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Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting.

ABSTRACT: 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).

SUBMITTER: Banefelt J

PROVIDER: S-EPMC9298264 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMuscle weakness is a key factor in the increase risk of falls and might also play a significant role in the increase of risk of hip fracture. Computed tomography-measured muscle size and muscle density are well-established imaging biomarkers used in studies of physical function, frailty or cancer, but limited to hip fracture. In particular, it is warranted to have a better understanding of the performance of muscle size and density in the discrimination of acute hip fractures. We also aim to determine age-related differences of muscle size and density in healthy controls and hip fracture patients.MethodsFour hundred thirty-eight low-energy acute hip fracture cases and 316 healthy controls from the China Action on Spine and Hip Status study were included in the study. Muscle cross-sectional area and density were measured for the gluteus maximus and gluteus medius and minimus. Areal bone mineral density (aBMD) of the femoral neck and total hip was measured. Using propensity score matching, we generated three samples with cases and controls matched for age, body mass index, and gender: femoral neck fracture (FNF), intertrochanteric fracture (ITF), and any hip fracture vs. controls, respectively.ResultsHandgrip strength, gluteus muscle area and density, and bone parameters of the matched hip fracture groups were lower than those of the correspondence control groups, respectively (P < 0.05). The univariate analysis showed that associations of aBMD with FNF and with ITF were significantly weaker than associations between fracture and muscle parameters. Gluteus medius and minimus muscle density showed the highest areas under the curve (AUC) with FNF (0.88, 95% confidence interval, 0.85-0.92) and trochanteric fracture (0.95, 95% confidence interval, 0.92-0.97). The model including all muscle and bone parameters provided the highest AUC (FNF: AUC 0.912; ITF: AUC 0.958), and AUC results of another selected model without muscle density showed that association with fracture significantly dropped (FNF: AUC 0.755; ITF: AUC 0.858). Separate results for the two age groups younger and older than 70 years showed no age-related significant differences in discriminate models.ConclusionsMuscle density performs better than aBMD from hip computed tomography X-ray absorptiometry and muscle size in discrimination of hip fracture. Combination of aBMD and muscle density provided the best discrimination. The integration of muscle assessments may trigger a paradigm shift in hip fracture prediction. Gluteus muscle density should also be evaluated as treatment outcome.

Project description:ImportanceScreening for osteoporosis with bone mineral density (BMD) is recommended for older adults. It is unclear whether repeating a BMD screening test improves fracture risk assessment.ObjectivesTo determine whether changes in BMD after 4 years provide additional information on fracture risk beyond baseline BMD and to quantify the change in fracture risk classification after a second BMD measure.Design, setting, and participantsPopulation-based cohort study involving 310 men and 492 women from the Framingham Osteoporosis Study with 2 measures of femoral neck BMD taken from 1987 through 1999.Main outcomes and measuresRisk of hip or major osteoporotic fracture through 2009 or 12 years following the second BMD measure.ResultsMean age was 74.8 years. The mean (SD) BMD change was -0.6% per year (1.8%). Throughout a median follow-up of 9.6 years, 76 participants experienced an incident hip fracture and 113 participants experienced a major osteoporotic fracture. Annual percent BMD change per SD decrease was associated with risk of hip fracture (hazard ratio [HR], 1.43 [95% CI, 1.16 to 1.78]) and major osteoporotic fracture (HR, 1.21 [95% CI, 1.01 to 1.45]) after adjusting for baseline BMD. At 10 years' follow-up, 1 SD decrease in annual percent BMD change compared with the mean BMD change was associated with 3.9 excess hip fractures per 100 persons. In receiver operating characteristic (ROC) curve analyses, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance. The area under the curve (AUC) was 0.71 (95% CI, 0.65 to 0.78) for the baseline BMD model compared with 0.68 (95% CI, 0.62 to 0.75) for the BMD percent change model. Moreover, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance (AUC, 0.72 [95% CI, 0.66 to 0.79]). Using the net reclassification index, a second BMD measure increased the proportion of participants reclassified as high risk of hip fracture by 3.9% (95% CI, -2.2% to 9.9%), whereas it decreased the proportion classified as low risk by -2.2% (95% CI, -4.5% to 0.1%).Conclusions and relevanceIn untreated men and women of mean age 75 years, a second BMD measure after 4 years did not meaningfully improve the prediction of hip or major osteoporotic fracture. Repeating a BMD measure within 4 years to improve fracture risk stratification may not be necessary in adults this age untreated for osteoporosis.

Project description:Background:Both copper deficiency and overexposure have been associated with adverse health effects. Evidence linking copper to bone mineral density (BMD) and total fracture, however, is limited. Methods:This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (2011-2014) in the United States. Using unadjusted and multivariate adjusted logistic regression analyses and a two-piecewise linear regression model with a smoothing function, we evaluated the associations between serum copper levels, bone mineral density and total fracture in 722 participants. Results:The study sample (n = 722, mean age: 56.47 ± 11.55 y) represented a population of which 47.2% were men; 43.91% were non-Hispanic white, 18.84% non-Hispanic black and 13.71% Mexican American; 25.9% had total fracture. In the multivariate logistic regression analysis, individuals in the lowest category (<98.5 ?g/dL) of serum copper concentration had 0.049 g/cm2 lower total femur BMD and 0.045 g/cm2 lower femoral neck BMD than those in the second concentration category (98.5-114 ?g/dL). Individuals in the highest category (?134 ?g/dL) of serum copper concentration had an approximately 4-fold increase in the risk of total fracture than those in the second concentration category. There were no significant associations between per 10 ?g/dL increases in serum copper levels and total fracture in multivariate logistic regression analysis after multivariate adjustment (all p > 0.05). However, a differential association between serum copper levels and total fractures between men and women was observed (odds ratio = 1.81, 95% confidence interval 1.08-3.03, p = 0.026 for men and odds ratio = 1.07, 95% confidence interval 0.86-1.32, p = 0.552 for women). Conclusion:Moderate serum copper levels are critically important for bone health. Lower serum copper levels are significantly associated with decreased BMD in the total femur and femoral neck. Higher serum copper levels are significantly associated with increased total fracture, especially in men. The Translational Potential of this Article:The impact of serum copper concentrations on bone mineral density and total fracture can provide insights into clinical application of copper-containing supplements and biomaterials.

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Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting.

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