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ObjectiveOur objective was to investigate the overall and sex-specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults.MethodsMale and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Aging completed standing knee radiographs and knee pain assessments. Participants were divided into three groups using Kellgren-Lawrence grade (KLG) of KOA severity (0-1, 2, or 3-4). Outcome measures included whole-body muscle mass, thigh fat-free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics.ResultsOverall, the presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (P trend < 0.036). Sex-specific analysis revealed reduced energetics only in female patients with KOA (P trend < 0.007) compared to female patients without KOA. In models adjusted for age, sex, race, nonsteroidal anti-inflammatory drug administration, site or technician, physical activity, height, and participants with abdominal adiposity with KLG 3 to 4 had greater MFI (mean 0.008%, 95% confidence interval [CI] 0.004%-0.011%) and lower leg power (mean -51.56 W, 95% CI -74.03 to -29.10 W) and specific power (mean -5.38 W/L, 95% CI -7.31 to -3.45 W/L) than those with KLG 0 to 1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power, and specific power.ConclusionMuscle health is associated with the presence and severity of KOA and differs by sex. Although muscle composition and power are lower in both male and female patients with KOA, regardless of pain status, mitochondrial energetics is reduced only in female patients.

BackgroundLow grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.AimWe examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.MethodsParticipants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).ResultsMean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.ConclusionsGrip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

BackgroundObesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression.MethodsWe included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (

Osteoporosis is the most common metabolic bone disease. With special respect to the aging population, it is very common, not only due to changes in lifestyle and diet but as a result of the aging process there is low-grade inflammation and immune system activation that directly affects bone strength and quality. This article provides a review of the incidence, etiology, and approach to screening and management of osteoporosis in the aging population. A thorough screening of lifestyle, environmental, and clinical conditions will be reviewed which identifies appropriate candidates for screening and treatment.

BackgroundMusculoskeletal pain, a possible marker of central sensitization, is associated with higher prevalence of lower urinary tract symptoms (LUTS) among older men. We investigated whether musculoskeletal pain is associated with LUTS progression.MethodsParticipants were 5 569 men age ≥65 years enrolled in the prospective, multicenter Osteoporotic Fractures in Men (MrOS) Study. Self-reported musculoskeletal pain within 12 months before baseline was categorized as any pain and multilocation pain. Pain interference within 4 weeks of baseline was assessed with the SF-12 questionnaire. LUTS were assessed repeatedly with the American Urological Association Symptom Index (AUA-SI). Men with severe LUTS at baseline were excluded. LUTS progression was defined as the first occurrence of a ≥4-point AUA-SI increase during a 2-year follow-up interval. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using multivariable pooled logistic regression.ResultsLUTS progression was 37% higher among men with any musculoskeletal pain compared with men without pain (IRR 1.37, 95% CI: 1.21, 1.54). Positive associations were also observed between LUTS progression and pain at 1 (IRR 1.31, 95% CI: 1.13, 1.48) and ≥2 locations (IRR 1.42, 95% CI: 1.24, 1.60). Compared with men without pain interference, men with quite a bit/extreme pain interference were most likely to experience LUTS progression (minimal interference IRR 1.15, 95% CI: 1.03, 1.26; moderate interference IRR 1.28, 95% CI: 1.11, 1.45; quite a bit/extreme interference IRR 1.47, 95% CI: 1.22, 1.71).ConclusionsAmong men initially without severe LUTS, musculoskeletal pain is associated with an increased risk of LUTS progression. Studies using validated measures of central sensitization and LUTS progression among men are warranted.

BackgroundOsteoporosis is often considered to be a disease of women. Over the last few years, owing to the increasing clinical and economic burden, the awareness and imperative for identifying and managing osteoporosis in men have increased substantially. With the approval of agents to treat men with osteoporosis, more economic evaluations have been conducted to assess the potential economic benefits of these interventions. Despite this concern, there is no specific overview of cost-effectiveness analyses for the treatment of osteoporosis in men.ObjectivesThis study aims (1) to systematically review economic evaluations of interventions for osteoporosis in men; (2) to critically appraise the quality of included studies and the source of model input data; and (3) to investigate the comparability of results for studies including both men and women.MethodsA literature search mainly using MEDLINE (via Ovid) and Embase databases was undertaken to identify original articles published between 1 January, 2000 and 30 June, 2022. Studies that assessed the cost effectiveness of interventions for osteoporosis in men were included. The Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the International Osteoporosis Foundation osteoporosis-specific guideline was used to assess the quality of design, conduct, and reporting of included studies.ResultsOf 2973 articles identified, 25 studies fulfilled the inclusion criteria, classified into economic evaluations of active drugs (n = 8) or nutritional supplements (n = 4), intervention thresholds (n = 5), screening strategies (n = 6), and post-fracture care programs (n = 2). Most studies were conducted in European countries (n = 15), followed by North America (n = 9). Bisphosphonates (namely alendronate) and nutritional supplements were shown to be generally cost effective compared with no treatment in men over 60 years of age with osteoporosis or prior fractures. Two other studies suggested that denosumab was cost effective in men aged 75 years and older with osteoporosis compared with bisphosphates and teriparatide. Intervention thresholds at which bisphosphonates were found to be cost effective varied among studies with a 10-year probability of a major osteoporotic fracture that ranged from 8.9 to 34.2% for different age categories. A few studies suggested cost effectiveness of screening strategies and post-fracture care programs in men. Similar findings regarding the cost effectiveness of drugs and intervention thresholds in women and men were captured, with slightly greater incremental cost-effectiveness ratios in men. The quality of the studies included had an average score of 18.8 out of 25 (range 13-23.5). Hip fracture incidence and mortality risk were mainly derived from studies in men, while fracture cost, treatment efficacy, and disutility were commonly derived from studies in women or studies combining both sexes.ConclusionsAnti-osteoporosis drugs and nutritional supplements are generally cost effective in men with osteoporosis. Screening strategies and post-fracture care programs also showed economic benefits for men. Cost-effectiveness and intervention thresholds were generally similar in studies conducted in both men and women, with slightly greater incremental cost-effectiveness ratios in men.

The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength

IntroductionHyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.MethodsMen aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity.ResultsDuring a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend

BackgroundApproximately 30% to 40% of older adults have hyperkyphosis, defined as excessive curvature of the thoracic spine. Hyperkyphosis is associated with increased morbidity and mortality. This study aimed to determine whether hyperkyphosis (Cobb's angle) and upper extremity tasks were independently associated with the 6-min walk test (6MWT) in community-dwelling older adults with hyperkyphosis.MethodsIn this cross-sectional study, we studied 71 women and 28 men aged 60-87 from the study of hyperkyphosis, exercise, and function trial (SHEAF) who had kyphosis, 3 timed upper extremity tasks and the 6MWT assessed at their baseline visit. We used standing lateral spine radiographs and a standardized protocol for thoracic kyphosis (T4-T12) to measure Cobb angle of kyphosis. In addition, 3 activity of daily living (ADL) extremity tests (putting on and removing a laboratory coat, picking up a penny from the floor, and lifting a 7-lb. book to a shelf) were used.ResultsThe mean ± SD age was 70.1 ± 6.1 years. The mean ± SD Cobb angle of kyphosis was 57.4 ± 12.5 degrees. On average ± SD, the participants walked 504.8 ± 84.2 m in 6 min and took 2.4 ± 2.2 prescription medications. The mean ± SD height was 164.7 ± 8.5 cm, weight was 68.7 ± 13.1 kg, and BMI was 25.2 ± 4.0 kg/m2. Multivariate regression revealed that age, height, upper extremity book lift task, and the number of prescribed medications were significant predictors of performance on the 6MWT (p

Age-related hyperkyphosis is associated with adverse health outcomes, such as falls, fractures, and mortality. However, few studies investigated the relationship between the severity of hyperkyphosis and physical endurance in older adults. This study examined whether a degree of hyperkyphosis curvature was independently associated with the 6-minute walk test (6MWT) distance. We analyzed the baseline data of 112 older adults aged 60-92 enrolled in the Specialized Center of Research (SCOR) Kyphosis trial. The majority of the sample had at least a college degree and were white. On average, participants walked 503.9 (SD 82.3) meters in 6 minutes. Multivariate regression results showed that the degree of hyperkyphosis curvature was not independently associated with the 6MWT distance, but taller height, lighter weight, and less prescription medication were significant predictors of better performance on the 6MWT distance. Validation of the study findings in a large, diverse older adult population is warranted.

