OBJECTIVE:Few studies have explored specific trajectories or patterns of falls over time in older adults, and the role of sex and self-reported risk factors for these trajectories were overlooked. This study aimed to identify sex-specific fall trajectories over 3 years and the self-reported risk factors associated with each trajectory in European older adults. DESIGN:Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. SETTING AND PARTICIPANTS:Multicenter trial conducted in 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without major health events in the 5 years prior to enrollment, with sufficient mobility and good cognitive status. METHODS:Falls were recorded prospectively via phone calls and in-person assessments every 3 months over 3 years of follow-up. Group-based trajectory modeling was used to identify sex-specific trajectories based on the number of falls experienced over the follow-up, and penalized logistic regression models identified the self-reported risk factors most associated with each trajectory. RESULTS:A total of 1958 participants were included in this analysis (mean age: 74.9 years, 61.7% women). We identified a "lower fall trajectory" and a "higher fall trajectory" among women and a "lower fall trajectory" and an "increasing fall trajectory" among men. In women, living alone was the only self-reported risk factor associated with the higher fall trajectory. In men, living alone (marginal), as well as reporting fatigue, pain or discomfort, mobility issues, and higher self-rated health, were significantly associated with experiencing the increasing fall trajectory. CONCLUSIONS AND IMPLICATIONS:This study provides a comprehensive assessment of falls over 3 years, highlighting differences in fall patterns and associated self-reported risk factors between men and women. These findings may offer valuable insights for developing sex-specific fall risk prediction models and targeted fall prevention strategies.

Vertebral fractures (VFs) are among the most common osteoporotic fractures. The effect of vitamin D3, omega-3s or a simple home exercise program (SHEP) on VFs is unclear. We examined whether vitamin D3, omega-3s, or SHEP, alone or in combination, over 3 years, reduce the incidence rate of VFs among European older adults. DO-HEALTH is a multi-center, 2 × 2 × 2 factorial design, randomized controlled trial, which included older adults (≥70 years) free from major health events in the 5 years prior to enrollment. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination. Quantitative and qualitative VF assessment was determined from lateral thoracolumbar DXA scans. The primary outcome for this analysis was the incidence rate (IR) of total VFs, defined as the number of any new and progressed VFs over the 3-year follow-up. Sensitivity analyses were conducted for only new VFs and only VF progressions. Negative binomial regression models were fit, adjusted for age, sex, prior fall, BMI, study site and participants' follow-up time. 1488 participants (mean age 74.9 years; 77% had low bone mass or osteoporosis; 43.8% had 25(OH)D levels <20 ng/mL) were included. There were 93 incident VFs, of which 58 were new VFs and 35 were progressions. None of the three treatments reduced the IR of total VFs overall, however, the IR was reduced with SHEP compared to the control exercise program in women (IR ratio 0.52, 95% CI 0.28, 0.98). In the sensitivity analysis for VF progressions, SHEP reduced the IR (IR ratio 0.34, 95% CI 0.16, 0.75). Among generally healthy older adults, vitamin D3 and omega-3s supplementation did not reduce the incidence rate of VFs. SHEP reduced the incidence rate of total VFs in women and of VF progressions overall. Exercise may play a role in the prevention of VFs.

FRAXplus® facilitates adjustment of FRAX® fracture probabilities for additional clinical risk factors. This study examined how FRAXplus adjustments affect the proportion of older Swedish women eligible for treatment at a major osteoporotic fracture (MOF) probability intervention threshold (IT) ≥ 26

