Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Borhan S, Papaioannou A, Gajic-Veljanoski O, Kennedy C, Ioannidis G, Berger C, Goltzman D, Josse R, Kovacs CS, Hanley DA, Prior JC, Morin SN, Kaiser SM, Cheung AM, Thabane L, Adachi J. Incident Fragility Fractures Have a Long-Term Negative Impact on Health-Related Quality of Life of Older People: The Canadian Multicentre Osteoporosis Study. J Bone Miner Res 2019;34:838-848. [PMID: 30723960 DOI: 10.1002/jbmr.3666] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/10/2018] [Accepted: 12/22/2018] [Indexed: 11/06/2022]

For:	Borhan S, Papaioannou A, Gajic-Veljanoski O, Kennedy C, Ioannidis G, Berger C, Goltzman D, Josse R, Kovacs CS, Hanley DA, Prior JC, Morin SN, Kaiser SM, Cheung AM, Thabane L, Adachi J. Incident Fragility Fractures Have a Long-Term Negative Impact on Health-Related Quality of Life of Older People: The Canadian Multicentre Osteoporosis Study. J Bone Miner Res 2019;34:838-848. [PMID: 30723960 DOI: 10.1002/jbmr.3666] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/10/2018] [Accepted: 12/22/2018] [Indexed: 11/06/2022]

Number

Cited by Other Article(s)

Curtis JR, Arora T, Liu Y, Lin TC, Spangler L, Brunetti VC, Stad RK, McDermott M, Bradbury BD, Kim M. Comparative effectiveness of denosumab vs alendronate among postmenopausal women with osteoporosis. J Bone Miner Res 2024;39:826-834. [PMID: 38753892 PMCID: PMC11301726 DOI: 10.1093/jbmr/zjae079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 04/23/2024] [Accepted: 05/15/2024] [Indexed: 05/18/2024]

Abstract

Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab vs alendronate in reducing fracture risk among women with PMO in the US. Women with PMO ≥ 66 yr of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria. A doubly robust inverse-probability of treatment and censoring weighted function was used to estimate the risk ratio associated with the use of denosumab compared with alendronate for hip, nonvertebral (NV; includes hip, humerus, pelvis, radius/ulna, other femur), non-hip nonvertebral (NHNV), hospitalized vertebral (HV), and major osteoporotic (MOP; consisting of NV and HV) fractures. Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate. Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of fracture risk reduction with increasing duration of exposure was also observed for other NV fracture outcomes. In this cohort of almost half-a-million treatment-naive women with PMO, we observed clinically significant reductions in the risk of MOP, hip, NV, NHNV, and HV fractures for patients on denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk.

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Schlacht TZ, Haque I, Skelton DA. What are the Effects of Exercise on Trabecular Microarchitecture in Older Adults? A Systematic Review and Meta-analysis of HR-pQCT Studies. Calcif Tissue Int 2023;113:359-382. [PMID: 37725127 PMCID: PMC10516781 DOI: 10.1007/s00223-023-01127-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 08/14/2023] [Indexed: 09/21/2023]

Hueg TK, Hickey M, Beck AL, Wilson LF, Uldbjerg CS, Priskorn L, Abildgaard J, Lim Y, Bräuner EV. Risk of Fracture After Bilateral Oophorectomy. JBMR Plus 2023;7:e10750. [PMID: 37457875 PMCID: PMC10339092 DOI: 10.1002/jbm4.10750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 04/07/2023] [Indexed: 07/18/2023] Open

Abstract

Fragility fractures, resulting from low-energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow-up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time-varying bilateral oophorectomy (all ages, <51/≥51 years) and incident fragility fracture (any and site-specific [forearm, hip, spine, and other]). Exposure and outcome were ascertained from nationwide patient registries. During 491,626 person-years of follow-up, 6600 nurses (25.5%) with incident fragility fractures were identified, and 1938 (7.5%) nurses had a bilateral oophorectomy. The frequency of fragility fractures was 24.1% in nurses who were <51 years at time of bilateral oophorectomy and 18.1% in nurses who were ≥51 years. No statistically significant associations were observed between bilateral oophorectomy at any age and fragility fractures at any site. Neither HT use, hysterectomy, physical activity level, BMI, nor smoking altered the results. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Affiliation(s)

