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Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9-6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5-9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score -1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (-3.0 to -0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD-fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

The metabolic state of the body can be a major determinant of bone health. We used a Mendelian randomization approach to identify metabolites causally associated with bone mass to better understand the biological mechanisms of osteoporosis. We tested bone phenotypes (femoral neck, total hip, and lumbar spine bone mineral density [BMD]) for association with 280 fasting blood metabolites in 6055 women from TwinsUK cohort with genomewide genotyping scans. Causal associations between metabolites and bone phenotypes were further assessed in a bidirectional Mendelian randomization study using genetic markers/scores as instrumental variables. Significant associations were replicated in 624 participants from the Hong Kong Osteoporosis Study (HKOS). Fifteen metabolites showed direct associations with bone phenotypes after adjusting for covariates and multiple testing. Using genetic instruments, four of these metabolites were found to be causally associated with hip or spine BMD. These included androsterone sulfate, epiandrosterone sulfate, 5alpha-androstan-3beta17beta-diol disulfate (encoded by CYP3A5), and 4-androsten-3beta17beta-diol disulfate (encoded by SULT2A1). In the HKOS population, all four metabolites showed significant associations with hip and spine BMD in the expected directions. No causal reverse association between BMD and any of the metabolites were found. In the first metabolome-genomewide Mendelian randomization study of human bone mineral density, we identified four novel biomarkers causally associated with BMD. Our findings reveal novel biological pathways involved in the pathogenesis of osteoporosis. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

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). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

The rate of bone loss varies across the aging period via multiple complex mechanisms. Therefore, the role of genetic factors on bone loss may also change similarly. In this study, we investigated the effect of age on the genetic component of bone loss in a large twin-based longitudinal study. During 17 years of follow-up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and lumbar spine dual-energy X-ray absorptiometry (DXA) scans were performed in 7056 twins. Out of these subjects, 2716 female twins aged >35 years with at least two scans separated for >4 years (mean follow-up 9.7 years) were included in this analysis. We used a mixed-effects random-coefficients regression model to predict hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55, 60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height, and duration of hormone replacement therapy. We then estimated heritability of the changes in BMD measures between these age ranges. Heritability estimates for cross-sectional hip and spine BMD were high (ranging between 69% and 88%) at different ages. Heritability of change of BMD was lower and more variable, generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40 and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%-53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%-58%) for femoral neck, and 69.5% (95% CI, 59%-77%) for lumbar spine. These estimates decreased with increasing age, and there appeared to be no heritability of BMD changes after the age of 65 years. There was some evidence at the spine for shared genetic effects between cross-sectional and longitudinal BMD. Whereas genetic factors appear to have an important role in bone loss in early postmenopausal women, nongenetic mechanisms become more important determinants of bone loss with advanced age., (Copyright © 2012 American Society for Bone and Mineral Research.)

While estimates of relative risks associated with risk factors such as age and bone mineral density (BMD) may be of interest for etiologic and comparative purposes, clinical questions such as who might benefit most from preventive interventions or BMD monitoring depend on estimates of absolute fracture risk. The European prospective investigation into cancer (EPIC)-Norfolk study included 25,311 participants (11,476 men) aged 4,079 years in 1993-1997. All participants were followed for osteoporotic fractures to March 2007. Ten-year absolute risk of fracture in men and women were calculated using the baseline survivor function in multivariable Cox proportional-hazards models adjusting for age, sex, history of fractures, body mass index, smoking, and alcohol intake. In comparison of those without history of fracture versus those with history of fracture, the 10-year absolute risk of any fracture in men ranged from 1.0 vs. 1.2% at age 40 years to 3.0 vs. 4.4% at age 75 years. The respective estimates in women ranged from 0.7 vs. 1.0% at age 40 years to 9.3 vs. 17.2% at age 75 years. Statistically significant interaction between age and sex was found (P < 0.001), which contributed to the differences in predicted absolute fracture risks for men and women at different ages. Our study shows the need for population-specific data to develop efficient well calibrated algorithms for assessment of fracture risk. The interaction observed between sex and age points to the need for further prospective studies among men.

