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Osteoporosis International : a Journal... Jul 2023The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the... (Meta-Analysis)
Meta-Analysis Review
Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.
The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I = 20%, TH BMD) to substantial (I = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.
Topics: Female; Humans; Bone Density; Postmenopause; Osteoporosis, Postmenopausal; Exercise; Osteoporosis; Femur Neck; Lumbar Vertebrae
PubMed: 36749350
DOI: 10.1007/s00198-023-06682-1 -
Journal of Orthopaedic Surgery and... Nov 2021Osteoporosis is one of the most common bone system diseases that is associated with an increased risk of bone fractures and causes many complications for patients. With... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is one of the most common bone system diseases that is associated with an increased risk of bone fractures and causes many complications for patients. With age, the prevalence of this disease increases so that it has become a serious problem among the elders. In this study, the prevalence of osteoporosis among elders around the world is examined to gain an understanding of its prevalence pattern.
METHODS
In this systematic review and meta-analysis, articles that have focused on prevalence of osteoporosis in the world's elders were searched with these key words, such as Prevalence, Osteoporosis, Elders, Older adult in the Science Direct, Embase, Scopus, PubMed, Web of Science (WoS) databases and Google Scholar search engine, and extracted without time limit until March 2020 and transferred to information management software (EndNote). Then, duplicate studies were eliminated and the remaining studies were evaluated in terms of screening, competence and qualitative evaluation based on inclusion and exclusion criteria. Data analysis was performed with Comprehensive Meta-Analysis software (Version 2) and Begg and Mazumdar test was used to check the publication bias and I test was used to check the heterogeneity.
RESULTS
In a review of 40 studies (31 studies related to Asia, 5 studies related to Europe and 4 studies related to America) with a total sample size of 79,127 people, the prevalence of osteoporosis in the elders of the world; 21.7% (95% confidence interval: 18.8-25%) and the overall prevalence of osteoporosis in older men and women in the world, 35.3% (95% confidence interval: 27.9-43.4%), 12.5% (95% confidence interval: 9.3-16.7%) was reported. Also, the highest prevalence of osteoporosis in the elders was reported in Asia with; 24.3% (95% confidence interval: 20.9-28.1%).
CONCLUSION
The results of the present study showed that the prevalence of osteoporosis in the elders and especially elders' women is very high. Osteoporosis was once thought to be an inseparable part of elders' lives. Nowadays, Osteoporosis can be prevented due to significant scientific advances in its causes, diagnosis, and treatment. Regarding the growing number of elderly people in the world, it is necessary for health policy-makers to think of measures to prevent and treat osteoporosis among the elders.
Topics: Aged; Europe; Female; Humans; Male; Osteoporosis; Prevalence
PubMed: 34774085
DOI: 10.1186/s13018-021-02821-8 -
Frontiers in Public Health 2022Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.
METHODS
We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.
RESULTS
Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) ( = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 ( = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, = 0.76).
CONCLUSIONS
The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.
Topics: Bone Density Conservation Agents; Female; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Vitamin K 2
PubMed: 36033779
DOI: 10.3389/fpubh.2022.979649 -
The Cochrane Database of Systematic... Jul 2011Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass.
OBJECTIVES
To examine the effectiveness of exercise interventions in preventing bone loss and fractures in postmenopausal women.
SEARCH STRATEGY
During the update of this review we updated the original search strategy by searching up to December 2010 the following electronic databases: the Cochrane Musculoskeletal Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE; EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled Clinical Trials; and AMED. We attempted to identify other studies by contacting experts, searching reference lists and searching trial registers.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that met our predetermined inclusion criteria.
DATA COLLECTION AND ANALYSIS
Pairs of members of the review team extracted the data and assessed trial quality using predetermined forms. For dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed-effect model. For continuous data, we calculated mean differences (MDs) of the percentage change from baseline. Where heterogeneity existed (determined by the I(2) statistic), we used a random-effects model.
MAIN RESULTS
Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. The most effective type of exercise intervention on bone mineral density (BMD) for the neck of femur appears to be non-weight bearing high force exercise such as progressive resistance strength training for the lower limbs (MD 1.03; 95% confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64) compared with control groups. Fractures and falls were reported as adverse events in some studies. There was no effect on numbers of fractures (odds ratio (OR) 0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in the meta-analyses was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up.
AUTHORS' CONCLUSIONS
Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density compared with control groups. Exercise has the potential to be a safe and effective way to avert bone loss in postmenopausal women.
Topics: Bone Density; Exercise; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 21735380
DOI: 10.1002/14651858.CD000333.pub2 -
Bone Dec 2017The optimal duration of osteoporosis treatment is controversial. As opposed to bisphosphonates, denosumab does not incorporate into bone matrix and bone turnover is not... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The optimal duration of osteoporosis treatment is controversial. As opposed to bisphosphonates, denosumab does not incorporate into bone matrix and bone turnover is not suppressed after its cessation. Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures.
