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Background: 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.Methods: 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 Results: mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2: 0.0%]; SDOC [2.75 (2.28, 3.31), I2: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2: 58.3%].Conclusions: there was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.

Supplemental Material for Perceived Neighborhood Characteristics and Later-Life Pain Outcomes: Evidence From the Health and Retirement Study by Yulin Yang, Kendra D. Sims, Nancy E. Lane, Kate A. Duchowny, and Jacqueline M. Torres in Journal of Aging and Health

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.

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.

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 vs. muscle fat to adverse outcomes have been unclear.MethodsIn a large cohort of older men (N= 1017), we measured muscle mass (D3 creatine dilution), muscle density (high resolution peripheral 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% CI: 0.74, 0.70), 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.

BackgroundAdipose tissue has recently gained interest as an independent imaging biomarker for osteoarthritis.PurposeTo explore 1) cross-sectional associations between local subcutaneous fat (SCF) thickness at the knee and the extent of degenerative changes in overweight and obese individuals and 2) associations between local fat distribution and progression of osteoarthritis over 4 years.Study typeRetrospective cohort study.Population338 obese and overweight participants from the Osteoarthritis Initiative cohort without radiographic evidence of osteoarthritis.Field strength3T: 3D-FLASH-WE; 3D-DESS-WE; T1w-SE; MSME.AssessmentBaseline SCF thickness was measured in standardized locations medial, lateral and anterior to the knee and the average joint-adjacent SCF (ajSCF) was calculated. Right thigh SCF cross-sectional area was assessed. Quantitative cartilage T2 relaxation times and semi-quantitative whole organ MRI scores (WORMS) were obtained at baseline and 4-year follow-up. WORMSsum was calculated as sum of cartilage, bone marrow edema, subchondral cyst, and meniscal scores.Statistical testsAssociations of SCF measures with baseline, and 4-year change in T2 and WORMS were analyzed using regression models. SCF measurements were standardized using the equation ValueParticipant-MeanCohortStandard deviation . Analyses were adjusted for age, sex, physical activity, and BMI.ResultsCross-sectionally, significant associations between lateral SCF, lateral compartment WORMS and T2 were found ( ΔWORMSsum1SDchange in lateralSCF , [95% CI]: 0.53, [0.12-0.95], P

Nerve growth factor (NGF) is a neurotrophin that mediates pain sensitization in pathologic states, including osteoarthritis. In clinical trials, antibodies to NGF reduce pain and improve physical function due to osteoarthritis of the knee or hip and have a long duration of action. Rapidly progressive osteoarthritis is a dose-dependent adverse event with these agents, and additional joint safety signals, such as subchondral insufficiency fractures and increased rates of total joint replacement, are reported. The effects on pain and potential mechanisms behind these joint events both are of considerable importance in the consideration of future use of anti-NGF therapies for osteoarthritis.

Background Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years. Methods Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0–96) and subscores for cartilage (0–36), menisci (0–24), and bone marrow abnormalities and subchondral cyst-like lesions (0–18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0–100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade. Results Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8]

BACKGROUND. The extent of medial meniscal extrusion (MME) that is associated with structural and symptomatic progression of knee osteoarthritis has not been defined yet. OBJECTIVE. The purpose of our study was to investigate MRI-based thresholds of MME that are associated with structural progression of knee degenerative disease and symptoms over a period of 4 years. METHODS. We studied 328 knees of 235 participants that were randomly selected from the Osteoarthritis Initiative cohort. MME was quantified on coronal sections of intermediate-weighted MRI sequences obtained at 3 T. Knee pain and cartilage abnormalities were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and the cartilage whole-organ MRI score (WORMS). General estimating equations with logistic regression models were used to correlate baseline MME and changes in pain (WOMAC) and cartilage damage (WORMS). ROC analyses were performed to determine the area under the ROC curve (AUROC). Individual thresholds were determined by maximizing the product of sensitivity and specificity. RESULTS. The AUROC for predicting progression of knee pain, medial compartment cartilage damage, and medial tibial cartilage damage were 0.71, 0.70, and 0.72, respectively, and the individual thresholds for MME were 2.5, 2.7, and 2.8 mm. A single threshold of 2.5 mm was determined by maximizing the mean of the product of sensitivity and specificity of the three outcome variables (knee pain progression, medial compartmental cartilage damage progression, and medial tibial cartilage damage progression). CONCLUSION. MME was associated with knee pain and cartilage damage progression over 4 years. A single threshold of 2.5 mm was found to be the most useful threshold for predicting knee pain, medial compartment cartilage damage progression, and tibial cartilage damage progression over 4 years. CLINICAL IMPACT. This threshold could be used to standardize the diagnostic criterion of extrusion and to better characterize the risk for subsequent structural and symptomatic progression of knee osteoarthritis.

