Osteoporosis management in adults with schizophrenia following index hip fracture event: a 10-year population-based retrospective cohort study, Ontario, Canada.

Little is known about the incidence of osteoporosis testing and treatment in individuals with schizophrenia, who may be more likely to fracture. Using competing risk models, we found that schizophrenia was associated with lower incidence of testing or treatment. Implications are for understanding barriers and solutions for this disadvantaged group. PURPOSE: Evidence suggests that individuals with schizophrenia may be more likely to experience hip fractures than the general population; however, little is known about osteoporosis management in this disadvantaged subpopulation. Our study objective was to compare bone mineral density (BMD) testing and pharmacologic treatment in hip fracture patients with versus without schizophrenia. METHODS: This was a retrospective population-based cohort study leveraging health administrative databases, and individuals aged 66-105 years with hip fracture between fiscal years 2009 and 2018 in Ontario, Canada. Schizophrenia was ascertained using a validated algorithm. The outcome was a composite measure of (1) pharmacologic prescription for osteoporosis; or (2) a BMD test. Inferential analyses were conducted using Fine-Gray subdistribution hazard regression, with mortality as the competing event. RESULTS: A total of 52,722 individuals aged 66 to 105 years who sustained an index hip fracture in Ontario during the study period were identified, of whom 1890 (3.6%) had schizophrenia. Hip fracture patients with vs without schizophrenia were more likely to be long-term care residents (44.3% vs. 18.1%; standardized difference, 0.59), frail (62.5% vs. 36.5%; standardized difference, 0.54) and without a primary care provider (9.2% vs. 4.8%; standardized difference, 0.18). In Fine-Gray models, schizophrenia was associated with a lower incidence of testing or treatment (0.795 (0.721, 0.877)). CONCLUSIONS: In this population-based retrospective cohort study, a schizophrenia diagnosis among hip fracture patients was associated with a lower incidence of testing or treatment, after accounting for mortality, and several enabling and predisposing factors. Further research is required to investigate barriers to osteoporosis management in this disadvantaged population.

Geographic variation in bone mineral density and prevalent fractures in the Canadian longitudinal study on aging.

Awareness of the prevalence of osteoporosis and fractures across jurisdictions can guide the development of local preventive programs and healthcare policies. We observed geographical variations in total hip bone mineral density and in the prevalence of major osteoporotic fractures across Canadian provinces, which persisted after adjusting for important covariates. PURPOSE: We aimed to describe sex-specific total hip bone mineral density (aBMD) and prevalent major osteoporotic fractures (MOF) variation between Canadian provinces. METHODS: We used baseline data from 21,227 Canadians (10,716 women, 10,511 men) aged 50-85 years in the Canadian Longitudinal Study on Aging (CLSA; baseline: 2012-2015). Linear and logistic regression models were used to examine associations between province of residence and total hip aBMD and self-reported MOF, stratified by sex. CLSA sampling weights were used to generate the prevalence and regression estimates. RESULTS: The mean (SD) age of participants was 63.9 (9.1) years. The mean body mass index (kg/m2) was lowest in British Columbia (27.4 [5.0]) and highest in Newfoundland and Labrador (28.8 [5.3]). Women and men from British Columbia had the lowest mean total hip aBMD and the lowest prevalence of MOF. Alberta had the highest proportion of participants reporting recent falls (12.0%), and Manitoba (8.4%) the fewest (p-value=0.002). Linear regression analyses demonstrated significant differences in total hip aBMD: women and men from British Columbia and Alberta, and women from Manitoba and Nova Scotia had lower adjusted total hip aBMD than Ontario (p-values<0.02). Adjusted odds ratios (95% confidence intervals, CI) for prevalent MOF were significantly lower in women from British Columbia (0.47 [95% CI: 0.32; 0.69]) and Quebec (0.68 [95% CI: 0.48; 0.97]) and in men from British Columbia (0.40 [95% CI:0.22; 0.71]) compared to Ontario (p-values<0.03). Results were similar when adjusting for physical performance measures and when restricting the analyses to participants who reported White race/ethnicity. CONCLUSION: Geographical variations in total hip aBMD and in the prevalence of MOF between provinces persisted after adjusting for important covariates which suggests an association with unmeasured individual and environmental factors.

