Total Hip Areal Bone Mineral Density Research Articles

The Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial design and methods

BackgroundAmong older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use. MethodsAll participants will receive the same group-mediated dietary intervention targeting 8–10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT++PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT++BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover. DiscussionBEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL.Clinical Trials Registration: NCT05764733

Vitamin D supplementation for improving bone density in vitamin D–deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials

BackgroundVitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D–deficient children are unclear. ObjectivesThis study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D–deficient individuals. MethodsThis is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1–19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. ResultsEleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. ConclusionsClinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets).This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772

DXA-Based 3D Analysis of the Cortical and Trabecular Bone of Hip Fracture Postmenopausal Women: A Case-Control Study

Methods using statistical shape and appearance models have been proposed to analyze bone mineral density (BMD) in 3D from dual energy X-ray absorptiometry (DXA) scans. This paper presents a retrospective case-control study assessing the association of DXA-derived 3D measurements with osteoporotic hip fracture in postmenopausal women. Patients who experienced a hip fracture between 1 and 6 years from baseline and age-matched controls were included in this study. The 3D-SHAPER software (version 2.7, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from hip DXA scans at baseline. DXA and 3D measurements were compared between groups. Total hip areal BMD of hip fracture group as measured by DXA was 10.7% lower compared to control group. Differences in volumetric BMD (total hip) as measured by 3D-SHAPER were more pronounced in the trabecular compartment (−23.3%) than in the cortex (−8.2%). The area under the receiver operating curve was 0.742 for trabecular volumetric BMD, 0.706 for cortical volumetric BMD, and 0.712 for total hip areal BMD. Differences in the cortex were locally more pronounced at the medial aspect of the shaft, the lateral aspect of the greater trochanter, and the superolateral aspect of the neck. Marked differences in volumetric BMD were observed in the greater trochanter. This case-control study showed the association of DXA-derived 3D measurements with hip fracture. Analysis of large cohorts will be performed in future work to determine if DXA-derived 3D measurements could improve fracture risk prediction in clinical practice.

Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial

Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy. This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of -2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301. Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and -0·6% (-1·0 to -0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 [13%] of 218 in the romosozumab group vs 22 [10%] of 214 in the teriparatide group), hypercalcaemia (two [<1%] vs 22 [10%]), and arthralgia (22 [10%] vs 13 [6%]). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal. Transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture. Amgen, Astellas, and UCB Pharma.

Vertebral and femoral bone mineral density and bone strength in prostate cancer patients assessed in phantomless PET/CT examinations

PurposeBone fracture risk assessed ancillary to positron emission tomography with computed tomography co-registration (PET/CT) could provide substantial clinical value to oncology patients with elevated fracture risk without introducing additional radiation dose. The purpose of our study was to investigate the feasibility of obtaining valid measurements of bone mineral density (BMD) and finite element analysis-derived bone strength of the hip and spine using PET/CT examinations of prostate cancer patients by comparing against values obtained using routine multidetector-row computed tomography (MDCT) scans—as validated in previous studies—as a reference standard. Materials and methodsMen with prostate cancer (n=82, 71.6±8.3 years) underwent Fluorine-18 NaF PET/CT and routine MDCT within three months. Femoral neck and total hip areal BMD, vertebral trabecular BMD and femur and vertebral strength based on finite element analysis were assessed in 63 paired PET/CT and MDCT examinations using phantomless calibration and Biomechanical-CT analysis. Men with osteoporosis or fragile bone strength identified at either the hip or spine (vertebral trabecular BMD ≤80mg/cm3, femoral neck or total hip T-score ≤−2.5, vertebral strength ≤6500N and femoral strength ≤3500N, respectively) were considered to be at high risk of fracture. PET/CT- versus MDCT-based BMD and strength measurements were compared using paired t-tests, linear regression and by generating Bland-Altman plots. Agreement in fracture-risk classification was assessed in a contingency table. ResultsAll measurements from PET/CT versus MDCT were strongly correlated (R2=0.93–0.97; P<0.0001 for all). Mean differences for total hip areal BMD (0.001g/cm2, 1.1%), femoral strength (−60N, 1.3%), vertebral trabecular BMD (2mg/cm3, 2.6%) and vertebral strength (150N; 1.7%) measurements were not statistically significant (P>0.05 for all), whereas the mean difference in femoral neck areal BMD measurements was small but significant (−0.018g/cm2; −2.5%; P=0.007). The agreement between PET/CT and MDCT for fracture-risk classification was 97% (0.89 kappa for repeatability). ConclusionAncillary analyses of BMD, bone strength, and fracture risk agreed well between PET/CT and MDCT, suggesting that PET/CT can be used opportunistically to comprehensively assess bone integrity. In subjects with high fracture risk such as cancer patients this may serve as an additional clinical tool to guide therapy planning and prevention of fractures.

Exercise capacity independently predicts bone mineral density and proximal femoral geometry in patients with acute decompensated heart failure.