ContextWhether repeated bone mineral density (BMD) screening improves fracture prediction in men is uncertain.ObjectiveWe evaluated whether a second BMD 7 years after the initial BMD improves fracture prediction in older men.MethodsAmong 3651 community-dwelling men (mean age 79.1 years) with total hip BMD at baseline and Year 7 (Y7), self-reported fractures after Y7 were confirmed by radiographic reports. Fracture prediction assessed using Cox proportional hazards regression and logistic regression with receiver operating characteristic curves for models based on initial BMD, BMD change, and the combination of initial BMD and BMD change (combination model).ResultsDuring an average follow-up of 8.2 years after Y7, 793 men experienced ≥ 1 clinical fractures, including 426 men with major osteoporotic fractures (MOF) and 193 men with hip fractures. Both initial BMD and BMD change were associated with risk of fracture outcomes independent of each other, but the association was stronger for initial BMD. For example, the multivariable hazard ratio of MOF in the combination model per 1 SD decrement in BMD was 1.76 (95% CI 1.57-1.98) for initial BMD and 1.19 (95% CI 1.08-1.32) for BMD change. Discrimination of fracture outcomes with initial BMD models was somewhat better than with BMD change models and similar to combination models (AUC value for MOF 0.68 [95% CI 0.66-0.71] for initial BMD model, 0.63 [95% CI 0.61-0.66] for BMD change model, and 0.69 [95% CI 0.66-0.71] for combination model).ConclusionRepeating BMD after 7 years did not meaningfully improve fracture prediction at the population level in community-dwelling older men.

BackgroundMuscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat versus muscle fat to adverse outcomes have been unclear.MethodIn a large cohort of older men (N = 1 017), we measured muscle mass (D3-creatine dilution), muscle density (high-resolution peripheral quantitative computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual-energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years.ResultsIn combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% confidence interval: 0.74, 0.96), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively.ConclusionsMuscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

Study designExpert consensus study.ObjectiveThis expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction.Summary of background dataCurrently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes.MethodsA multidisciplinary panel with 18 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus.ResultsPanelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared with antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months.ConclusionBased on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.Level of Evidence: 5.

Chronic increases in pro-inflammatory cytokines in older adults, known as inflammaging, are an important risk factor for morbidity and mortality in the aging population. It has been suggested that circadian disruption may play a role in chronic inflammation, but there has been limited study that investigated the overall profile of 24-hour rest-activity rhythms in relation to inflammation using longitudinal data. In the Outcomes of Sleep Disorders in Older Men Study, we applied the extended cosine model to derive multiple rest-activity rhythm characteristics using multiday actigraphy, and examined their associations with 6 inflammatory markers (ie, C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α], tumor necrosis factor alpha soluble receptor II [TNF-α-sRII], interleukin-1β [IL-1β], interferon gamma [IFN-γ]) measured from fasting blood. We assessed both the cross-sectional association between rest-activity rhythms and inflammatory markers measured at baseline, and the prospective association between baseline rest-activity rhythms and changes in inflammatory markers over 3.5 years of follow-up. We found that multiple rest-activity characteristics, including lower amplitude and relative amplitude, and decreased overall rhythmicity, were associated with higher levels of CRP, IL-6, TNF-α, and TNF-α-sRII, but not IL-1β and IFN-γ at baseline. Moreover, the lowest quartile of these 3 rest-activity characteristics was associated with an approximately 2-fold increase in the odds of having elevated inflammation (ie, having 3 or more markers in the highest quartile) at baseline. However, we found little evidence supporting a relationship between rest-activity rhythm characteristics and changes in inflammatory markers. Future studies should clarify the dynamic relationship between rest-activity rhythms and inflammation in different populations, and evaluate the effects of improving rest-activity profiles on inflammation and related disease outcomes.

BackgroundHyperkyphosis is common in older adults and associated with low physical function and reduced health related quality of life (HrQol). Improved kyphosis has been previously established in kyphosis-targeted interventions in randomized controlled trials in older adults with hyperkyphosis; however, evidence for improved physical function is conflicting. Few studies have investigated change in physical function after a targeted kyphosis intervention in older adults with low physical function. The primary aim in this descriptive study was to explore change in physical function after a progressive high-intensity 3-month targeted kyphosis exercise and posture training intervention in older adults with low physical function and hyperkyphosis. Secondary aims were to explore change in HrQol, spinal strength and spinal curvature, and adherence and safety of the intervention.MethodsIn this secondary analysis of the Specialized Center of Research (SCOR) Kyphosis randomized trial, 101 community dwelling older men and women with hyperkyphosis who completed the intervention were divided into a low function group (LFG) and high function group (HFG). Baseline characteristics were compared between LFG and HFG. Physical function, HrQol, spinal strength and spinal curvature (kyphosis and lordosis) pre/post intervention change scores were explored within and between groups. Adherence and adverse events were examined in the LFG and HFG.ResultsTwenty-six (26%) older adults were LFG, mean Short Phyiscal Performance Battery (SPPB) 9.62 (SD = 1.17) points. At baseline, the LFG was older than HFG (p = 0.005), experienced more pain, (p = 0.060), had worse physical function and HrQol (p ≤ 0.001), and comparable kyphosis (p = 0.640). SPPB changed 0.62 (95% CI: - 0.20 to 1.44) points in the LFG and - 0.04 (95%CI: - 0.28 to 0.19) points in the HFG, p = 0.020. Gait speed changed 0.04 (95% CI: - 0.02 to 0.10) m/s in the LFG. Kyphosis improved equally in both groups. Adherence to the intervention was 83% in the LFG and 79% in the HFG. There were no adverse events in either group.ConclusionsOlder adults with low physical function and hyperkyphosis may improve physical function after a kyphosis targeted intervention. Older adults with low physical function may safely participate in targeted high-intensity kyphosis exercise and posture training. This observation needs to be confirmed in larger adequately powered studies.Trial registrationClinicaltrials.gov identifier: NCT01766674 .

ObjectiveTo identify joint structural risk factors, measured using quantitative compositional and semiquantitative magnetic resonance imaging (MRI) scoring, associated with the development of accelerated knee osteoarthritis (AKOA) compared with a more normal rate of knee osteoarthritis (OA) development.DesignFrom the Osteoarthritis Initiative we selected knees with no radiographic OA (Kellgren-Lawrence grade [KL] 0/1) that developed advanced-stage OA (KL 3/4; AKOA) within a 4-year timeframe and a comparison group with a more normal rate of OA development (KL 0/1 to KL 2 in 4 years). MRIs at the beginning of the 4-year timeframe were assessed for cartilage T2 values and structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of MRI findings with AKOA versus normal OA were assessed using multivariable logistic regression models.ResultsA total of 106 AKOA and 168 subjects with normal OA development were included. Mean cartilage T2 values were not significantly associated with AKOA (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.82-1.36). Risk factors for AKOA development included higher meniscus maximum scores (OR 1.37; 95% CI 1.11-1.68), presence of meniscal extrusion (OR 6.30; 95% CI 2.57-15.49), presence of root tears (OR 4.64; 95% CI 1.61-13.34), and higher medial tibia cartilage lesion scores (OR 1.96; 95% CI 1.19-3.24).ConclusionsWe identified meniscal damage, especially meniscal extrusion and meniscal root tears as risk factors for AKOA development. These findings contribute to identifying subjects at risk of AKOA at an early stage when preventative measures targeting modifiable risk factors such as meniscal repair surgery could still be effective.