Fracture definitions in observational osteoporosis drug effects studies that leverage healthcare administrative (claims) data: a scoping review.

Healthcare administrative (claims) data are commonly utilized to estimate drug effects. We identified considerable heterogeneity in fracture outcome definitions in a scoping review of 57 studies that estimated osteoporosis drug effects on fracture risk. Better understanding of the impact of different fracture definitions on study results is needed. PURPOSE: Healthcare administrative (claims) data are frequently used to estimate the real-world effects of drugs. Fracture incidence is a common outcome of osteoporosis drug studies. We aimed to describe how fractures are defined in studies that use claims data. METHODS: We searched MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and gray literature for studies published in English between 2000 and 2020 that estimated fracture effectiveness (hip, humerus, radius/ulna, vertebra) or safety (atypical fracture of the femur, AFF) of osteoporosis drugs using claims data in Canada and the USA. Literature searches, screening and data abstraction were completed independently by two reviewers. RESULTS: We identified 57 eligible studies (52 effectiveness, 3 safety, 2 both). Hip fracture was the most common fracture site studied (93%), followed by humerus (66%), radius/ulna (59%), vertebra (61%), and AFF (9%). Half (n = 29) of the studies did not indicate specific data sources, codes, or cite a validation paper. Of the papers with sufficient detail, heterogeneity in fracture definitions was common. The most common definition within each fracture site was used by less than half of the studies that examined effectiveness (12 definitions in 29 hip fracture papers, 8 definitions in 17 humerus papers, 8 definitions in 13 radius/ulna papers, 9 definitions in 15 vertebra papers), and 3 definitions among 4 AFF papers. CONCLUSION: There is ambiguity and heterogeneity in fracture outcome definitions in studies that leverage claims data. Better transparency in outcome reporting is needed. Future exploration of how fracture definitions impact study results is warranted.

The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions.

High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions.

Over half of seniors who start oral bisphosphonate therapy are exposed for 3 or more years: novel rolling window approach and patterns of use.

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years. INTRODUCTION: The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up. METHODS: Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy. RESULTS: We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab. CONCLUSIONS: Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.

Atopic dermatitis and bone health: a systematic review.

Atopic dermatitis (AD) is associated with systemic inflammation and systemic corticosteroid use which can lead to poor bone health. The aim of this systematic review is to investigate the relationship between AD and bone mineral density (BMD), osteoporosis and fractures. We searched Web of Science, Cochrane Database of Systematic Reviews, MEDLINE and Embase. Title, abstract and full-text screening, and data extraction were done in duplicate. Quality appraisal was performed using the Agency for Healthcare Research and Quality Methodology Checklist (cross-sectional studies) and Newcastle-Ottawa Scale (cohort studies). We screened 3800 abstracts and included fifteen studies (twelve cross-sectional, three cohort). In cross-sectional studies, AD was associated with decreased BMD and increased fractures. In cross-sectional studies and a cohort study, AD was associated with a higher prevalence of osteoporosis compared to controls. There was inconsistency across studies, with some finding no association. In a large cohort study, AD was associated with increased risk of fractures of the hip (HR: 1.06, 95% CI: 1.02 to 1.11), spine (HR: 1.14, 95% CI: 1.06 to 1.23) and wrist (HR: 1.06, 95% CI: 1.01 to 1.10), with further increased risk with more severe AD. Differences between studies precluded quantitative synthesis. There is some evidence supporting an association between AD and poor bone health. Research is needed to clarify this association, underlying mechanisms and develop strategies to improve bone health of individuals with AD.

"Left to my own devices, I don't know": using theory and patient-reported barriers to move from physical activity recommendations to practice.

