Lee, David C.

Abstract With the goal of preventing more hip fractures, a next generation of the VirtuOst Biomechanical Computed Tomography (BCT) test was developed that integrates measurements from a clinical CT scan related to fall risk, impact force, and femoral strength, the three main determinants of hip fracture. Here, we introduce the test and validate it against BMD and FRAX. Our source population from a large healthcare system comprised of 341364 patients (≥65 yr) with an abdominal-pelvic CT during care. Using data from 3035 patients (1790 with hip fracture), we developed a “BCT Risk Score” (range: 0-100) having input risk factors of age, femoral strength, ratio of trabecular/cortical BMD, muscle area, intramuscular fat, FN volume, hip width, and posterior fat thickness. In a geographically distinct set of 2124 patients (1293 with hip fracture), we then compared the BCT Risk Score against a DXA-equivalent hip BMD T-score (lowest hip value, measured from the CT scan by VirtuOst) and FRAX hip fracture risk (with BMD but without parental fracture history) for predicting a first incident hip fracture within 5 yr. For the women, the c-statistic for predicting fracture was higher for BCT (0.89, 95% CI: 0.87-0.90) than for BMD (0.81, 0.79-0.84) or FRAX (0.85, 0.83-0.87). Using binary thresholds to identify high-risk patients, sensitivity for BCT (Risk Score ≥ 75) was higher than for BMD (T-score ≤ −2.5) and FRAX (hip risk ≥ 3.0%): 81.4% vs 47.8% vs 75.9%, respectively; positive predictive values confirmed comparable high-risk status (BCT 13.6% vs BMD 15.3% vs FRAX 12.7%). Similar trends were observed for the men, 2-yr outcomes, and identifying very-high-risk patients. We conclude that, compared to both BMD and FRAX, the integrative BCT test better predicted hip fracture and its high sensitivity should improve fracture prevention.

Abstract Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip BMD T-score ≤ −2.5, measured from the CT scan using VirtuOst). We defined “treated” as at least six months of any osteoporosis medication by prescription fill data during follow-up; “not-treated” was no prescription fill. Sex-specific odds ratios of hip fracture for treated vs not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, BMD-treatment interaction, BMD, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2,211 patients) and 24.0% of the men (175/728 patients) were treated primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated vs not-treated was 0.26 (95% confidence interval: 0.21–0.33) for women and 0.21 (0.13–0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47–1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.

Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual‐energy X‐ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual‐energy abdominal triple‐phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA‐based osteoporosis was defined as a T score ≤−2.5 at the hip or spine. BCT‐based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3. Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2. Using DXA as the clinical reference, sensitivity of BCT to detect DXA‐defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple‐phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.

ABSTRACT Given non-optimal testing rates for dual-energy X-ray absorptiometry (DXA) and the high use of computed tomography (CT) in some Asian countries, biomechanical computed tomography analysis (BCT)-based bone strength testing, which utilizes previously taken clinical CT scans, may improve osteoporosis testing rates. However, an understanding of ethnic differences in such bone strength measurements between Whites and Asians is lacking, which is an obstacle to clinical interpretation. Using previously taken CT and DXA scans, we analyzed bone strength and bone mineral density (BMD) at the hip and spine in two sex- and age-matched community-based cohorts, aged 40 to 80 years: Whites (Rochester, MN, USA) and Koreans (Seoul, South Korea). For both the spine and femur, the age dependence of bone strength was similar for both groups, White (n = 371; women n = 202, 54.5%) and Korean (n = 396; women n = 199, 50.3%). For both sexes, mean spine strength did not differ between groups, but femur strength was 9% to 14% higher in Whites (p ≤ 0.001), an effect that became non-significant after weight adjustment (p = 0.375). For Koreans of both sexes, the fragile bone strength thresholds for classifying osteoporosis, when derived from regional DXA BMD T-score references, equaled the clinically validated thresholds for Whites (in women and men, femoral strength, 3000 N and 3500 N; vertebral strength 4500 N and 6500 N, respectively). Using these thresholds, classifications for osteoporosis for Koreans based on bone strength versus based on DXA BMD T-scores were consistent (89.1% to 94.4% agreement) at both the hip and spine and for both sexes. The BCT-based, clinically validated bone strength thresholds for Whites also applied to Koreans, which may facilitate clinical interpretation of CT-based bone strength measurements for Koreans. © 2020 American Society for Bone and Mineral Research (ASBMR).