Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902).

The strongest Brønsted acid: protonation of alkanes by H(CHB(11)F(11)) at room temperature.

What is the strongest acid? Can a simple Brønsted acid be prepared that can protonate an alkane at room temperature? Can that acid be free of the complicating effects of added Lewis acids that are typical of common, difficult-to-handle superacid mixtures? The carborane superacid H(CHB11 F11 ) is that acid. It is an extremely moisture-sensitive solid, prepared by treatment of anhydrous HCl with [Et3 SiHSiEt3 ][CHB11 F11 ]. It adds H2 O to form [H3 O][CHB11 F11 ] and benzene to form the benzenium ion salt [C6 H7 ][CHB11 F11 ].

Prediction models of prevalent radiographic vertebral fractures among older men.

No studies have compared how well different prediction models discriminate older men who have a radiographic prevalent vertebral fracture (PVFx) from those who do not. We used area under receiver operating characteristic curves and a net reclassification index to compare how well regression-derived prediction models and nonregression prediction tools identify PVFx among men age ≥65 yr with femoral neck T-score of -1.0 or less enrolled in the Osteoporotic Fractures in Men Study.

Mammographic density and risk of breast cancer by age and tumor characteristics.

Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.

Methods: Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique.

Snoring, daytime sleepiness, and incident cardiovascular disease in the health, aging, and body composition study.

Objectives: To examine the association between snoring and incident cardiovascular disease (CVD).

Design Settings And Participants: This is a prospective study in which community dwelling older adults were evaluated at baseline, and followed up for an average of 9.9 years.

Mitochondrial DNA sequence associations with dementia and amyloid-β in elderly African Americans.

Mitochondrial dysfunction occurs early in the course of several neurodegenerative diseases, and is potentially related to increased oxidative damage and amyloid-β (Aβ) formation in Alzheimer's disease. The goals of this study were to assess mtDNA sequence associations with dementia risk, 10-year cognitive change, and markers of oxidative stress and Aβ among 1089 African-Americans in the population-based Health, Aging, and Body Composition Study. Participants were free of dementia at baseline, and incidence was determined in 187 (18%) cases over 10 to 12 follow-up years.

Diabetes and risk of hospitalized fall injury among older adults.

Objective: To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization.

Research Design And Methods: The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified.

Age, body mass, usage of exogenous estrogen, and lifestyle factors in relation to circulating sex hormone-binding globulin concentrations in postmenopausal women.

Background: Circulating concentrations of sex hormone-binding globulin (SHBG) have been associated with cardiovascular diseases, type 2 diabetes, metabolic syndrome, and hormone-dependent cancers; however, correlates of SHBG concentrations are not well understood.

Methods: We comprehensively investigated correlates of SHBG concentrations among 13 547 women who participated in the Women's Health Initiative and who had SHBG measurements. We estimated study- and ethnicity-specific associations of age, reproductive history, usage of exogenous estrogen, body mass index (BMI), and lifestyle factors such as physical activity, smoking, alcohol consumption, coffee intake, and dietary factors with SHBG concentrations.

Sex hormone levels and risk of breast cancer with estrogen plus progestin.

Background: Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer.

Methods: We conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

Background: Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches.

High hip fracture risk in men with severe aortic calcification: MrOS study.

A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged ≥ 65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score.

The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension.

Context: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years.

Objective: The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure.

Design, Setting, And Participants: This was a multicenter, international, open-label study of 4550 women.

Comparison between southern blots and qPCR analysis of leukocyte telomere length in the health ABC study.

Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.

The QT interval and risk of incident atrial fibrillation.

Background: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.

Objective: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.

Methods: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study.

Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women.

Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) but also have higher rates of fracture compared to those without DM. Limited evidence suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed BMD data in the Study of Osteoporotic Fractures (SOF) between 1986 and 1998.

Adipose tissue density, a novel biomarker predicting mortality risk in older adults.

Background: Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics.

Methods: VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs).

High mammographic density in women of Ashkenazi Jewish descent.

Introduction: Percent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD.

Methods: We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD.

Sclerostin and bone strength in women in their 10th decade of life.

Sclerostin is a potent inhibitor of bone formation but has been shown to correlate positively with areal bone mineral density (aBMD). Little is known about its relationship to parameters of bone strength and volumetric BMD (vBMD) as measured by peripheral quantitative computed tomography (pQCT). We measured both serum sclerostin and parameters of tibial bone size and strength by pQCT to characterize this relationship.

Interactive informed consent: randomized comparison with paper consents.

Informed consent is the cornerstone of human research subject protection. Many subjects sign consent documents without understanding the study purpose, procedures, risks, benefits, and their rights. Proof of comprehension is not required and rarely obtained.

Common genetic variants in ARNTL and NPAS2 and at chromosome 12p13 are associated with objectively measured sleep traits in the elderly.

Study Objectives: To determine the association between common genetic variation in the clock gene pathway and objectively measured acti-graphic sleep and activity rhythm traits.

Design: Genetic association study in two population-based cohorts of elderly participants: the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men (MrOS) study.

Setting: Population-based.

Treat-to-target for osteoporosis: is now the time?

Objectives: Current clinical practice guidelines identify patients at high risk for fracture who are likely to benefit from pharmacological therapy and suggest ways to monitor for effectiveness of therapy. However, there is no clear guidance on when fracture risk has been reduced to an acceptably low level. As a consequence, some patients at low risk for fracture may be treated for longer than necessary, whereas others at high risk for fracture may have treatment stopped when they might benefit from continuation of the same treatment or a change to a more potent therapeutic agent.

Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials.

In rodent models, undercarboxylated osteocalcin (ucOC) acts as a hormone that promotes insulin sensitivity and secretion. If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes. We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N = 6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N = 7113) of zoledronic acid (3 years), and Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N = 7076) of denosumab (3 years).

Cystatin C and risk of hip fractures in older women.

To test the hypothesis that older women with higher cystatin C are at increased risk of hip fracture independent of traditional risk factors including hip bone mineral density (BMD), we performed a case-cohort analysis nested in a cohort of 4709 white women attending a Year 10 (1997-1998) examination of the Study of Osteoporotic Fractures that included a random sample of 1170 women and the first 300 women with incident hip fracture occurring after Year 10 examination. Serum cystatin C and creatinine were measured in Year 10 sera. In a model adjusted for age, clinical site, body mass index, and total hip BMD, higher cystatin C was associated with an increased risk of hip fracture (p for linear trend 0.

Goal-directed treatment of osteoporosis.

Drug treatment for osteoporosis typically begins with an oral bisphosphonate, regardless of initial bone mineral density (BMD) or fracture risk, and decisions to continue or change treatment are often based on evidence of response to treatment based on changes in BMD, bone turnover markers, and occurrence of fractures. This pattern differs from preventive therapy for other conditions, such as hypertension, where treatment is based on achieving a goal. We propose that a goal be established to guide treatments to reduce fracture risk.