METHODS
The European Calcified Tissue Society (ECTS) formed a working group to perform a systematic review of existing literature on the effects of stopping denosumab and provide advice on management.
RESULTS
Data from phase 2 and 3 clinical trials underscore a rapid decrease of bone mineral density (BMD) and a steep increase in bone turnover markers (BTMs) after discontinuation of denosumab. Clinical case series report multiple vertebral fractures after discontinuation of denosumab and a renewed analysis of FREEDOM and FREEDOM Extension Trial suggests, albeit does not prove, that the risk of multiple vertebral fractures may be increased when denosumab is stopped due to a rebound increase in bone resorption.
CONCLUSION
There appears to be an increased risk of multiple vertebral fractures after discontinuation of denosumab although strong evidence for such an effect and for measures to prevent the occurring bone loss is lacking. Clinicians and patients should be aware of this potential risk. Based on available data, a re-evaluation should be performed after 5years of denosumab treatment. Patients considered at high fracture risk should either continue denosumab therapy for up to 10years or be switched to an alternative treatment. For patients at low risk, a decision to discontinue denosumab could be made after 5years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover. However, since the optimal bisphosphonate regimen post-denosumab is currently unknown continuation of denosumab can also be considered until results from ongoing trials become available. Based on current data, denosumab should not be stopped without considering alternative treatment in order to prevent rapid BMD loss and a potential rebound in vertebral fracture risk.
Topics: Biomarkers; Bone Density; Bone Remodeling; Denosumab; Diphosphonates; Humans; Osteoporosis; Societies, Medical; Withholding Treatment
PubMed: 28789921
DOI: 10.1016/j.bone.2017.08.003 -
Arthritis & Rheumatology (Hoboken, N.J.) Aug 2017To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). (Review)
Review
OBJECTIVE
To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).
METHODS
We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users.
RESULTS
Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made.
CONCLUSION
This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Topics: Bone Density Conservation Agents; Calcium, Dietary; Consensus; Denosumab; Diphosphonates; Glucocorticoids; Humans; Osteoporosis; Osteoporotic Fractures; Raloxifene Hydrochloride; Rheumatic Diseases; Rheumatology; Societies, Medical; Teriparatide; United States; Vitamin D
PubMed: 28585373
DOI: 10.1002/art.40137 -
Annals of Internal Medicine Jul 2019Optimal long-term osteoporosis drug treatment (ODT) is uncertain.
BACKGROUND
Optimal long-term osteoporosis drug treatment (ODT) is uncertain.
PURPOSE
To summarize the effects of long-term ODT and ODT discontinuation and holidays.
DATA SOURCES
Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies.
STUDY SELECTION
48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB).
DATA EXTRACTION
Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy.
DATA SYNTHESIS
Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).
LIMITATION
No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays.
CONCLUSION
Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms.
PRIMARY FUNDING SOURCE
National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Diphosphonates; Drug Administration Schedule; Duration of Therapy; Female; Hip Fractures; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Spinal Fractures; Zoledronic Acid
PubMed: 31009947
DOI: 10.7326/M19-0533 -
Nutrients Nov 2019Osteoporosis is a vital healthcare issue among elderly people. During the aging process, a gradual loss of bone mass results in osteopenia and osteoporosis. Heritable...
Osteoporosis is a vital healthcare issue among elderly people. During the aging process, a gradual loss of bone mass results in osteopenia and osteoporosis. Heritable factors account for 60%-80% of optimal bone mineralization, whereas modifiable factors such as nutrition, weight-bearing exercise, body mass, and hormonal milieu affect the development of osteopenia and osteoporosis in adulthood. Osteoporosis substantially increases the risk of skeletal fractures and further morbidity and mortality. The effective prevention of fractures by reducing the loss of bone mass is the primary goal for physicians treating people with osteoporosis. Other than pharmacologic agents, lifestyle adjustment, nutritional support, fall prevention strategies, exercise, and physical modalities can be used to treat osteoporosis or prevent further osteoporotic fracture. Each of these factors, alone or in combination, can be of benefit to people with osteoporosis and should be implemented following a detailed discussion with patients. This review comprises a systematic survey of the current literature on osteoporosis and its nonpharmacologic and nonsurgical treatment. It provides clinicians and healthcare workers with evidence-based information on the assessment and management of osteoporosis. However, numerous issues regarding osteoporosis and its treatment remain unexplored and warrant future investigation.
Topics: Adult; Aged; Bone Density; Bone Remodeling; Diet, Healthy; Dietary Supplements; Exercise; Exercise Therapy; Female; Humans; Male; Middle Aged; Nutritional Status; Nutritional Support; Osteoporosis; Protective Factors; Risk Assessment; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Young Adult
PubMed: 31757101
DOI: 10.3390/nu11122848 -
Calcified Tissue International Jun 2023To assess the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen... (Meta-Analysis)
Meta-Analysis Review
The Clinical Effectiveness of Denosumab (Prolia®) for the Treatment of Osteoporosis in Postmenopausal Women, Compared to Bisphosphonates, Selective Estrogen Receptor Modulators (SERM), and Placebo: A Systematic Review and Network Meta-Analysis.