Knowledge exchange with community-dwelling individuals across Ontario revealed barriers to implementation of physical activity recommendations that reflected capability, opportunity, and motivation; barriers unique to individuals with osteoporosis include fear of fracturing, trust in providers, and knowledge of exercise terminology. Using the Behaviour Change Wheel, we identified interventions (training, education, modeling) and policy categories (communication/marketing, guidelines, service provision). INTRODUCTION: Physical activity recommendations exist for individuals with osteoporosis; however, to change behavior, we must address barriers and facilitators to their implementation. The purposes of this project are (1) to identify barriers to and facilitators of uptake of disease-specific physical activity recommendations (2) to use the findings to identify behavior change strategies using the Behaviour Change Wheel (BCW). METHODS: Focus groups and semi-structured interviews were conducted with community-dwelling individuals attending osteoporosis-related programs or education sessions in Ontario. They were stratified by geographic area, urban/rural, and gender, and transcribed verbatim. Two researchers coded data and identified emerging themes. Using the Behaviour Change Wheel framework, themes were categorized into capability, opportunity, and motivation, and interventions were identified. RESULTS: Two hundred forty community-dwelling individuals across Ontario participated (mean ± SD age = 72 ± 8.28). Barriers were as follows: capability: disease-related symptoms hinder exercise and physical activity participation, lack of exercise-related knowledge, low exercise self-efficacy; opportunity: access to exercise programs that meet needs and preferences, limited resources and time, physical activity norms and preferences; motivation: incentives to exercise, fear of fracturing, trust in exercise providers. Interventions selected were training, education, and modeling. Policy categories selected were communication/marketing, guidelines, and service provision. CONCLUSIONS: Barriers unique to individuals with osteoporosis included the following: lack of knowledge on key exercise concepts, fear of fracturing, and trust in providers. Behavior change techniques may need tailoring to gender, age, or presence of comorbid conditions.

Build better bones with exercise (B3E pilot trial): results of a feasibility study of a multicenter randomized controlled trial of 12 months of home exercise in older women with vertebral fracture.

We pilot-tested a trial of home exercise on individuals with osteoporosis and spine fracture. Our target enrollment was met, though it took longer than expected. Participants stayed in the study and completed the exercise program with no safety concerns. Future trials should expand the inclusion criteria and consider other changes. PURPOSE: Osteoporotic fragility fractures create a substantial human and economic burden. There have been calls for a large randomized controlled trial examining the effect of exercise on fracture incidence. The B3E pilot trial was designed to evaluate the feasibility of a large trial examining the effects of home exercise on individuals at high risk of fracture. METHODS: Community-dwelling women ≥ 65 years with radiographically confirmed vertebral compression fractures were recruited at seven sites in Canada and Australia. We randomized participants in a 1:1 ratio to a 12-month home exercise program or equal attention control group, both delivered by a physiotherapist (PT). Participants received six PT home visits in addition to monthly phone calls from the PT and a blinded research assistant. The primary feasibility outcomes of the study were recruitment rate (20 per site in 1 year), retention rate (75% completion), and intervention adherence rate (60% of weeks meeting exercise goals). Secondary outcomes included falls, fractures and adverse events. RESULTS: One hundred forty-one participants were recruited; an average of 20 per site, though most sites took longer than anticipated. Retention and adherence met the criteria for success: 92% of participants completed the study; average adherence was 66%. The intervention group did not differ significantly in the number of falls (IRR 0.97, 95% CI 0.58 to 1.63) or fragility fractures (OR 1.11, 95% CI 0.60 to 2.05) compared to the control group. There were 18 serious adverse events in the intervention group and 12 in the control group. CONCLUSION: An RCT of home exercise in women with vertebral fractures is feasible but recruitment was a challenge. Suggestions are made for the conduct of future trials.

Peripheral Quantitative Computed Tomography: Review of Evidence and Recommendations for Image Acquisition, Analysis, and Reporting, Among Individuals With Neurological Impairment.