Trine K Hueg Department of Growth and ReproductionCopenhagen University Hospital – RigshospitaletCopenhagenDenmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)Copenhagen University Hospital – RigshospitaletCopenhagenDenmark
Martha Hickey Department of Obstetrics and GynaecologyUniversity of MelbourneMelbourneAustralia
Astrid L Beck Department of Growth and ReproductionCopenhagen University Hospital – RigshospitaletCopenhagenDenmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)Copenhagen University Hospital – RigshospitaletCopenhagenDenmark
Louise F Wilson NHMRC Centre for Research Excellence on Women and Non‐communicable Diseases (CREWaND), School of Public HealthThe University of QueenslandHerstonAustralia
Cecilie S Uldbjerg Department of Growth and ReproductionCopenhagen University Hospital – RigshospitaletCopenhagenDenmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)Copenhagen University Hospital – RigshospitaletCopenhagenDenmark
Lærke Priskorn Department of Growth and ReproductionCopenhagen University Hospital – RigshospitaletCopenhagenDenmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)Copenhagen University Hospital – RigshospitaletCopenhagenDenmark
Julie Abildgaard Centre for Physical Activity ResearchRigshospitalet, University of CopenhagenCopenhagenDenmark
Youn‐Hee Lim Section of Environmental Health, Department of Public HealthUniversity of CopenhagenCopenhagenDenmark Seoul National UniversityMedical Research CenterSeoulRepublic of Korea
Elvira V Bräuner Department of Growth and ReproductionCopenhagen University Hospital – RigshospitaletCopenhagenDenmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)Copenhagen University Hospital – RigshospitaletCopenhagenDenmark

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Chhoda A, Hernandez-Woodbine MJ, Addo NAA, Nasir SA, Grimshaw A, Gunderson C, Ahmed A, Freedman SD, Sheth SG. Burden of bone disease in chronic pancreatitis: A systematic review and meta-analysis. World J Gastroenterol 2023;29:1374-1394. [PMID: 36925454 PMCID: PMC10011962 DOI: 10.3748/wjg.v29.i8.1374] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 01/15/2023] [Accepted: 02/15/2023] [Indexed: 02/28/2023] Open

Abstract

BACKGROUND

Bone disease is an under-recognized cause of morbidity in chronic pancreatitis (CP). Over the past decade, publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.

AIM

To quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and investigate the associated clinical features and outcomes.

METHODS

A systematic search identified studies investigating bone disease in CP patients from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The outcomes included prevalence of osteopenia, osteoporosis, and fragility fractures, which were meta-analyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.

RESULTS

Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression revealed significant association of pancreatic enzyme replacement therapy (PERT) use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. We observed no associations with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes with prevalence of osteopenia, osteoporosis or fragility fractures. Paucity of data on systemic inflammation, CP severity, and bone mineralization parameters precluded a formal meta-analysis.

CONCLUSION

This meta-analysis confirms significant bone disease in patients with CP. Other than PERT use, we observed no patient or study-specific factor to be significantly associated with CP-related bone disease. Further studies are needed to identify confounders, at-risk population, and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

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Kim MJ, Kim MS, Lee HB, Roh JH, Jeon JH. Relationship between the High Fatty Liver Index and Risk of Fracture. Gut Liver 2023;17:119-129. [PMID: 35892266 PMCID: PMC9840917 DOI: 10.5009/gnl210571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 04/15/2022] [Accepted: 05/03/2022] [Indexed: 02/01/2023] Open

Zuo H, Zheng T, Wu K, Yang T, Wang L, Nima Q, Bai H, Dong K, Fan Z, Huang S, Luo R, Wu J, Zhou J, Xu H, Zhang Y, Feng S, Zeng P, Xiao X, Guo B, Wei Y, Pei X, Zhao X. High-altitude exposure decreases bone mineral density and its relationship with gut microbiota: Results from the China multi-ethnic cohort (CMEC) study. ENVIRONMENTAL RESEARCH 2022;215:114206. [PMID: 36058270 DOI: 10.1016/j.envres.2022.114206] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 08/12/2022] [Accepted: 08/21/2022] [Indexed: 06/15/2023]

Abstract

BACKGROUND

Geographic altitude is a potent environmental factor for human microbiota and bone mineral density. However, little evidence exists in population-based studies with altitude diversity ranges across more than 3000 m. This study assessed the associations between a wide range of altitudes and bone mineral density, as well as the potential mediating role of microbiota in this relationship.

METHODS

A total of 99,556 participants from the China Multi-Ethnic Cohort (CMEC) study were enrolled. The altitude of each participant was extracted from global Shuttle Radar Topography Mission (SRTM) 4 data. Bone mineral density was measured by calcaneus quantitative ultrasound index (QUI). Stool samples were collected for 16S rRNA gene sequencing (n = 1384). The metabolites of gut microbiota, seven kinds of short-chain fatty acids (SCFAs), were detected by gas chromatography-mass spectrometry (GC-MS, n = 128). After screening, 73,974 participants were selected for the "altitude-QUI" analysis and they were placed into the low-altitude (LA) and high-altitude (HA) groups. Additionally, a subgroup (n = 1384) was further selected for the "altitude-microbiota-QUI" analysis. Multivariate linear regression models and mediation analyses were conducted among participants.

