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Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically significant cognitive decline (≥3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged ≥65 years from the population‐based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed‐effects models; and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE ≥ 24). The annual % change in MMSE was similar for both genders (women −0.33, interquartile range [IQR] −0.70 to +0.00; and men −0.34, IQR: −0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5%; 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61; 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. © 2021 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The association between muscle weakness and fracture is not well understood. This study sought to examine the contribution of muscle strength at baseline and change in muscle strength to the observed risk of fragility fracture in older people. The study involved 595 men and 1066 women aged 60+ years (median 69 years) who had been followed for a median of 11 years (range, 4 to 22 years). Quadriceps isometric muscle strength (MS) measured at baseline and biennially was adjusted for height. Femoral neck bone mineral density (FNBMD) was measured by DXA. Low-trauma fracture was ascertained from X-ray reports and interview. The relationship between baseline MS and serial MS and fracture assessed by time-invariant and time-variant Cox's regression models was expressed as hazard ratio (HR) and 95% confidence interval (CI). During the follow-up period, 282 (26%) women and 89 (15%) men sustained a fragility fracture. From age 60 years, women lost 0.28 kg/m (1.6%) of MS per year, whereas men lost 0.39 kg/m (1.5%) of MS per year. In the time-variant model, using serial MS, each 1 SD (4.7 kg/m) lower MS was associated with a 27% increase in the risk of fracture in women (HR 1.27; 95% CI, 1.11 to 1.43); and 46% increase in men (HR 1.46; 95% CI, 1.22 to 1.75). After adjusting for FNBMD, age and prior fracture, history of fall and smoking, HR per SD of lower MS was 1.13 (95% CI, 0.99 to 1.28) for women and 1.35 (95% CI, 1.18 to 1.64) for men. These data indicate that muscle weakness is an independent determinant of fracture risk in men, but not in women. This sex difference suggests that apart from mechanical load effect of muscle on bone, there are other muscle-bone interactions that need to be investigated in future studies. The accuracy of fracture risk prediction for men may be improved by incorporating muscle strength. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Half of fragility fractures occur in individuals with nonosteoporotic BMD (BMD T-score > -2.5); however, there is no information on postfracture adverse events of subsequent fracture and mortality for different BMD levels. The objective of this work was to determine the risk and predictors of subsequent fracture and excess mortality following initial fracture according to BMD. The subjects were community-dwelling participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with incident fractures followed from 1989 to 2011. The outcome measurements were as follows: risk of subsequent fracture and mortality according to BMD categorized as normal ( T-score < -1), osteopenia ( T-score ≤ -1 and > -2.5), and osteoporosis ( T-score ≤ -2.5). There were 528 low-trauma fractures in women and 187 in men. Of these, 12% occurred in individuals with normal BMD (38 women, 50 men) and 42% in individuals with osteopenia (221 women, 76 men). The relative risk (RR) of subsequent fracture was >2.0-fold for all levels of BMD (normal BMD: 2.0 [1.2 to 3.3] for women and 2.1 [1.2 to 3.8] for men; osteopenia: 2.1 [1.7 to 2.6] for women and 2.5 [1.6 to 4.1] for men; and osteoporosis 3.2 [2.7 to 3.9] for women and 2.1 [1.4 to 3.1] for men. The likelihood of falling and reduced quadriceps strength contributed to subsequent fracture risk in women with normal BMD. By contrast with subsequent fracture risk, postfracture mortality was increased particularly in individuals with low BMD (age-adjusted standardized mortality ratio [SMR] for osteopenia 1.3 [1.1 to 1.7] and 2.2 [1.7 to 2.9] for women and men, respectively, and osteoporosis 1.7 [1.5 to 2.0] and 2.7 [2.0 to 3.6] for women and men, respectively). This study demonstrates the high burden of subsequent fracture in individuals with normal BMD and osteopenia, and excess mortality particularly for those with osteopenia (and osteoporosis). These findings highlight the importance of these fractures and underscore the gap in evidence for benefit of antiosteoporotic treatment for fragility fracture, in those with only mildly low BMD. