Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Hip fracture rate and osteoporosis treatment in Ontario: A population-based retrospective cohort study.

This population-based study analyzes hip fracture and osteoporosis treatment rates among older adults, stratified by place of residence prior to fracture. Hip fracture rates were higher among older adults living in the community and discharged to long-term care (LTC) after fracture, compared to LTC residents and older adults living in the community. Only 23% of LTC residents at high fracture risk received osteoporosis treatment. PURPOSE: This population-based study examines hip fracture rate and osteoporosis management among long-term care (LTC) residents > 65 years of age compared to community-dwelling older adults at the time of fracture and admitted to LTC after fracture, in Ontario, Canada. METHODS: Healthcare utilization and administrative databases were linked using unique, encoded identifiers from the ICES Data Repository to estimate hip fractures (identified using the Public Health Agency of Canada algorithm and International Classification of Diseases (ICD)-10 codes) and osteoporosis management (pharmacotherapy) among adults > 66 years from April 1, 2014 to March 31, 2018. Sex-specific and age-standardized rates were compared by pre-fracture residency and discharge location (i.e., LTC to LTC, community to LTC, or community to community). Fracture risk was determined using the Fracture Risk Scale (FRS). RESULTS: At baseline (2014/15), the overall age-standardized hip fracture rate among LTC residents was 223 per 10,000 person-years (173 per 10,000 females and 157 per 10,000 males), 509 per 10,000 person-years (468 per 10,000 females and 320 per 10,000 males) among the community to LTC cohort, and 31.5 per 10,000 person-years (43.1 per 10,000 females and 25.6 per 10,000 males). During the 5-year observation period, the overall annual average percent change (APC) for hip fracture increased significantly in LTC (AAPC = + 8.6 (95% CI 5.0 to 12.3; p = 0.004) compared to the community to LTC group (AAPC = + 2.5 (95% CI - 3.0 to 8.2; p = 0.248)) and the community-to-community cohort (AAPC - 3.8 (95% CI - 6.7 to - 0.7; p = 030)). However, hip fracture rate remained higher in the community to LTC group over the study period. There were 33,594 LTC residents identified as high risk of fracture (FRS score 4 +), of which 7777 were on treatment (23.3%). CONCLUSION: Overall, hip fracture rates have increased in LTC and among community-dwelling adults admitted to LTC after fracture. However, hip fracture rates among community-dwelling adults have decreased over time. A non-significant increase in osteoporosis treatment rates was observed among LTC residents at high risk of fracture (FRS4 +). Residents in LTC are at very high risk for fracture and require individualized based on goals of care and life expectancy.

Exploring the perspectives of older adults who are pre-frail and frail to identify interventions to reduce sedentary behaviour and improve mobility: a thematic content analysis.

Older adults who are frail are one of the most sedentary and the least physically active age groups. Prolonged sedentary time is associated with increased risk of negative health outcomes. To help design effective and sustainable content and optimize the uptake of sedentary behaviour interventions, an in-depth understanding of older adults' perceptions of sedentary behaviour is needed; however, most qualitative studies have been conducted in healthy older adults. The aim of this study was to explore perspectives of sedentary behaviour within the context of older adults who are pre-frail and frail after the winter and spring. We included participants if they: (1) spoke English or attended with a translator or caregiver, (2) were ≥ 60 years, and (3) were frail on the Morley Frail Scale. We utilized a qualitative description methodology including a semi-structured in-depth interview and thematic content analysis. Concepts from the COM-B (Capability Opportunity Motivation-Behaviour) model were used to guide the semi-structured interviews and analysis. To ensure credibility of the data, we used an audit trail and analyst triangulation. We recruited 21 older adults (72 ± 7.3 years, 13 females, 13 frail) from southwestern Ontario, Canada. Two individuals were lost to follow-up due to medical mistrust and worse health. We transcribed 39 audio recordings. We identified three salient themes: (1) older adults rationalize their sedentary behaviours through cognitive dissonance (reflective motivation), (2) urban cities in southwestern Ontario may not be "age-friendly" (physical opportunity), and (3) exercise is something people "have to do", but hobbies are for enjoyment despite medical conditions (psychological capability). Perspectives of sedentary behaviour were different in the winter versus spring, with participants perceiving themselves to be less active in winter. Incorporating dissonance-based interventions as part of an educational program could be used to target the reflective motivation and psychological capability components. Future research should consider interdisciplinary collaborations with environmental gerontology to develop age-friendly communities that promote meaningful mobility to target physical opportunity.