RESULTS

A significant negative association between high-altitude and QUI was obtained (mean difference = -0.373 standard deviation [SD], 95% confidence interval [CI]: -0.389, -0.358, n = 73,974). The same negative association was also observed in the population with microbiota data (mean difference = -0.185 SD, 95%CI: -0.360, -0.010, n = 1384), and a significant mediating effect of Catenibacteriumon on the association between altitude and QUI (proportion mediated = 25.2%, P = 0.038) was also noticed. Additionally, the acetic acid, butyric acid, and total amount of seven SCFAs of the low-altitude group were significantly higher than that of the high-altitude group (P < 0.05).

CONCLUSION

High-altitude exposure may decrease bone mineral density in adults, thus increasing the risk of osteoporosis. The modulation of gut microbiota may be a potential strategy for alleviating the decrease of bone mineral density.

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Affiliation(s)

Haojiang Zuo West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Tianli Zheng West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Kunpeng Wu West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Tingting Yang School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China.
Lingyao Wang West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Qucuo Nima Tibet Center for Disease Control and Prevention, Lhasa City, Tibet Autonomous Region, 850000, China.
Hua Bai College of Public Health, Kunming Medical University, Kunming, 650500, China.
Ke Dong West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Ziwei Fan West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Shourui Huang West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Ruocheng Luo West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Jialong Wu West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Junmin Zhou West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Huan Xu West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Yingcong Zhang West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Shiyu Feng West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Peibin Zeng West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Xiong Xiao West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Bing Guo West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.
Yonglan Wei Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan, 610041, China.
Xiaofang Pei West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, 610041, Chengdu, China.
Xing Zhao West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041, Chengdu, China.

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Chin KY, Ng BN, Rostam MKI, Muhammad Fadzil NFD, Raman V, Mohamed Yunus F, Syed Hashim SA, Ekeuku SO. A Mini Review on Osteoporosis: From Biology to Pharmacological Management of Bone Loss. J Clin Med 2022;11:6434. [PMID: 36362662 PMCID: PMC9657533 DOI: 10.3390/jcm11216434] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 07/25/2023] Open

Okuda R, Osaki M, Saeki Y, Okano T, Tsuda K, Nakamura T, Morio Y, Nagashima H, Hagino H. Effect of coordinator-based osteoporosis intervention on quality of life in patients with fragility fractures: a prospective randomized trial. Osteoporos Int 2022;33:1445-1455. [PMID: 35195752 DOI: 10.1007/s00198-021-06279-6] [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: 06/16/2021] [Accepted: 12/17/2021] [Indexed: 10/19/2022]

Abstract

UNLABELLED

We examined the effects of the coordinator-based intervention on quality of life (QOL) in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL. The coordinator-based interventions mitigated the decrease in QOL. Secondary fracture after primary fracture, however, was a significant predictor of lower QOL.

PURPOSE

This study aimed to determine the effects of the coordinator-based intervention on QOL in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL, in an Asian population.

METHODS

Patients with new fractures in the intervention group received the coordinator-based intervention by a designated nurse certified as a coordinator, within 3 months of injury. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scale before the fracture (through patient recollections) and at 0.5, 1, and 2 years after the primary fracture.

RESULTS

Data for 141 patients were analyzed: 70 in the liaison intervention (LI) group and 71 in the non-LI group. Significant intervention effects on QOL were observed at 6 months after the fracture; the QOL score was 0.079 points higher in the LI group than in the non-LI group (p=0.019). Further, the LI group reported significantly less pain/discomfort at 2 years after the fracture, compared to the non-LI group (p=0.037). In addition, secondary fractures were found to significantly prevent improvement and maintenance of QOL during the recovery period (p=0.015).

CONCLUSION

Short-term intervention effects were observable 6 months after the primary fracture, with the LI group mitigated the decrease in QOL. Few patients in the LI group reported pain/discomfort 2 years after the fracture, but there is uncertainty regarding its clinical significance. Secondary fracture after initial injury was a significant predictor of lower QOL after a fracture.