Hip fractures in elderly women pose significant healthcare challenges. Promoting walking for exercise as a cost-effective intervention may help reduce the risk of fractures in this population. This study aimed to examine the relationship between walking and hip fracture risk among women aged 65 years and older. A 20-year prospective study (1986–2006) included 9704 women from the Study of Osteoporotic Fractures (SOF) in the USA. Participants were followed biennially, and walking exposure was assessed by the number of city blocks walked for exercise, routine activity, and total blocks walked daily. Cox regression models with time-varying covariates assessed associations, with competing risks addressed using Fine and Gray models. Penalized splines were used to explore dose–response relationships. In total, 1419 hip fractures were identified through the study period. The mean and median follow-up times for hip fractures or censoring were 15.0 and 15.8 years in the walking for exercise group, vs. 13.2 and 13.7 years in the not walking for exercise group. The hip fracture incidence rate was 10.0 cases per 1000 person-years (py) in the walking for exercise group compared to 10.9 per 1000 py in the not walking for exercise group. All-cause mortality was 37.1 per 1000 py in the walking for exercise group compared to 46.4 per 1000 py in the not walking for exercise group. Adjusted models showed that walking for exercise significantly reduced hip fracture risk (HR, 0.864; 95

Using data from a meta-analysis including 606,715 women, we found that the predictive value of a fall the past year for future hip fractures in women significantly decreases with age, resulting in a diminishing population attributable risk with increasing age.PurposeIn a recent meta-analysis of 40 cohorts, we demonstrated that a fall history in the past year was associated with an increased risk of hip fracture. An interaction between fall history and age was observed in women, with lower hazard ratios (HR) for older women. This study aimed to determine the population-attributable risk (PAR) for hip fracture due to increased fall risk in women of different ages.MethodsFall history associated attributable risk (AR, %) for hip fracture was calculated [100(1-1/relative risk (HR))] for women per age stratum, using previously calculated HRs. PAR (%) of hip fractures in the female population (>= 50 years) that could be prevented if the fall history-mediated risk increase could be eliminated was calculated as 100Pexp(HR-1)/[1 + Pexp(HR-1)] where Pexp was the exposed proportion of the population (i.e. the proportion with past falls).ResultsA total of 606,715 women included from 40 cohorts, with fall risk documented in the past year (fall history yes/no or 2 or more falls) and prospective information about hip fracture and death, were analysed. The proportion of fallers increased progressively with age from 24.6% at age 50-54 years to 45.5% at age 90-94 years. In contrast, the AR due to falls decreased, from 54.8% at age 50-54 years to 8.3% at age 90-94 years, and the PAR diminished with age, from 23.9% in women 50-54 years old to 3.9% in women 90-94 years old.ConclusionsAs falls become more common with age, their predictive value for future hip fractures in women significantly decreases. This suggests that the effectiveness of fall prevention strategies in reducing hip fractures is lower in older women, who are at higher risk for serious falls and hip fractures.

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3

A surrogate FRAX® model for Mongolia has been constructed using age- and sex-specific hip fracture rates for mainland China and age- and sex-specific mortality rates from Mongolia. FRAX models are frequently requested for countries with little or no data on the incidence of hip fracture. In such circumstances, the development of a surrogate FRAX model is recommended based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country. This report describes the development and characteristics of a surrogate FRAX model for Mongolia. The FRAX model used the ethnic-specific incidence of hip fracture in mainland China, combined with the death risk for Mongolia in 2015–2019. Intervention thresholds were developed based on fracture probabilities equivalent to women with a prior fragility fracture, and their impact was assessed in a referral cohort comprising men at age 50 and above and postmenopausal women. The number of hip fractures in 2015 and 2050 was estimated based on United Nations’ predicted changes in population demography. The surrogate model gave similar hip fracture probabilities to estimates from China. Age-dependent intervention thresholds for a major osteoporotic fracture ranged from a 10-year probability of 2.4

Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.

