Exploration of the miR-187-3p/CNR2 pathway in modulating osteoblast differentiation and treating postmenopausal osteoporosis through mechanical stress.

This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR-187-3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8-week treadmill exercise. Post-training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro-CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR-187-3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR-187-3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both in vivo and in vitro experiments have confirmed that mechanical stress downregulates miR-187-3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR-187-3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.

Guidelines for fracture risk assessment and management of osteoporosis in postmenopausal women and men above the age of 50 in Qatar.

We present comprehensive guidelines for osteoporosis management in Qatar. Formulated by the Qatar Osteoporosis Association, the guidelines recommend the age-dependent Qatar fracture risk assessment tool for screening, emphasizing risk-based treatment strategies and discouraging routine dual-energy X-ray scans. They offer a vital resource for physicians managing osteoporosis and fragility fractures nationwide. PURPOSE: Osteoporosis and related fragility fractures are a growing public health issue with an impact on individuals and the healthcare system. We aimed to present guidelines providing unified guidance to all healthcare professionals in Qatar regarding the management of osteoporosis. METHODS: The Qatar Osteoporosis Association formulated guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men above the age of 50. A panel of six local rheumatologists who are experts in the field of osteoporosis met together and conducted an extensive review of published articles and local and international guidelines to formulate guidance for the screening and management of postmenopausal women and men older than 50 years in Qatar. RESULTS: The guidelines emphasize the use of the age-dependent hybrid model of the Qatar fracture risk assessment tool for screening osteoporosis and risk categorization. The guidelines include screening, risk stratification, investigations, treatment, and monitoring of patients with osteoporosis. The use of a dual-energy X-ray absorptiometry scan without any risk factors is discouraged. Treatment options are recommended based on risk stratification. CONCLUSION: Guidance is provided to all physicians across the country who are involved in the care of patients with osteoporosis and fragility fractures.

[Update on the DVO Guideline 2023 "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50"-What's new for rheumatology?] / Update DVO-Leitlinie 2023 "Prophylaxe, Diagnostik und Therapie der Osteoporose bei postmenopausalen Frauen und bei Männern ab dem 50. Lebensjahr" ­ Was ist neu für die Rheumatologie?

In October 2023, the organization of the German-speaking scientific osteological societies (DVO) published the revised guideline on the "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50." This review article reflects the new features of the guideline and their relevance in the care of patients with inflammatory rheumatic diseases.A key innovation is the change from the 10-year fracture risk to the 3­year fracture risk. Basic diagnostics are currently performed without a defined fracture threshold. Treatment thresholds for specific osteological therapy constitute another key innovation, defined as 3% to < 5%, 5% to < 10%, and from 10% for vertebral body and femoral neck fractures. If the 3­year fracture risk is > 10%, osteoanabolic therapy should primarily be carried out and antiresorptive therapy is initiated following osteoanabolic therapy. In addition, patients with osteoporosis and prolonged glucocorticoid therapy should primarily be treated osteoanabolically with teriparatide. In summary, the changes to the DVO guideline reflect the latest scientific study findings in osteology and lead to detailed differential therapy for osteoporosis.

Experiences of postmenopausal osteoporosis: a narrative review.

PURPOSE: A narrative review was conducted to identify, critically appraise, and synthesise primary research on the lived experiences of postmenopausal women with osteoporosis. MATERIALS AND METHODS: A systematic search of qualitative studies published between January 1960 and August 2021 was conducted across seven databases. The selected qualitative studies reported the lived experiences of postmenopausal women with osteoporosis, both with and without a history of fragility fractures. RESULTS: A total of 17 publications (n = 334) were identified. These results suggest that osteoporosis and fragility fractures significantly affected postmenopausal women's lives. They reported difficulties in carrying out daily activities due to pain and change in their routines to cope with health problems. Some women were satisfied with the information provided by healthcare professionals. Their medicine adherence was also determined by their belief in the importance of their scheduled treatment for osteoporosis. CONCLUSION: Qualitative studies that explored the lived experiences of postmenopausal women with osteoporosis can provide important insights into the impact of the disease on women's lives and potential pathways for improving care and management.Implications for rehabilitationOsteoporosis and fragility fractures affect the quality of life of postmenopausal women worldwide.The provision of targeted and tailored health information for postmenopausal women with osteoporosis is paramount in improving their health literacy and aiding in the long-term management of their bone health.What is already knownOsteoporosis and related fragility fractures are common, affecting more than 200 million people worldwide, including three million people in the UK.Osteoporotic fractures have significant clinical and public health impacts.What this study addsOsteoporosis, particularly fragility fractures, has a significant impact on the lives of postmenopausal women, including pain and functional impairment.Women's belief in the importance of their scheduled treatment plays a significant role in their concordance with the prescribed medications for osteoporosis.Provision of targeted health information for postmenopausal women with osteoporosis is key to their involvement in decision-making and disease management.