Mapping sedentary behaviour (MAPS-B) in winter and spring using wearable sensors, indoor positioning systems, and diaries in older adults who are pre-frail and frail: A feasibility longitudinal study.

Older adults who are frail are likely to be sedentary. Prior interventions to reduce sedentary time in older adults have not been effective as there is little research about the context of sedentary behaviour (posture, location, purpose, social environment). Moreover, there is limited evidence on feasible measures to assess context of sedentary behaviour in older adults. The aim of our study was to determine the feasibility of measuring context of sedentary behaviour in older adults with pre-frailty or frailty using a combination of objective and self-report measures. We defined "feasibility process" using recruitment (20 participants within two-months), retention (85%), and refusal (20%) rates and "feasibility resource" if the measures capture context and can be linked (e.g., sitting-kitchen-eating-alone) and are all participants willing to use the measures. Context was assessed using a wearable sensor to assess posture, a smart home monitoring system for location, and an electronic or hard-copy diary for purpose and social context over three days in winter and spring. We approached 80 potential individuals, and 58 expressed interest; of the 58 individuals, 37 did not enroll due to lack of interest or medical mistrust (64% refusal). We recruited 21 older adults (72±7.3 years, 13 females, 13 frail) within two months and experienced two dropouts due to medical mistrust or worsening health (90% retention). The wearable sensor, indoor positioning system, and electronic diary accurately captured one domain of context, but the hard copy was often not completed with enough detail, so it was challenging to link it to the other devices. Although not all participants were willing to use the wearable sensor, indoor positioning system, or electronic diary, we were able to triage the measures of those who did. The use of wearable sensors and electronic diaries may be a feasible method to assess context of sedentary behaviour, but more research is needed with device-based measures in diverse groups.

Postfracture survival in a population-based study of adults aged ≥66 yr: a call to action at hospital discharge.

Postfracture survival rates provide prognostic information but are rarely reported along with other mortality outcomes in adults aged ≥50 yr. The timing of survival change following a fracture also needs to be further elucidated. This population-based, matched-cohort, retrospective database study examined 98 474 patients (73% women) aged ≥66 yr with an index fracture occurring at an osteoporotic site (hip, clinical vertebral, proximal non-hip non-vertebral [pNHNV], and distal non-hip non-vertebral [dNHNV]) from 2011 to 2015, who were matched (1:1) to nonfracture individuals based on sex, age, and comorbidities. All-cause 1- and 5-yr overall survival and relative survival ratios (RSRs) were assessed, and time trends in survival changes were characterized starting immediately after a fracture. In both sexes, overall survival was markedly decreased over 6 yr of follow-up after hip, vertebral, and pNHNV fractures, and as expected, worse survival rates were observed in older patients and males. The lowest 5-yr RSRs were observed after hip fractures in males (66-85 yr, 51.9%-63.9%; ≥86 yr, 34.5%), followed by vertebral fractures in males (66-85 yr, 53.2%-69.4%; ≥86 yr, 35.5%), and hip fractures in females (66-85 yr, 69.8%-79.0%; ≥86 yr, 52.8%). Although RSRs did not decrease as markedly after dNHNV fractures in younger patients, relatively low 5-yr RSRs were observed in females (75.9%) and males (69.5%) aged ≥86 yr. The greatest reduction in survival occurred within the initial month after hip, vertebral, and pNHNV fractures, indicating a high relative impact of short-term factors, with survival-reduction effects persisting over time. Therefore, the most critical period for implementing interventions aimed at improving post-fracture prognosis appears to be immediately after a fracture; however, considering the immediate need for introducing such interventions, primary fracture prevention is also crucial to prevent the occurrence of the initial fracture in high-risk patients.

Sedentary behavior does not predict low BMD nor fracture-population-based Canadian Multicentre Osteoporosis Study.

Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1-L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture.