Parathyroid hormone (PTH) regulates bone homeostasis. Intermittent exposure to PTH results in bone formation being greater than bone resorption, and this effect has been harnessed through the development of agonists of the PTH and PTH-related protein type 1 receptor (PTH1R) to treat osteoporosis. Teriparatide, an analogue of the first 34 amino acids of PTH, and abaloparatide, which resembles PTH-related protein (PTHrP) in structure, are PTH1R agonists currently in clinical use. Both medications have been shown to increase bone mineral density at the lumbar spine, femoral neck and total hip. Randomized controlled trials with teriparatide or abaloparatide have also provided evidence of reduction in vertebral and non-vertebral fractures. The ACTIVE trial suggested slightly greater efficacy for major osteoporotic fractures (as an exploratory end point) for abaloparatide than for teriparatide. A similar potential superiority was suggested for hip fracture in a real-world, observational study. Side effects of these medications are usually transient, and although a risk of osteosarcoma was suggested by studies using murine models, no such risk has been observed in extensive human studies. Overall, both teriparatide and abaloparatide have demonstrated convincing clinical effectiveness and cost-effectiveness, with a reassuring safety profile. Potential differences in their effects on bone mineral density and their antifracture effects offer avenues for differentiation but require further validation in appropriately designed studies. This Review summarizes clinical effectiveness, health economics and safety data on the parathyroid hormone receptor agonists teriparatide and abaloparatide, discussing potential strategies and drug combinations to achieve best outcomes in patients with osteoporosis.

Our ability to optimally manage bone health across the lifecourse, and so minimise the risk of fractures, has advanced substantially in recent decades. Whilst fractures and osteoporosis in older age were historically viewed simply as inherent in normal ageing, they are now recognised as manifestations of age-related disease. Key to advancing the field was the development of conceptual (relating to impaired bone mass and microarchitecture with increased propensity to fracture), and subsequent World Health Organization densitometric definitions of osteoporosis, cementing the role of dual-energy X-ray absorptiometry in bone health management. However, whilst low bone mineral density is a strong risk factor for fracture, many individuals who do fracture have normal or only modestly reduced bone mineral density. Furthermore, the existence of two definitions constituting a condition called "osteoporosis", one based on a measurement, and the other conceptual, has led to uncertainty in clinical practice. The field is therefore moving towards calculation of an individual's absolute fracture risk, based on clinical risk factors, with the option to incorporate bone mineral density (if available) as a risk factor rather than as an indication for treatment. Uptake of this new direction has been variable internationally, with many parts of the world, particularly low- and middle-income countries, still predicating treatment (where osteoporosis services exist) on bone mineral density, despite poor availability of densitometry in many such settings. In this Position Paper, on behalf of the International Osteoporosis Foundation, we review the current barriers which prevent equitable access to optimal bone health management worldwide and recommend potential solutions which might be implemented to overcome them.

The National Osteoporosis Guideline Group (NOGG) has updated the revised UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. This guideline is relevant for all healthcare professionals involved in osteoporosis management. The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013, 2017 and 2021. This paper presents a minor update of the 2021 guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women and men aged 50 years and older. Where available, systematic reviews, meta-analyses and randomised controlled trials have been used to provide the evidence base. Conclusions and recommendations have been systematically graded according to the strength of the available evidence. Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, as well as models of care for fracture prevention. Recommendations are made for training, service leads and commissioners of healthcare, and for review criteria for audit and quality improvement. Specific 2024 updates include guidance on fracture risk assessment by ethnicity, Parkinson’s disease, Down’s syndrome and lower-limb amputation; furthermore, the definition of very high fracture risk has been clarified. Hormone replacement therapy (HRT) is now recommended as a first-line treatment option in younger postmenopausal women with high fracture risk and low baseline risk for adverse events; recommendations regarding abaloparatide are included; additional training resources have been added. The guideline provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Osteoporosis in men is an underdiagnosed and undertreated condition that leads to significant morbidity and mortality, particularly in the aging population. This consensus report provides tailored guidelines for diagnosing, preventing, and treating male osteoporosis in the Asia–Pacific region by integrating global best practices with regional adaptations. To establish evidence-based, region-specific guidelines for the management of male osteoporosis in the Asia–Pacific region, addressing demographic and lifestyle factors. Expert feedback was gathered through premeeting reviews, consensus conferences, and collaborative discussions. A life-course approach was employed to align international best practices with Asia–Pacific-specific needs, emphasizing continuous monitoring and intervention from middle age onward. The 12 consensus strategies systematically approach male osteoporosis management, addressing screening, diagnosis, treatment, and long-term follow-up. Recommendations include the assessment of fracture risk for men aged 50 years and above, use of dual-energy X-ray absorptiometry (DXA) testing for men aged 70 years and above, lifestyle modifications, and pharmacological interventions such as bisphosphonates, denosumab, and anabolic agents for high-risk patients. Secondary causes of osteoporosis were highlighted, along with the establishment of fracture liaison services (FLSs) to improve long-term care. A life-course approach was proposed to optimize bone health throughout men’s lives. This consensus provides a comprehensive framework tailored to the Asia–Pacific region for diagnosing, preventing, and managing osteoporosis in men. By addressing region-specific challenges and promoting evidence-based interventions, the latest guidelines incorporating the consensus may depict the conceptual direction in reducing fracture risk and improving long-term bone health outcomes for osteoporosis in men.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Tr & oslash;ndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined. The authors developed a proteomic risk score that improved the prediction of hip fractures in three validation cohorts analyzed by two different proteomic platforms. This risk score constitutes a new tool to stratify patients by hip fracture risk.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 +/- 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (>= 20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.

