Muscle Strength and Physical Performance Improve Fracture Risk Prediction Beyond Garvan and FRAX: The Osteoporotic Fractures in Men (MrOS) Study

Muscle strength and physical performance are associated with fracture risk in men. However, it is not known whether these measurements enhance fracture prediction beyond Garvan and FRAX tools. A total of 5665 community-dwelling men, aged ≥65 years, from the Osteoporotic Fractures in Men (MrOS) Study, who had data on muscle strength (grip strength) and physical performance (gait speed and chair stand tests), were followed from 2000 to 2019 for any fracture, major osteoporotic fracture (MOF), initial hip, and any hip fracture. The contributions to different fracture outcomes were assessed using Cox's proportional hazard models. Tool-specific analysis approaches and outcome definitions were used. The added predictive values of muscle strength and physical performance beyond Garvan and FRAX were assessed using categorical net reclassification improvement (NRI) and relative importance analyses. During a median follow-up of 13 (interquartile range 7–17) years, there were 1014 fractures, 536 MOFs, 215 initial hip, and 274 any hip fractures. Grip strength and chair stand improved prediction of any fracture (NRI for grip strength 3.9% and for chair stand 3.2%) and MOF (5.2% and 6.1%). Gait speed improved prediction of initial hip (5.7%) and any hip (7.0%) fracture. Combining grip strength and the relevant performance test further improved the models (5.7%, 8.9%, 9.4%, and 7.0% for any, MOF, initial, and any hip fractures, respectively). The improvements were predominantly driven by reclassification of those with fracture to higher risk categories. Apart from age and femoral neck bone mineral density, muscle strength and performance were ranked equal to or better than the other risk factors included in fracture models, including prior fractures, falls, smoking, alcohol, and glucocorticoid use. Muscle strength and performance measurements improved fracture risk prediction in men beyond Garvan and FRAX. They were as or more important than other established risk factors. These measures should be considered for inclusion in fracture risk assessment tools. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Preventing the development and progression of diabetic kidney disease: Where do we stand?

Diabetic kidney disease (DKD) is a major factor associated with increased cardiovascular (CV) and all-cause mortality and morbidity in patients with diabetes. Current standard therapy includes intensive management of hyperglycemia and blood pressure control with renin-angiotensin-aldosterone system (RAAS) blockers. Despite the implementation of this strategy, DKD remains the leading cause of end-stage renal disease (ESRD), mainly because of the increasing burden of diabetes mellitus. The aim of this review is to evaluate the available evidence, focusing on the benefit of current treatment in the development and progression of DKD.     

Lung-Specific Risk Factors Associated With Incident Hip Fracture in Current and Former Smokers

Hip fractures are associated with significant morbidity and mortality in smokers with lung disease, but whether lung-specific factors are associated with fracture risk is unknown. Our goal was to determine whether lung-specific factors associate with incident hip fracture and improve risk discrimination of traditional fracture risk models in smokers. The analysis consisted of a convenience sample of 9187 current and former smokers (58,477 participant follow-up years) participating in the Genetic Epidemiology of chronic obstructive pulmonary disease (COPD) longitudinal observational cohort study. Participants were enrolled between 2008 and 2011 with follow-up data collection through July 2018. Traditional risk factors associated with incident hip fracture (n = 361) included age, female sex, osteoporosis, prevalent spine and hip fracture, rheumatoid arthritis, and diabetes. Lung-specific risk factors included post-bronchodilator percent forced expiratory volume in 1 s (FEV₁%) predicted (OR, 0.95; 95% CI, 0.92–0.99 for each 10% increase), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (OR, 1.09; 95% CI, 1.002–1.19 for each higher stage), presence of CT-determined emphysema (OR, 1.34; 95% CI, 1.06–1.69), symptom scores (OR, 1.10; 95% CI, 1.03–1.19 for each higher unit score), 6-min walk distance (OR, 0.92; 95% CI, 0.90–0.95 for each 30-m increase), body mass index, airflow obstruction, dyspnea, and exercise (BODE) index (OR, 1.07; 95% CI, 1.01–1.13 for each higher unit score), total exacerbations (OR, 1.13; 95% CI, 1.10–1.16 per exacerbation), and annual exacerbations (OR, 1.37; 95% CI, 1.21–1.55 per exacerbation). In multivariable modeling, age, black race, osteoporosis, prevalent hip and spine fracture, rheumatoid arthritis, and diabetes were associated with incident hip fracture. The presence of emphysema, 6-min walk distance, and total number of exacerbations added to traditional models improved risk discrimination (integrated discrimination improvement [IDI] values 0.001 [95% CI, 0.0003–0.002], 0.001 [95% CI, 0.0001–0.002], and 0.008 [95% CI, 0.003–0.013], corresponding to relative IDIs of 12.8%, 6.3%, and 34.6%, respectively). These findings suggest that the incorporation of lung-specific risk factors into fracture risk assessment tools may more accurately predict fracture risk in smokers. © 2020 American Society for Bone and Mineral Research.     