In 2015, the International Society for Clinical Densitometry (ISCD) position statement regarding peripheral quantitative computed tomography (pQCT) did not recommend routine use of pQCT, in clinical settings until consistency in image acquisition and analysis protocols are reached, normative studies conducted, and treatment thresholds identified. To date, the lack of consensus-derived recommendations regarding pQCT implementation remains a barrier to implementation of pQCT technology. Thus, based on description of available evidence and literature synthesis, this review recommends the most appropriate pQCT acquisition and analysis protocols for clinical care and research purposes, and recommends specific measures for diagnosis of osteoporosis, assigning fracture risk, and monitoring osteoporosis treatment effectiveness, among patients with neurological impairment. A systematic literature search of MEDLINE, EMBASE©, CINAHL, and PubMed for available pQCT studies assessing bone health was carried out from inception to August 8th, 2017. The search was limited to individuals with neurological impairment (spinal cord injury, stroke, and multiple sclerosis) as these groups have rapid and severe regional declines in bone mass. Of 923 references, we identified 69 that met review inclusion criteria. The majority of studies (n = 60) used the Stratec XCT 2000/3000 pQCT scanners as reflected in our evaluation of acquisition and analysis protocols. Overall congruence with the ISCD Official Positions was poor. Only 11% (n = 6) studies met quality reporting criteria for image acquisition and 32% (n = 19) reported their data analysis in a format suitable for reproduction. Therefore, based on current literature synthesis, ISCD position statement standards and the authors' expertise, we propose acquisition and analysis protocols at the radius, tibia, and femur sites using Stratec XCT 2000/3000 pQCT scanners among patients with neurological impairment for clinical and research purposes in order to drive practice change, develop normative datasets and complete future meta-analysis to inform fracture risk and treatment efficacy evaluation.

The FRAX-based Lebanese osteoporosis treatment guidelines: rationale for a hybrid model.

We describe our approach to develop FRAX-based osteoporosis treatment guidelines in Lebanon, a country with low-moderate fracture rates. A hybrid assessment algorithm that combines a fixed 10 % intervention threshold until age 70 years, and an age-dependent threshold thereafter, was deemed most suitable. INTRODUCTION: The FRAX risk calculator is used to guide intervention thresholds in several national osteoporosis guidelines. This study aimed to describe the approach in developing FRAX-based osteoporosis treatment guidelines in Lebanon, a country with relatively low fracture rates. METHODS: We reassessed previous national guidelines combined with an evaluation of age-dependent and fixed FRAX-based intervention threshold models used in the UK, the USA, and Canada. We took into consideration the risk for major osteoporotic fractures (MOF) and the proportions of subjects considered for therapy using such thresholds, before finalizing a model for Lebanon. RESULTS: The new Lebanese guidelines retained the recommendation to treat individuals with fragility fracture at the hip or spine. A femoral neck T-score ≤-2.5 in subjects without fractures was dropped, since it would imply consideration of therapy for individuals with a 10-year risk for MOF of <10 %, up to age 75 years in women. After considering the impact of both age-dependent and fixed intervention thresholds, we chose a new hybrid algorithm, combining a fixed 10 % treatment threshold until age 70 years and an age-dependent threshold thereafter. CONCLUSION: The Lebanese FRAX-based hybrid model takes into consideration the risk for MOF and the proportions of subjects considered for treatment. This model avoids consideration of drug therapy in a large proportion of younger subjects at low risk for fracture and targets high risk elderly individuals. It was deemed most suitable for Lebanon and may be an option for other countries with relatively low fracture rates.

Atypical femur fractures: a survey of current practices in orthopedic surgery.

The results of a self-administered online survey demonstrate that orthopedic surgeons' management practices for AFF are variable. These data will inform the development of clinical practice guidelines. INTRODUCTION: We aimed to determine current AFF treatment practices of orthopedic surgeons to inform clinical practice guideline development. METHODS: A self-administered online survey was developed and sequentially posted on the Orthopaedic Trauma Association (OTA) website from July to August 2015 and the Canadian Orthopaedic Association (COA) website from December 2015 to January 2016. Level of confidence in diagnosis and treatment as well as treatment preferences between respondents who self-identified as trauma surgeons vs. non-trauma surgeons were compared. RESULTS: A total of 172 completed surveys were obtained (OTA, N = 100, 58%; COA, N = 72, 8%). Seventy-eight percent of respondents had treated ≥1 AFF in the previous 6 months. Seventy-six percent reported feeling extremely or very confident in diagnosing AFF (trauma 84% vs. non-trauma surgeons 70%, p = 0.04), and 63% reported feeling extremely or very confident in treating AFF (trauma 82%, non-trauma surgeons 50%, p < 0.01). Preferred management for complete and symptomatic incomplete AFFs was surgical fixation with a cephalomedullary nail (CMN) by 88 and 79%, respectively, while close follow-up was preferred for asymptomatic incomplete AFFs in 72% of respondents. Trauma surgeons used the CMN more frequently than non-trauma surgeons (90 vs. 76% p = 0.03). In patients with bilateral AFFs, with one side surgically treated, 56% were extremely likely to surgically treat the contralateral side, if symptomatic. Most felt guidelines (81%) and educational resources (73%) would be valuable. CONCLUSIONS: Current orthopedic treatment practices for AFFs are variable. The results of this survey will inform the development of practice guidelines and educational resources.

