Functional decline after incident wrist fractures—Study of Osteoporotic Fractures: prospective cohort study

Objective To study the effect of an incident wrist fracture on functional status in women enrolled in the Study of Osteoporotic Fractures

Epidemiology of rib fractures in older men: Osteoporotic Fractures in Men (MrOS) prospective cohort study

Objective To study the causes and consequences of radiologically confirmed rib fractures (seldom considered in the context of osteoporosis) in community dwelling older men

Urinary Nâ Telopeptide as Predictor of Onset of Menopauseâ Related Bone Loss in Preâ and Perimenopausal Women

The menopause transition (MT) is a period of rapid bone loss and has been proposed to be a timeâ limited window for early intervention to prevent permanent microarchitectural damage and reduce the risk of subsequent fracture. To intervene early, however, we first need to be able to determine whether menopauseâ related bone loss is about to begin, in advance of substantial bone loss. The objective of this study was, therefore, to assess whether urinary Nâ telopeptide (Uâ NTX) in preâ or early perimenopause can predict the onset of menopauseâ related bone loss. Repeated Uâ NTX measurements were obtained during preâ and early perimenopause in 1243 participants from the Study of Women’s Health Across the Nation (SWAN). We examined the ability of Uâ NTX to predict the onset of significant menopauseâ related bone loss (categorical outcome, yes versus no) at the lumbar spine (LS) and femoral neck (FN), defined as annualized bone mineral density (BMD) decline at a rate faster than the smallest detectable change in BMD over the 3 to 4 years from the time of Uâ NTX measurement. Adjusting for age, race/ethnicity, body mass index, urine collection time, starting BMD, and study site in multivariable, modified Poisson regression, every standard deviation increment in Uâ NTX, measured at baseline in early perimenopausal women, was associated with an 18% and 22% greater risk of significant bone loss at the LS (pâ =â 0.003) and FN (pâ =â 0.003), respectively. The area under the receiverâ operator curve for predicting LS and FN bone loss was 0.72 and 0.72, respectively. In mixedâ effects analysis of all repeated measures of early perimenopausal Uâ NTX over followâ up, Uâ NTX predicted onset of bone loss at the LS (pâ =â 0.002) but not at the FN. We conclude that Uâ NTX can be used early in the MT to determine if a woman is about to experience significant LS bone loss before there has been substantial skeletal deterioration. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/1/jbm410116_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/2/jbm410116.pd

Estradiol and Follicleâ Stimulating Hormone as Predictors of Onset of Menopause Transitionâ Related Bone Loss in Preâ and Perimenopausal Women

The menopause transition (MT) may be an opportunity for early intervention to prevent rapid bone loss. To intervene early, we need to be able to prospectively identify preâ and perimenopausal women who are beginning to lose bone. This study examined whether estradiol (E2), or follicleâ stimulating hormone (FSH), measured in preâ and perimenopausal women, can predict significant bone loss by the next year. Bone loss was considered significant if bone mineral density (BMD) decline at the lumbar spine (LS) or femoral neck (FN) from a preâ or early perimenopausal baseline to 1â year after the E2 or FSH measurement was greater than the least detectable change. We used data from 1559 participants in the Study of Women’s Health Across the Nation and tested E2 and FSH as separate predictors using repeated measures modified Poisson regression. Adjusted for MT stage, age, race/ethnicity, and body mass index, women with lower E2 (and higher FSH) were more likely to lose BMD: At the LS, each halving of E2 and each doubling of FSH were associated with 10% and 39% greater risk of significant bone loss, respectively (pâ <â 0.0001 for each). At the FN, each halving of E2 and each doubling of FSH were associated with 12% (p = 0.01) and 27% (pâ <â 0.001) greater risk of significant bone loss. FSH was more informative than E2 (assessed by the area under the receiverâ operator curve) at identifying women who were more versus less likely to begin losing bone, especially at the LS. Prediction was better when hormones were measured in preâ or early perimenopause than in late perimenopause. Tracking withinâ individual change in either hormone did not predict onset of bone loss better than a single measure. We conclude that measuring FSH in the MT can help prospectively identify women with imminent or ongoing bone loss at the LS. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/1/jbmr3856_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/2/jbmr3856.pd