AimsFeatures of central sensitization (CS) are present in almost all chronic pain conditions, including painful urinary conditions and back pain. Recently CS was proposed as a mechanism of nonpainful lower urinary tract symptoms (LUTS). Using musculoskeletal pain as an indicator of CS, we investigated whether the prevalence of musculoskeletal pain is greater among community-dwelling men with moderate or severe LUTS compared to those with mild LUTS.MethodsWe conducted a cross-sectional study of 5966 men ≥65 years who attended the Osteoporotic Fractures in Men Study baseline visit. LUTS were assessed with the American Urological Association Symptom Index (AUA-SI) and categorized as none/mild (0-7), moderate (8-19), or severe (≥20). Self-reported back, neck, hip, or knee pain within the 12 months before baseline was categorized as any pain and multilocation pain. We tested our hypothesis using odds ratios (OR) and 95% confidence intervals (CI) estimated from multivariable logistic regression models.ResultsThe adjusted odds of any pain were higher among men with moderate (OR 1.49, 95% CI: 1.29-1.72) and severe LUTS (OR 1.76, 95% CI: 1.28-2.40) compared to those with no/mild LUTS. The adjusted odds of pain at ≥ 2 locations were 69% higher among men with moderate (OR 1.69, 95% CI: 1.45-196) and more than double among men with severe LUTS (OR 2.24, 95% CI: 1.62-3.10) compared to men with no/mild LUTS.ConclusionsMusculoskeletal pain, especially at multiple locations, is associated with greater LUTS severity among older men. CS may represent a novel shared mechanism of pain and LUTS.

Background and purposeTreatments that prevent worsening kyphosis are important due to the progressive nature of kyphosis with aging. We assessed long-term efficacy of treatment effects after a short-term kyphosis exercise and posture training intervention in a cohort study among older adults with hyperkyphosis, and investigated whether long-term treatment effects differ among males and females.MethodsIn the original kyphosis intervention, 112 older adults enrolled in a waitlist design randomized controlled trial. One hundred three participants, mean age 70.0 (5.7) years and kyphosis 52.0° (7.4°), completed a twice weekly, 3-month, group exercise and posture training intervention, and were eligible to enroll in the follow-up study. We compared (1) change in outcomes pre-/postintervention to change postintervention over the follow-up period, (2) change in outcomes pre-/postintervention and postintervention to follow-up, stratified by sex, and (3) long-term change postintervention to follow-up in males and females. Primary outcome was change in kyphometer-measured thoracic kyphosis. Secondary outcomes were change in lumbar lordosis, objective measures of physical function, self-reported measures of physical activity, and health-related quality of life (HRQoL).Results and discussionForty-three participants, 42% of the eligible cohort, returned for follow-up, a mean 3.0 (0.7) years after completing the original intervention. Participants (27 females and 16 males) were 73.8 (6.1) years old, with mean kyphosis 48.9° (11.9°) at follow-up. Kyphosis declined -1.5° (95% confidence interval [CI]: -3.9° to 1.0°) postintervention to follow-up and this was no different than change pre-/postintervention, P = .173. Lordosis improved 8.9° (95% CI: 6.2° to 11.6°), more than change pre-/postintervention, P < .001. Gait speed measure of physical function increased 0.08 (95% CI: 0.02 to 0.14) m/s, Physical Activity Scale for the Elderly (PASE) measure of physical activity increased 4 (95% CI: -16 to 24) points, and Patient-Reported Outcomes Measurement Information System (PROMIS) mental health T-score measure of HRQoL increased 1.1 (95% CI: -1.0 to 3.1) points, but these improvements were not significantly more than change pre-/postintervention, P > .050. Other measures of physical function (modified Physical Performance Test [PPT], Timed Up and Go, and 6-minute walk) and HRQoL (Scoliosis Research Society [SRS-30] self-image and PROMIS physical function and physical health) declined at follow-up, significantly more than change pre/postintervention, P ≤ .050. Comparing change in outcomes pre-/postintervention and postintervention to follow-up, stratified by sex, both males and females increased lordosis, and decreased modified PPT and 6-minute walk measures of physical function, P < .050. Males and females differed in long-term change postintervention to follow-up. Time loaded standing and PASE improved in females compared with males, P = .008 and P = .092, respectively, and PROMIS mental health, physical health, and physical function declined in females compared with males, P = .073, P = .025, and P = .005, respectively.ConclusionsIn our follow-up study, a mean of 3.0 (0.07) years after a 3-month kyphosis exercise and posture training intervention, kyphosis maintained and did not progress as expected with age. There was long-term improvement in lordosis. Compared with treatment effects from the short-term intervention, gait speed maintained equally well in males and females, while trunk endurance improved in females. Further investigation of long-term benefits of a short-term kyphosis exercise and posture training intervention is warranted.

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as

ObjectiveThe aim of this study was to investigate the associations between weight cycling and knee joint degeneration in individuals with overweight or obesity with different patterns of weight change over 4 years.MethodsA total of 2,271 individuals from the Osteoarthritis Initiative database were assessed (case-control study). Linear regression models using annual BMI measurements over 4 years were used to classify participants as weight cyclers or noncyclers. 3-T magnetic resonance imaging was used to quantify knee cartilage transverse relaxation time (T2) and cartilage thickness annually over 4 years in all subjects. Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone-marrow abnormalities in 958 subjects at baseline and at the 4-year follow-up. The longitudinal differences in cartilage T2 and thickness between weight cyclers and noncyclers were assessed using general estimating equations, whereas the differences in WORMS outcomes were compared using general linear models.ResultsNo significant differences in the rate of change of cartilage thickness or T2 were found between weight cyclers and noncyclers. However, increases in maximum cartilage WORMS (P = 0.0025) and bone-marrow abnormalities (P = 0.04) were significantly greater in weight cyclers than in noncyclers.ConclusionsAlthough participants' intent for weight cycling in this study was unknown, weight cyclers had significantly greater increases in cartilage and bone-marrow abnormalities over 4 years than noncyclers, independent of weight gain and loss.

ObjectiveTo assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway.MethodsParticipants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids).ResultsAmong 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use.ConclusionParticipants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

PurposeOsteoarthritis (OA) is a frequently occurring, chronic condition; however, few studies describe the clinical characteristics of individuals with OA and the treatments they use to manage their symptoms. We conducted a study to characterize the OA population in the US and describe the nonsurgical management used by this population based on consumer research data collected through an online survey.MethodsData from the 2017 US National Health and Wellness Survey (NHWS) for adults aged ≥35 years were used to evaluate the relationship between OA and certain study participant characteristics and to identify the most commonly used treatment options. NHWS data were collected through a survey of individuals drawn from the internet panel maintained by Lightspeed Research (Bridgewater, New Jersey) and its panel partners. Weighted estimates were generated using data from the 2016 Current Population Survey (Annual Demographics File) of the US Census Bureau. Comparisons between the general and OA populations were made based on body mass index (BMI), exercise frequency, and comorbid diagnoses of hypertension or diabetes. Among the OA population, the use of dietary supplements, prescription or over-the-counter (OTC) treatments with chondroitin with or without glucosamine (Ch ± Gl), prescription treatment by time since OA diagnosis, and utilization of a physical therapist were also recorded.ResultsThe prevalence of OA in the overall population was 17.6 % and was higher for individuals with a BMI ≥ 25 (21.9 %), patients diagnosed with hypertension or diabetes (36.2 %), and those who did not exercise regularly (19.0 %). Adults without OA were more likely to exercise regularly (12 days per month or more) than adults diagnosed with OA. Ch ± Gl (6.0 %) was the most commonly used OTC dietary supplement in the OA population, followed by omega-3 fatty acids (2.8 %), vitamin D (1.9 %), calcium (1.1 %), and multivitamins (0.7 %). Individuals using Ch ± Gl were more likely to use OTC only products (75.4 % vs 37.3 %) or prescription medications, namely non-steroidal anti-inflammatory drugs (NSAIDs) and/or opioids, and OTC products (24.6 % vs 13.0 %) compared with individuals not using Ch ± Gl, while individuals not using Ch ± Gl were more likely to be untreated (30.3 % vs 0) or to use prescription medications only (19.4 % vs 0). Nearly 32 % of individuals with OA reported using prescription treatments, and the likelihood of using a prescription treatment increased with number of years since OA diagnosis (

The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood.

ObjectiveDisruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes, yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.Research design and methodsBaseline rest-activity rhythms were derived from actigraphy with use of extended cosine model analysis. With subjects fasting, glucose, insulin, and HOMA of insulin resistance (HOMA-IR) were measured from blood at baseline and after ∼3.5 years. Type 2 diabetes was defined based on self-report, medication use, and fasting glucose.ResultsIn the cross-sectional analysis (n = 2,450), lower 24-h amplitude-to-mesor ratio (i.e., mean activity-adjusted rhythm amplitude) and reduced overall rhythmicity were associated with higher fasting insulin and HOMA-IR (all P trend < 0.0001), indicating increased insulin resistance. The odds of baseline type 2 diabetes were significantly higher among those in the lowest quartile of amplitude (Q1) (odds ratio [OR]Q1 vs. Q4 1.63 [95% CI 1.14, 2.30]) and late acrophase group (ORlate vs. normal 1.46 [95% CI 1.04, 2.04]). In the prospective analysis (n = 861), multiple rest-activity characteristics predicted a two- to threefold increase in type 2 diabetes risk, including a lower amplitude (ORQ1 vs. Q4 3.81 [95% CI 1.45, 10.00]) and amplitude-to-mesor ratio (OR 2.79 [95% CI 1.10, 7.07]), reduced overall rhythmicity (OR 3.49 [95% CI 1.34, 9.10]), and a late acrophase (OR 2.44 [1.09, 5.47]).ConclusionsRest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident type 2 diabetes.

ObjectivesTo study the natural history of new horizontal meniscal tears and their association with progression of cartilage degeneration in individuals at risk for or with mild to moderate knee osteoarthritis over 4 years.MethodsIndividuals who developed a new meniscal tear in the right knee over 2 years were selected from the Osteoarthritis Initiative 3T MRI studies. Knee structural changes were analyzed at the time of tear appearance (baseline), and after 4 years using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Meniscal tears were classified as either horizontal tears or non-horizontal tears. Individuals without a meniscal tear were 1:3 frequency matched according to BMI, gender, race, and age and served as the control group. Linear regression analysis was used to compare cross-sectional and longitudinal changes in cartilage WORMS scores.ResultsForty-one subjects developed horizontal tears, including one indiviudal who developed a tear in both menisci, and 34 developed non-horizonal tears. We found that (29/41 (70.7%)) of horizontal and (20/34 (58.8%)) of non-horizonatal tears were stable during follow-up (p = 0.281). Although knees with an incident tear had higher than controls WORMS MAX total knee scores at baseline (coef. = 0.47, p = 0.044, 95% CI = 0.01 to 0.93), there were no significant differences between the horizontal subgroup and knees without tears in overall cartilage scores at baseline and in progression over 4 years of follow-up.ConclusionsNew horizontal meniscal tears tended to be stable over 4 years and presented no significant differences in progression of cartilage degeneration when compared with knees without tears.Key points• Most of horizonal meniscal tears were stable over 4 years. • There were no statistically significant differences in overall progression of cartilage degenerative changes between knees with horizonal meniscal tears and control knees without tears • Horizontal tears most often occurred at the posterior horn of the medial meniscus and at the body of the lateral meniscus.

ObjectiveTo assess the safety and efficacy of a novel Wnt pathway modulator, lorecivivint (SM04690), for treating pain and inhibiting structural progression in moderately to severely symptomatic knee osteoarthritis (OA).MethodsSubjects in this 52-week, phase IIa, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial received a single 2-ml intraarticular injection of lorecivivint (dose of 0.03 mg, 0.07 mg, or 0.23 mg) or placebo. Efficacy was assessed based on change from baseline on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score subscales for pain and function (scale 0-100 for each) and change from baseline in the radiographic medial joint space width (JSW). Baseline-adjusted analysis of covariance with multiple imputation was performed separately to evaluate efficacy. This proof-of-concept study evaluated the intent-to-treat population as well as a prespecified group of subjects with unilateral symptoms of knee OA (designated UNI) and an additional post hoc subgroup of subjects with unilateral symptoms but without widespread pain (designated UNI WP-).ResultsIn this trial, 455 subjects were randomized to a treatment group. The primary end point, significant improvement in the WOMAC pain score compared with placebo at week 13, was not met by any lorecivivint dose group (mean ± SD change from baseline, -23.3 ± 2.2 in the 0.03 mg group, -23.5 ± 2.1 in the 0.07 mg group, -21.3 ± 2.2 in the 0.23 mg group, and -22.1 ± 2.1 in the placebo group; each P > 0.05 versus placebo). All groups (including placebo) demonstrated clinically meaningful (≥20-point) improvements from baseline in the WOMAC pain score. The durability of response was evaluated through week 52. In the prespecified UNI group and post hoc UNI WP- group at week 52, treatment with 0.07 mg lorecivivint significantly improved the WOMAC pain score (between-group difference versus placebo, -8.73, 95% confidence interval [95% CI] -17.44, -0.03 [P = 0.049] and -11.21, 95% CI -20.99, -1.43 [P = 0.025], respectively) and WOMAC function score (between-group difference versus placebo, -10.26, 95% CI -19.82, -0.69 [P = 0.036] and -13.38, 95% CI -24.33, -2.43 [P = 0.017], respectively). Relative to baseline, the mean change in the medial JSW at week 52 was -0.04 mm in the 0.03 mg cohort, -0.09 mm in the 0.07 mg cohort, -0.16 mm in the 0.23 mg cohort, and -0.14 mm in the placebo cohort; no treatment group achieved a significant change in medial JSW compared with placebo at week 52. In both unilateral symptom subgroups, the 0.07 mg lorecivivint dose significantly increased medial JSW compared with placebo at week 52 (medial JSW 0.39 mm, 95% CI 0.06, 0.72 in the UNI group [P = 0.021] and 0.42 mm, 95% CI 0.04, 0.80 in the UNI WP- group [P = 0.032]). Changes observed in the 0.03 mg and 0.23 mg dose groups were not significantly different from those in the placebo group for any of these measures. Lorecivivint appeared safe and well tolerated.ConclusionThis phase IIa, proof-of-concept trial in patients with symptomatic knee OA did not meet its primary end point. Nevertheless, the study identified a target population in whom to evaluate the potential efficacy of lorecivivint for the treatment of knee OA.