The number of hours of sitting in a day (often called "sedentary behavior") is currently understood to be "bad for bone health" both because of increased bone loss and a higher risk for fractures. Very few studies in randomly sampled men and women from a whole population have consistently asked about hours of sitting and examined baseline bone density. Fewer still have compared hours of sitting and its changes over 10 yr with changes in bone density and the number of new fractures that occurred. The Canadian Multicentre Osteoporosis Study obtained sitting hours from 5708 women and 2564 men aged 25 to 80+ yr and compared it with the spine, total hip (TH), and femoral neck (FN) bone density values. The average sitting at 7.4 h in men was associated with slightly lower adjusted femoral neck bone density; in women, sitting 6.7 h/d was associated with slightly lower adjusted FN and TH bone density. Ten-year follow-up data (now in about 5000 people) showed no relationship between the slightly longer sitting (an increase of 18% in men and 22% in women) and bone loss or new bone fractures. In this large country-wide population-based study, hours of sitting each day were not associated with 10-yr BMD loss in women or men nor did sitting more associate with new bone fractures. These data are reassuring; women and men who walk regularly and have some moderate-vigorous physical activity each day, despite more sitting, do not seem to be at greater risk for osteoporosis.

Automatic Radar-Based Step Length Measurement in the Home for Older Adults Living with Frailty.

With an aging population, numerous assistive and monitoring technologies are under development to enable older adults to age in place. To facilitate aging in place, predicting risk factors such as falls and hospitalization and providing early interventions are important. Much of the work on ambient monitoring for risk prediction has centered on gait speed analysis, utilizing privacy-preserving sensors like radar. Despite compelling evidence that monitoring step length in addition to gait speed is crucial for predicting risk, radar-based methods have not explored step length measurement in the home. Furthermore, laboratory experiments on step length measurement using radars are limited to proof-of-concept studies with few healthy subjects. To address this gap, a radar-based step length measurement system for the home is proposed based on detection and tracking using a radar point cloud followed by Doppler speed profiling of the torso to obtain step lengths in the home. The proposed method was evaluated in a clinical environment involving 35 frail older adults to establish its validity. Additionally, the method was assessed in people's homes, with 21 frail older adults who had participated in the clinical assessment. The proposed radar-based step length measurement method was compared to the gold-standard Zeno Walkway Gait Analysis System, revealing a 4.5 cm/8.3% error in a clinical setting. Furthermore, it exhibited excellent reliability (ICC(2,k) = 0.91, 95% CI 0.82 to 0.96) in uncontrolled home settings. The method also proved accurate in uncontrolled home settings, as indicated by a strong consistency (ICC(3,k) = 0.81 (95% CI 0.53 to 0.92)) between home measurements and in-clinic assessments.

Correction: Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

[This corrects the article DOI: 10.1371/journal.pone.0292788.].

Risk Factors and Clinical Outcomes Associated With Sarcopenia in Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

