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

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

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

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

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men.

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment

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

Frailty and Risk of Falls, Fracture, and Mortality in Older Women: The Study of Osteoporotic Fractures

Background. A standard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults. However, the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain. Methods. To determine whether a standard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index (BMI), we ascertained frailty status in a cohort of 6724 women ≥ 69 years and followed them prospectively for incident falls, fractures, and mortality. Frailty was defined by the presence of three or more of the following criteria: unintentional weight loss, weakness, self-reported poor energy, slow walking speed, and low physical activity. Incident recurrent falls were defined as at least two falls during the subsequent year. Incident fractures (confirmed with x-ray reports), including hip fractures, and deaths were ascertained during an average of 9 years of follow-up. Results. After controlling for multiple confounders such as age, health status, medical conditions, functional status, depressive symptoms, cognitive function, and bone mineral density, frail women were subsequently at increased risk of recurrent falls (multivariate odds ratio = 1.38, 95% confidence interval [CI], 1.02-1.88), hip fracture (multivariate hazards ratio [MHR] = 1.40, 95% CI, 1.03-1.90), any nonspine fracture (MHR = 1.25, 95% CI, 1.05-1.49), and death (MHR = 1.82, 95% CI, 1.56-2.13). The associations between frailty and these outcomes persisted among women ≥ 80 years. In addition, associations between frailty and an increased risk of falls, fracture, and mortality were consistently observed across categories of BMI, including BMI ≥ 30 kg/m2. Conclusion. Frailty is an independent predictor of adverse health outcomes in older women, including very elderly women and older obese wome