Comparative efficacy of acupuncture-related therapy for postmenopausal osteoporosis: protocol for Bayesian network meta-analysis.

INTRODUCTION: The review aims to conduct the first network meta-analysis to comprehensively evaluate the application of multiple acupuncture techniques in patients with postmenopausal osteoporosis, ranking the best acupuncture treatment and providing a reference for clinical treatment extensively. METHODS AND ANALYSIS: Randomised controlled trials of different acupuncture-related therapies for postmenopausal osteoporosis will be searched in the following databases from 1 January 2002 to 31 December 2022, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database and China Biomedical Literature Database. Overall, clinical efficacy rate, bone mineral density and a Visual Analogue Scale score are used as the primary outcome indicators. In addition, the secondary outcome indicator is adverse reactions. The entire screening process will be conducted by two independent investigators; meanwhile, Stata (V.14.0) and RevMan (V.5.4) will be used to conduct the network meta-analysis. If the data are permissible and feasible, we will also perform meta-regression and subgroup analyses to address the underlying causes of data inconsistency and heterogeneity in the statistical analyses. Besides, to improve the credibility of this network meta-analysis, we will evaluate the quality of evidence in this research according to the GRADE assessment. ETHICS AND DISSEMINATION: Ethics approval is not required for network meta-analyses, which do not involve animals' or people's welfare. The results of this network meta-analysis will be submitted to a recognised journal for publication. PROSPERO REGISTRATION NUMBER: CRD42023401003.

Long non-coding RNA Homeobox D gene cluster antisense growth-associated long noncoding RNA/microRNA-182-5p/Homeobox protein A10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells.

BACKGROUND: Studies have illuminated that long non-coding RNA (lncRNA) influences bone cell differentiation and formation. Nevertheless, whether lncRNA Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) was implicated in postmenopausal osteoporosis (PMOP) was yet uncertain. PURPOSE: The research was to explore HAGLR's role in the osteogenic differentiation (OD) process of bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated from mouse bone marrow tissues and identified by electron microscope and flow cytometry. HAGLR, microRNA (miR)-182-5p, and homeobox protein A10 (Hoxa10) levels in BMSCs were detected. Mouse BMSC OD process was induced, and calcium deposition and alkaline phosphatase content were analyzed, as well as expressions of runt-related transcription factor 2, osteopontin, and osteocalcin, and cell apoptosis. Bilateral ovaries were resected from mice to construct the ovariectomized model and bone mineral density, maximum bending stress, maximum load, and elastic modulus of the femur were tested, and the femur was histopathologically evaluated. Chondrocyte apoptosis in the articular cartilage of mice was analyzed. Analysis of the interaction of HAGLR, miR-182-5p with Hoxa10 was conducted. RESULTS: HAGLR and Hoxa10 were down-regulated and miR-182-5p was elevated in PMOP patients. During the BMSC OD process, HAGLR and Hoxa10 levels were suppressed, while miR-182-5p was elevated. Promotion of HAGLR or suppression of miR-182-5p accelerated OD of BMSCs. Inhibition of miR-182-5p reversed the inhibitory effect of HAGLR on BMSC OD. In in vivo experiments, up-regulating HAGLR alleviated PMOP, while silencing Hoxa10 reversed the effects of upregulating HAGLR. HAGLR performed as a sponge for miR-182-5p, while miR-182-5p targeted Hoxa10. CONCLUSION: In general, HAGLR boosted the OD process of BMSCs and relieved PMOP via the miR-182-5p/Hoxa10 axis. These data preliminarily reveal the key role of HAGLR in PMOP, and the research results have a certain reference for the treatment of PMOP.