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Implementing and Evaluating the Impact of BoneRx: A Healthy Bone Prescription for Men with Prostate Cancer Initiating Androgen Deprivation Therapy. J Clin Med 2022;11:jcm11102703. [PMID: 35628830 PMCID: PMC9144215 DOI: 10.3390/jcm11102703] [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: 04/22/2022] [Revised: 05/03/2022] [Accepted: 05/07/2022] [Indexed: 11/19/2022] Open

Wu XY, Li HL, Shen Y, Tan LH, Yuan LQ, Dai RC, Zhang H, Peng YQ, Xie ZJ, Sheng ZF. Effect of Body Surface Area on Severe Osteoporotic Fractures: A Study of Osteoporosis in Changsha China. Front Endocrinol (Lausanne) 2022;13:927344. [PMID: 35937839 PMCID: PMC9354973 DOI: 10.3389/fendo.2022.927344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/21/2022] [Indexed: 11/30/2022] Open

Abstract

Clinical vertebral fractures and femoral neck fractures are severe osteoporotic fractures that increase morbidity and mortality. Anthropometric variables are associated with an increased risk of osteoporotic fractures, but it is not clear whether body surface area (BSA) has an effect on clinically severe osteoporotic fractures. The study included total of 3,694 cases of clinical vertebral fractures and femoral neck fractures (2,670 females and 1,024 males) and 3,694 controls without fractures who were matched with the cases by sex and age. There was a significant positive correlation between BSA and bone mineral density (BMD) in female and male fracture patients (females: r = 0.430-0.471, P < 0.001; males: r = 0.338-0.414, P < 0.001). There was a significant systematic increase in BMD in both genders at various skeletal sites, grouped by BSA quartile. The osteoporosis rates of the lumbar spine (97.9%), femoral neck (92.4%) and total hip (87.1%) in the female Q1 group were significantly higher than those in the Q4 group (P < 0.001), which were 80.0%, 57.9% and 36.9%, respectively, in the Q4 group; the osteoporosis rates of the lumbar spine, femoral neck, and total hip were 53.9%, 59.4%, and 36.3% in the male Q1 group, and 15.2%, 21.9%, and 7.03% in the Q4 group, which were significantly lower than those in the Q1 group (P < 0.001). In age-adjusted Cox regression models, the risk of fracture in the remaining three groups (Q2, Q3, and Q4) for weight, BMI, and BSA for both genders, compared with the highest quartile (Q1 by descending quartile stratification) were significantly higher. In models adjusted for age and BMD, only men in the BSA Q3 (HR = 1.55, 95% CI = 1.09-2.19) and BSA Q4 groups (HR = 1.41, 95% CI = 1.05-1.87) had significantly higher fracture risks. In models adjusted for age, height, weight, BMI, and BSA, low BMD was the greatest fracture risks for both sexes. Our results showed that BSA was closely related to BMD, prevalence of osteoporosis, and fracture risk, and that a decline in BSA may be a new potential risk factor for osteoporotic fractures in Chinese men.

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Affiliation(s)

Xi-Yu Wu Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
Hong-Li Li Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, China
Yi Shen Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, China
Li-Hua Tan Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
Ling-Qing Yuan Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
Ru-Chun Dai Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
Hong Zhang Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
Yi-Qun Peng Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
Zhong-Jian Xie Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
Zhi-Feng Sheng Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China *Correspondence: Zhi-Feng Sheng,

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Barcelos A, Lopes DG, Canhão H, da Cunha Branco J, Rodrigues AM. Multimorbidity is associated with fragility fractures in women 50 years and older: A nationwide cross-sectional study. Bone Rep 2021;15:101139. [PMID: 34754887 PMCID: PMC8564033 DOI: 10.1016/j.bonr.2021.101139] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/19/2021] [Accepted: 10/01/2021] [Indexed: 11/01/2022] Open

Abstract

INTRODUCTION

Multimorbidity is a worldwide health problem, especially in elderly patients who have a higher risk of fragility fracture. Currently, there is insufficient knowledge about the burden of multimorbidity in patients with previous fragility fracture. The aim of this study was to evaluate the association between multimorbidity and previous fragility fracture, and to assess the effect of fragility fracture and/or multimorbidity in the perception of quality-of-life and physical function, in women 50 years of age and older.

METHODS

Women aged ≥50 years from the EpiReumaPt study (2011-2013), a nationwide population-based study, were evaluated. Self-reported data regarding sociodemographics, health-related quality of life, physical functioning, fragility fracture, and multimorbidity were collected using a semi-structured questionnaire. Multimorbidity was defined as 2 or more chronic non-communicable diseases. Descriptive exploratory analysis of the data was performed using hypothesis testing. Multiple logistic regression modelling was used to assess the association between multimorbidity and fragility fractures, and linear regression was used for the quality-of-life and physical function outcomes.