In the version of this article initially published, NIAMS grant R01AR061445 was not included in the Acknowledgements. The error has been corrected in the HTML and PDF versions of the article.

Glucocorticoids increase bone fragility in patients in a manner that is underestimated by bone mass measurement. This study aimed to determine if the adult mouse could model this bone strength/bone mass discrepancy. Forty-two 13-week-old BALB/cJ mice were randomized into vehicle and glucocorticoid groups, implanted with vehicle or 6-methylprednisolone pellets, and necropsied after 60 and 120 days. Bone strength and bone mass/microarchitecture were assessed at the right central femur (CF; cortical-bone-rich) and sixth lumbar vertebral body (LVB6; trabecular-bone-rich). Bound water (BW) of the whole right femur was analyzed by proton-nuclear magnetic resonance (1H-NMR) relaxometry. Data were analyzed by two-factor ANOVA with time (day 60 and day 120) and treatment (vehicle and glucocorticoid) as main effects for all data. Significant interactions were further analyzed with a Tukey's post hoc test. Most bone strength measures in the CF were lower in the glucocorticoid group, regardless of the duration of treatment, with no time × treatment interaction. However, bone mass measures in the CF showed a significant time × treatment interaction (p = 0.0001). Bone strength measures in LVB6 showed a time × treatment interaction (p

Additional file 2:. Age and sex adjusted mean change pre/post intervention in outcome measures in the HFG, LFG with confidence intervals (CI).

Additional file 1:. Age-adjusted mean change pre/post intervention in outcome measures in the HFG, LFG with confidence intervals (CI).

Additional file 3:. Numeric Results for Comparing Mean Change in a Repeated Measures Design – Sample size estimation to determine change in Short Physical Performance Battery (SPPB) in a low functioning cohort after a kyphosis intervention.

ObjectiveThis work aims to study (i) the relationship between body mass index (BMI) and knee synovial inflammation using non-contrast-enhanced MRI and (ii) the association of synovial inflammation versus degenerative abnormalities and pain.Materials and methodsSubjects with risk for and mild to moderate radiographic osteoarthritis were selected from the Osteoarthritis Initiative. Subjects were grouped into three BMI categories with 87 subjects per group: normal weight (BMI, 20-24.9kg/m2), overweight (BMI, 25-29.9kg/m2), and obese (BMI, ≥ 30kg/m2), frequency matched for age, sex, race, Kellgren-Lawrence grade, and history of knee surgery and injury. Semi-quantitative synovial inflammation imaging biomarkers were obtained including effusion-synovitis, size and intensity of infrapatellar fat pad signal abnormality, and synovial proliferation score. Cartilage composition was measured using T2 relaxation time and structural abnormalities using the whole-organ magnetic resonance imaging score (WORMS). The Western Ontario and McMasters (WOMAC) Osteoarthritis Index was used for pain assessment. Intra- and inter-reader reproducibility was assessed by kappa values.ResultsOverweight and obese groups had higher prevalence and severity of all synovial inflammatory markers (p ≤ 0.03). Positive associations were found between synovial inflammation imaging biomarkers and average T2 values, WORMS maximum scores and total WOMAC pain scores (p

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.

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.

Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

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 30steps/min over 24h) and time spent in a given level of activity: sedentary (reference

Anti-resorptive and anabolic treatments can be used sequentially to treat osteoporosis, but their effects on bone composition are incompletely understood. Osteocytes may influence bone tissue composition with sequential therapies because bisphosphonates diffuse into the canalicular network and anabolic treatments increase osteocyte lacunar size. Cortical bone composition of osteopenic, ovariectomized (OVX) rats was compared to that of Sham-operated rats and OVX rats given monotherapy or sequential regimens of single approved anti-osteoporosis medications. Adult female Sprague-Dawley rats were OVX (N = 37) or Sham-OVXd (N = 6). After 2months, seven groups of OVX rats were given three consecutive 3-month periods of treatment with vehicle (V), h-PTH (1-34) (P), alendronate (A), or raloxifene (R), using the following orders: VVV, PVV, RRR, RPR, AAA, AVA, and APA. Compositional properties around osteocyte lacunae of the left tibial cortex were assessed from Raman spectra in perilacunar and non-perilacunar bone matrix regions. Sequential treatments involving parathyroid hormone (PTH) caused lower mean collagen maturity relative to monotherapies. Mean mineral:matrix ratio was 2.2% greater, mean collagen maturity was 1.4% greater, and mean carbonate:phosphate ratio was 2.2% lower in the perilacunar than in the non-perilacunar bone matrix region (all P

Author(s): Kaufmann, Christopher N; Shen, Jian; Woods, Gina N; Lane, Nancy E; Stone, Katie L; Kado, Deborah M; Osteoporotic Fractures in Men (MrOS) Study Research Group | Abstract: 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 g3 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

Additional file 7: Table S1. Characteristics of participants by joint trajectories in total hip BMD and walking speed in older men. Table S2. Characteristics of participants by joint trajectories in ALM/ht2 and total hip BMD in older men. Table S3. Characteristics of participants by joint trajectories in grip strength and walking speed in older men. Table S4. Characteristics of participants by joint trajectories in grip strength and ALM/ht2 in older men. Table S5. Characteristics of participants by joint trajectories in walking speed and ALM/ht2 in older men.

ObjectiveTo analyze structural, longitudinal MRI findings during the development of accelerated knee osteoarthritis (AKOA) over 4years.Materials and methodsFrom the Osteoarthritis Initiative (OAI), knees with no radiographic osteoarthritis (KL 0/1) developing advanced-stage osteoarthritis (KL 3/4; AKOA) within a 4-year (y) timeframe were selected. MRIs were graded using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) at the beginning of the 4-year timeframe (index visit), at 2-year, and 4-year follow-up. Morphological and clinical findings associated with KL 3/4 onset within 2years compared to 4years were assessed using generalized estimating equations.ResultsAKOA was found in 162 knees of 149 subjects (age 63.25 ± 8.3; 103 females; BMI 29.4 ± 3.9). Moderate to severe meniscal lesions WORMS ≥3 were present in 25% (41/162) at the index visit, 64% (104/162) at 2-year and 93% (151/162) at 4-year follow-up. Meniscal extrusion was the most prevalent finding (ranging from 18% at the index visit, 45% at 2-year and 94% at 4-year follow-up) and root tears were the most common types of tears (9% at the index visit; 22% at 2years and 38% at 4years). Risk factors associated with KL 3/4 onset within 2years included root tears at the index visit (adjusted OR, 2.82; 95% CI: 1.33, 6.00; p = 0.007) and incident knee injury (42%, 49/116 vs. 24%, 11/46, p = 0.032).ConclusionsMeniscal abnormalities, in particular extrusion and root tears, were the most prevalent morphological features found in subjects with AKOA. These results suggest that meniscal abnormalities have a significant role in accelerated progression of OA.

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.

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

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

BACKGROUND: Disrupted rest-activity rhythms (RAR) have been associated with incident dementia and mild cognitive impairment (MCI) in older women; no longitudinal studies have examined RAR and cognitive decline in older men. METHODS: We used data from the Osteoporotic Fractures in Men (MrOS) and ancillary Outcomes of Sleep Disorders in Men (MrOS Sleep) studies (n=2754; mean age 76.0 ± 5.3 years). The Modified Mini-Mental State examination (3MS) was used to assess cognition at baseline (2003–05) and follow-up exams (2005–06 and 2007–09). Wrist actigraphy was used to measure 24-hour activity counts at baseline. RAR variables included amplitude (strength of the 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, mesor and pseudo F-statistic showed greater decline in 3MS performance (amplitude: −0.7 point Q1 vs. −0.5 point Q4, p

© 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. 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 < 0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

© 2017 International Society for Magnetic Resonance in Medicine Background: Osteoarthritis (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. Purpose: To 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 Type: Retrospective. Subjects: 641 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/Sequence: MR images were obtained using 3.0T. Assessment: Compartment-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 Tests: Best subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA. Results: Model 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 Conclusion: We 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 Evidence: 2. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2018;47:1517–1526.

