
This study was designed to characterize cortical bone by histomorphometry in a predialysis population, to correlate turnover, mineralization, and volume between cortical and trabecular bone, and to compare the findings with those in patients treated with maintenance dialysis. We evaluated cortical bone by histomorphometry in 16 patients with stage 3 or stage 4 chronic kidney disease and in 16 dialysis patients. Dual-energy X-ray absorptiometry (DXA) of the distal end of the forearm was performed in seven predialysis patients, and the findings correlated with histologic parameters. Predialysis patients compared with dialysis patients showed increased cortical bone thickness (p = 0.027) and decreased osteonal bone formation rate (p = 0.020) and adjusted apposition rate (p = 0.018), mainly for external cortical bone. In this predialysis population, trabecular bone volume positively correlated with external cortical porosity (r = 0.723, p = 0.003), external cortical thickness (r = 0.569, p = 0.034), and external osteonal accumulation (osteonal osteoid thickness, r = 0.530, p = 0.05; osteonal osteoid volume to bone volume ratio, r = 0.921, p < 0.001; and osteonal osteoid surface to bone surface ratio, r = 0.631, p = 0.016). These correlations were not observed in the internal cortical bone. Cortical osteonal mineralization surface negatively correlated with DXA Z and T scores and bone mineral density for the distal end of the forearm. The osteonal bone formation rate of both internal cortical bone and external cortical bone correlated with Z score (r = -0.975, p = 0.005 and r = -0.880, p = 0.021 respectively). We found no significant correlations between cortical thickness or porosity and DXA parameters for either external cortical bone or internal cortical bone. Our results suggest that a greater degree of kidney disease is associated with thinner cortices, eventually contributing to the higher fracture rate observed in the chronic kidney disease population. In predialysis patients, parathyroid hormone seems to have a modulating effect on both trabecular bone and cortical bone, particularly in external cortical bone.
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Affiliation(s)
- Catarina Carvalho
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
- Department of Renal, Urological and Infectious Diseases, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
- Department of Nephrology, Braga Hospital, Braga, Portugal.
| | - J Magalhães
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
| | - R Neto
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Department of Renal, Urological and Infectious Diseases, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
- Department of Nephrology, São João Hospital Center, Porto, Portugal
| | - L Pereira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Department of Renal, Urological and Infectious Diseases, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
- Department of Nephrology, São João Hospital Center, Porto, Portugal
| | - P Branco
- Department of Nephrology, Santa Cruz Hospital, Carnaxide, Portugal
| | - T Adragão
- Department of Nephrology, Santa Cruz Hospital, Carnaxide, Portugal
| | - J M Frazão
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Department of Renal, Urological and Infectious Diseases, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
- Department of Nephrology, São João Hospital Center, Porto, Portugal
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Yamane H, Takakura A, Shimadzu Y, Kodama T, Lee JW, Isogai Y, Ishizuya T, Takao-Kawabata R, Iimura T. Acute development of cortical porosity and endosteal naïve bone formation from the daily but not weekly short-term administration of PTH in rabbit. PLoS One 2017; 12:e0175329. [PMID: 28394900 PMCID: PMC5386260 DOI: 10.1371/journal.pone.0175329] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 03/23/2017] [Indexed: 12/18/2022] Open
Abstract
Teriparatide [human parathyroid hormone (1–34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 μg/kg/day (D20), 40 μg/kg/day (D40), 140 μg/kg/week (W140) and 280 μg/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naïve bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment.
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Affiliation(s)
- Hiroshi Yamane
- Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
| | - Aya Takakura
- Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
- Division of Analytical Bio-Medicine, Graduate School of Medicine, Ehime University, Shitukawa, Toon city, Ehime, Japan
| | - Yukari Shimadzu
- Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
| | - Toshiyuki Kodama
- Laboratory for Safety Assessment and ADME, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
| | - Ji-Won Lee
- Division of Bio-Imaging, Proteo-Science Center (PROS), Ehime University, Shitukawa, Toon city, Ehime, Japan
| | - Yukihiro Isogai
- Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
- Medical Affairs Department, Pharmaceutical Business Administration Division, Asahi Kasei Pharma Corporation, Tokyo, Japan
| | - Toshinori Ishizuya
- Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
| | - Ryoko Takao-Kawabata
- Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan
- * E-mail: (RT-K); (TI)
| | - Tadahiro Iimura
- Division of Analytical Bio-Medicine, Graduate School of Medicine, Ehime University, Shitukawa, Toon city, Ehime, Japan
- Division of Bio-Imaging, Proteo-Science Center (PROS), Ehime University, Shitukawa, Toon city, Ehime, Japan
- Division of Analytical Bio-Medicine, Advanced Research Support Center (ADRES), Ehime University, Shitukawa, Toon city, Ehime, Japan
- Artificial Joint Integrated Center, Ehime University Hospital, Shitukawa, Toon city, Ehime, Japan
- * E-mail: (RT-K); (TI)
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Jokihaara J, Pörsti IH, Sievänen H, Kööbi P, Kannus P, Niemelä O, Turner RT, Iwaniec UT, Järvinen TLN. Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency. PLoS One 2016; 11:e0163022. [PMID: 27658028 PMCID: PMC5033583 DOI: 10.1371/journal.pone.0163022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Accepted: 09/01/2016] [Indexed: 11/19/2022] Open
Abstract
Introduction Phosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI. Methods Forty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography). Results Sevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p<0.05 for all versus Sham), while sevelamer increased bone mineral density (+2%) and prevented the deleterious changes in bone. In the femoral neck, CRI reduced bone mineral density (-11%) and breaking load (-10%), while sevelamer prevented the decrease in bone mineral density (+6%) so that breaking load did not differ from controls. Conclusions In this model of stage 3–4 CRI, sevelamer-HCl treatment ameliorated the decreases in femoral midshaft and neck mineral density, and restored bone strength despite prevailing acidosis. Therefore, treatment with sevelamer can efficiently preserve mechanical competence of bone in CRI.