ObjectiveTo determine the cross-sectional and longitudinal associations of vitamin C and D intake with magnetic resonance imaging (MRI) measures of cartilage composition (T2) and joint structure (cartilage, meniscus, and bone marrow) using data from the Osteoarthritis Initiative (OAI) cohort.MethodsA total of 1,785 subjects with radiographic Kellgren/Lawrence knee grades 0-3 in the right knee were selected from the OAI database. Vitamins C and vitamin D intake (diet, supplements, and total) were assessed using the Block Brief 2000 Food Frequency Questionnaire at baseline. The MRI analysis protocol included 3T cartilage T2 quantification and semiquantitative joint morphology gradings (Whole-Organ Magnetic Resonance Imaging Score [WORMS]) at baseline and 4 years. Linear regression was used to assess the association between standardized baseline vitamin intake and both baseline WORMS scores and standardized cartilage T2 values.ResultsHigher vitamin C intake was associated with lower average cartilage T2 values, medial tibia T2 values, and medial tibia WORMS scores (standardized coefficient range -0.07 to -0.05, P < 0.05). Higher vitamin D intake was associated with a lower cartilage WORMS sum score and medial femur WORMS score (standardized coefficient range -0.24 to -0.09, P < 0.05). Consistent use of vitamin D supplements of 400 IU at least once a week over 4 years was associated with significantly less worsening of cartilage, meniscus, and bone marrow abnormalities (odds ratio range 0.40-0.56, P < 0.05).ConclusionSupplementation with vitamin D over 4 years was associated with significantly less progression of knee joint abnormalities. Given the observational nature of this study, future longitudinal randomized controlled trials of vitamin D supplementation are warranted.

BackgroundKnee osteoarthritis (OA) is more common in females than in males; however, the biological mechanisms for the difference in sex in patients with knee OA are not well understood. Knee shape is associated with OA and with sex, but the patterns of change in the bone's shape over time and their relation to sex and OA are unknown and may help inform how sex is associated with shape and OA and whether the effect is exerted early or later in life.Questions/purposes (1) Does knee shape segregate stably into different groups of trajectories of change (groups of knees that share similar patterns of changes in bone shape over time)? (2) Do females and males have different trajectories of bone shape changes? (3) Is radiographic OA at baseline associated with trajectories of bone shape changes?MethodsWe used data collected from the NIH-funded Osteoarthritis Initiative (OAI) to evaluate a cohort of people aged 45 to 79 years at baseline who had either symptomatic knee OA or were at high risk of having it. The OAI cohort included 4796 participants (58% females; n = 2804) at baseline who either had symptomatic knee OA (defined as having radiographic tibiofemoral knee OA and answering positively to the question "have you had pain, aching or stiffness around the knee on most days for at least one month during the past 12 months") or were at high risk of symptomatic knee OA (defined as having knee symptoms during the prior 12 months along with any of the following: overweight; knee injury; knee surgery other than replacement; family history of total knee replacement for OA; presence of Heberden's nodes; daily knee bending activity) or were part of a small nonexposed subcohort. From these participants, we limited the eligible group to those with radiographs available and read at baseline, 2 years, and 4 years, and randomly selected participants from each OAI subcohort in a manner to enrich representation in the study of the progression and nonexposed subcohorts, which were smaller in number than the OA incidence subcohort. From these patients, we randomly sampled 473 knees with radiographs available at baseline, 2 years, and 4 years. We outlined the shape of the distal femur and proximal tibia on radiographs at all three timepoints using statistical shape modelling. Five modes (each mode represents a particular type of knee bone shape variation) were derived for the proximal tibia and distal femur's shape, accounting for 78% of the total variance in shape. Group-based trajectory modelling (a statistical approach to identify the clusters of participants following a similar progression of change of bone shape over time, that is, trajectory group) was used to identify distinctive patterns of change in the bone shape for each mode. We examined the association of sex and radiographic OA at baseline with the trajectories of each bone shape mode using a multivariable polytomous regression model while adjusting for age, BMI, and race.ResultsKnee bone shape change trajectories segregated stably into different groups. In all modes, three distinct trajectory groups were derived, with the mean posterior probabilities (a measure of an individual's probability of being in a particular group and often used to characterize how well the trajectory model is working to describe the population) ranging from 84% to 99%, indicating excellent model fitting. For most of the modes of both the femur and tibia, the intercepts for the three trajectory groups were different; however, the rates of change were generally similar in each mode. Females and males had different trajectories of bone shape change. For Mode 1 in the femur, females were more likely to be in trajectory Groups 3 (odds ratio 30.2 [95% CI 12.2 to 75.0]; p < 0.001) and 2 than males (OR 4.1 [95% CI 2.3 to 7.1]; p < 0.001); thus, females had increased depth of the intercondylar fossa and broader shaft width relative to epicondylar width compared with males. For Mode 1 in the tibia, females were less likely to be in trajectory Group 2 (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.01) than males (that is, knees of females were less likely to display superior elevation of tibial plateau or decreased shaft width relative to head width). Radiographic OA at baseline was associated with specific shape-change trajectory groups. For Mode 1 in the femur, knees with OA were less likely to be in trajectory Groups 3 (OR 0.4 [95% CI 0.2 to 0.8]; p = 0.008) and 2 (OR 0.6 [95% CI 0.3 to 1.0]; p = 0.03) than knees without OA; thus, knees with OA had decreased depth of the intercondylar fossa and narrower shaft width relative to epicondylar width compared with knees without OA. For Mode 1 in the tibia, knees with OA were not associated with trajectory.ConclusionsThe shapes of the distal femur and proximal tibia did not change much over time. Sex and baseline knee radiographic OA status are associated with the trajectory of change in the bone's shape, suggesting that both may contribute earlier in life to the associations among trajectories observed in older individuals. Future studies might explore sex-related bone shape change earlier in life to help determine when the sex-specific shapes arise and also the degree to which these sex-related shapes are alterable by injury or other events.Level of evidenceLevel III, prognostic study.

ObjectiveTo examine the associations of prevalent arthritis with systemic inflammation in older men and to test whether sleep health mediates the associations.MethodsCross-sectional data came from 2,562 community-dwelling older men (all were age 65 years or older; mean age 76 years) in the Osteoporotic Fractures in Men Study who participated in a sleep ancillary study in 2003-2005. Participants were classified as having osteoarthritis (OA) (24%) or rheumatoid arthritis (RA) (0.7%) based on self-reported diagnoses and medication use. We constructed a composite score of multidimensional sleep health (i.e., perceived sleep quality, sleepiness, frequency of daytime napping, wake after sleep onset, and sleep duration) measured by both self-report and actigraphy. We also created binary indicators of elevated inflammation using C-reactive protein (CRP) (>3 mg/liter) and interleukin-6 (IL-6) (>1.08 pg/ml) levels. Analyses controlled for age, diagnosed sleep disorders, body mass index, smoking status, relevant medication use, and comorbidities.ResultsOlder men with OA did not have higher risk of elevated CRP or IL-6 levels. However, indirect associations of OA through sleep health were found. OA was associated with poorer sleep health, which was further associated with 16% higher odds of elevated CRP (P < 0.001) and 12% higher odds of elevated IL-6 (P < 0.01) levels after controlling for OA. Older men with RA had higher odds of elevated CRP and IL-6 levels, but the associations were not mediated by sleep health.ConclusionFindings suggest that promoting sleep health may help reduce the risk of systemic inflammation in older men with OA.