The objective of this work was to estimate the incidence rate of cardiovascular disease (CVD) events (myocardial infarction, stroke, or CVD death) at 1 year among three cohorts of patients at high risk of fracture (osteoporosis, previous fracture, and anti‐osteoporosis medication) and to identify the key risk factors of CVD events in these three cohorts. To do so, this prospective cohort study used data from the Clinical Practice Research Datalink, a primary care database from United Kingdom. Major adverse cardiovascular events (MACE, a composite outcome for the occurrence of either myocardial infarction [MI], stroke, or CVD death) were identified in patients aged 50 years or older at high or imminent fracture risk identified in three different cohorts (not mutually exclusive): recently diagnosed with osteoporosis (OST, n = 65,295), incident fragility fracture (IFX, n = 67,065), and starting oral bisphosphonates (OBP, n = 145,959). About 1.90%, 4.39%, and 2.38% of the participants in OST, IFX, and OBP cohorts, respectively, experienced MACE events. IFX was the cohort with the higher risk: MACE incidence rates (cases/1000 person‐years) were 19.63 (18.54–20.73) in OST, 52.64 (50.7–54.5) in IFX, and 26.26 (25.41–27.12) in OBP cohorts. Risk of MACE events at 1 year was predicted in the three cohorts. Models using a set of general, CVD, and fracture candidates selected by lasso regression had a good discrimination (≥70%) and internal validity and generally outperformed the models using only the CVD risk factors of general population listed in QRISK tool. Main risk factors common in all MACE models were sex, age, smoking, alcohol, atrial fibrillation, antihypertensive medication, prior MI/stroke, established CVD, glomerular filtration rate, systolic blood pressure, cholesterol levels, and number of concomitant medicines. Identified key risk factors highlight the differences of patients at high risk of fracture versus general population. Proposed models could improve prediction of CVD events in patients with osteoporosis in primary care settings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The article discusses a study on the predictive capability of quantitative ultrasound (QUS) and dual x-ray absorptiometry (DXA) in terms of the 10-year absolute risk of fracture. It notes that DXA stands as the accepted reference method in bone mass density (BMD) measurement while a decline in BMD is linked to an increased risk of fracture. Under the study, the participants were subjected to either hip BMD measurement and QUS assessment. Results show that QUS assessment exhibited performance that is similar to that of DXA in predicting fracture risks.

This article discusses the results of a research study conducted to measure forced expiratory volume (FEV) as a means of predicting the risks of osteoporosis and hip fracture in a population between 42 and 81 years of age. The study finds that low respiratory function increases the risks of osteoporosis and hip fracture and suggests FEV as an effective method of identifying risk.

The article reports on the results of research which was conducted in an effort to perform a heteroscedastic regression analysis of the factors affecting bone mineral density monitoring in patients with osteoporosis. Researchers found that with samples of men and women, heteroscedastic regression outperformed models that assumed homogeneous variance and that it is a powerful tool in analyzing longitudinal bone mineral data that can be used to generate individualized predictions of bone mineral density change.

This article focuses on a prospective population study on the relationship between height loss and fractures. The article contains an introduction, materials and methods, results, conclusions, as well as charts and graphs. The study found that in middle-aged and older men and women, a height loss of greater than 0.5 centimeters increased risk of hip and other fractures.

Background: Diagnostic discordance for osteoporosis is the observation that the T-score of an individual patient varies from one key measurement site to another, falling into two different diagnostic categories identified by the World Health Organization (WHO) classification system. This study was conducted to evaluate the presence and risk factors for this phenomenon in a large sample of Iranian population. Methods: Demographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database on 4229 patients referred to a community-based outpatient osteoporosis testing center from 2000 to 2003. Dual-energy X-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hip for all cases. Minor discordance was defined as present when the difference between two sites was no more than one WHO diagnostic class. Major discordance was present when one site is osteoporotic and the other is normal. Subjects with incomplete data were excluded. Results: In 4188 participants (3848 female, mean age 53.4 ± 11.8 years), major discordance, minor discordance, and concordance of T-scores were seen in 2.7%, 38.9% and 58.3%, respectively. In multivariate logistic regression analysis, older age, menopause, obesity, and belated menopause were recognized as risk factors and hormone replacement therapy as a protective factor against Tscore discordance. Conclusion: The high prevalence of T-score discordance may lead to problems in interpretation of the densitometry results for some patients. This phenomenon should be regarded as a real and prevalent finding and physicians should develop a particular strategy approaching to these patients. [ABSTRACT FROM AUTHOR]