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The selective cathepsin K inhibitor odanacatib (ODN) progressively increased bone mineral density (BMD) and decreased bone-resorption markers during 2 years of treatment in postmenopausal women with low BMD. A 1-year extension study further assessed ODN efficacy and safety and the effects of discontinuing therapy. In the base study, postmenopausal women with BMD T-scores between −2.0 and −3.5 at the lumbar spine or femur received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients ( n = 189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Endpoints included BMD at the lumbar spine (primary), total hip, and hip subregions; levels of bone turnover markers; and safety assessments. Continued treatment with 50 mg of ODN for 3 years produced significant increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine cross-linked N-telopeptide of type I collagen (NTx) remained suppressed at year 3 (−50.5%), but bone-specific alkaline phosphatase (BSAP) was relatively unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, bone turnover markers increased transiently above baseline, but this increase largely resolved by month 36. There were similar overall adverse-event rates in both treatment groups. It is concluded that 3 years of ODN treatment resulted in progressive increases in BMD and was generally well tolerated. Bone-resorption markers remained suppressed, whereas bone-formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation. © 2011 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the role of the cathepsin K inhibitor odanacatib in osteoporosis. The clinical trial involved postmenopausal women with low bone mineral density (BMD). The clinical trial found that two years of weekly treatment with odanacatib was generally well tolerated by the patients. The drug also increased lumbar spine and total hip BMD in the patients.

Abstract Purpose Low trauma rib fracture (hereinafter, rib fracture) is common in the elderly, but its risk factors and mortality consequence are rarely studied. We sought to define the epidemiology of rib fracture and the association between rib fracture and postfracture mortality. Methods The study was part of the Dubbo Osteoporosis Epidemiology Study, which was designed as a population-based prospective study, and consisted of 2041 women and men (aged ≥ 60). The incidence of rib fracture was ascertained from X-ray reports. Bone mineral density (BMD) was measured by DXA (GE-Lunar). The time-dependent Cox model was used to access the relationship between rib fracture and mortality. Results During the median follow-up of 13 years, 59 men and 78 women had sustained a rib fracture, making the annual incidence of 4.8/1000 person-years. Each SD (0.15 g/cm2) lower in femoral neck BMD was associated with ~2-fold increase in the hazard of fracture (hazard ratio [HR] 1.9; 95% CI, 1.4 to 2.6 in men; and HR 2.1; 95% CI, 1.6 to 2.8 in women). Among those with a rib fracture, the incidence of subsequent fractures was 10.2/100 person-years. Compared with those without a fracture, the risk of mortality among those with a fracture was increased by ~7.8-fold (95% CI, 2.7 to 22.5) in men and 4.9-fold (95% CI 2.0 to 11.8) in women within the first year postfracture. Conclusions A rib fracture signifies an increased risk of subsequent fractures and mortality. The increased risk of mortality during the first 2.5 years postfracture suggests a window of opportunity for treatment. Highlights • Rib fracture is common in the elderly, accounting for 7% of all fragility fractures. • Risk factors for rib fracture were old age, osteoporosis, prior fracture and fall. • An existing rib fracture signifies a greater risk of subsequent fractures and death. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Individuals with hip fracture are at substantially increased risk of mortality. The aim of this study was to estimate the excess mortality attributable to hip fracture in elderly men and women. Methods: The Dubbo Osteoporosis Epidemiology Study was designed as a prospective epidemiologic investigation, in which more than 2000 men and women aged 60+ as of 1989 had been followed for 21years. During the follow-up period, the incidence of atraumatic hip fractures was ascertained by X-ray reports, and mortality was ascertained by the New South Wales Birth, Death and Marriage Registry. Relative survival ratios were estimated by taking into account the age-and-sex specific expected survival in the general Australian population