BackgroundWe examined cross-sectional associations between dietary patterns, macronutrient intake, and measures of muscle mass and lean mass in older men.MethodsParticipants in the Osteoporotic Fractures in Men (MrOS) cohort (n = 903; mean ± SD age 84.2 ± 4 years) completed brief Block food frequency questionnaires (May 2014-May 2016); factor analysis was used to derive dietary patterns. The D3-creatine (D3Cr) dilution method was used to measure muscle mass; dual-energy x-ray absorptiometry (DXA) was used to measure appendicular lean mass (ALM). Generalized linear models were used to report adjusted means of outcomes by dietary pattern. Multiple linear regression models were used to determine associations between macronutrients and D3Cr muscle mass and DXA ALM. Multivariable models were adjusted for age, race, clinic site, education, depression, total energy intake, height, and percent body fat.ResultsGreater adherence to a Western dietary pattern (high factor loadings for red meat, fried foods, and high-fat dairy) was associated with higher D3Cr muscle mass (p-trend = .026). Adherence to the Healthy dietary pattern (high factor loadings for fruit, vegetables, whole grains, and lean meats) was not associated with D3Cr muscle mass or DXA ALM. Total protein (β = 0.09, 95% CI = 0.03, 0.14) and nondairy animal protein (β = 0.16, 95% CI = 0.10, 0.21) were positively associated with D3Cr muscle mass. Nondairy animal protein (β = 0.06, 95% CI = 0.002, 0.11) was positively associated with DXA ALM. Associations with other macronutrients were inconsistent.ConclusionsNondairy animal protein intake (within a Western dietary pattern and alone) was positively associated with D3Cr muscle mass in older men.

BackgroundDeclines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men.MethodsUsing repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.ResultsThe patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.ConclusionsOur description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

Our aim was to determine the association between objectively measured physical activity (PA) and bone strength of the distal limbs among older men. We studied 994 men from the MrOS cohort study (mean age 83.9) who had repeat (Year 7 and 14) 5-day activity assessment with at least 90% wear time (SenseWearPro3 Armband) and Year 14 measures using high resolution peripheral quantitative tomography (HR-pQCT) (Scanco). Total energy expenditure (TEE), total steps per day, peak cadence (mean of top 30 steps/min over 24 h) and time spent in a given level of activity: sedentary (reference,

ObjectivesHyperkyphosis is associated with restricted pulmonary function and posture, potentially contributing to poor sleep. A previous study reported older women with hyperkyphosis had worse self-reported sleep quality, but it is less clear if this association exists in men. We examined the association between hyperkyphosis and subjective and objective sleep quality in a cohort of older men.DesignLongitudinal analysis of data from large cohort of older men participating in the Osteoporotic Fractures in Men Study (MrOS).SettingCommunity.ParticipantsWe studied 754 men participants in MrOS who had kyphosis measured during the 3rd clinic visit (2007-2009) and future subjective and objective sleep quality assessed between 2009-2012 (an average of 2.9 years later).InterventionN/A.MeasurementsTo measure kyphosis, 1.7 cm thick wooden blocks were placed under the participant's head to achieve a neutral spine position while lying supine on a DXA table. We collected data on both subjective (Pittsburgh Sleep Quality Index [PSQI], and Epworth Sleepiness Scale [ESS]) and objective (wrist actigraphy: Total Sleep Time [TST], Wake After Sleep Onset [WASO], Sleep Efficiency [SE], Sleep Onset Latency [SOL]; and polysomnography: Apnea Hypopnea Index [AHI]) sleep measurements. Those who required >3 blocks were considered hyperkyphotic (n = 145 or 19.2%).ResultsIn unadjusted and multivariable analyses, men with hyperkyphosis did not report having worse self-reported sleep characteristics based on PSQI and ESS. Similarly, there were no significant associations between hyperkyphosis and objective sleep measures. When examined as a continuous predictor (blocks ranging from 0-8), results were no different.ConclusionsAlthough we hypothesized that poor posture in those with hyperkyphosis would interfere with sleep, in this sample of older men, worse kyphosis was not associated with self-reported or objectively measured poor sleep quality.

ObjectiveThe association of diabetes mellitus (DM) with increased risk of knee osteoarthritis (OA) is uncertain. We evaluated associations of DM and biomarkers of abnormal glucose metabolism with incident radiographic knee OA, controlling for body mass index (BMI).MethodsParticipants (mean ± SD age 60.6 ± 7.8 years; mean ± SD body mass index [BMI] 29.1 ± 4.9 kg/m2 ) were from the Multicenter Osteoarthritis Study and did not have radiographic knee OA at baseline (Kellgren/Lawrence [K/L] grade

In the randomized, placebo-controlled, double-blind phase 3 ACTIVE study (NCT01343004), 18 months of abaloparatide 80 μg daily (subcutaneous injection) in postmenopausal women at risk of osteoporotic fracture significantly reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and significantly increased bone mineral density (BMD) versus placebo regardless of baseline risk factors. Women from the abaloparatide and placebo groups who completed ACTIVE were eligible for ACTIVExtend (NCT01657162), in which all enrollees received sequential, open-label monotherapy with alendronate 70 mg once weekly for up to 24 months. This prespecified analysis evaluated whether fracture risk reductions and bone mineral density (BMD) gains associated with abaloparatide during ACTIVE persisted through the full 43-month ACTIVE-ACTIVExtend study period in nine prespecified baseline risk subgroups. Baseline risk subgroups included BMD T-score at the lumbar spine, total hip, and femoral neck (≤ - 2.5 versus > - 2.5 and ≤ -3.0 versus > - 3.0), history of nonvertebral fracture (yes/no), prevalent vertebral fracture (yes/no), and age (

AimsThere is an increasing demand for hip arthroplasty in China. We aimed to describe trends in in-hospital mortality after this procedure in China and to examine the potential risk factors.Patients and methodsWe included 210 450 patients undergoing primary hip arthroplasty registered in the Hospital Quality Monitoring System in China between 2013 and 2016. In-hospital mortality after hip arthroplasty and its relation to potential risk factors were assessed using multivariable Poisson regression.ResultsDuring the study period, 626 inpatient deaths occurred within 30 days after hip arthroplasty. Mortality decreased from 2.9% in 2013 to 2.6% in 2016 (p for trend = 0.02). Compared with their counterparts, old age, male sex, and divorced or widowed patients had a higher rate of mortality (all p < 0.05). Risk ratio (RR) for mortality after arthroplasty for fracture was two-fold higher (RR 2.0, 95% confidence interval (CI) 1.5 to 2.6) than that for chronic disease. RRs for mortality were 3.3 (95% CI 2.7 to 3.9) and 8.2 (95% CI 6.5 to 10.4) for patients with Charlson Comorbidity Index (CCI) of 1 to 2 and CCI ≥ 3, respectively, compared with patients with CCI of 0. The rate of mortality varied according to geographical region, the lowest being in the East region (1.8%), followed by Beijing (2.1%), the North (2.9%), South-West (3.6%), South-Central (3.8%), North-East (4.1%), and North-West (5.2%) regions.ConclusionWhile in-hospital mortality after hip arthroplasty in China appears low and declined during the study period, discrepancies in mortality after this procedure exist according to sociodemographic factors. Healthcare resources should be allocated more to underdeveloped regions to further reduce mortality. Cite this article: Bone Joint J 2019;101-B:1209-1217.

BackgroundWhile the gut microbiota is relatively stable through adulthood, its composition is influenced by various host and environmental factors, including changes in health, gastrointestinal processes (e.g., transit time, gastric acidity), medication use, and diet. The association of habitual diet, in the form of a posteriori-derived dietary patterns, and microbiota composition has not been adequately studied, particularly in older men.ObjectiveThe objective was to investigate the association of dietary patterns with the composition and diversity of the gut bacterial microbiota in community-dwelling, older men.MethodsThis cross-sectional study included 517 men who were participants in the Osteoporotic Fractures in Men (MrOS) Study (≥65 y of age at baseline in 2000-2002) and who provided a stool sample and completed an FFQ at MrOS Visit 4 in 2014-2016. Dietary patterns were derived by factor analysis. 16S ribosomal RNA target gene sequencing was performed and taxonomy assignments were derived using the Greengenes database. Linear regression and permutational multivariate analysis of variance (PERMANOVA) considered variations in alpha and beta diversity by dietary pattern, and a model that implements a 0-inflated Gaussian distribution of mean group abundance for each taxa (metagenomeSeq) assessed taxonomic variations by dietary pattern.ResultsIn multivariable-adjusted models, greater adherence to the Western pattern was positively associated with families Mogibacteriaceae and Veillonellaceae and genera Alistipes, Anaerotruncus, CC-115, Collinsella, Coprobacillus, Desulfovibrio, Dorea, Eubacterium, and Ruminococcus, while greater adherence to the prudent pattern was positively associated with order Streptophyta, family Victivallaceae, and genera Cetobacterium, Clostridium, Faecalibacterium, Lachnospira, Paraprevotella, and Veillonella. The relative abundance of the dominant gut bacterial phyla, Bacteroidetes and Firmicutes, did not differ between participants with greater adherence to the Western pattern, compared with those with greater adherence to the prudent pattern. Dietary patterns were not associated with measures of alpha diversity, but beta diversity measures were significantly associated with both Western and prudent patterns.ConclusionsWe observed significant associations between dietary patterns and measures of gut microbial composition in this sample of community-dwelling, older men.