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Affiliation(s)
- Jarkko Jokihaara
- Department of Hand and Microsurgery, Tampere University Hospital, Tampere, Finland
- Center for Hip Health and Mobility, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada
- * E-mail:
| | | | | | - Peeter Kööbi
- Medical School, University of Tampere, Tampere, Finland
| | - Pekka Kannus
- Bone Research Group, UKK-Institute, Tampere, Finland
| | - Onni Niemelä
- Medical School, University of Tampere, Tampere, Finland
- Department of Laboratory Medicine, Seinäjoki Central Hospital Laboratory, Seinäjoki, Finland
| | - Russell T. Turner
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, United States of America
| | - Urszula T. Iwaniec
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, United States of America
| | - Teppo L. N. Järvinen
- Center for Hip Health and Mobility, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada
- Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland
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Lima GAC, de Paula Paranhos-Neto F, Silva LC, de Mendonça LMC, Delgado AG, Leite M, Gomes CP, Farias MLF. Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease. J Clin Densitom 2016; 19:146-53. [PMID: 24709549 DOI: 10.1016/j.jocd.2014.01.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2013] [Accepted: 01/22/2014] [Indexed: 01/10/2023]
Abstract
Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (p<0.001), FGF-23 (p=0.029), and lowest 25-hydroxyvitamin D (p=0.016), bicarbonate (p<0.001), total femur (p=0.003), and femoral neck (p=0.011) T-scores compared with stage 3 CKD patients. Total femur and femoral neck T-scores were directly correlated with serum bicarbonate (p=0.003, r=0.447 and p=0.005, r=0.427, respectively) and estimated glomerular filtration rate (p=0.024, r=0.325 and p=0.003, r=0.313, respectively) but were not significantly associated with parathyroid hormone, 25-hydroxyvitamin D, or FGF-23. Only 3.9% of the participants had osteoporosis on DXA scan, whereas 31.4% reported a low-impact fracture. Our data point to a pivotal role of metabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients.
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Affiliation(s)
- Guilherme Alcantara Cunha Lima
- Division of Endocrinology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
| | - Francisco de Paula Paranhos-Neto
- Division of Endocrinology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
| | - Luciana Colonese Silva
- Division of Endocrinology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
| | - Laura Maria Carvalho de Mendonça
- Division of Rheumatology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
| | - Alvimar Gonçalves Delgado
- Division of Nephrology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
| | - Maurilo Leite
- Division of Nephrology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
| | - Carlos Perez Gomes
- Division of Nephrology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
| | - Maria Lucia Fleiuss Farias
- Division of Endocrinology, Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
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Lee YY, Kim HB, Lee JW, Lee GM, Kim SY, Hur JA, Cho HC. The Association between Urine Albumin to Creatinine Ratio and Osteoporosis in Postmenopausal Women with Type 2 Diabetes. J Bone Metab 2016; 23:1-7. [PMID: 26981514 PMCID: PMC4791432 DOI: 10.11005/jbm.2016.23.1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2015] [Revised: 02/05/2016] [Accepted: 02/07/2016] [Indexed: 11/25/2022] Open
Abstract
Background Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass density and destruction of microstructure, which can lead to an increased risk of fracture. Although many studies have been published about the relationship between end-stage renal disease and osteoporosis, research on the relationship between proteinuria and the prevalence of osteoporosis is still lacking. Methods We assessed 91 postmenopausal women with type 2 diabetes who visited our hospital from January 2009 to January 2012. Results Among 91 patients, the prevalence of osteoporosis and osteopenia was 35.2% (32 cases) and 32.9% (30 cases) according to bone mineral density. The patients with microalbuminuria and macroalbuminuria (urine albumin-to-creatinine ratio [UACR] ≥ 30) had a significantly higher incidence of osteoporosis compared to subjects with normoalbuminuria (P<0.05). Conclusions This study indicates that UACR may be a useful biomarker for increased risk of osteoporosis in postmenopausal women with type 2 diabetes who have been linked to higher UACR levels.