Heart failure is associated with increased risk of osteoporosis. We evaluated the prevalence and predictors of osteoporosis in hospitalized patients with ADHF using quantitative computed tomography. Osteoporosis and vertebral fracture are prevalent in patients with ADHF and exercise capacity independently predicts bone mass and femoral bone geometry. Heart failure is associated with reduced bone mass and increased risk of osteoporotic fractures. However, the prevalence and predictors of osteoporosis in hospitalized patients with acute decompensated heart failure (ADHF) are not well understood. Sixty-five patients (15 postmenopausal females and 50 males) with ADHF were prospectively and consecutively enrolled. After stabilization of heart failure symptoms, quantitative computed tomography for bone mineral density (BMD) and femoral geometry as well as biochemical, echocardiographic, and cardiopulmonary exercise tests were performed. Fifteen postmenopausal female showed a high prevalence of osteoporosis (40%) and vertebral fracture (53%). Among 50 male patients, 12% had osteoporosis and 32% had osteopenia, while vertebral fracture was found in 12%. Lumbar volumetric BMD (vBMD) was significantly lower in ischemic patients than non-ischemic patients (107.9 ± 47.5 vs. 145.4 ± 40.9 mg/cm(3), p = 0.005) in male. Exercise capacity, indicated by peak oxygen consumption (VO2), was significantly associated with lumbar vBMD (r = 0.576, p < 0.001) and total hip areal BMD (aBMD) (r = 0.512, p = 0.001) and cortical thickness of the femur neck (r = 0.544, p = 0.001). When controlled for age, body mass index, N-terminal proBrain natriuretic protein (NT-proBNP), etiology of heart failure, hemoglobin, and thigh circumference, multivariate regression analysis revealed peak VO2 independently predicted lumbar vBMD (β = 0.448, p = 0.031), total hip aBMD (β = 0.547, p = 0.021), and cortical thickness of the femur neck (β = 0.590, p = 0.011). In male patients with ADHF, osteoporosis and vertebral fracture are prevalent, and exercise capacity independently predicts bone mass and geometry. Given that heart failure patients with reduced exercise capacity carry a substantial increased risk of fracture, proper osteoporosis evaluation is important in these patients.

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5-year case-control study of 1110 women and men over age 65 years from the AGES-Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age-adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age-adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD-based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for "fragile bone strength" (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture.

“Timed Up and Go Test and Bone Mineral Density Measurement for Fracture Prediction

Two major factors associated with skeletal fracture in older persons are intrinsic bone strength and risk of falling. This study examined the role of Timed Up and Go (TUG) test performance, a validated predictor of falling, and hip areal bone mineral density (BMD), a validated predictor of bone strength in fracture prediction in a 10-year longitudinal study. The study participants were 1126 women (mean [SD] age at baseline, 75.0 [2.6] years) living in Perth, Western Australia. Assessments included TUG test at baseline and dual-energy x-ray absorptiometry total hip areal BMD measurement at year 1. Incident clinical osteoporotic fracture over 10 years was confirmed by radiographic records. Complete incident hip fracture data were obtained from a hospital morbidity database. One-third (32.7%) of participants had slow TUG test performance (>10.2 seconds), and 54.2% of participants had low hip areal BMD (T-score of less than -1). Relative to risks among participants having normal TUG test performance and normal BMD, risks of nonvertebral fracture and hip fracture were significantly higher among participants who had slow TUG test performance and normal hip BMD (nonvertebral fracture hazard ratio [HR], 1.84; hip fracture HR, 2.48) or both slow TUG test performance and low hip BMD (nonvertebral fracture HR, 2.51; hip fracture HR, 4.68). For nonvertebral fracture and hip fracture, the population-attributable risks of slow TUG test performance with normal hip BMD were 19.3% and 32.3%, of normal TUG test performance with low hip BMD were 31.3% and 50.3%, and of both slow TUG test performance and low hip BMD were 30.1% and 55.9%, respectively. TUG test performance is an independent risk factor for incident nonvertebral fracture and a feasible inexpensive physical performance assessment for use in clinical practice to screen patients with increased risk of fracture.

Relationship between hip bone mineral density and lumbar disc degeneration: A study in elderly subjects using an eight‐level MRI‐based disc degeneration grading system

To study the relationship between hip bone mineral density (BMD), lumbar disc degeneration, and lumbar disc space narrowing in elderly subjects. The study cohort comprised 196 females and 163 males (age range, 67-89 years) with no age difference between the two groups. Anteroposterior total hip areal BMD was measured with DXA and lumbar spine MRI was acquired using a 1.5 Tesla scanner. Lumbar disc degeneration was assessed using an eight-level grading system wherein each grade represents a stepwise progression from normal disc to severe disc degeneration and disc space narrowing. After controlling for the age effect, no significant relationship was observed between total hip T-score status and severity of disc degeneration. There was no significant difference in total hip BMD in the subjects with or without the disc space narrowing (P < 0.05). Female subjects are more likely to have a narrowed disc space than males at all levels, and being statistically significant at L3/4 and L4/5 levels, and with an overall significance of P = 0.007. There was no association observed between hip BMD and lumbar disc degeneration. Elderly females were more likely to have a narrowed lumbar disc space than elderly males.

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) > or = 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMD(a)) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMD(a) (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men.