RESULTS

The estimated prevalence of fragility fracture in women older than 50 years was 17.5%. A higher prevalence of multimorbidity (74.6%) was found in the group of women with previous fragility fracture than in those without previous fragility fracture. Multivariate logistic regression analysis revealed that women with multimorbidity had a higher odds of fragility fracture (adjusted odds ratio, 1.38; 95% confidence interval, 1.12-1.69), compared with women with 1 or no self-reported non-communicable chronic diseases. In women with previous fragility fracture, rheumatic diseases (62.7%) and hypertension (58.6%) were the most frequently self-reported non-communicable chronic diseases. The combination of fragility fracture and multimorbidity was associated with a lower quality of life and higher degree of disability.

CONCLUSIONS

Women 50 years and older with multimorbidity had a significantly increased odds of fragility fracture. Fragility fracture combined with multimorbidity was negatively associated with quality of life and positively associated with disability. This study emphasizes the need to redesign health services to care for patients to prevent non-communicable chronic diseases and fragility fracture, particularly in women 50 years and older, in whom these diseases are likely to potentiate the risk of fragility fracture.

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Chen CH, Cheng TL, Chang CF, Huang HT, Lin SY, Wu MH, Kang L. Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats. Biomedicines 2021;9:biomedicines9091114. [PMID: 34572301 PMCID: PMC8466068 DOI: 10.3390/biomedicines9091114] [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] [Received: 08/04/2021] [Revised: 08/22/2021] [Accepted: 08/24/2021] [Indexed: 12/15/2022] Open

Abstract

Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and β-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic β-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced β-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and β-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, β-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in β-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.

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Affiliation(s)

Chung-Hwan Chen Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 80420, Taiwan Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan Graduate Institute of Materials Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan
Tsung-Lin Cheng Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan
Chi-Fen Chang Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan
Hsuan-Ti Huang Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan
Sung-Yen Lin Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80701, Taiwan
Meng-Hsing Wu Department of Obstetrics & Gynecology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Lin Kang Department of Obstetrics & Gynecology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan

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Fowler TW, Mitchell TL, Janda CY, Xie L, Tu S, Chen H, Zhang H, Ye J, Ouyang B, Yuan TZ, Lee SJ, Newman M, Tripuraneni N, Rego ES, Mutha D, Dilip A, Vuppalapaty M, Baribault H, Yeh WC, Li Y. Development of selective bispecific Wnt mimetics for bone loss and repair. Nat Commun 2021;12:3247. [PMID: 34059688 PMCID: PMC8167098 DOI: 10.1038/s41467-021-23374-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 04/27/2021] [Indexed: 02/07/2023] Open

Bouvard B, Briot K, Legrand E, Blain H, Breuil V, Chapurlat R, Duquenne M, Guggenbuhl P, Lespessailles E, Thomas T, Cortet B. Recommandations françaises de la prise en charge et du traitement de l’ostéoporose masculine. ACTA ACUST UNITED AC 2021. [DOI: 10.1016/j.rhum.2021.02.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]

The Effects of Add-On Self-Care Therapy on Epidural Catheter Analgesia and Pain in Patients after Surgical Stabilization of Multiple Rib Fractures. Pain Manag Nurs 2021;22:764-768. [PMID: 33674241 DOI: 10.1016/j.pmn.2021.01.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 12/29/2020] [Accepted: 01/24/2021] [Indexed: 11/22/2022]

Hayes KN, Baschant U, Hauser B, Burden AM, Winter EM. When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis. Front Endocrinol (Lausanne) 2021;12:782118. [PMID: 34975756 PMCID: PMC8715727 DOI: 10.3389/fendo.2021.782118] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/19/2021] [Indexed: 01/28/2023] Open

Valentin G, Friis K, Nielsen CP, Larsen FB, Langdahl BL. Fragility fractures and health-related quality of life: does socio-economic status widen the gap? A population-based study. Osteoporos Int 2021;32:63-73. [PMID: 32681362 DOI: 10.1007/s00198-020-05540-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/07/2020] [Indexed: 01/09/2023]

Abstract

UNLABELLED

Studying 12,839 fracture cases and 91,426 controls, we found that fractures of the spine and hip are associated with clinically important HRQoL deficits up to 5 years post-fracture. Fracture cases with a low educational attainment are more likely to report very low HRQoL due to a low pre-fracture HRQoL.

INTRODUCTION

The aim of this study was to explore the short-term and long-term impact of fractures on health-related quality of life (HRQoL) and to study the effect of educational attainment as a proxy for socio-economic status (SES) on post-fracture HRQoL.