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Affiliation(s)
- Ye Yeon Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Han Byul Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Jong Won Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Gyu Min Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang Yoon Kim
- Department of Internal Medicine, Andong Medical Group Hospital, Andong, Korea
| | - Ji An Hur
- Department of Internal Medicine, School of Medicine, Yeungnam University, Daegu, Korea
| | - Ho Chan Cho
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
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27
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Rodda C. Nutritional Aspects of Disease Affecting the Skeleton. Clin Nutr 2015. [DOI: 10.1002/9781119211945.ch19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Byon CH, Chen Y. Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature. Curr Osteoporos Rep 2015; 13:206-15. [PMID: 25947259 PMCID: PMC4489999 DOI: 10.1007/s11914-015-0270-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and increases mortality in those patients. Impaired calcium and phosphate homeostasis, increased oxidative stress, and loss of calcification inhibitors have been linked to vascular calcification in CKD. Additionally, impaired bone may perturb serum calcium/phosphate and their key regulator, parathyroid hormone, thus contributing to increased vascular calcification in CKD. Therapeutic approaches for CKD, such as phosphate binders and bisphosphonates, have been shown to ameliorate bone loss as well as vascular calcification. The precise mechanisms responsible for vascular calcification in CKD and the contribution of bone metabolism to vascular calcification have not been elucidated. This review discusses the role of systemic uremic factors and impaired bone metabolism in the pathogenesis of vascular calcification in CKD. The regulation of the key osteogenic transcription factor Runt-related transcription factor 2 (Runx2) and the emerging role of Runx2-dependent receptor activator of nuclear factor kappa-B ligand (RANKL) in vascular calcification of CKD are emphasized.
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Affiliation(s)
- Chang Hyun Byon
- Department of Pathology, University of Alabama at Birmingham, 614 Shelby Biomedical Research Bldg., 1825 University Blvd., Birmingham, AL 35294, USA
| | - Yabing Chen
- Department of Pathology, University of Alabama at Birmingham, 614 Shelby Biomedical Research Bldg., 1825 University Blvd., Birmingham, AL 35294, USA
- Department of Pathology, Birmingham Veterans Affairs Medical Center, Birmingham, AL 35294, USA
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West SL, Patel P, Jamal SA. How to predict and treat increased fracture risk in chronic kidney disease. J Intern Med 2015; 278:19-28. [PMID: 25758353 DOI: 10.1111/joim.12361] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Men and women with chronic kidney disease (CKD) are at an increased risk of fracture, and this risk increases as kidney function deteriorates. Fractures are associated with morbidity, mortality and economic costs. Despite this, there is a paucity of data regarding how to evaluate risk for fractures in CKD and how to treat high-risk patients. Evidence suggests that bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA) is associated with fractures and can also predict future fractures in predialysis (stages 1-3) patients with CKD. In the absence of considerable abnormalities in markers of mineral metabolism, treatment with antiresorptive agents in men and women with early CKD at high fracture risk may be appropriate. Of note, recent data suggest that low BMD as measured by DXA can also predict fractures in patients with more advanced CKD (stages 4, 5 and 5D). However, treatment in patients with advanced CKD requires bone biopsy, the gold standard to assess bone turnover, prior to treatment. Further research, focusing on noninvasive methods to assess fracture risk and bone turnover, together with randomized controlled trials of treatments to reduce fractures in patients at all stages of CKD, is required.
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Affiliation(s)
- S L West
- Women's College Research Institute, University of Toronto, Toronto, ON, Canada
| | - P Patel
- Women's College Research Institute, University of Toronto, Toronto, ON, Canada
| | - S A Jamal
- Women's College Research Institute, University of Toronto, Toronto, ON, Canada
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Cannata-Andía JB, Carrera F. The Pathophysiology of Secondary Hyperparathyroidism and the Consequences of Uncontrolled Mineral Metabolism in Chronic Kidney Disease: The Role of COSMOS. NDT Plus 2015; 1:i2-i6. [PMID: 25983952 PMCID: PMC4421153 DOI: 10.1093/ndtplus/sfm037] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2007] [Accepted: 09/10/2007] [Indexed: 12/20/2022] Open
Abstract
The development of secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease. SHPT develops as a consequence of mineral metabolism disturbances and is characterized by elevated serum parathyroid hormone (PTH) and parathyroid hyperplasia. Evidence suggests that SHPT contributes to the development of vascular calcification and cardiovascular disease, as well as to the development of renal osteodystrophy. The elevated serum calcium, phosphorus, calcium–phosphorus product and PTH that accompany SHPT have been independently associated with an increased relative risk of mortality. Despite the danger that these risks represent, achieving control of mineral metabolism in SHPT is difficult. Recent evidence from the Current Management of Secondary Hyperparathyroidism: Multicentre Observational Study has shown that fewer than 1 in 10 haemodialysis patients simultaneously meet their National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for serum calcium, phosphorus, calcium–phosphorus product and PTH with standard treatments. There is therefore an urgent need for new strategies and novel pharmacologic therapies that improve control of mineral metabolism and PTH secretion in SHPT and thus reduce the mortality associated with this condition.
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Cunningham J, Floege J, London G, Rodriguez M, Shanahan CM. Clinical outcomes in secondary hyperparathyroidism and the potential role of calcimimetics. NDT Plus 2015; 1:i29-i35. [PMID: 25983954 PMCID: PMC4421154 DOI: 10.1093/ndtplus/sfm042] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2007] [Accepted: 09/10/2007] [Indexed: 12/26/2022] Open
Abstract
Cinacalcet, a type II calcimimetic agent that interacts with the calcium-sensing receptor on the parathyroid gland and increases its sensitivity to calcium, has proved an effective therapy for the treatment of the biochemical derangements that comprise uraemic secondary hyperparathyroidism. These patients experience high cardiovascular attrition with evidence that this is associated with vascular calcification, arterial stiffening and increased pulse wave velocity, and with some of the disturbances of bone and mineral metabolism in uraemia. Thus, it is possible that improved biochemical control in calcimimetic-treated patients might lead to better clinical outcomes. This hypothesis was investigated by retrospective analyses of randomized placebo-controlled phase 3 studies. The addition of cinacalcet to standard therapy with active vitamin D and phosphate binders was found to result in a 93% reduction in the rate of parathyroidectomy, a 54% reduction in fracture rate and 39% reduction in the rate of cardiovascular hospitalization, as well as improvements in some measures of quality of life. These encouraging results point to the need for a more robust assessment of the impact of cinacalcet on cardiovascular and skeletal outcomes.
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Affiliation(s)
- John Cunningham
- The Royal Free and University College Medical School , London , UK
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Miller PD. Renal osteodystrophy. Rheumatology (Oxford) 2015. [DOI: 10.1016/b978-0-323-09138-1.00205-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Jung YS, Hwang HJ, Yun BH, Chon SJ, Cho S, Choi YS, Kim YT, Lee BS, Seo SK. Renal function is associated with bone mineral density and arterial stiffness in healthy postmenopausal women. Gynecol Obstet Invest 2014; 78:124-9. [PMID: 25034396 DOI: 10.1159/000363746] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 05/18/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS This study aimed to investigate the effect of renal function on bone mineral density (BMD) and arterial stiffness in postmenopausal women. METHODS This is a retrospective cross-sectional study. We studied 252 postmenopausal women who visited a health promotion center for a medical checkup. The estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault (CG) formula and the modification of diet in renal disease (MDRD) formula. Areal BMD measurements were performed using dual-energy X-ray absorptiometry, and arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). RESULTS The eGFR according to the CG formula was significantly correlated with age, BMI, follicle-stimulating hormone, thyroid-stimulating hormone, high-density lipoprotein cholesterol, baPWV, and BMD at the lumbar spine, femoral neck, and total hip sites. However, the eGFR according to the MDRD formula was significantly correlated with age and baPWV but not with BMD at the lumbar spine, femoral neck, and total hip sites. Decreased renal function (eGFR <60 ml/min/1.73 m(2) according to the CG formula) was independently associated with decreased BMD at the femoral neck site and with increased baPWV (>1,500 cm/s) after adjusting for confounding variables. CONCLUSION Postmenopausal women with decreased renal function are more likely to have a decreased BMD and greater arterial stiffness.
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Affiliation(s)
- Yeon Soo Jung
- Department of Obstetrics and Gynecology, National Health Insurance Service Ilsan Hospital Goyang, Goyang, Korea
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McKiernan FE, Berg RL, Fuehrer J. Clinical and radiographic findings in adults with persistent hypophosphatasemia. J Bone Miner Res 2014; 29:1651-60. [PMID: 24443354 DOI: 10.1002/jbmr.2178] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 01/14/2014] [Accepted: 01/15/2014] [Indexed: 01/11/2023]
Abstract
A serum alkaline phosphatase value below the age-adjusted lower limits of normal (hypophosphatasemia) is uncommonly encountered in clinical practice. The electronic and paper medical records of 885,165 patients treated between 2002 and 2012 at a large, rural, multispecialty health clinic were interrogated to estimate the prevalence and characterize the clinical and radiographic findings of adults whose serum alkaline phosphatase was almost always low (persistent hypophosphatasemia). We hypothesized that some of these patients might harbor previously unrecognized hypophosphatasia, a rare, inherited condition of impaired mineralization of bones and teeth. Persistent hypophosphatasemia (serum alkaline phosphatase ≤ 30 IU/L) was found in 1 of 1544 adult patients. These adult patients had more crystalline arthritis, orthopedic surgery, chondrocalcinosis, calcific periarthritis, enthesopathy, and diffuse idiopathic skeletal hyperostosis than a general adult patient population. A gender effect was observed. The clinical and radiographic findings of adult patients with persistent hypophosphatasemia resemble those of the adult form of hypophosphatasia. Clinicians should take notice of persistent hypophosphatasemia, consider the diagnosis of hypophosphatasia, and be cautious when considering potent anti-remodeling therapy in these adults. This population warrants further evaluation.
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Trombetti A, Stoermann C, Chevalley T, Van Rietbergen B, Herrmann FR, Martin PY, Rizzoli R. Alterations of bone microstructure and strength in end-stage renal failure. Osteoporos Int 2013; 24:1721-32. [PMID: 23100118 DOI: 10.1007/s00198-012-2133-4] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Accepted: 08/27/2012] [Indexed: 10/27/2022]
Abstract
UNLABELLED End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients. INTRODUCTION Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density. METHODS We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0 ± 12.6 years) and 33 age-matched healthy controls. RESULTS Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with "Kidney Disease: Improving Global Outcomes" working group PTH level categories (r = 0.36, p < 0.04). BMI correlated positively with trabecular number (r = 0.4, p < 0.02) and negatively with trabecular spacing (r = -0.37, p < 0.03) and trabecular network heterogeneity (r = -0.4, p < 0.02). Biomechanics positively correlated with BMI and negatively with BALP. CONCLUSION Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone fragility in ESRD patients.
