Bone microarchitecture and bone fragility in men: DXA and histomorphometryin humans and in the orchidectomized rat model

In men, the risk of fragility fractures increases as bone mineral declines but there is an overlap in the bone mineral density (BMD) measurements betw een patients with and those without fractures. Biomechanical competence of trabecular (Th) bone depends on the amount of bone and on microarchitecture . We have developed new histomorphometric methods for evaluating microarchi tecture on histological sections. These methods were used in the orchidecto mized male rat (ORX - a model of hypogonadism-induced osteoporosis) and on transiliac bone biopsies performed in male osteoporotic patients. ORX rats were studied at 2, 4, 8, and 16 weeks post-ORX. Bone mineral content (BMC) was reduced at 16 weeks. Trabecular bone volume (BV/TV) was significantly d ecreased from the 4(th) week. Differences in the sensitivity of the methods were found. Fractal dimension was modified as early as 2 weeks and appeare d the most potent descriptor of Tb disorganization. The architectural chang es in this model mimic those observed in hypogonadic men. We examined the r elationships among BMD, micro-architecture, and vertebral fracture in 108 m en with lumbar osteopenia (T-score <-2.5). At least one vertebral fracture was observed in 62 patients and none in 46 patients. After adjusting for ag e, body mass index (BMI), and BMD, there was no significant difference betw een the two groups in BV/TV, Tb.Th, and Star volume. In contrast, the mean values of ICI and Tb.Sp were significantly higher whereas Tb.N and nodes we re lower in patients With vertebral fracture. Logistic regression analysis showed that ICI, strut analysis, and Tb.N were significant predictors of th e presence of vertebral fracture: odds ratios for an alteration of 1 SD ran ged from 1.7 for nodes to 3.2 for ICI. These results strongly suggest that bone Tb microarchitecture is a major and independent determinant of vertebr al fracture in men with osteoporosis.