BACKGROUND:To examine the associations between objective physical activity measures and subsequent health care utilization. METHODS:We studied 1,283 men (mean age 79.1 years, SD 5.3) participating in the Osteoporotic Fractures in Men Study. Participants wore a SenseWear® Pro Armband monitor for 1 week. Data was summarized as daily (i) step counts, (ii) total energy expenditure, (iii) active energy expenditure, and (iv) activity time (sedentary, ≥ light, ≥ moderate). The outcome measures of 1-year hospitalizations/duration of stay from Medicare data were analyzed with a two-part hurdle model. Covariates included age, clinical center, body mass index, marital status, depressive symptoms, medical conditions, cognitive function, and prior hospitalization. RESULTS:Each 1 SD = 3,092 step increase in daily step count was associated with a 34% (95% confidence interval [CI]: 19%-46%) lower odds of hospitalization in base model (age and center) and 21% (95% CI: 4%-35%) lower odds of hospitalization in fully adjusted models. Similar but smaller associations held for other physical activity measures, but these associations were not significant in fully adjusted models. Among those hospitalized, higher step count was associated with shorter total duration of acute/postacute care stays in the base model only. There was a fourfold significant difference (from model-based estimates) in predicted care days comparing those with 2,000 versus 10,000 daily steps in the base model, but only a twofold difference (not significant) in the full model. CONCLUSION:Daily step count is an easily determined measure of physical activity that may be useful in assessment of future health care burden in older men.

BackgroundKnee bone shape differs between men and women and the incidence of knee osteoarthritis (OA) is higher in women than in men. Therefore, the purpose of the present study was to determine whether the observed difference in the incidence of knee radiographic OA (ROA) between men and women is mediated by bone shape.MethodsWe randomly sampled 304 knees from the OAI with incident ROA (i.e., development of Kellgren/Lawrence grade ≥ 2 by month 48) and 304 knees without incident ROA. We characterized distal femur and proximal tibia shape on baseline radiographs using Statistical Shape Modeling. If a specific bone shape was associated with the risk of incident ROA, marginal structural models were generated to assess the mediation effect of that bone shape on the relation of sex and risk of incident knee ROA adjusting for baseline covariates.ResultsCase and control participants were similar by age, sex and race, but case knees were from higher body mass index (BMI) participants (29.4 vs. 27.0; p

OBJECTIVE:To examine rest-activity circadian rhythm (RAR) and cognitive decline in older men. DESIGN:Longitudinal. SETTING:Osteoporotic Fractures in Men (MrOS) and ancillary Outcomes of Sleep Disorders in Men (MrOS Sleep) studies. PARTICIPANTS:MrOS and MrOS Sleep participants (N=2,754; mean age 76.0 ± 5.3). MEASUREMENTS:The Modified Mini-Mental State examination (3MS) was used to assess cognition at baseline (2003-05) and follow-up examinations (2005-06 and 2007-09). Wrist actigraphy was used to measure 24-hour activity counts at baseline. RAR variables included amplitude (strength of activity rhythm), mesor (mean activity level), pseudo F-statistic (overall circadian rhythm robustness), and acrophase (time of daily peak activity). RESULTS:After an average of 3.4 ± 0.5 years, men with lower amplitudes, mesors, and pseudo F-statistics had greater decline in 3MS performance (amplitude: -0.7 points Q1 vs -0.5 points Q4, p

ObjectiveStudies suggest that persons with a leg length inequality (LLI) of ≥2 cm have an increased risk of developing knee osteoarthritis (OA) in that limb. The present study was undertaken to examine whether LLI also confers an increased risk of hip OA.MethodsUsing long limb radiographs from subjects in the Multicenter Arthritis Study (MOST) and the Osteoarthritis Initiative (OAI), we measured LLI and scored hip radiographs that were obtained at baseline and 3-5-year follow-up. The associations of LLI of ≥1 cm and LLI of ≥2 cm with radiographic hip OA were examined cross-sectionally and longitudinally, assessing risk in shorter limbs and longer limbs compared to limbs from subjects with no LLI. We carried out logistic regression analyses with generalized estimating equations and adjusted for age, sex, body mass index, height, and cohort of origin.ResultsThere were 1,966 subjects from the MOST and 2,627 subjects from the OAI. Twelve percent had LLI of ≥1 cm and 1% had LLI of ≥2 cm. For LLI ≥1 cm, the adjusted odds ratio for prevalent hip OA in the shorter leg was 1.47 (95% confidence interval [95% CI] 1.07-2.02) and for LLI ≥2 cm, it was 2.15 (95% CI 0.87-5.34). For LLI ≥1 cm, the odds of incident hip OA in the shorter leg were 1.39 (95% CI 0.81-2.39) while for LLI ≥2 cm, they were 4.20 (95% CI 1.26-14.03). We found no increased risk of hip OA in longer limbs.ConclusionOur findings suggest that, as with knee OA, legs that are at least 2 cm shorter than the contralateral leg are at increased risk of hip OA.

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.

We proposed the term "dysmobility syndrome" (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height2 30%, spine or hip T-score ≤ -2.5, grip strength

Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n = 3591 placebo, n = 3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p

BackgroundOsteoarthritis (OA), a multifactorial disease causing joint degeneration, often leads to severe disability. The rising rates of disability highlight the need for implementing preventative measures at early stages of the disease, which would especially benefit subjects at high risk for OA development.PurposeTo develop a risk prediction tool for moderate-severe OA (TOARP) over 8 years based on subject characteristics, knee radiographs, and MRI data at baseline using data from the Osteoarthritis Initiative (OAI).Study typeRetrospective.Subjects641 subjects with no/mild radiographic OA (Kellgren-Lawrence [KL] 0-2) and no clinically significant symptoms (Western Ontario and McMaster Universities Arthritis Index [WOMAC] 0-1) were selected from the OAI.Field strength/sequenceMR images were obtained using 3.0T.AssessmentCompartment-specific cartilage and meniscus morphology and cartilage T2 were assessed. Baseline subject demographics, risk factors, KL score, cartilage WORMS score, presence of meniscus tear, and cartilage T2 were used to predict the development of moderate/severe OA (KL = 3-4 or WOMAC pain ≥5 or total knee replacement [TKR]) over 8 years.Statistical testsBest subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA.ResultsModel 1 included KL score, previous knee injury in the last 12 months, age, gender, and BMI. Model 2 included all variables in Model 1 plus presence of cartilage defects in the lateral femur and patella, and presence of a meniscal tear. Model 3 included all variables in Models 1 and 2, plus cartilage T2 in the medial tibia and medial femur. Compared to Model 1 (cross-validated AUC = 0.67), Model 3 performed significantly better (AUC = 0.72, P = 0.04), while Model 2 showed a statistical trend (AUC = 0.71, P = 0.08).Data conclusionWe established a risk calculator for the development of moderate/severe knee OA over 8 years that includes radiographic and MRI data. The inclusion of MRI-based morphological abnormalities and cartilage T2 significantly improved model performance.Level of evidence2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526.