To assess the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs; bazedoxifene, raloxifene) or placebo, for the treatment of osteoporosis in postmenopausal women (PMW). Systematic searches were run in PubMed, Embase & Cochrane Library on 27-April-2022. Randomized controlled trials (RCTs) that included osteoporotic PMW allocated to denosumab, SERMs, bisphosphonates, or placebo were eligible for inclusion. RCTs were appraised using Cochrane Risk of Bias 2.0. Bayesian network and/or pairwise meta-analyses were conducted on predetermined outcomes (i.e. vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, adverse events [AEs], serious AEs (SAEs), withdrawals due to AEs, AEs caused by denosumab discontinuation). A total of 12 RCTs (k = 22 publications; n = 25,879 participants) were included in the analyses. Denosumab, reported a statistically significant increase in lumbar spine (LS) and total hip (TH) BMD, compared to placebo. Similarly, denosumab also resulted in a statistically significant increase in TH BMD compared to the raloxifene and bazedoxifene. However, relative to denosumab, alendronate, ibandronate and risedronate resulted in significant improvements in both femoral neck (FN) and LS BMD. With regards to vertebral fractures and all safety outcomes, there were no statistically significant differences between denosumab and any of the comparator. Relative to placebo, denosumab was associated with significant benefits in both LS and TH BMD. Additionally, denosumab (compared to placebo) was not associated with reductions in vertebral and nonvertebral fractures. Finally, denosumab was not associated with improvement in safety outcomes, compared to placebo. These findings should be interpreted with caution as some analyses suffered from statistical imprecision.
Topics: Female; Humans; Diphosphonates; Selective Estrogen Receptor Modulators; Denosumab; Alendronate; Bone Density Conservation Agents; Risedronic Acid; Raloxifene Hydrochloride; Ibandronic Acid; Network Meta-Analysis; Postmenopause; Osteoporosis, Postmenopausal; Osteoporosis; Bone Density; Spinal Fractures; Treatment Outcome
PubMed: 37016189
DOI: 10.1007/s00223-023-01078-z -
Osteoporosis International : a Journal... Aug 2020This systematic review and meta-analysis set out to determine the effect of dynamic resistance exercise (DRT) on areal bone mineral density (aBMD) in postmenopausal... (Meta-Analysis)
Meta-Analysis
Effects of dynamic resistance exercise on bone mineral density in postmenopausal women: a systematic review and meta-analysis with special emphasis on exercise parameters.
This systematic review and meta-analysis set out to determine the effect of dynamic resistance exercise (DRT) on areal bone mineral density (aBMD) in postmenopausal women and derive evidence-based recommendations for optimized training protocols. A systematic review of the literature according to the PRISMA statement included (a) controlled trials, (b) of isolated DRT with at least one exercise and one control group, (c) with intervention durations ≥ 6 months, (d) aBMD assessments at lumbar spine or proximal femur, (e) in cohorts of postmenopausal women. We searched eight electronic databases up to March 2019 without language restrictions. The meta-analysis was performed using a random-effects model. Standardized mean differences (SMD) for BMD changes at lumbar spine (LS), femoral neck (FN), and total hip (TH) were defined as outcome measures. Moderators of the exercise effects, i.e., "intervention length," "type of DRT," "training frequency," "exercise intensity," and "exercise volume," were addressed by sub-group analyses. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42018095097. Seventeen articles with 20 exercise and 18 control groups were eligible. SMD average is 0.54 (95% CI 0.22-0.87) for LS-BMD, 0.22 (0.07-0.38) for FN-BMD, and 0.48 (0.22-0.75) for TH-BMD changes (all p ≤ 0.015). While sub-group analysis for FN-BMD revealed no differences within categories of moderators, lower training frequency (< 2 sessions/week) resulted in significantly higher BMD changes at LS and TH compared to higher training frequency (≥ 2 sessions/week). Additionally, free weight training was significantly superior to DRT devices for improving TH-BMD. This work provided further evidence for significant, albeit only low-moderate, effects of DRT on LS-, FN-, and TH-BMD. Unfortunately, sub-analysis results did not allow meaningful exercise recommendations to be derived. This systematic review and meta-analysis observed a significant low-moderate effect of dynamic resistance exercise on bone mineral density changes in postmenopausal women. However, sub-group analyses focusing on exercise characteristics found no results that enable the derivation of meaningful exercise recommendations in the area of exercise and osteoporosis prevention or therapy.
Topics: Aged; Bone Density; Exercise; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Resistance Training
PubMed: 32399891
DOI: 10.1007/s00198-020-05441-w