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among postmenopausal women across eight European countries.

A population-level, cross-sectional model was developed to estimate the clinical and economic burden of osteoporosis among women (≥ 70 years) across eight European countries. Results demonstrated that interventions aimed at improving fracture risk assessment and adherence would save 15.2% of annual costs in 2040. PURPOSE: Osteoporosis is associated with significant clinical and economic burden, expected to further increase with an ageing population. This modelling analysis assessed clinical and economic outcomes under different hypothetical disease management interventions to reduce this burden. METHODS: A population-level, cross-sectional cohort model was developed to estimate numbers of incident fractures and direct costs of care among women (≥ 70 years) in eight European countries under different hypothetical interventions: (1) an improvement in the risk assessment rate, (2) an improvement in the treatment adherence rate and (3) a combination of interventions 1 and 2. A 50% improvement from the status quo, based on existing disease management patterns, was evaluated in the main analysis; scenario analyses evaluated improvement of either 10 or 100%. RESULTS: Based on existing disease management patterns, a 44% increase in the annual number of fractures and costs was predicted from 2020 to 2040: from 1.2 million fractures and €12.8 billion in 2020 to 1.8 million fractures and €18.4 billion in 2040. Intervention 3 provided the greatest fracture reduction and cost savings (a decrease of 17.9% and 15.2% in fractures and cost, respectively) in 2040 compared with intervention 1 (decreases of 8.7% and 7.0% in fractures and cost, respectively) and intervention 2 (10.0% and 8.8% reductions in fracture and cost, respectively). Scenario analyses showed similar patterns. CONCLUSION: These analyses suggest that interventions which improve fracture risk assessment and adherence to treatments would relieve the burden of osteoporosis, and that a combination strategy would achieve greatest benefits.

Effect of laser acupuncture on pain and density of bone in osteoporotic postmenopausal women: a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the value of laser acupuncture (LA) on forearm bone mineral density (BMD) and wrist pain in osteoporotic postmenopausal women. METHODS: Sixty-eight postmenopausal women diagnosed with osteoporosis were randomly allocated equally to one of two sets. The drug-only group received calcium and vitamin D 3 supplement containing fluoride daily for 12 weeks, whereas the drug/LA group received LA therapy for 20 minutes per session, three sessions weekly, in addition to the same supplementation. The primary outcome parameter was assessment of BMD of the nondominant arm. Other outcomes included wrist pain. RESULTS: There was a highly significant improvement in the T-score of forearm BMD in both groups (-2.844 ± 0.476 to -2.597 ± 0.478 and -2.944 ± 0.486 to -1.652 ± 0.728 in the drug-only and drug/LA groups, respectively; P < 0.0001) and visual analog scale score (7.50 ± 0.79 to 4.24 ± 1.07 and 7.24 ± 0.82 to 3.09 ± 0.75 in the drug-only and drug/LA group, respectively; P < 0.0001). The improvement of both BMD and pain score was significantly higher in the drug/LA group (-1.303 and 4.15) compared with the drug-only group (-0.247 and 3.26; P < 0.0001). CONCLUSIONS: LA in combination with calcium and vitamin D supplementation containing fluoride is an effective modality in improving forearm BMD and reducing pain in osteoporotic postmenopausal women.

Influence of Coaching on Effectiveness, Participation, and Safety of an Exercise Program for Postmenopausal Women with Osteoporosis: A Randomized Trial.