The purpose of this study was to investigate the prevalence of three sarcopenia definitions and their associations with fracture risk in older Swedish women when adjusted for fracture risk assessment (FRAX)-based risk factors; 2,883 women with a mean age of 77.8 years were included. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC; low handgrip strength [kg] and gait speed (m/s)), revised European Working Group on Sarcopenia in Older People (EWGSOP2; low appendicular lean mass index, appendicular lean mass [ALM]/height; kg/m2], and hand grip strength [kg]), and Asian Working Group for Sarcopenia (AWGS; low ALM (kg), and hand grip strength [kg]) definitions. Femoral neck T-score was obtained from dual-energy X-ray absorptiometry. All fractures, confirmed by X-ray or medical record review, were subsequently categorized as major osteoporotic fractures (MOFs) and hip fractures. Deaths were verified through regional registers. The total follow-up time was 6.4 ± 1.3 (mean ± SD) yr. Cox regression (hazard ratios [HR] and 95% CIs) analyses were performed with adjustment for age, FRAX variables, and femoral neck T-score. Sarcopenia prevalence was 4.5% (n = 129) according to SDOC, 12.5% (n = 360) for EWGSOP2, and 10.3% (n = 296) defined by AWGS. Individuals with sarcopenia defined by SDOC had a higher mortality risk than individuals without sarcopenia (HR: 3.41; 95% CI: 2.51, 4.62) after adjusting for age and FRAX variables. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased fracture risk after adjusting for age and FRAX variables. Individuals with sarcopenia defined by SDOC had a higher risk for any fractures (HR: 1.48; 95% CI: 1.10, 1.99) and MOF (HR: 1.42; 95% CI: 1.03, 1.98) compared with individuals without sarcopenia after adjusting for clinical risk factors used in FRAX. In conclusion, sarcopenia defined by SDOC, incorporating muscle function/strength, was the only sarcopenia definition associated with fracture risk in older women.

ObjectiveAlthough aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults.DesignObservational analysis of DO-HEALTH, a double-blind, randomized controlled trial.Setting and ParticipantsMulticenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status.MethodsThe numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids.ResultsAmong the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P = .003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P = .007).Conclusions and ImplicationsOur findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults.

Evidence on the effects of Vitamin D, omega-3s, and exercise on areal bone mineral density (aBMD) in healthy older adults is limited. We examined whether vitamin D3, omega-3s, or a simple home-based exercise program (SHEP), alone or in combination, over 3 years, improve lumbar spine (LS), femoral neck (FN), or total hip (TH) aBMD assessed by DXA. Areal BMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in eight treatment arms. Mixed effects models were used, adjusting for age, sex, BMI, prior fall, study site, and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by age, sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/mL). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D versus no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI, 0.0011, 0.0059] g/cm). Furthermore, there was a benefit for vitamin D versus no vitamin D treatment on LS aBMD in the male subgroup (interaction P = .003; ∆AM: 0.0070 [95% CI, 0.0007, 0.0132] g/cm). Omega-3s and SHEP had no benefit on aBMD in healthy, active, and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men; however, effect sizes were very modest and the clinical impact of these findings is unclear.