"I do not have time. Is there a handout I can use?": combining physicians' needs and behavior change theory to put physical activity evidence into practice.

Guidelines for physical activity exist and following them would improve health. Physicians can advise patients on physical activity. We found barriers related to physicians' knowledge, a lack of tools and of physician incentives, and competing demands for limited time with a patient. We discuss interventions that could reduce these barriers. INTRODUCTION: Uptake of physical activity (PA) guidelines would improve health and reduce mortality in older adults. However, physicians face barriers in guideline implementation, particularly when faced with needing to tailor recommendations in the presence of chronic disease. We performed a behavioral analysis of physician barriers to PA guideline implementation and to identify interventions. The Too Fit To Fracture physical activity recommendations were used as an example of disease-specific PA guidelines. METHODS: Focus groups and semi-structured interviews were conducted with physicians and nurse practitioners in Ontario, stratified by type of physician, geographic area, and urban/rural, and transcribed verbatim. Two researchers coded data and identified emerging themes. Using the behavior change wheel framework, themes were categorized into capability, opportunity and motivation, and interventions were identified. RESULTS: Fifty-nine family physicians, specialists, and nurse practitioners participated. Barriers were as follows: Capability-lack of exercise knowledge or where to refer; Opportunity-pragmatic tools, fit within existing workflow, available programs that meet patients' needs, physical activity literacy and cultural practices; Motivation-lack of incentives, not in their scope of practice or professional identity, competing priorities, outcome expectancies. Interventions selected: education, environmental restructuring, enablement, persuasion. Policy categories: communications/marketing, service provision, guidelines. CONCLUSIONS: Key barriers to PA guideline implementation among physicians include knowledge on where to refer or what to say, access to pragmatic programs or resources, and things that influence motivation, such as competing priorities or lack of incentives. Future work will report on the development and evaluation of knowledge translation interventions informed by the barriers.

Muscle and Myotendinous Tissue Properties at the Distal Tibia as Assessed by High-Resolution Peripheral Quantitative Computed Tomography.

High-resolution peripheral quantitative computed tomography (HR-pQCT) quantifies bone microstructure and density at the distal tibia where there is also a sizable amount of myotendinous (muscle and tendon) tissue (MT); however, there is no method for the quantification of MT. This study aimed (1) to assess the feasibility of using HR-pQCT distal tibia scans to estimate MT properties using a custom algorithm, and (2) to determine the relationship between MT properties at the distal tibia and mid-leg muscle density (MD) obtained from pQCT. Postmenopausal women from the Hamilton cohort of the Canadian Multicenter Osteoporosis Study had a single-slice (2.3 ± 0.5 mm) 66% site pQCT scan measuring muscle cross-sectional area (MCSA) and MD. A standard HR-pQCT scan was acquired at the distal tibia. HR-pQCT-derived MT cross-sectional area (MTCSA) and MT density (MTD) were calculated using a custom algorithm in which thresholds (34.22-194.32 mg HA/cm3) identified muscle seed volumes and were iteratively expanded. Pearson and Bland-Altman plots were used to assess correlations and systematic differences between pQCT- and HR-pQCT-derived muscle properties. Among 45 women (mean age: 74.6 ± 8.5 years, body mass index: 25.9 ± 4.3 kg/m2), MTD was moderately correlated with mid-leg MD across the 2 modalities (r = 0.69-0.70, p < 0.01). Bland-Altman analyses revealed no evidence of directional bias for MTD-MD. HR-pQCT and pQCT measures of MTCSA and MCSA were moderately correlated (r = 0.44, p < 0.01). Bland-Altman plots for MTCSA revealed that larger MCSAs related to larger discrepancy between the distal and the mid-leg locations. This is the first study to assess the ability of HR-pQCT to measure MT size, density, and morphometry. HR-pQCT-derived MTD was moderately correlated with mid-leg MD from pQCT. This relationship suggests that distal MT may share common properties with muscle throughout the length of the leg. Future studies will assess the value of HR-pQCT-derived MT properties in the context of falls, mobility, and balance.