Erythropoietin treatment and the risk of hip fractures in hemodialysis patients

Erythropoietin (EPO) is the primary regulator of bone marrow erythropoiesis. Mouse models have provided evidence that EPO also promotes bone remodeling and that EPO-stimulated erythropoiesis is accompanied by bone loss independent of increased red blood cell production. EPO has been used clinically for three decades to treat anemia in end-stage renal disease, and notably, although the incidence of hip fractures decreased in the United States generally after 1990, it rose among hemodialysis patients coincident with the introduction and subsequent dose escalation of EPO treatment. Given this clinical paradox and findings from studies in mice that elevated EPO affects bone health, we examined EPO treatment as a risk factor for fractures in hemodialysis patients. Relationships between EPO treatment and hip fractures were analyzed using United States Renal Data System (USRDS) datasets from 1997 to 2013 and Consolidated Renal Operations in a Web-enabled Network (CROWNWeb) datasets for 2013. Fracture risks for patients treated with <50 units of EPO/kg/week were compared to those receiving higher doses by multivariable Cox regression. Hip fracture rates for 747,832 patients in USRDS datasets (1997–2013) increased from 12.0 per 1000 patient years in 1997 to 18.9 in 2004, then decreased to 13.1 by 2013. Concomitantly, average EPO doses increased from 11,900 units/week in 1997 to 18,300 in 2004, then decreased to 8,800 by 2013. During this time, adjusted hazard ratios for hip fractures with EPO doses of 50–149, 150–299, and ≥ 300 units/kg/week compared to <50 units/kg/week were 1.08 (95% confidence interval [CI], 1.01–1.15), 1.22 (95% CI, 1.14–1.31), and 1.41 (95% CI, 1.31–1.52), respectively. Multivariable analyses of 128,941 patients in CROWNWeb datasets (2013) replicated these findings. This study implicates EPO treatment as an independent risk factor for hip fractures in hemodialysis patients and supports the conclusion that EPO treatment may have contributed to changing trends in fracture incidence for these patients during recent decades. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Prevalent Vertebral Fractures on Chest CT: Higher Risk for Future Hip Fracture