ABSTRACT: Sarcopenia is underrecognized in patients with rheumatoid arthritis (RA). Risk factors of sarcopenia and its impact on outcomes in RA patients are relatively unknown. We conducted a systematic review to identify factors and outcomes associated with sarcopenia in RA. We conducted this review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. We searched PubMed, Embase, CINAHL, and Web of Science databases by combining the following search concepts: (1) RA and (2) sarcopenia. Articles were included if they included RA patients, assessed for sarcopenia using a consensus working group definition, and assessed for clinical outcomes. Meta-analysis was performed using studies that shared the same sarcopenia definition and consistency in reporting patient or disease variables. Our search identified 3602 articles. After removal of duplicates, title and abstract screen, and full-text review, 16 articles were included for final analysis. All studies had observational study designs. The pooled prevalence of sarcopenia ranged from 24% to 30%, depending on the criteria for sarcopenia used. Factors associated with sarcopenia included higher 28-joint Disease Activity Scale scores (+0.39; 95% confidence interval, +0.02 to +0.77) and baseline methotrexate use (odds ratio, 0.70; 95% confidence interval, 0.51-0.97). Baseline glucocorticoid use had a positive correlation with sarcopenia in multiple studies. Several studies found lower bone mineral density and higher incidence of falls and fractures in patients with sarcopenia. Sarcopenia is prevalent in RA, and it may be associated with higher RA disease activity, lower bone mineral density, and increased falls and fractures. Therefore, early screening of sarcopenia in RA patients is important to incorporate into clinical rheumatology practice.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Associations between Osteosarcopenia and Falls, Fractures, and Frailty in Older Adults: Results From the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: To explore if older adults with osteosarcopenia are at a greater risk of falls, fractures, frailty, and worsening life satisfaction and activities of daily living (ADL) compared to those with normal bone mineral density (BMD) and without sarcopenia. DESIGN: The baseline and 3-year follow-up of a longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling people aged 65 years or older in Canada. METHODS: Caucasian participants 65 years or older that completed the Canadian Longitudinal Study on Aging (CLSA) 2015 baseline interview, physical measurements and 3-year follow-up were included. Osteopenia/osteoporosis was defined as BMD T score below -1 SD according to the World Health Organization, and sarcopenia was defined as low grip strength and/or low gait speed according to the Sarcopenia Definition Outcomes Consortium. Osteosarcopenia was defined as the coexistence of osteopenia/osteoporosis and sarcopenia. Self-reported incident falls and fractures in the last 12 months before the 3-year follow-up were measured. Frailty was assessed through the Rockwood Frailty Index (FI); life satisfaction through the Satisfaction With Life Scale (SWLS); and ADL through the Older American Resources and Services modules. Multivariable logistic and linear regression, including subgroup analyses by sex, were conducted. RESULTS: The sample of 8888 participants (49.1% females) had a mean age (SD) of 72.7 (5.6) years. At baseline, neither osteopenia/osteoporosis nor sarcopenia (reference group) was present in 30.1%, sarcopenia only in 18.4%, osteopenia/osteoporosis only in 29.2%, and osteosarcopenia in 22.3%. Osteosarcopenia was significantly associated with incident falls and fractures in males [adjusted odds ratio (aOR), 1.90, 95% CI 1.15, 3.14, and aOR 2.60, 95% CI 1.14, 5.91, respectively] compared to males without osteopenia/osteoporosis or sarcopenia. Participants with osteosarcopenia had worsening ADL of 0.110 (estimated ß coefficient 0.110, 95% CI 0.029, 0.192) and a decrease in their SWLS by 0.660 (estimated ß coefficient -0.660, 95% CI -1.133, -0.187), compared to those without. Osteosarcopenia was not associated with frailty for both males and females. CONCLUSIONS AND IMPLICATIONS: Osteosarcopenia was associated with self-reported incident falls and fractures in males and worse life satisfaction and ADL for all participants. Assessing and identifying osteosarcopenia is essential for preventing falls and fractures. Furthermore, it improves life satisfaction and ADL.

Opportunistic Screening of Low Bone Mineral Density From Standard X-Rays.

BACKGROUND: Osteoporosis, characterized by loss of bone mineral density (BMD), is underscreened. Osteoporosis and low bone mass are diagnosed by a BMD T-score ≤ -2.5, and between -1.0 and -2.5, respectively, at the femoral neck or lumbar vertebrae (L1-4), using dual energy x-ray absorptiometry (DXA). The ability to estimate BMD at those anatomic sites from standard radiographs would enable opportunistic screening of low BMD (T-score < -1) in individuals undergoing x-ray for any clinical indication. METHODS: Radiographs of the lumbar spine, thoracic spine, chest, pelvis, hand, and knee, with a paired DXA acquired within 1 year, were obtained from community imaging centers (62,023 x-ray-DXA pairs of patients). A software program called Rho was developed that uses x-ray, age, and sex as inputs, and outputs a score of 1 to 10 that corresponds with the likelihood of low BMD. The program's performance was assessed using receiver-operating characteristic analyses in three independent test sets, as follows: patients from community imaging centers (n = 3,729; 83% female); patients in the Canadian Multicentre Osteoporosis Study (n = 1,780; 71% female); and patients in the Osteoarthritis Initiative (n = 591; 50% female). RESULTS: The areas under the receiver-operating characteristic curves were 0.89 (0.87-0.90), 0.87 (0.85-0.88), and 0.82 (0.79-0.85), respectively, and subset analyses showed similar results for each sex, body part, and race. CONCLUSION: Rho can opportunistically screen patients at risk of low BMD (at femoral neck or L1-4) from radiographs of the lumbar spine, thoracic spine, chest, pelvis, hand, or knee.

The effect of femur positioning on dual-energy X-ray absorptiometry (DXA) measures and statistical shape and appearance modeling (SSAM) fracture risk assessments.