Purpose: We compared two different strategies providing professional coaching to administer an exercise program for women with postmenopausal osteoporosis (POP): individual training (IT) at home with trainer's supervision provided by telephone contacts at regular time-intervals or group training (GT) with trainer's live supervision. Our working hypothesis was that IT is a valid alternative to GT when GT is not feasible. Patients and Methods: This was a single-blind, randomized study. We recruited 52 women with POP, without significant comorbidity, and no participation in any structured exercise program within the previous 6 months. They were assigned randomly to IT or GT groups (n = 26 each). Distribution of age (IT: 68±4, GT: 67±8 years) and body mass index (IT: 23.0±2.5, GT: 21.4±5.1) was similar between groups. Each group performed the exercise program in two 1-hour sessions per week for 18 months. Primary outcome measure was Health-Related Quality of Life (HRQoL), as measured by the Short Osteoporosis Quality of Life Questionnaire. Secondary outcome measures focused on domains acknowledged to influence HRQoL (disability, fear of falling, weekly physical activity, physical function) or the effectiveness of the exercise program (retention, adherence, and safety). Significance level was set at p < 0.05. Results: No significant differences were observed between IT and GT groups for any domain. Retention, adherence, and safety were also similar. HRQoL, disability and fear of falling did not change between baseline and follow-up for either group. However, for both groups, physical function (knee flexion, shoulder mobility) and functional capacity (6-minute walking test) improved. Weekly physical activity levels increased from moderate range at baseline to intense at final assessment for both groups. Conclusion: IT and GT supervised exercise programs for women with POP provide similar effectiveness, participation and safety. Hence, both modalities should be considered for future translation in clinical practice of exercise recommendations for POP.

Exosomes derived from human umbilical cord mesenchymal stem cells promote osteogenesis through the AKT signaling pathway in postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMO) is a relatively common disease characterized by low bone mass and microstructural changes of trabecular bone. The reduced bone strength is caused a variety of complications, including fragility fracture and sarcopenia. We used CCK-8 and EdU assays to evaluate cell proliferation rates. The osteogenesis effect was detected using ALP staining, alizarin red staining, and q-PCR. In vivo, the effects of exosomes derived from HUC-MSCs were evaluated using HE staining, IHC staining and Masson staining. In addition, we explored the mechanism of exosomes and found that the AKT signaling pathway played an important role in osteogenesis and cell proliferation. This paper mainly explored the function of exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) and provided a new strategy for the treatment of postmenopausal osteoporosis. In conclusion, exogenous administration of exosomes can contribute to the treatment postmenopausal osteoporosis to a certain extent.

[Effect of Lingnan Chen's acupuncture on postmenopausal osteoporosis and serum GH and IGF-1].

OBJECTIVE: To compare the therapeutic effect on postmenopausal osteoporosis (PMOP) between Lingnan Chen's needling technique and calcitriol soft capsules and investigate the effect mechanism in view of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1). METHODS: Seventy patients of PMOP were randomized into an observation group (35 cases, 4 cases dropped off ) and a control group (35 cases, 3 cases dropped off ). The patients of both groups were treated with calcium carbonate D3 tablets orally (600 mg each time, once daily). In the observation group, acupuncture was delivered at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Sanyinjiao (SP 6), etc. with the specific reinforcing-reducing technique and qi-conducting technique of Lingnan Chen's acupuncture, once every two days, three times a week. In the control group, calcitriol soft capsules were taken orally, 0.25 µg each time, twice a day. The intervention measures of two groups all lasted 12 weeks. Before and after treatment, the bone mineral density (BMD), the levels of serum GH and IGF-1 were assessed in two groups. Before treatment and 4, 8 and 12 weeks after treatment, TCM symptoms score and the MOS item short form health survey (SF-36) score were evaluated and the therapeutic effects were compared between groups. RESULTS: In both within-group and between-group comparisons, the difference in BMD was not significant before and after treatment (P>0.05). After treatment, the levels of serum GH and IGF-1 were increased in the observation group (P<0.05), and higher than the control group (P<0.05). After 4, 8 and 12 weeks of treatment, the scores of TCM symptoms were reduced in both groups compared with those before treatment (P<0.05), and the score in the observation group was lower than that in the control group (P<0.05). After 4, 8 and 12 weeks of treatment, except the score of general health 4 weeks after treatment in the control group, the scores of the other domains in SF-36 were increased in both groups compared with those before treatment (P<0.05). After 12 weeks of treatment, except the score for the general health and social functions, the scores of the other domains of SF-36 in the observation group were all higher than those in the control group (P<0.05). The total effective rate was 83.9% (26/31) in the observation group, higher than 59.4% (19/32) in the control group (P<0.05). CONCLUSION: Lingnan Chen's needling technique is effective on postmenopausal osteoporosis. This therapy may relieve the symptoms of osteoporosis and improve the quality of life, better than calcitriol soft capsules, and the effect mechanism may be related to the up-regulation of serum GH and IGF-1 in the patients.

Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications.

Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. The number of people suffering from PMO has increased over the years because of the rapidly aging population worldwide. However, several pharmacological agents for the treatment of PMO have many safety risks and impose a heavy financial burden to patients and society. In recent years, the "gut-bone" axis has been proposed as a new approach in the prevention and treatment of PMO. This paper reviews the relationship between the gut microbiota and PMO, which mainly includes the underlying mechanisms between hormones, immunity, nutrient metabolism, metabolites of the gut microbiota and intestinal permeability, and explores the possible role of the gut microbiota in these processes. Finally, we discuss the therapeutic effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the gut microbiota.

An antagonistic monoclonal anti-Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis.

Osteoporosis and multiple sclerosis are highly prevalent diseases with limited treatment options. In light of these unmet medical needs, novel therapeutic approaches are urgently sought. Previously, the activation of the transmembrane receptor Plexin-B1 by its ligand semaphorin 4D (Sema4D) has been shown to suppress bone formation and promote neuroinflammation in mice. However, it is unclear whether inhibition of this receptor-ligand interaction by an anti-Plexin-B1 antibody could represent a viable strategy against diseases related to these processes. Here, we raised and systematically characterized a monoclonal antibody directed against the extracellular domain of human Plexin-B1, which specifically blocks the binding of Sema4D to Plexin-B1. In vitro, we show that this antibody inhibits the suppressive effects of Sema4D on human osteoblast differentiation and mineralization. To test the therapeutic potential of the antibody in vivo, we generated a humanized mouse line, which expresses transgenic human Plexin-B1 instead of endogenous murine Plexin-B1. Employing these mice, we demonstrate that the anti-Plexin-B1 antibody exhibits beneficial effects in mouse models of postmenopausal osteoporosis and multiple sclerosis in vivo. In summary, our data identify an anti-Plexin-B1 antibody as a potential therapeutic agent for the treatment of osteoporosis and multiple sclerosis.

Pulse Electromagnetic Field for Treating Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Postmenopausal osteoporosis is a type of chronic disease with high morbidity and high economic burden. Due to the adverse effects of long-term drug therapy, physical therapy, such as pulsed electromagnetic fields (PEMF), is widely implemented in clinical practice. Therefore, we first conducted the meta-analysis on the efficacy and safety of PEMF in the treatment of postmenopausal osteoporosis. We searched eight databases to acquire potentially eligible studies. Outcome indicators include bone mineral density (BMD), visual analogue scale (VAS), biochemical markers of alkaline phosphatase (ALP), osteocalcin, bone-specific alkaline phosphatase (BSAP), type I collagen carboxy-terminal peptide (CTX), and adverse events. The results showed that a total of 19 studies (1303 patients) were retrieved from eight databases. Compared with conventional medications, PEMF combined with conventional medications significantly increased BMD of lumbar vertebra, femoral, Ward's triangle, bone-specific biochemical indicators of ALP, BSAP, and osteocalcin, and relieved pain. However, The incidence of adverse events was not statistically significant between PEMF combined with conventional medications and conventional medications alone. Compared with conventional medications, PEMF significantly increased the BMD of the femur and reduced the degree of pain, but there was no statistical difference in the BMD of the lumbar spine between PEMF and placebo. Except osteocalcin, BSAP, CTX, and ALP showed no significant difference. In view of its efficacy and safety, PEMF intervention can be considered as a potentially effective complementary therapy for postmenopausal women with osteoporosis. © 2022 Bioelectromagnetics Society.