BackgroundAccumulating evidence supports the neuroprotective effects of bioactive compounds from tea leaves. There are limited data from black tea consumption populations.ObjectiveTo determine whether black tea consumption is associated with cognitive decline among older men.MethodsWe chose to study the association between black tea consumption and cognition using data from the Osteoporotic Fractures in Men (MrOS) cohort, which collected information on tea consumption at baseline and has repeatedly assessed cognitive function in 3,844 men aged 65+ years (mean = 72.4 years). We defined tea drinkers as those who drank black tea at least once per week and further grouped them into weekly drinkers and daily drinkers. Cognitive function was assessed at baseline and approximately 7 years later using the Modified Mini-Mental State Examination (3MSE). Multivariable logistic regression and linear regression models were constructed to assess the association between black tea consumption and risk of fast cognitive decline as a binary variable and change in 3MSE scores as continuous variable. Fast cognitive decline was defined as decline in 3MSE >1.5 standard deviation of mean change score. Models were adjusted for age, education level, and baseline cognitive scores.ResultsWeekly and daily black tea drinkers were 24.8% and 12.4% of the study cohort, respectively. Fast cognitive decline occurred in 243 (6.3%) participants. Tea consumption was not associated with risk of cognitive decline, nor was tea associated with cognitive decline measured by absolute change in 3MSE scores.ConclusionsThere was no association of black tea consumption and cognitive decline among older men in the US.

BACKGROUND:Hyperkyphosis, an excessive anterior curvature in the thoracic spine, is associated with reduced health status in older adults. Hyperkyphosis is highly prevalent, more common in older women than men. There is no standard intervention to reduce age-related hyperkyphosis. Sex differences in response to a kyphosis-specific exercise intervention are not known. METHODS:We conducted a randomized controlled trial of a targeted kyphosis-specific exercise and postural training program on the primary outcome Cobb angle of kyphosis, and investigated whether the magnitude of change differed between men and women. One hundred twelve participants aged ≥60 years with kyphosis ≥40° were enrolled and randomized to exercise or waitlist control, and 101 participants had analyzable baseline and follow-up radiographs for Cobb angle measurements. A group intervention including 10 participants per group was delivered by a physical therapist, 1-h, twice a week for 3-months. Controls were placed on a waitlist for 3 months before receiving a delayed intervention. Primary outcome was change from baseline to 3-months in Cobb angle measured from standing lateral spine radiographs. Secondary outcomes included change over 3-months in kyphometer-measured kyphosis, physical function and quality of life. Groups were combined for analysis after both received the intervention, and sex differences in response to the intervention were tested with ANOVA. RESULTS:Participants (60 women, 41 men) were 70.0 (SD = 5.7) years old with mean Cobb angle 55.9 (SD = 12.2) degrees at baseline. The active group had higher baseline modified Physical Performance Test scores than control, p = 0.03. Men had greater baseline kyphometer-measured kyphosis, p = 0.09, and higher bone mineral density (BMD), spine strength, more vertebral fractures and diffuse idiopathic skeletal hyperostosis (DISH) than women, p ≤ 0.01. There was no statistically significant difference between groups in change in Cobb at 3-months, p = 0.09, however change in kyphometer-measured kyphosis differed by 4.8 (95% CI:-6.8,-2.7) degrees, p  0.1. CONCLUSIONS:A 3-month targeted spine strengthening exercise and posture training program reduced kyphometer-measured, but not radiographic-measured kyphosis. Despite sex differences in baseline kyphosis, BMD, spine strength, fractures and DISH, sex did not affect treatment response. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01766674.

Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and three externally generated fracture risk tools had similar accuracy to identify older men who developed osteoporotic fractures. Risk tools with femoral neck BMD performed better than those without BMD. The externally developed risk tools were poorly calibrated.IntroductionWe compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality.MethodsA comparative ROC curve analysis assessed the ability of the QFracture, FRAX® and Garvan fracture risk tools, and femoral neck bone mineral density (BMD) T score with or without age to identify incident fracture in community-dwelling men aged 65 years or older (N = 4994) without hip or clinical vertebral fracture or antifracture treatment at baseline.ResultsAmong risk tools calculated with BMD, the discriminative ability to identify men with incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC 0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI 0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73), FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67, 0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk scores calculated with BMD compared with QFracture (P

ObjectivesTo describe the natural history of frailty transitions in a large cohort of community-dwelling older men and identify predictors associated with progression to or improvement from states of greater frailty.DesignProspective cohort study.SettingSix U.S. sites.ParticipantsCommunity-dwelling men aged 65 and older (N = 5,086).MeasurementsFrailty was measured at baseline and an average of 4.6 years later. Frailty was defined as having three or more of the following components (low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed); prefrailty was defined as having one or two components. Separate multivariable logistic regression models were analyzed for progression and improvement in frailty status.ResultsOf the 5,086 men, 8% were frail, 46% were prefrail, and 46% were robust at baseline. Between baseline and follow-up, 35% progressed in frailty status or died, 56% had no change in frailty status, and 15% of prefrail or frail participants improved, although only 0.5% improved across two levels, from frail to robust. In multivariable models, factors associated with improvement in frailty status included greater leg power, being married, and good or excellent self-reported health, whereas presence of any instrumental activity of daily living (IADL) limitations, low albumin levels, high interleukin-6 levels, and presence of chronic obstructive pulmonary disease or diabetes mellitus were associated with lower likelihood of improvement in frailty status.ConclusionImprovement in frailty status was possible in this cohort of community-dwelling older men, but improvement from frail to robust was rare. Several predictors were identified as possible targets for intervention, including prevention and management of comorbid medical conditions, prevention of IADL disability, physical exercise, and nutritional and social support.

Prior data in women suggest that incident clinically undiagnosed radiographic vertebral fractures (VFs) often are symptomatic, but misclassification of incident clinical VF may have biased these estimates. There are no comparable data in men. To evaluate the association of incident clinically undiagnosed radiographic VF with back pain symptoms and associated activity limitations, we used data from the Osteoporotic Fractures in Men (MrOS) Study, a prospective cohort study of community-dwelling men aged ≥65 years. A total of 4396 men completed spine X-rays and symptom questionnaires at baseline and visit 2, about 4.6 years later. Incident clinical VFs during this interval were defined by self-reported clinical diagnosis plus community imaging showing a centrally adjudicated ≥1 increase in semiquantitative (SQ) grade in any thoracic or lumbar vertebra versus baseline study X-rays. Incident radiographic VFs (≥1 increase in SQ grade between baseline and visit 2 study X-rays) were categorized as radiographic-only (not clinically diagnosed) or radiographic plus clinical (also clinically diagnosed). Multivariable-adjusted log binomial regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs). Men with incident radiographic plus clinical VF were most likely to have back pain symptoms and associated activity limitation at follow-up. However, versus men without incident VF, those with incident radiographic-only VF also were significantly more likely at follow-up to report any back pain (70% versus 59%; PR, 1.2 [95% CI, 1.1 to 1.3]), severe back pain (8% versus 4%; PR, 1.9 [95% CI, 1.1 to 3.3]), bother from back pain most/all the time (22% versus 13%; PR, 1.7 [95% CI, 1.3 to 2.2]), and limited usual activity from back pain (34% versus 18%; PR, 1.9 [95% CI, 1.5 to 2.4]). Clinically undiagnosed, incident radiographic VFs were associated with an increased likelihood of back pain symptoms and associated activity limitation. Results suggest incident radiographic-only VFs often were symptomatic, and were associated with both new and worsening back pain. Preventing these fractures may reduce back pain and related disability in older men. © 2017 American Society for Bone and Mineral Research.