The diagnosis of osteoporosis using Dual-energy X-ray Absorptiometry (DXA) relies on accurate hip scans, whereby variability in measurements may be introduced by altered patient positioning, as could occur with repeated scans over time. The goal herein was to test how altered postures affect diagnostic metrics (i.e., standard clinical metrics and a newer image processing tool) for femur positioning. A device was built to support cadaveric femurs and adjust their orientation in 3° increments in flexion and internal/external rotation. Seven isolated femurs were scanned in six flexion postures (0° (neutral) to 15° of flexion) and eleven rotational postures (15° external to 15° internal rotation) while collecting standard clinical DXA-based measures for each scan. The fracture risk tool was applied to each scan to calculate fracture risk. Two separate one-way repeated measures ANOVAs (α = 0.05) were performed on the DXA-based measures and fracture risk prediction output. Flexion had a significant effect on T-score, Bone Mineral Density (BMD), and Bone Mineral Content (BMC), but not area, at angles greater than 12°. Internal and external rotation did not have a significant effect on any clinical metric. Fracture risk (as assessed by the image processing tool) was not affected by either rotation mode. Overall, this suggests clinicians can adjust patient posture to accommodate discomfort if deviations are less than 12 degrees, and the greatest care should be taken in flexion. Furthermore, the tool is relatively insensitive to postural adjustments, and as such may be a good option for tracking risk over repeated patient scans.

Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: The aim is to investigate whether social isolation and loneliness are associated with changes in grip strength, gait speed, BMD, and fractures. METHODS: Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort participants aged 65 years and older at baseline (2012-2015) who completed the three-year follow-up interview (2015-2018) were included in this analysis (n = 11,344). Social isolation and loneliness were measured using the CLSA social isolation index (CLSA-SII, range 0-10). We calculated absolute and percent change in grip strength (kg) and gait speed (m/s) and annualized absolute (g/cm2) and percent change in femoral neck and total hip BMD during the three-year follow-up. Self-reported incident fractures of all skeletal sites in the previous 12 months were measured at three-year follow-up. Multivariable analyses were conducted. Odd ratio (OR) and 95% confidence interval (CI) are reported. RESULTS: The mean age (standard deviation [SD]) was 72.9 (5.6) years and 49.9% were female. The mean (SD) of CLSA-SII at baseline was 3.5 (1.4). Mean absolute and percentage change (SD) in grip strength (kg) and gait speed (m/s) were -1.33 (4.60), -3.02% (16.65), and -0.05 (0.17), -3.06% (19.28) during the three-year follow-up, respectively. Mean annualized absolute (g/cm2) and percentage change (SD) in femoral neck and total hip BMD were -0.004 (0.010), -0.47% (1.43) and -0.005 (0.009), -0.57% (1.09), respectively. 345 (3.1%) participants had incident fractures. As CLSA-SII increased (per one unit change), participants had 1.13 (adjusted OR 1.13, 95% CI 1.01-1.27) times greater odds for incident fractures. The interaction term between the CLSA-SII and centre for epidemiology studies depression 9 scale (CES-D 9) for self-reported incident fractures was shown (interaction OR 1.02, 95% CI 1.00-1.04). CONCLUSIONS: Socially isolated and lonely older adults were more likely to have had incident fractures, but social isolation was not associated with the three-year changes in grip strength, gait speed, or BMD.

Performance of methods for analyzing continuous data from stratified cluster randomized trials - A simulation study.

Background: The adoption of cluster randomized trials (CRTs) with the stratified design is currently gaining widespread interest. In the stratified design, clusters are first grouped into two or more strata and then randomized into treatment groups within each stratum. In this study, we evaluated the performance of several commonly used methods for analyzing continuous data from stratified CRTs. Methods: This is a simulation study where we compared four methods: mixed-effects, generalized estimating equation (GEE), cluster-level (CL) linear regression and meta-regression methods to analyze the continuous data from stratified CRTs using a simulation study with varying numbers of clusters, cluster sizes, intra-cluster correlation coefficients (ICCs) and effect sizes. This study was based on a stratified CRT with one stratification variable with two strata. The performance of the methods was evaluated in terms of the type I error rate, empirical power, root mean square error (RMSE), and width and coverage of the 95% confidence interval (CI). Results: GEE and meta-regression methods had high type I error rates, higher than 10%, for the small number of clusters. All methods had similar accuracy, measured through RMSE, except meta-regression. Similarly, all methods but meta-regression had similar widths of 95% CIs for the small number of clusters. For the same sample size, the empirical power for all methods decreased as the value of the ICC increased. Conclusion: In this study, we evaluated the performance of several methods for analyzing continuous data from stratified CRTs. Meta-regression was the least efficient method compared to other methods.