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Affiliation(s)
- A Trombetti
- Bone Diseases Service, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland.
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Characteristics of bisphosphonate-related osteonecrosis of the jaw after kidney transplantation. J Craniofac Surg 2013; 23:e510-4. [PMID: 22976726 DOI: 10.1097/scs.0b013e31825b33f6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Renal transplantation is the definitive treatment of chronic renal failure, and osteoporosis in patients after renal transplantation is caused by the use of high-dose corticosteroids, reduced renal function, and the use of immunosuppressant. While bisphosphonates inhibit osteoclastic activities, they are the drug of choice for the treatment and prevention of osteoporosis. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) becomes a problematic issue. There are few reports on BRONJ in patients after renal transplantation, so many oral bisphosphonates commonly prescribed in patients after renal transplantation to prevent osteoporosis have no warning of BRONJ. We analyzed the records of patients with BRONJ from January 2009 to December 2010. Among the patients with BRONJ, we selected patients who underwent transplantation of the kidney. Demographic data, drug-related factors, and clinical characteristics were evaluated using chart review. A total of 128 patients were categorized as having BRONJ, and there were 3 patients with a history of kidney transplantation. The average age was 54.6 years, and 2 victims were men. All patients received oral bisphosphonates for more than 2 years (range, 2-7 y; average, 58.6 mo). All patients had hypertension, diabetes mellitus, history of high-dose corticosteroids, and taking immunosuppressant drugs. Bisphosphonate-related osteonecrosis of the jaw occurred in the maxilla in all patients, which is classified as stage 3 because of the involved sinus. Extraction was the main provoking factor in all patients. In conclusion, even at a relatively young age, BRONJ in the maxilla can be developed by intake of oral bisphosphonate after kidney transplantation. Dental care for patients before and after undergoing renal transplantation should be emphasized to reduce the risk of BRONJ.
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Nybo M, Jespersen B, Aarup M, Ejersted C, Hermann AP, Brixen K. Determinants of bone mineral density in patients on haemodialysis or peritoneal dialysis--a cross-sectional, longitudinal study. Biochem Med (Zagreb) 2013; 23:342-50. [PMID: 24266305 PMCID: PMC3900080 DOI: 10.11613/bm.2013.042] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 09/16/2013] [Indexed: 11/28/2022] Open
Abstract
INTRODUCTION The aim of the study was to identify biomarkers of alteration in bone mineral density (BMD) in patients on haemodialysis (HD) and peritoneal dialysis (PD). MATERIALS AND METHODS In a cross-sectional, longitudinal study dual-energy X-ray absorptiometry scans were performed in 146 HD-patients and 28 PD-patients. Follow-up after 14 months (mean) was conducted in 73 patients. As potential biomarkers we investigated parathyroid hormone (PTH), 25-hydroxy vitamin-D, ionised calcium, albumin, phosphate, and total alkaline phosphatases (t-ALP). RESULTS Both groups of dialysis patients had lower BMD in the femoral neck (BMD(neck)) (P < 0.001) and forearm (BMD(forearm)) (P < 0.001) compared to healthy controls, but comparable BMD in the lumbar spine (BMD(spine)). BMD did not differ between dialysis types, but patients ever-treated with glucocorticoids had significantly lower BMD, while patients with polycystic kidney disease had higher BMD. BMD correlated with body weight, actual age, age at initiation of dialysis, duration of dialysis and levels of PTH and t-ALP. However, t-ALP only remained associated with low BMD(spine) after adjusting for other factors (P = 0.001). In the follow-up study all patients had decreased BMD in all three locations, but only for the lumbar spine there was a significant association between BMD and the bone markers t-ALP (P = 0.009) and PTH (P = 0.013). CONCLUSIONS Both HD and PD patients have low BMD, and increased concentrations of t-ALP is associated BMD(spine) after adjustment, while PTH and t-ALP is associated with decrease in BMD(spine) over time. This substantiates the use of these biomarkers in both types of dialysis patients.
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Affiliation(s)
- Mads Nybo
- Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark.
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Jamal SA, Cheung AM, West SL, Lok CE. Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease. Osteoporos Int 2012; 23:2805-13. [PMID: 22297732 DOI: 10.1007/s00198-012-1908-y] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Accepted: 01/12/2012] [Indexed: 10/14/2022]
Abstract
UNLABELLED Fractures are common in chronic kidney disease (CKD). We determined if bone mineral density testing by dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR pQCT) could discriminate fracture status in CKD patients. Both tests were able to discriminate fracture status. Further, the addition of HR pQCT measurements to DXA measurements did not improve fracture discrimination. INTRODUCTION The optimal method to identify individuals with CKD at high fracture risk is unknown. METHODS We determined if bone mineral density (BMD) by DXA and HR pQCT could discriminate fracture status in 211 adult men and women with stages 3 to 5 CKD, attending predialysis clinics in Toronto Canada, using logistic regression. Results are expressed as the odds ratio (OR) of fracture (prevalent vertebral and/or low trauma since age 40 years) per standard deviation decrease in the predictor adjusted for age, weight, sex, and CKD stage. We constructed receiver operating characteristic curves to examine the discriminative ability of BMD measures for fracture. RESULTS Most participants were Caucasian men with a mean age of 63.3 ± 15.5 years. There were 77 fractures in 74 participants. Decreases in BMD were associated with increased fracture risk: OR = 1.56 (95% confidence interval (CI), 1.41 to 1.71) for BMD by DXA at the ultradistal radius, and OR = 1.24 (95% CI, 1.12 to 1.36) for cortical area by HR pQCT. Further, while both tests were able to discriminate fracture status, the addition of HR pQCT measures to BMD by DXA did not improve fracture discrimination ability. CONCLUSIONS Among CKD patients not yet requiring renal replacement therapy, BMD by DXA is able to discriminate fracture status.