METHODS

In a population-based survey including 12,839 fracture cases and 91,426 controls, HRQoL was measured using the physical component score (PCS) and the mental component score (MCS) of the 12-Item Short Form Health Survey (SF-12). Information about fractures, age, sex, ethnicity, comorbidity and SES was obtained from national registers. Multiple regression analysis was conducted to measure the mean HRQoL difference, termed deficit, between non-fracture controls and fracture cases (all fractures combined and fractures at six different skeletal sites).

RESULTS

PCS and MCS were significantly lower among fracture cases than among controls. Statistically and clinically important PCS deficits (≥ 5 points) were observed among people with fractures of the spine and hip up to 5 years post-fracture and among people with upper arm fractures up to 1 year post-fracture. Greater deficits were observed for MCS but not for PCS in post-fracture HRQoL in the low than in the high SES group.

CONCLUSION

Fractures of the spine and hip are associated with clinically important deficits in physical HRQoL up to 5 years post-fracture. Low educational attainment widened the gap in mental but not in physical post-fracture HRQoL. However, due to low pre-fracture PCS and MCS, people with a low educational attainment and fractures were more likely to report very low HRQoL post-fracture.

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Huang HT, Cheng TL, Lin SY, Ho CJ, Chyu JY, Yang RS, Chen CH, Shen CL. Osteoprotective Roles of Green Tea Catechins. Antioxidants (Basel) 2020;9:E1136. [PMID: 33207822 PMCID: PMC7696448 DOI: 10.3390/antiox9111136] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/08/2020] [Accepted: 11/12/2020] [Indexed: 02/07/2023] Open

Abstract

Osteoporosis is the second most common disease only secondary to cardiovascular disease, with the risk of fracture increasing with age. Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes. Osteoclastogenesis may be enhanced, osteoblastogenesis may be reduced, or both may be evident. Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation. Catechins, the main polyphenols found in green tea with potent anti-oxidant and anti-inflammatory properties, can counteract the deleterious effects of the imbalance of osteoblastogenesis and osteoclastogenesis caused by osteoporosis. Green tea catechins can attenuate osteoclastogenesis by enhancing apoptosis of osteoclasts, hampering osteoclastogenesis, and prohibiting bone resorption in vitro. Catechin effects can be directly exerted on pre-osteoclasts/osteoclasts or indirectly exerted via the modulation of mesenchymal stem cells (MSCs)/stromal cell regulation of pre-osteoclasts through activation of the nuclear factor kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Catechins also can enhance osteoblastogenesis by enhancing osteogenic differentiation of MSCs and increasing osteoblastic survival, proliferation, differentiation, and mineralization. The in vitro effects of catechins on osteogenesis have been confirmed in several animal models, as well as in epidemiological observational studies on human subjects. Even though randomized control trials have not shown that catechins provide anti-fracture efficacy, safety data in the trials are promising. A large-scale, placebo-controlled, long-term randomized trial with a tea regimen intervention of optimal duration is required to determine anti-fracture efficacy.

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Affiliation(s)

Hsuan-Ti Huang Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan; (H.-T.H.); (T.-L.C.); (S.-Y.L.); (C.-J.H.) Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan
Tsung-Lin Cheng Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan; (H.-T.H.); (T.-L.C.); (S.-Y.L.); (C.-J.H.) Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan
Sung-Yen Lin Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan; (H.-T.H.); (T.-L.C.); (S.-Y.L.); (C.-J.H.) Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan
Cheng-Jung Ho Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan; (H.-T.H.); (T.-L.C.); (S.-Y.L.); (C.-J.H.) Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan
Joanna Y. Chyu School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA;
Rong-Sen Yang Department of Orthopedics, National Taiwan University Hospital, Taipei 100229, Taiwan;
Chung-Hwan Chen Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan; (H.-T.H.); (T.-L.C.); (S.-Y.L.); (C.-J.H.) Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80701, Taiwan
Chwan-Li Shen Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA

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Tran T, Bliuc D, Pham HM, van Geel T, Adachi JD, Berger C, van den Bergh J, Eisman JA, Geusens P, Goltzman D, Hanley DA, Josse RG, Kaiser SM, Kovacs CS, Langsetmo L, Prior JC, Nguyen TV, Center JR. A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly. J Bone Miner Res 2020;35:1923-1934. [PMID: 32460361 DOI: 10.1002/jbmr.4100] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 04/29/2020] [Accepted: 05/14/2020] [Indexed: 12/23/2022]

Abstract

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. © 2020 American Society for Bone and Mineral Research.