Individual and joint trajectories of change in bone, lean mass and physical performance 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

Vertebral bone marrow fat, bone mineral density and diabetes : The Osteoporotic Fractures in Men (MrOS) study

Elevated vertebral bone marrow fat (BMF) among individuals with osteoporosis has been established in histomorphometric studies. Several studies have found a negative correlation between BMF and bone mineral density (BMD) at the spine in men and women across different age groups. Animal studies have also observed bone loss with increased BMF in mice with induced diabetes. Our study objective was to test the hypothesis that the association between BMF and BMD varies by diabetic status. We performed a cross-sectional study of 156 men aged 74-96years from the Osteoporotic Fractures in Men study at the Pittsburgh clinical site. All men had spine BMF scans using proton magnetic resonance spectroscopy and spine and hip BMD scans by dual-energy X-ray absorptiometry. BMF was expressed as lipid to "lipid+water" ratio (%). Men were considered diabetic if they self-reported a physician diagnosis of diabetes, diabetes medication or had a fasting glucose ≥126mg/dl. Men with diabetes (n=38) had a significantly higher spine BMF (58.9 vs. 54.6%, p=0.0035), spine BMD (1.20 vs. 1.10g/cm(2), P=0.007) and total hip BMD (1.00 vs. 0.94g/cm(2), p=0.04) than those without, while no differences were observed for body weight, body mass index or waist circumference. Pearson correlation tests showed no significant correlation of spine BMF with age or BMD in non-diabetics. Significant inverse correlations were observed between BMF and BMD (-0.30 for femoral neck and -0.39 for total hip) among diabetic men. In conclusion, men with diabetes had a higher BMF compared to non-diabetic men. The correlation between BMF and BMD differed by diabetes status. Further investigation of the association of diabetes with BMF and BMD may provide a better understanding of the high fracture rates among individuals with diabetes despite their higher BMD

Femoral Neck External Size but not aBMD Predicts Structural and Mass Changes for Women Transitioning Through Menopause

The impact of adult bone traits on changes in bone structure and mass during aging is not well understood. Having shown that intracortical remodeling correlates with external size of adult long bones led us to hypothesize that ageâ related changes in bone traits also depend on external bone size. We analyzed hip dualâ energy Xâ ray absorptiometry images acquired longitudinally over 14 years for 198 midlife women transitioning through menopause. The 14â year change in bone mineral content (BMC, R2â =â 0.03, pâ =â 0.015) and bone area (R2â =â 0.13, pâ =â 0.001), but not areal bone mineral density (aBMD, R2â =â 0.00, pâ =â 0.931) correlated negatively with baseline femoral neck external size, adjusted for body size using the residuals from a linear regression between baseline bone area and height. The dependence of the 14â year changes in BMC and bone area on baseline bone area remained significant after adjusting for race/ethnicity, postmenopausal hormone use, the 14â year change in weight, and baseline aBMD, weight, height, and age. Women were sorted into tertiles using the baseline bone areaâ height residuals. The 14â year change in BMC (pâ =â 0.009) and bone area (pâ =â 0.001) but not aBMD (pâ =â 0.788) differed across the tertiles. This suggested that women showed similar changes in aBMD for different structural and biological reasons: women with narrow femoral necks showed smaller changes in BMC but greater increases in bone area compared to women with wide femoral necks who showed greater losses in BMC but without large compensatory increases in bone area. This finding is opposite to expectations that periosteal expansion acts to mechanically offset bone loss. Thus, changes in femoral neck structure and mass during menopause vary widely among women and are predicted by baseline external bone size but not aBMD. How these different structural and mass changes affect individual strengthâ decline trajectories remains to be determined. © 2017 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137625/1/jbmr3082.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137625/2/jbmr3082_am.pd

Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability — Results from the Women’s Health Initiative hormone therapy trials

Summary In a combined analysis of 25,389 postmenopausal women aged 50–79 years, enrolled in the two Women’s Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history. Introduction The aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women’s Health Initiative (WHI) hormone therapy trials. Methods A total of 25,389 postmenopausal women aged 50–79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort. Results Over 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65–0.78]), MOF (HR 0.60 [95% CI, 0.53–0.69]), and hip fracture (0.66 [95% CI, 0.45–0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls. Conclusion In the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women