Management of Postmenopausal Osteoporosis: ACOG Clinical Practice Guideline No. 2.

PURPOSE: To provide updated evidence-based recommendations for the treatment of postmenopausal osteoporosis. TARGET POPULATION: Postmenopausal patients with primary osteoporosis. METHODS: This guideline was developed using an a priori protocol in conjunction with a writing team consisting of two specialists in obstetrics and gynecology appointed by the ACOG Committee on Clinical Practice Guidelines-Gynecology and one external subject matter expert. ACOG medical librarians completed a comprehensive literature search for primary literature within Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements. RECOMMENDATIONS: This Clinical Practice Guideline includes updated recommendations on who should receive osteoporosis pharmacotherapy, the benefits and risks of available pharmacotherapy options, treatment monitoring and follow-up, and the role of calcium and vitamin D in the management of postmenopausal osteoporosis. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence.

Disparities in osteoporosis care among postmenopausal women in the United States.

Osteoporosis and fragility fractures result in significant morbidity and mortality and contribute to substantial healthcare costs. Despite being a treatable disease, osteoporosis remains both underdiagnosed and undertreated in the US general population, with significant disparities in care between non-White and White women. These disparities are evident from screening to post-fracture treatment. Non-White women are less likely to be screened for osteoporosis, to be prescribed pharmacotherapy, or to receive treatment post-fracture; furthermore, the mortality rate after fracture is higher in non-White women. Given existing diagnostic and treatment disparities, additional studies and interventions are needed to optimize the bone health of Asian, Black, Hispanic, and Native American women, and to reduce morbidity and mortality from osteoporosis and fragility fractures.

The effect of low-intensity whole-body vibration with or without high-intensity resistance and impact training on risk factors for proximal femur fragility fracture in postmenopausal women with low bone mass: study protocol for the VIBMOR randomized controlled trial.

BACKGROUND: The prevailing medical opinion is that medication is the primary (some might argue, only) effective intervention for osteoporosis. It is nevertheless recognized that osteoporosis medications are not universally effective, tolerated, or acceptable to patients. Mechanical loading, such as vibration and exercise, can also be osteogenic but the degree, relative efficacy, and combined effect is unknown. The purpose of the VIBMOR trial is to determine the efficacy of low-intensity whole-body vibration (LIV), bone-targeted, high-intensity resistance and impact training (HiRIT), or the combination of LIV and HiRIT on risk factors for hip fracture in postmenopausal women with osteopenia and osteoporosis. METHODS: Postmenopausal women with low areal bone mineral density (aBMD) at the proximal femur and/or lumbar spine, with or without a history of fragility fracture, and either on or off osteoporosis medications will be recruited. Eligible participants will be randomly allocated to one of four trial arms for 9 months: LIV, HiRIT, LIV + HiRIT, or control (low-intensity, home-based exercise). Allocation will be block-randomized, stratified by use of osteoporosis medications. Testing will be performed at three time points: baseline (T0), post-intervention (T1; 9 months), and 1 year thereafter (T2; 21 months) to examine detraining effects. The primary outcome measure will be total hip aBMD determined by dual-energy X-ray absorptiometry (DXA). Secondary outcomes will include aBMD at other regions, anthropometrics, and other indices of bone strength, body composition, physical function, kyphosis, muscle strength and power, balance, falls, and intervention compliance. Exploratory outcomes include bone turnover markers, pelvic floor health, quality of life, physical activity enjoyment, adverse events, and fracture. An economic evaluation will also be conducted. DISCUSSION: No previous studies have compared the effect of LIV alone or in combination with bone-targeted HiRIT (with or without osteoporosis medications) on risk factors for hip fracture in postmenopausal women with low bone mass. Should either, both, or combined mechanical interventions be safe and efficacious, alternative therapeutic avenues will be available to individuals at elevated risk of fragility fracture who are unresponsive to or unwilling or unable to take osteoporosis medications. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (www. anzctr.org.au ) (Trial number ANZCTR12615000848505, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 368962 ); date of registration 14/08/2015 (prospectively registered). Universal Trial Number: U1111-1172-3652.