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Affiliation(s)

Thach Tran Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, Australia.,Clinical School, St Vincent's Hospital, Faculty of Medicine, UNSW Sydney, Sydney, Australia
Dana Bliuc Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, Australia.,Clinical School, St Vincent's Hospital, Faculty of Medicine, UNSW Sydney, Sydney, Australia
Hanh M Pham Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, Australia.,Vinmec Research Institute of Stem Cell and Gene Technology, Hanoi, Vietnam
Tineke van Geel Department of Data and Analytics, Máxima Medical Centre, Veldhoven, The Netherlands
Jonathan D Adachi Department of Medicine, McMaster University, Hamilton, Canada
Claudie Berger Research Institute of the McGill University Health Centre, Montreal, Canada
Joop van den Bergh Department of Internal Medicine, Subdivision of Rheumatology, Maastricht University Medical Center, Research School Nutrim, Maastricht, The Netherlands.,Department of Internal Medicine, VieCuri Medical Centre of Noord-Limburg, Venlo, The Netherlands.,Biomedical Research Institute, University Hasselt, Hasselt, Belgium
John A Eisman Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, Australia.,Clinical School, St Vincent's Hospital, Faculty of Medicine, UNSW Sydney, Sydney, Australia.,School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia
Piet Geusens Biomedical Research Institute, University Hasselt, Hasselt, Belgium
David Goltzman Department of Medicine, McGill University, Montreal, Canada
David A Hanley Department of Medicine, University of Calgary, Calgary, Canada
Robert G Josse Department of Medicine, University of Toronto, Toronto, Canada
Stephanie M Kaiser Department of Medicine, Dalhousie University, Halifax, Canada
Christopher S Kovacs Faculty of Medicine, Memorial University, St. John's, Canada
Lisa Langsetmo School of Public Health, University of Minnesota, Twin Cities, Minneapolis, MN, USA
Jerilynn C Prior Department of Medicine and Endocrinology, University of British Columbia, Vancouver, Canada
Tuan V Nguyen Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, Australia.,Clinical School, St Vincent's Hospital, Faculty of Medicine, UNSW Sydney, Sydney, Australia.,School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia.,School of Biomedical Engineering, University of Technology, Sydney, Australia
Jacqueline R Center Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, Australia.,Clinical School, St Vincent's Hospital, Faculty of Medicine, UNSW Sydney, Sydney, Australia

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Myint ZW, Kunos CA. Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006-2013. Front Oncol 2020;10:1125. [PMID: 32760670 PMCID: PMC7372304 DOI: 10.3389/fonc.2020.01125] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 06/04/2020] [Indexed: 11/13/2022] Open

Abstract

Introduction: Androgen deprivation therapy (ADT) is a primary treatment option for patients diagnosed with locally advanced-stage or metastatic prostate cancer. Androgen deprivation can be achieved either by radical orchiectomy or by medical castration using a gonadotropin-releasing hormone agonist. ADT has been linked to an initial 12-month loss of bone mineral density, a risk factor for weight-bearing bone fracture, and therefore, a confounding hazard for adverse event when patients are enrolled on early phase trials. To better understand the frequency of ADT-investigational agent-related bone fracture, we conducted a retrospective study of National Cancer Institute Cancer Therapy Evaluation Program (CTEP)-sponsored early phase trials to determine the number of fractures observed among enrolled prostate cancer patients. Patients and Methods: 464 locally advanced-stage or metastatic prostate cancer patients were identified among seven ADT-investigational agent trials conducted between 2006 and 2013. Demographic, co-morbidity, treatment, and adverse event variables were abstracted from CTEP databases and descriptive statistics were used. Results: 464 men had a median age of 64 years, were mostly white (90%), and had a performance status of 0 or 1 (98%). The number of new bone fractures occurring on or after ADT-investigational agent treatment was very low (4.6 per 1000 person-years). The median pretrial prostate specific antigen level was 29 ng/mL and most men (71%) had prostate cancer histopathology Gleason 7 score or higher. In these trials, 43 percent of men had bone only and 35 percent had bone and visceral metastatic disease. The most frequent grade 1 or 2 adverse events were fatigue (36%), hot flashes (27%), and anemia (17%). Grade 3 or higher adverse events were rare, with hypertension (3%) and hyperglycemia (3%) observed. Conclusions: Identifying bone health factors may still be relevant in selected early phase ADT-investigational agent trial patients, emphasizing the need for improved methods for capturing baseline bone health and studying ADT-investigational agent and concurrent medication interactions on bone health.