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Affiliation(s)
- S A Jamal
- Women's College Research Institute, 790 Bay Street, Suite 725, Toronto, ON, M5G 1N8, Canada.
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Douthat WG, Chiurchiu CR, Massari PU. New options for the management of hyperparathyroidism after renal transplantation. World J Transplant 2012; 2:41-5. [PMID: 24175195 PMCID: PMC3782233 DOI: 10.5500/wjt.v2.i3.41] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Revised: 04/08/2012] [Accepted: 06/01/2012] [Indexed: 02/05/2023] Open
Abstract
The persistence and severity of hyperparathyroidism (HPT) post-renal transplantation is relatively frequent and primarily associated with the timing and its magnitude in the pre-transplant period and with the presence of parathyroid adenomas. HPT after renal transplantation is clinically manifested with hypercalcemia, hypophosphatemia, bone pain, fractures, and in more serious cases with cardiovascular calcifications that affect the survival. The primary clinical objective for patients with secondary HPT after renal transplantation is to obtain a level of parathyroid hormone (PTH) adequate to the renal transplanted function and to normalize levels of calcium, phosphorus and vitamin D. In many cases during this period, the development of hypercalcemia and/or hypophosphatemia makes it necessary to take different therapeutic measures. The use of vitamin D or its analogues has been extrapolated from the management of pre-transplant HPT obtaining variable outcomes, although its use is limited by its capacity to produce hypercalcemia. Calcimimetics are drugs that have proven be effective in reducing PTH levels in patients with HPT on dialysis and has been effective in reducing up to 50% PTH levels in moderate to severe HPT in post-renal transplantation.When HPT persists after renal transplantation and does not respond to medical treatment, invasive management by percutaneous ethanol injection therapy of parathyroid glands or parathyroidectomy should be considered. The emergence of new methods for the management of HPT expands the availability of therapeutic tools for transplant patients.
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Affiliation(s)
- Walter Guillermo Douthat
- Walter Guillermo Douthat, Carlos Raul Chiurchiu, Pablo Ulises Massari, Bone and Mineral Metabolism Section, Renal Service, Hospital Privado, Centro Médico de Córdoba, 5016 Córdoba, Argentina
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Chue CD, Wall NA, Crabtree NJ, Zehnder D, Moody WE, Edwards NC, Steeds RP, Townend JN, Ferro CJ. Aortic calcification and femoral bone density are independently associated with left ventricular mass in patients with chronic kidney disease. PLoS One 2012; 7:e39241. [PMID: 22723973 PMCID: PMC3377619 DOI: 10.1371/journal.pone.0039241] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2012] [Accepted: 05/22/2012] [Indexed: 01/06/2023] Open
Abstract
Background Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. Methodology and Principal Findings A total of 120 patients were recruited (54% male, mean age 55±14 years, mean glomerular filtration rate 50±13 ml/min/1.73 m2). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60±1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56±16 vs. 48±12 g/m2, P = 0.002), as did patients with femoral Z-scores below zero (56±15 vs. 49±13 g/m2, P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Z-score inversely correlated with left ventricular mass (r = −0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). Conclusions In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted.
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Affiliation(s)
- Colin D. Chue
- School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
- Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Nadezhda A. Wall
- School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Nicola J. Crabtree
- Department of Endocrinology, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - Daniel Zehnder
- Clinical Sciences Research Institute, University of Warwick, Coventry, United Kingdom
| | - William E. Moody
- School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
- Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Nicola C. Edwards
- School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
- Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Richard P. Steeds
- Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Jonathan N. Townend
- Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Charles J. Ferro
- Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
- * E-mail:
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St-Arnaud R, Arabian A, Akhouayri O, Knutson JC, Strugnell SA. Differential effects of oral doxercalciferol (Hectorol) or paricalcitol (Zemplar) in the Cyp27b1-null mouse model of uremia. Nephron Clin Pract 2011; 119:e67-74. [PMID: 21849802 DOI: 10.1159/000329663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2010] [Accepted: 05/20/2011] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND/AIMS Kidney disease patients experience declining calcitriol levels and develop secondary hyperparathyroidism (SHPT). Animal models of uremia based on 5/6 nephrectomy (NTX) do not consistently reproduce this calcitriol deficiency. We developed an animal model, the NTX Cyp27b1-null mouse, which completely lacks endogenous calcitriol, and examined the suitability of this model for evaluation of treatment with vitamin D analogs in uremia. METHODS NTX was performed at 2 months of age. One week post-NTX, animals were treated for 4 weeks with vehicle; doxercalciferol at 30, 100 or 300 pg/g body weight (b.w.); or paricalcitol at 100, 300 or 1,000 pg/g b.w. by gavage 3 times per week. RESULTS Serum blood urea nitrogen and creatinine were elevated. Vehicle-treated NTX null mice had hypocalcemia and SHPT. Doxercalciferol at 100 or 300 pg/g b.w. normalized serum calcium and parathyroid hormone (PTH) levels. Paricalcitol at 300 or 1,000 pg/g normalized serum calcium, but PTH levels remained elevated. Osteomalacia was corrected by 100 pg/g b.w. of doxercalciferol or 1,000 pg/g b.w. of paricalcitol. The highest dose of doxercalciferol, but not of paricalcitol, significantly reduced osteitis fibrosa. CONCLUSION Our results reveal the differential efficacy of doxercalciferol and paricalcitol in this novel animal model incorporating both calcitriol deficiency and renal insufficiency.