Too Fit To Fracture: outcomes of a Delphi consensus process on physical activity and exercise recommendations for adults with osteoporosis with or without vertebral fractures.

UNLABELLED: An international consensus process resulted in exercise and physical activity recommendations for individuals with osteoporosis. Emphasis was placed on strength, balance, and postural alignment. Rather than providing generic restrictions, activity should be encouraged while considering impairments, fracture risk, activity history, and preference, and guidance on spine sparing techniques should be provided. INTRODUCTION: The objectives of this study were to establish expert consensus on key questions posed by patients or health care providers regarding recommended assessment domains to inform exercise prescription, therapeutic goals of exercise, and physical activity and exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. METHODS: The Too Fit To Fracture expert panel identified researchers and clinicians with expertise in exercise and osteoporosis and stakeholder groups. We delivered a modified online Delphi survey (two rounds) to establish consensus on assessment, exercise, and physical activities for three cases with varying risk (osteoporosis based on bone mineral density; 1 spine fracture and osteoporosis; multiple spine fractures, osteoporosis, hyperkyphosis, and pain). Duplicate content analyses of free text responses were performed. RESULTS: Response rates were 52% (39/75) and 69% (48/70) for each round. Key consensus points are the following: (a) Current physical activity guidelines are appropriate for individuals with osteoporosis without spine fracture, but not for those with spine fracture; (b) after spine fracture, physical activity of moderate intensity is preferred to vigorous; (c) daily balance training and endurance training for spinal extensor muscles are recommended for all; (d) providing guidance on spine-sparing techniques (e.g., hip hinge) during activities of daily living or leisure, considering impairments, fracture risk, activity history, and preference, is recommended rather than providing generic restrictions (e.g., lifting <10 lbs, no twisting), but for those with vertebral fracture, especially in the presence of pain, multiple fractures, or hyperkyphosis, the risks of many activities may outweigh the benefits-physical therapist consultation is recommended. Examples of spine-sparing techniques and exercise prescription elements are provided. CONCLUSIONS: Our recommendations guide health care providers on assessment, exercise prescription, and safe movement for individuals with osteoporosis.

Too Fit To Fracture: a consensus on future research priorities in osteoporosis and exercise.

UNLABELLED: An international consensus process identified the following research priorities in osteoporosis and exercise: study of exercise in high-risk cohorts, evaluation of multimodal interventions, research examining translation into practice and a goal to examine fracture outcomes. INTRODUCTION: To identify future research priorities related to exercise for people with osteoporosis with and without osteoporotic spine fracture via international consensus. METHODS: An international expert panel and representatives from Osteoporosis Canada led the process and identified opinion leaders or stakeholders to contribute. A focus group of four patient advocates identified quality of life, mobility, activities of daily living, falls, bone mineral density, and harms as outcomes important for decision-making. Seventy-five individuals were invited to participate in an online survey asking respondents to define future research priorities in the area of osteoporosis and exercise; the response rate was 57%. Fifty-five individuals from seven countries were invited to a half-day consensus meeting; 60% of invitees attended. The results of the online survey, knowledge synthesis activities, and results of the focus group were presented. Nominal group technique was used to come to consensus on research priorities. RESULTS: Research priorities included the study of exercise in high-risk cohorts (e.g., ≥ 65 years, low BMD, moderate/high risk of fracture, history of osteoporotic vertebral fractures, hyperkyphotic posture, functional impairments, or sedentary), the evaluation of multimodal interventions, research examining translation into practice, and a goal to examine fracture outcomes. The standardization of outcomes or protocols that could be evolved into large multicentre trials was discussed. CONCLUSIONS: The research priorities identified as part of the Too Fit To Fracture initiative can be used to inform the development of multicentre collaborations to evaluate and implement strategies for engaging individuals with osteoporosis in a safe and effective exercise.