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Matsumura Y, Li N, Alwaseem H, Pagovich OE, Crystal RG, Greenblatt MB, Stiles KM. Systemic Adeno-Associated Virus-Mediated Gene Therapy Prevents the Multiorgan Disorders Associated with Aldehyde Dehydrogenase 2 Deficiency and Chronic Ethanol Ingestion. Hum Gene Ther 2020;31:163-182. [PMID: 31801381 DOI: 10.1089/hum.2019.268] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open

Abstract

Aldehyde dehydrogenase type 2 (ALDH2), a key enzyme in ethanol metabolism, processes toxic acetaldehyde to nontoxic acetate. ALDH2 deficiency affects 8% of the world population and 35-45% of East Asians. The ALDH2*2 allele common genetic variant has a glutamic acid-to-lysine substitution at position 487 (E487K) that reduces the oxidizing ability of the enzyme resulting in systemic accumulation of acetaldehyde with ethanol ingestion. With chronic ethanol ingestion, mutations in ALDH2 are associated with a variety of hematological, neurological, and dermatological abnormalities, and an increased risk for esophageal cancer and osteoporosis. Based on our prior studies demonstrating that a one-time administration of an adeno-associated virus (AAV) serotype rh.10 gene transfer vector expressing the human ALDH2 cDNA (AAVrh.10hALDH2) prevents the acute effects of ethanol administration (the "Asian flush syndrome"), we hypothesized that AAVrh.10hALDH2 would also prevent the chronic disorders associated with ALDH2 deficiency and chronic ethanol ingestion. To assess this hypothesis, AAVrh.10hALDH2 (10¹¹ genome copies) was administered intravenously to two models of ALDH2 deficiency, Aldh2 knockout homozygous (Aldh2^-/-) and knockin homozygous (Aldh2^E487K+/+) mice (n = 10 per group). Four weeks after vector administration, mice were given drinking water with 10-15% ethanol for 12 weeks. Strikingly, compared with nonethanol drinking littermates, AAVrh.10hALDH2 administration prevented chronic ethanol-induced serum acetaldehyde accumulation and elevated liver malondialdehyde levels, loss of body weight, reduced hemoglobin levels, reduced performance in locomotor activity tests, accumulation of esophageal DNA damage and DNA adducts, and development of osteopenia. AAVrh.10hALDH2 should be considered as a preventative therapy for the increased risk of chronic disorders associated with ALDH2 deficiency and chronic alcohol exposure.

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Lesnyak O, Svedbom A, Belova K, Dobrovolskaya O, Ershova O, Golubev G, Grebenshikov V, Ivanov S, Kochish A, Menshikova L, Nikitinskaya O, Nurligayanov R, Solodovnikov A, Toroptsova N, Varavko J, Zotkin E, Borgstrom F, Kanis JA. Quality of life after fragility fracture in the Russian Federation: results from the Russian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (ICUROS). Arch Osteoporos 2020;15:37. [PMID: 32124066 PMCID: PMC7051923 DOI: 10.1007/s11657-020-0699-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 02/27/2020] [Indexed: 02/03/2023]

Abstract

UNLABELLED

Changes in health-related quality of life (QoL) due to hip, humeral, ankle, spine, and distal forearm fracture were measured in Russian adults age 50 years or more over the first 18 months after fracture. The accumulated mean QoL loss after hip fracture was 0.5 and significantly greater than after fracture of the distal forearm (0.13), spine (0.21), proximal humerus (0.26), and ankle (0.27).

INTRODUCTION

Data on QoL following osteoporotic fractures in Russia are scarce. The present study evaluated the impact of hip, vertebral, proximal humerus, distal forearm, and ankle fracture up to 18 months after fracture from the Russian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study.

METHODS

Individuals age ≥ 50 years with low-energy-induced humeral, hip, clinical vertebral, ankle, or distal forearm fracture were enrolled. After a recall of pre-fracture status, HRQoL was prospectively collected over 18 months of follow-up using EQ-5D-3L. Multivariate regression analysis was used to identify determinants of QALYs loss.

RESULTS

At 2 weeks, patients with hip fracture (n = 223) reported the lowest mean health state utility value (HSUV) compared with other fracture sites. Thereafter, utility values increased but remained significantly lower than before fracture. For spine (n = 183), humerus (n = 166), and ankle fractures (n = 214), there was a similar pattern of disutility with a nadir within 2 weeks and a progressive recovery thereafter. The accumulated mean QoL loss after hip fracture was 0.5 and significantly greater than after fracture of the distal forearm (0.13), spine (0.21), proximal humerus (0.26), and ankle (0.27). Substantial impairment in self-care and usual activities immediately after fracture were important predictors of recovery across at all fracture sites.

CONCLUSIONS

Fractures of the hip, vertebral, distal forearm, ankle, and proximal humerus incur substantial loss of QoL in Russia. The utility values derived from this study can be used in future economic evaluations.

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