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Affiliation(s)
- René St-Arnaud
- Genetics Unit, Shriners Hospital for Children, Montreal, Qué., Canada
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Landesberg R, Woo V, Cremers S, Cozin M, Marolt D, Vunjak-Novakovic G, Kousteni S, Raghavan S. Potential pathophysiological mechanisms in osteonecrosis of the jaw. Ann N Y Acad Sci 2011; 1218:62-79. [PMID: 21291478 DOI: 10.1111/j.1749-6632.2010.05835.x] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Bisphosphonates are used in the treatment of hypercalcemia of malignancy, skeletal complications associated with metastastic bone disease, Paget's disease, and osteoporosis. Osteonecrosis of the jaw (ONJ) is a recently described clinical condition that has been associated with the use of nitrogen-containing bisphosphonates. Reports describing this entity first appeared in the literature in 2003. While there have been significant numbers of case reports and a limited number of retrospective and prospective studies examining risk factors associated with ONJ, the pathophysiology of this condition remains elusive. In this review, we explore proposed mechanisms underlying ONJ development and identify potential areas for future investigation.
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Affiliation(s)
- Regina Landesberg
- University of Connecticut Health Center, Division of Oral and Maxillofacial Surgery, School of Dental Medicine, Farmington, Connecticut, USA.
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Kim HL, Park IY, Choi JM, Hwang SM, Kim HS, Lim JS, Kim M, Son MJ. A decline in renal function is associated with loss of bone mass in Korean postmenopausal women with mild renal dysfunction. J Korean Med Sci 2011; 26:392-8. [PMID: 21394308 PMCID: PMC3051087 DOI: 10.3346/jkms.2011.26.3.392] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Accepted: 12/14/2010] [Indexed: 01/15/2023] Open
Abstract
This study was conducted to assess the relationship between estimated glomerular filtration rate (eGFR) and bone mineral density (BMD) in Korean postmenopausal women with mild renal dysfunction. A total of 328 postmenopausal women who underwent BMD measurement during health check-up was investigated. BMD was measured in lumbar spine (L1-L4), femoral neck, total proximal femur and femoral trochanteric areas by dual energy radiography absorptiometry and renal function was estimated by eGFR using Cockcroft-Gault equation. Of the 328 subjects, 317 (96.6%) had an eGFR ≥60 mL/min/1.73 m(2). By using simple linear regression analysis, age, height, weight and eGFR were significantly associated with BMD for the 4 aforementioned anatomic sites, while serum levels of creatinine and blood urea nitrogen did not influence BMD. When multiple regression analyses were applied, age and body weight still had significant associations with BMD at 4 different anatomic sites (P < 0.001). A significant association of eGFR with BMD remained in the lumbar spine, femoral neck and proximal total femur (P < 0.05) but not in the trochanteric area (P = 0.300). Our study suggests that a decline of renal function is associated with lower BMD in the lumbar spine, femoral neck and total proximal femur areas in Korean menopausal women with mild renal dysfunction.
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Affiliation(s)
- Hack-Lyoung Kim
- Armed Forces Seoul Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | | | | | - Se-Min Hwang
- Department of Preventive Medicine, The Armed Forces Medical Commands, Seongnam, Korea
| | - Hyo Sang Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | | | - Min Kim
- Armed Forces Seoul Hospital, Seoul, Korea
| | - Min-Jeong Son
- Division of Nephrology, Department of Internal Medicine, The Armed Forces Capital Hospital, Seongnam, Korea
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Gupta R, Mohammed AM, Alenizi EK, Ben Nekhi A. Bone mineral density in Kuwaiti patients with end-stage renal disease. Med Princ Pract 2011; 20:156-8. [PMID: 21252572 DOI: 10.1159/000319775] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2009] [Accepted: 05/09/2010] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE This study compared an ethnically uniform group of end-stage renal disease (ESRD) Kuwaiti patients with a control group of healthy Kuwaiti subjects, in terms of their bone mineral density (BMD) and anthropometric measurements. SUBJECTS AND METHODS Included in the study were 94 males and 129 females with a mean age of 48 ± 10 years. Forty-five males and 53 females had ESRD. The remaining 49 males and 26 females were the control subjects. BMD was measured at total lumbar spine (L1-L4) and total left hip, using dual energy X-ray absorptiometry (HOLOGIC, QRS series, Europe, Belgium). The data were analyzed using SPSS, version 15 (SPSS Inc., Chicago, Ill., USA). The difference in BMD and the anthropometric measurements between the ESRD patients and the controls was assessed. Multivariate linear regression models were used to examine independent effects of ESRD on BMD while adjusting for relevant covariates. RESULTS The ESRD patients had a lower BMD than the controls at the hip (0.81 ± 0.11 vs. 0.92 ± 0.16) and the spine (0.84 ± 0.12 vs. 0.92 ± 0.16), p < 0.001. They also had a lower body mass index (27.80 ± 6.03 vs. 30.85 ± 6.54; p < 0.001) and were taller (162.56 ± 15.31 vs. 156.94 cm ± 10.03; p < 0.01). The reduced BMD persisted after controlling for confounding effects of sex, age and anthropometric measurements (p < 0.001). CONCLUSION Kuwaiti patients with ESRD had a lower BMD and, therefore, an increased risk of osteoporosis and bone fractures.