Background:Disrupted rest-activity circadian rhythm (RAR) patterns have been associated with poor health outcomes (i.e. diminished cognitive function, increased risk of dementia and falls). Circadian time cues in bone influence the differentiation of osteoblasts and osteoclasts, and bone turnover markers exhibit circadian variation; relationships between bone outcomes and RAR are emerging areas of research. We evaluated associations between RAR and areal bone mineral density (aBMD) at the total hip and femoral neck in older men from the Osteoporotic Fractures in Men (MrOS) cohort. We hypothesized that weaker RAR patterns would be associated with lower aBMD. Methods:MrOS is an ongoing prospective cohort study following ambulatory men ≥65years (n=5994) at 6 U.S. clinics (baseline enrollment 3/2000-4/2002); participants for this analysis are from an ancillary study, Outcomes of Sleep Disorders in Older Men (MrOS Sleep). We included data from men who had technically adequate measures of RAR and aBMD at Sleep Visit 1 (12/2003-3/2005), with repeat aBMD at core Visit 3 (3/2007-3/2009) (n=2412; mean age at Sleep Visit 1: 75.7±5.2years). aBMD was measured by dual energy x-ray absorptiometry (DXA). Actigraphs worn on the non-dominant wrist were used to collect circadian activity data over 4.8±0.8 consecutive 24-hour periods. An extension of the traditional cosine curve was used to fit RAR to the activity data [Ancoli-Israel et al., 2003; Marler et al., 2006]. Six RAR parameters were evaluated: acrophase (time of peak activity), amplitude (rhythm strength), mesor (mean of activity fitted curve), pseudo F-statistic (overall circadian rhythmicity of rest and activity), alpha statistic (daytime to nighttime activity ratio), and beta statistic (daytime activity). Associations between RAR and aBMD (Sleep Visit 1), and RAR and ΔaBMD (Sleep Visit 1-Visit 3) were assessed with generalized linear models. Covariates included age, clinic site, physical activity, race, comorbidity, body mass index (BMI), smoking, alcohol, caffeine, beta blocker use, serum 25(OH) vitamin D and urinary melatonin and calcium. Results:Pseudo F-statistic was significantly associated with total hip aBMD (p-trend=0.009), femoral neck aBMD (p-trend=0.007) and total hip ΔaBMD (p-trend=0.017) in minimally adjusted models but not after multivariate (MV) adjustment. Alpha statistic was significantly associated with femoral neck aBMD (p-trend=0.029) and femoral neck ΔaBMD (p-trend=0.019) in minimally adjusted models; significance was retained in the femoral neck ΔaBMD model (p-trend=0.034) after MV adjustment. There were no consistent, significant associations between the other RAR variables and aBMD or ΔaBMD. Conclusions:The data demonstrate modest associations between overall circadian rhythmicity of rest and activity (measured by pseudo F-statistic), as well as daytime to nighttime activity ratio (measured by alpha statistic), aBMD and ΔaBMD, but adjustment for covariates related to lifestyle, BMI and comorbidities attenuated most of these associations. These results suggest that RAR patterns are not independently associated with aBMD or four-year ΔaBMD at the total hip or femoral neck in older men, but additional research is needed.

