Short-term therapy with rosiglitazone exerts detrimental skeletal effects by inhibiting bone formation. Skeletal end points should be included in future long-term studies of thiazolidinedione use.

Objective-To determine if the use of the injectable contraceptive depot medroxyprogesterone (DMPA), which reduces ovarian oestrogen production, is associated with changes in bone density.Design-Population study. DMPA Main outcome measure-Lumbar spine and femoral neck bone mineral density assessed by dual energy x ray absorptiometry.Results-Compared with premenopausal controls matched for age, race, and body mass index, DMPA users had significantly reduced bone density in the lumbar spine (mean difference 7 5% (95% confidence interval 1-9% to 13-1%), p=0.002) and in the femoral neck (6-6%, (0.8% to 12-3%), p=0007). Compared with postmenopausal controls matched for body mass index and duration of oestrogen deficiency, DMPA users had greater bone density in the lumbar spine (8-9% (4.3% to 13.5%), p=0001), but in the femoral neck the difference in bone density was less (4-0% (-0-4% to 8.5%), p=004).

The assessment of vertebral bone mineral density (BMD) in the anterio-posterior projection has become widely used in the management and prevention of osteoporosis. Recently, it has been demonstrated that the presence of spinal osteophytes has a major impact on measured BMD in men, thus casting doubt on the value of these BMD measurements. We have assessed the impact of osteophytic and aortic calcification on spinal and femoral BMD measurements in 130 normal postmenopausal women, aged 45-71 yr. Lateral lumbar spine radiographs were obtained in all subjects and graded separately (0-3) for osteophytes and aortic calcification. Both forms of calcification increased with age, and BMD of all sites was correlated positively with body weight and negatively with age. The correlation coefficients between BMD and calcification scores were nonsignificant. Multiple regression analysis, including weight, age, and calcification scores, demonstrated a small but significant effect of osteophyte score on lumbar BMD (partial r2 = 0.04; P = 0.012) and a similar trend for Ward's triangle and the trochanteric region (partial r2 = 0.02; P less than 0.06). The aortic calcification score remained nonsignificant. It is concluded that the influence of spinal osteophytes on lumbar BMD in postmenopausal women is substantially less than that in men and is, therefore, unlikely to interfere with BMD estimation in most subjects. The relationship between proximal femoral BMD and osteophyte score suggests a real relationship between skeletal density and degenerative joint disease, as has been demonstrated by others.

Several lines of evidence suggest that imatinib may affect skeletal tissue. We show that inhibition by imatinib of PDGFR signaling in osteoblasts activates osteoblast differentiation and inhibits osteoblast proliferation and that imatinib inhibits osteoclastogenesis by both stromal cell-dependent and direct effects on osteoclast precursors. Introduction: Imatinib mesylate, an orally active inhibitor of the c-abl, c-kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, is in clinical use for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal cell tumors. Interruption of both c-kit and c-abl signaling in mice induces osteopenia, suggesting that imatinib might have adverse effects on the skeleton. However, biochemical markers of bone formation increase in patients with CML starting imatinib therapy, whereas bone resorption is unchanged, despite secondary hyperparathyroidism. We assessed the actions of imatinib on bone cells in vitro to study the cellular and molecular mechanism(s) underlying the skeletal effects we observed in imatinib-treated patients. Materials and Methods: Osteoblast differentiation was assessed using a mineralization assay, proliferation by [