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Affiliation(s)
- Renu Gupta
- Department of Radiology, Kuwait University, Jabriya, Kuwait. renu @ hsc.edu.kw
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HOW PP, ANATTIWONG P, MASON DL, ARRUDA JA, LAU AH. Phosphate-binding efficacy of crushed vs. chewed lanthanum carbonate in hemodialysis patients. Hemodial Int 2010; 15:95-9. [DOI: 10.1111/j.1542-4758.2010.00509.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Orlic L, Crncevic Z, Pavlovic D, Zaputovic L. Bone mineral densitometry in patients on hemodialysis: difference between genders and what to measure. Ren Fail 2010; 32:300-8. [PMID: 20370444 DOI: 10.3109/08860221003611661] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Chronic kidney disease (CKD) and osteoporosis are important health problems. There is an interrelationship between osteoporosis and CKD. Bone densitometry is the "gold" standard in the diagnosis of osteoporosis. Unfortunately, there are some problems with the interpretation of bone densitometry in CKD patients. The goal of this study was to determine bone mineral density (BMD) in CKD patients, to assess the difference between genders and different sites of bone densitometry correlation between BMD and laboratory parameters, and to assess the most optimal measuring site. METHODS We studied 134 hemodialysis (HD) patients (62 females, 72 males). The mean age was 56.4+/-12.4 years and the mean duration of HD was 54.4+/-60 months. BMD of the lumbar spine (posterior-anterior projection and lateral projection), hip (femoral neck, trochanter, intertrochanter, total femur, the Ward's Triangle), and forearm (ultradistal (UD), middistal (MID), distal third portion, and total forearm) was measured using dual X-ray absorptiometry (DXA) (Hologic Delphi apparatus). Values were expressed as BMD, T-score, and Z-score. RESULTS Females had lower values of BMD in all measurement points. There were no significant differences in T- and Z-scores of forearm between males and females. Age was in a positive correlation with lumbar spine BMD in males and females. There was a negative correlation with neck and forearm BMD in both groups. Serum parathyroid hormone (PTH) was also in negative correlation with hip and forearm BMD in both groups. The best correlation of BMD in different sites was between forearm and neck. CONCLUSION BMD data in CKD patients should be interpreted with caution and appendicular skeletal sites should be included in the evaluation.
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Affiliation(s)
- Lidija Orlic
- Department of Nephrology, University Hospital Rijeka, Rijeka, Croatia.
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Isaksson H, Turunen MJ, Rieppo L, Saarakkala S, Tamminen IS, Rieppo J, Kröger H, Jurvelin JS. Infrared spectroscopy indicates altered bone turnover and remodeling activity in renal osteodystrophy. J Bone Miner Res 2010; 25:1360-6. [PMID: 20200925 DOI: 10.1002/jbmr.10] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Renal osteodystrophy alters metabolic activity and remodeling rate of bone and also may lead to different bone composition. The objective of this study was to characterize the composition of bone in high-turnover renal osteodystrophy patients by means of Fourier transform infrared spectroscopic imaging (FTIRI). Iliac crest biopsies from healthy bone (n = 11) and patients with renal osteodystrophy (ROD, n = 11) were used in this study. The ROD samples were from patients with hyperparathyroid disease. By using FTIRI, phosphate-to-amide I ratio (mineral-to-matrix ratio), carbonate-to-phosphate ratio, and carbonate-to-amide I ratio (turnover rate/remodeling activity), as well as the collagen cross-link ratio (collagen maturity), were quantified. Histomorphometric analyses were conducted for comparison. The ROD samples showed significantly lower carbonate-to-phosphate (p < .01) and carbonate-to-amide I (p < .001) ratios. The spatial variation across the trabeculae highlighted a significantly lower degree of mineralization (p < .05) at the edges of the trabeculae in the ROD samples than in normal bone. Statistically significant linear correlations were found between histomorphometric parameters related to bone-remodeling activity and number of bone cells and FTIRI-calculated parameters based on carbonate-to-phosphate and carbonate-to-amide I ratios. Hence the results suggested that FTIRI parameters related to carbonate may be indicative of turnover and remodeling rate of bone.
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Affiliation(s)
- Hanna Isaksson
- Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland.
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McCann LM, Beto J. Roles of Calcium-Sensing Receptor and Vitamin D Receptor in the Pathophysiology of Secondary Hyperparathyroidism. J Ren Nutr 2010; 20:141-50. [DOI: 10.1053/j.jrn.2010.01.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2009] [Indexed: 01/01/2023] Open
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