Subclinical or undiagnosed vertebral fractures on routine chest computed tomography (CT) may be useful for detecting patients at increased risk of future hip fractures who might benefit from preventive interventions. We investigated whether prevalent vertebral fractures on routine chest CT are associated with future hip fractures. From a source population of 5679 patients ≥40 years old undergoing chest CT in one of three Dutch hospitals between 2002 and 2005, patients hospitalized for hip fractures (n = 149) during a median follow‐up of 4.4 years were identified. Following a case‐cohort design, a random sample of 576 patients was drawn from the source population and added to the cases. In this group, the presence and severity of vertebral fractures was determined using semiquantitative vertebral fracture assessment and multivariate case‐cohort appropriate Cox modeling. We found that cases were older (69 versus 63 years) and more often female (48% versus 38%) than the source population. Compared with those with no fracture, patients with any vertebral fracture had triple the risk of future hip fracture (age‐ and gender‐adjusted hazard ratio [HR] = 3.1, 95% confidence interval [CI] 2.1–4.7). This HR rose to 3.8 (CI 2.6–5.6) if mild fractures were discounted. Future fracture risk increased significantly with increasing severity of vertebral fracture status: from mild (HR = 2.4, CI 1.5–3.7) and moderate (HR = 4.8, CI 2.5–9.2) to severe (HR = 6.7, CI 2.9–15.5). The same was true for having higher cumulative fracture grades: 1 to 3 (HR = 2.7, CI 1.8–4.1), 4 to 6 (HR = 4.8, CI 2.2–10.5), or ≥7 (HR = 11.2, CI 3.7–34.6). In conclusion, prevalent vertebral fractures on routine clinical chest CT are associated with future hip fracture risk. © 2014 American Society for Bone and Mineral Research.     

Fracture Risk Predictions Based on Statistical Shape and Density Modeling of the Proximal Femur

Increased risk of skeletal fractures due to bone mass loss is a major public health problem resulting in significant morbidity and mortality, particularly in the case of hip fractures. Current clinical methods based on two‐dimensional measures of bone mineral density (areal BMD or aBMD) are often unable to identify individuals at risk of fracture. We investigated predictions of fracture risk based on statistical shape and density modeling (SSDM) methods using a case‐cohort sample of individuals from the Osteoporotic Fractures in Men (MrOS) study. Baseline quantitative computed tomography (QCT) data of the right femur were obtained for 513 individuals, including 45 who fractured a hip during follow‐up (mean 6.9 year observation, validated by physician review). QCT data were processed for 450 individuals (including 40 fracture cases) to develop individual models describing three‐dimensional bone geometry and density distribution. Comparison of mean fracture and non‐case models indicated complex structural differences that appear to be responsible for resistance to hip fracture. Logistic regressions were used to model the relation of baseline hip BMD and SSDM weighting factors to the occurrence of hip fracture. Area under the receiver operating characteristic (ROC) curve (AUC) for a prediction model based on weighting factors and adjusted by age was significantly greater than AUC for a prediction model based on aBMD and age (0.94 versus 0.83, respectively). The SSDM‐based prediction model adjusted by age correctly identified 55% of the fracture cases (and 94.7% of the non‐cases), whereas the clinical standard aBMD correctly identified 10% of the fracture cases (and 91.3% of the non‐cases). SSDM identifies subtle changes in combinations of structural bone traits (eg, geometric and BMD distribution traits) that appear to indicate fracture risk. Investigation of important structural differences in the proximal femur between fracture and no‐fracture cases may lead to improved prediction of those at risk for future hip fracture. © 2014 American Society for Bone and Mineral Research.     

Health-related quality of life in a sample of HIV-infected South Africans

The study aims to assess the health-related quality of life and HIV symptoms of a sample of people living with HIV (PLHIV) in South Africa. The sample included 607 PLHIV from all districts of the Eastern Cape Province, recruited either through a health facility, from the community through key informants, or through support groups. At the time of the study, 66% of the respondents reported having been given an AIDS diagnosis (advanced stage of HIV disease), 48% were on antiretroviral therapy (ART), and 35% were receiving a disability grant. The findings indicate a low degree of overall quality of life, with a mean score of 13.4 on the WHOQOL-HIV measure. Among the WHOQOL-HIV BREF subscales, logistic regression identified spirituality, environment, psychological health, and level of independence as predictors for overall quality of life. Among medical variables and HIV symptoms, CD4 cell count and having fewer HIV symptoms but not an AIDS diagnosis were identified as predictors for overall quality of life; among socio-economic variables, having sufficient food and a higher educational level were identified as predictors. The results highlight the need for better access to psychosocial support and medical services for PLHIV in South Africa, as well as the need to consider a patient's general health perceptions during the course of ART.