OBJECTIVE: Statistical shape modeling (SSM) of radiographs has been used to explore relationships between altered joint shape and hip osteoarthritis (OA). We aimed to apply SSM to Dual-energy X-ray Absorptiometry (DXA) hip scans, and examine associations between resultant hip shape modes (HSMs), radiographic hip OA (RHOA), and hip pain, in a large population based cohort.METHOD: SSM was performed on baseline hip DXA scans from the Osteoporotic Fractures in Men (MrOS) Study. Associations between the top ten HSMs, and prevalent RHOA from pelvic radiographs obtained 4.6 years later, were analysed in 4100 participants. RHOA was defined as Croft score ≥ 2. Hip pain was based on pain on walking, hip pain on examination, and Western Ontario and McMaster Universities Arthritis Index (WOMAC).RESULTS: The five HSMs associated with RHOA showed features of either pincer- or cam-type deformities. HSM 1 (increased pincer-type deformity) was positively associated with RHOA [1.23 (1.09,1.39)] [odds ratio and 95% CI]. HSM 8 (reduced pincer-type deformity) was inversely associated with RHOA [0.79 (0.70,0.89)]. HSM 10 (increased cam-type deformity) was positively associated with RHOA [1.21 (1.07,1.37)]. HSM 3 and HSM 4 (reduced cam-type deformity) were inversely associated with RHOA [0.73 (0.65,0.83) and 0.82 (0.73,0.93) respectively]. HSM 3 was inversely related to pain on examination [0.84 (0.76,0.92)] and walking [0.88, (0.81,0.95)], and to WOMAC score [0.87 (0.80,0.93)].CONCLUSIONS: DXA-derived measures of hip shape are associated with RHOA, and to a lesser extent hip pain, possibly reflecting their role in the pathogenesis of hip OA.

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.

© 2017 American Society for Bone and Mineral Research 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.

Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual-energy X-ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm2); expected loss (n = 2768; change between 0 g/cm2 and -0.034 g/cm2]); and accelerated loss (n = 545; change 1 SD below mean change or worse [≤-0.034 g/cm2]). Multivariate proportional hazards models adjusted for potential confounders estimated the risk of all-cause mortality over 8.1 ± 2.8 years following visit 2. Mortality was centrally adjudicated by physician review of death certificates. At visit 1, mean age was 72.9 ± 5.5 years. Men who maintained BMD were less likely to die during the subsequent follow-up period (33.7%) than men who had accelerated BMD loss (60.6%) (p < 0.001). Compared to men who had maintained BMD, those who had accelerated BMD loss had a 44% greater risk of mortality in multivariate-adjusted models (HR, 1.44; 95% CI, 1.23 to 1.68). Compared to men who had maintained BMD, there was no significant difference in mortality risk for men with expected loss of BMD (36.9% died) (multivariate HR, 1.00; 95% CI, 0.89 to 1.13). Further adjustment for visit 1 or visit 2 BMD measurement did not substantially alter these associations. Results for total hip BMD were similar. In conclusion, accelerated loss of BMD at the hip is a risk factor for mortality in men that is not explained by comorbidity burden, concurrent change in weight, or physical activity.

Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual-energy X-ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm2); expected loss (n = 2768; change between 0 g/cm2 and −0.034 g/cm2]); and accelerated loss (n = 545; change 1 SD below mean change or worse [≤−0.034 g/cm2]). Multivariate proportional hazards models adjusted for potential confounders estimated the risk of all-cause mortality over 8.1 ± 2.8 years following visit 2. Mortality was centrally adjudicated by physician review of death certificates. At visit 1, mean age was 72.9 ± 5.5 years. Men who maintained BMD were less likely to die during the subsequent follow-up period (33.7%) than men who had accelerated BMD loss (60.6%) (p < 0.001). Compared to men who had maintained BMD, those who had accelerated BMD loss had a 44% greater risk of mortality in multivariate-adjusted models (HR, 1.44; 95% CI, 1.23 to 1.68). Compared to men who had maintained BMD, there was no significant difference in mortality risk for men with expected loss of BMD (36.9% died) (multivariate HR, 1.00; 95% CI, 0.89 to 1.13). Further adjustment for visit 1 or visit 2 BMD measurement did not substantially alter these associations. Results for total hip BMD were similar. In conclusion, accelerated loss of BMD at the hip is a risk factor for mortality in men that is not explained by comorbidity burden, concurrent change in weight, or physical activity.

Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥0 g/cm2 , n = 453); expected loss (estimated change 0 to 1 SD below the estimated mean change, -0.034 g/cm2 for femoral neck, n = 1184); and accelerated loss (estimated change ≥1 SD below mean change, n = 237). Differential abundance values of 3946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss versus maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥1.1 or ≤0.9 (p

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual-energy X-ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow-up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41-fold (95% confidence interval [CI] 1.23 to 1.63) higher aged-adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age-adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m2 ; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI. © 2017 American Society for Bone and Mineral Research.

© 2016 American Society for Bone and Mineral Research Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow-up, 20.0% of men had an incident clinical fracture. In multivariate-adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate-adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR

Visceral adipose tissue (VAT) measured by computed tomography (CT) is related to insulin resistance, lipids, and serum inflammatory markers. Our objective was to compare the strength of the associations of VAT measured using dual-energy X-ray absorptiometry (DXA-VAT) and CT (CT-VAT) with insulin resistance, serum lipids, and serum markers of inflammation. For 1117 men aged 65 and older enrolled in the Osteoporotic Fractures in Men Study, the cross-sectional associations of DXA-VAT and CT-VAT with homeostasis model assessment of insulin resistance (homa2ir), C-reactive protein, and high-density lipoprotein (HDL) cholesterol were estimated with regression models and compared using a Hausman test. Adjusted for age and body mass index, DXA-VAT was moderately associated with homa2ir (effect size 0.38, 95% confidence interval [CI]: 0.28-0.47) and modestly associated with HDL cholesterol (DXA effect size -0.29, 95% CI: -0.38 to -0.21). These associations were significantly greater than those for CT-VAT with homa2ir (0.30, 95% CI: 0.24-0.37; p value for effect size difference 0.03) and CT-VAT with HDL cholesterol (-0.22, 95% CI: -0.29 to -0.15; p value for difference 0.005). Neither DXA-VAT nor CT-VAT was associated with C-reactive protein after adjustment for age and body mass index (DXA-VAT effect size 0.14, 95% CI: -0.04 to 0.32; CT-VAT effect size 0.08, 95% CI: -0.08 to 0.25; p value for difference 0.35). DXA-VAT has similar or greater associations with insulin resistance and HDL cholesterol as does CT-VAT in older men, confirming the concurrent validity of DXA-VAT. Investigations of how well DXA measurements of VAT predict incident cardiovascular disease events are warranted.

© 2016 Jungmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Anterior cruciate ligaments (ACL) injuries represent a major risk factor for early osteoarthritis (OA). Purpose: To evaluate the prevalence and 4-year progression of knee OA measured with 3T MR-imaging in individuals with ruptured, reconstructed or normal ACL and to assess the impact of thigh muscle characteristics. Methods: A total of 54 knees (23/54 male, 31/54 female) were recruited from the Osteoarthritis Initiative (OAI). At baseline, 15/54 subjects had prevalent ACL ruptures and 15/54 subjects had prevalent ACL reconstruction (24/54 normal ACL). Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores, Physical Activity Scores of the Elderly (PASE) and thigh muscle characteristics including strength, fat infiltration (Goutallier score) and thigh muscle cross-sectional area (CSA) MR measurements were obtained at baseline. Wholeorgan MR-imaging Scores (WORMS) were obtained at baseline and at a 4-year follow-up time-point. Multivariate regression models, adjusting for covariates (age, gender, body mass index), were used for statistical analysis. Results: At baseline, subjects with prevalent ACL ruptures had worse WORMS total scores (mean ±SEM, 44.1±3.5) than subjects with ACL reconstruction (30.8±4.0; P = 0.015) and worse than subjects with normal ACL (21.3±3.0; P

BackgroundStrong evidence implicates inflammation in the development of atherosclerotic heart disease but less is known about peripheral arterial disease (PAD). Our objective was to test the hypothesis that a composite index of inflammatory burden is associated with PAD.MethodsCross-sectional analysis of a randomly-selected group of 903 community-dwelling men in the MrOS cohort recruited between 2000 and 2002. Using blood samples, we measured seven cytokines and related these levels to prevalent PAD (ankle-brachial index (ABI)