from 1989 to 2010. Results: During the follow-up period 151 women and 55 men sustained a hip fracture. Death occurred in 86 (57%) women and 36 (66%) men. In women, the cumulative relative survival post hip-fracture at 1, 5 and 10years was 0.83 (95% confidence interval (CI) 0.76–0.89), 0.59 (95% CI 0.48–0.68), and 0.31 (95% CI 0.20–0.43), respectively; in men, the corresponding estimates of relative survival were: 0.63 (95% CI 0.48–0.75), 0.48 (95% CI 0.32–0.63), and 0.36 (95% CI 0.18–0.56). On average post hip-fracture women died 4years earlier (median: 4.1, inter-quartile range (IQR) 1.7–7.8) and men died 5years earlier (median=4.8, IQR 2.4–7.0) than expected. For every six women and for every three men with hip fracture one extra death occurred above that expected in the background population. Conclusion: Hip fracture is associated with reduced life expectancy, with men having a greater reduction than women, even after accounting for time-related changes in background mortality in the population. These data underscore that hip fracture is an independent clinical risk factor for mortality. [Copyright &y& Elsevier]

Abstract: Introduction: In animal model, mice treated with beta-blockers (BB) had increased bone mass. In humans, high bone mass is associated with reduce fracture risk. The present study sought to test the hypothesis that BB use is associated with reduced fracture risk. Materials and methods: Data from 3488 participants (1285 men) aged 50years and above in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Baseline characteristics of participants were obtained at the initial visit which had taken place between 1989 and 1993. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). Two hundred and sixty two (20%) men and 411 (19%) women had been on BB, as ascertained by direct interview and verification with medication history. The incidence of fragility fractures was ascertained during the follow-up period (1989–2008). Results: In men, BB use was associated with higher BMD at the femoral neck (0.96 versus 0.92g/cm2, P <0.01), higher lumbar spine (1.32 versus 1.25g/cm2, P <0.01), and lower fracture risk than those not on BB (odds ratio [OR]: 0.49; 95% CI: 0.32–0.75). In women, BB users also had higher femoral neck BMD (0.83 versus 0.81g/cm2, P <0.01), higher lumbar spine BMD (1.11 versus 1.06g/cm2, P <0.01), and lower risk of fracture than non-users (OR 0.68, 95% CI: 0.53–0.87). The associations between BB use and fracture risk were independent of age, BMD, and clinical risk factors. Subgroup analysis suggested that the association was mainly found in selective BB, not in non-selective BB. Conclusion: Beta-blockers use, particularly selective BB, was associated with reduced fracture risk in both men and women, and the association was independent of BMD. [Copyright &y& Elsevier]

Abstract: Background: Men with prostate cancer on androgen deprivation therapy (ADT) are at increased risk of bone loss. The present study sought to determine the incidence of low trauma fracture in men with prostate cancer (PC), and to characterize the association between potential risk factors and fracture risk in these men. Methods: In the prospective, population-based Dubbo Osteoporosis Epidemiology Study, 43 men aged 60+ years reported a history of prostate cancer; among whom, 22 men received ADT, and 21 men did not. Low-trauma fractures were ascertained between 1989 and 2004. Bone mineral density at the femoral neck (FNBMD), postural instability and lifestyle factors were obtained at baseline. Results: Men with prostate cancer had significantly higher lumbar spine BMD than those without cancer (p =0.013). During the follow-up period, 15 men with prostate cancer had sustained a fracture, yielding the age-adjusted incidence of fracture among this group was 31.6 per 1000 person-years, which was greater than those without cancer (22.1 per 1000 person-years). The age-adjusted incidence of fracture was more pronounced among those with prostate cancer on ADT (40.2 per 1000 person-years). After adjusting for age, the increase in fracture risk among prostate cancer patients was associated with lower femoral neck BMD (hazard ratio [HR] per SD=1.8, 95% CI: 1.0–3.4) and increased rate of bone loss (HR 2.3, 1.2–4.6). Conclusions: Men with prostate cancer, particularly those treated with ADT, had an increased fracture risk. Although the average BMD in men with prostate cancer was higher than men without cancer, a low BMD prior to treatment or increased rate of bone loss after initiating ADT treatment was each a significant predictor of fracture in these. [Copyright &y& Elsevier]