Too Fit To Fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture.

SUMMARY: A consensus process was conducted to develop exercise recommendations for individuals with osteoporosis or vertebral fractures. A multicomponent exercise program that includes balance and resistance training is recommended. INTRODUCTION: The aim was to develop consensus on exercise recommendations for older adults: (1) with osteoporosis and (2) with osteoporotic vertebral fracture(s). METHODS: The Grading of Recommendations Assessment, Development, and Evaluation method was used to evaluate the quality of evidence and develop recommendations. Outcomes important for decision making were nominated by an expert panel and patient advocates. They included falls, fractures, bone mineral density (BMD), and adverse events for individuals with osteoporosis/vertebral fractures, and pain, quality of life, and function for those with vertebral fracture. Meta-analyses evaluating the effects of exercise on the outcomes were reviewed. Observational studies or clinical trials were reviewed when meta-analyses were not available. Quality ratings were generated, and informed the recommendations. RESULTS: The outcome for which evidence is strongest is falls. Point estimates of the effects of exercise on falls, fractures, and BMD vary according to exercise type. There is not enough evidence to quantify the risks of exercise in those with osteoporosis or vertebral fracture. Few trials of exercise exist in those with vertebral fracture. The exercise recommendations for exercise in individuals with osteoporosis or osteoporotic vertebral fracture are conditional. The panel strongly recommends a multicomponent exercise program including resistance and balance training for individuals with osteoporosis or osteoporotic vertebral fracture. The panel recommends that older adults with osteoporosis or vertebral fracture do not engage in aerobic training to the exclusion of resistance or balance training. CONCLUSIONS: The consensus of our international panel is that exercise is recommended for older adults with osteoporosis or vertebral fracture, but our recommendations are conditional.

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

The effect of exercise on pQCT parameters of bone structure and strength in postmenopausal women--a systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Inconsistent study findings of exercise on areal bone density highlight the need to include parameters of bone geometry and volumetric bone density measurements. Using a systematic review and meta-analysis, we found a decrease in bone loss through the maintenance of cortical and trabecular volumetric bone mineral density (BMD). Studies with longer exercise durations and larger sample sizes are needed. INTRODUCTION: Exercise has long been recommended to prevent age-related loss of bone mass in postmenopausal women. However, inconsistent study findings on the effect of exercise on BMD preservation have highlighted the importance of extending the evaluation of bone to include the parameters of bone geometry. We conducted both a systematic review and meta-analysis of the effects of exercise on bone geometry and volumetric BMD in postmenopausal women. METHODS: We searched MEDLINE, PubMed, and EMBASE from 1950 to April 2009 and included prospective, randomized controlled trials of healthy postmenopausal women where the intervention involved exercise or sport and outcomes included quantitative or peripheral quantitative computed tomography bone parameters. Outcome variables included: total volumetric BMD, cortical volumetric BMD (CvBMD), trabecular volumetric BMD (TrvBMD), total bone mineral content, cortical BMC, total bone area, cortical area, polar stress-strain index, and bone strength index. RESULTS: Six studies satisfied our inclusion and exclusion criteria. Lower extremity exercises resulted in small (∼0.9%) but significant improvements in TrvBMD of the distal tibia (p = 0.0006) and in CvBMD of the tibial shaft (p = 0.0007). Studies with longer durations of exercise (12 months) and those in early postmenopausal women showed significant changes in CvBMD at the tibial shaft. CONCLUSIONS: We conclude that exercise in postmenopausal women may decrease bone loss by maintaining cortical and trabecular volumetric BMD. To better understand the effect of exercise on bone geometric structure and strength, more studies of longer duration and larger sample sizes are needed.

Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?

UNLABELLED: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted. INTRODUCTION: Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist. METHODS: We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day). RESULTS: Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses. CONCLUSIONS: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.