The Geras virtual frailty rehabilitation program to build resilience in older adults with frailty during COVID-19: a randomized feasibility trial.

BACKGROUND: The Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic. METHODS: Participants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component. RESULTS: The program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant's adherence levels included virtual exercise sessions 81% (95% CI: 75-88%), home-based exercise 50% (95% CI: 38-62%), protein supplements consumption 68% (95% CI: 55-80%), and medication optimization 38% (95% CI: 21-59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms. CONCLUSION: The GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant's intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366.

Exploring participant attrition in a longitudinal follow-up of older adults: the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort.

OBJECTIVE: We explored the magnitude of attrition, its pattern and risk factors for different forms of attrition in the cohort from the Global Longitudinal Study of Osteoporosis in Women. DESIGN: Prospective cohort study. SETTING: Participants were recruited from physician practices in Hamilton, Ontario. PARTICIPANTS: Postmenopausal women aged ≥55 years who had consulted their primary care physician within the last 2 years. OUTCOME MEASURES: Time to all-cause, non-death, death, preventable and non-preventable attrition. RESULTS: All 3985 women enrolled in the study were included in the analyses. The mean age of the cohort was 69.4 (SD: 8.9) years. At the end of the follow-up, 30.2% (1206/3985) of the study participants had either died or were lost to follow-up. The pattern of attrition was monotone with most participants failing to return after a missed survey. The different types of attrition examined shared common risk factors including age, smoking and being frail but differed on factors such as educational level, race, hospitalisation, quality of life and being prefrail. CONCLUSION: Attrition in this ageing cohort was selective to some participant characteristics. Minimising potential bias associated with such non-random attrition would require targeted measures to achieve maximum possible follow-rates among the high-risk groups identified and dealing with specific reasons for attrition in the study design and analysis.

Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.

Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Association Among Cognition, Frailty, and Falls and Self-Reported Incident Fractures: Results From the Canadian Longitudinal Study on Aging (CLSA).

Cognition, frailty, and falls have been examined independently as potential correlates of fracture risk, but not simultaneously. Our objective was to explore the association between cognition, frailty, and falls and self-reported incident fractures to determine if these factors show significant independent associations or interactions. We included participants who completed the Canadian Longitudinal Study on Aging (CLSA) 2012-2015 baseline comprehensive assessment, did not experience any self-reported fractures in the year prior to cohort recruitment, and completed the follow-up questionnaire at year 3 (n = 26,982). We compared all baseline cognitive measures available in the CLSA, the Rockwood Frailty Index (FI), and presence of self-reported falls in the past 12 months in those with versus without self-reported incident fractures in year 3 of follow-up. We used multivariable logistic regression adjusted for covariates and examined two-way interactions between cognition, frailty, and prior falls. CLSA specified analytic weights were applied. The mean ± standard error (SE) age of participants was 59.5 ± 0.1 years and 52.2% were female. A total of 715 participants (2.7%) self-reported incident fractures at 3-year follow-up. Participants who experienced incident fractures had similar baseline cognition scores (mean ± SE; Rey Auditory Verbal Learning Test [RAVLT]: Immediate recall 6.1 ± 0.1 versus 5.9 ± 0.0; standardized difference [d] 0.124); higher FI scores (mean ± SE; FI 0.134 ± 0.005 versus 0.116 ± 0.001; d 0.193), and a greater percentage had fallen in the past 12 months (weighted n [%] 518 [7.2] versus 919 [3.5]; d 0.165). FI (each increment of 0.08) was associated with a significantly increased risk of self-reported incident fractures in participants of all ages and those aged 65 years or older (adjusted odd ratio [OR] 1.24, 95% confidence limit [CL] 1.10-1.40; adjusted OR 1.44, 95% CL 1.11-1.52, respectively). The adjusted odds for self-reported incident fractures in participants of all ages was also significantly associated with falls in the past 12 months prior to baseline (adjusted OR 1.83; 95% CL 1.13-2.97), but not in those aged 65 years or older. No interactions between cognition, frailty, and prior falls were found. However, considering the relatively young age of our cohort, it may be appropriate to make strong inferences in individuals older than 65 years of age. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial.

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 µg or placebo for 12 months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n = 149; placebo, n = 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T-score, -2.1). At 12 months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p < 0.0001). The most common (≥5%) treatment-emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12 months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).