Abnormal bone remodeling in patients with spontaneous painful vertebral fracture


  • Presented at the Sixth International Symposium on Clinical Disorders of Bone Metabolism, Venice, Italy, 1999; proceedings published by Centro Italiano Congressi, Rome.


The application of tetracycline-based iliac bone histomorphometry to the study of the pathogenesis of osteoporosis has given conflicting results. Accordingly, we performed this procedure in 78 postmenopausal white women with one or more vertebral fractures identified according to rigorous criteria that excluded other causes of vertebral deformity and 66 healthy postmenopausal white women recruited from the same geographic region; the groups did not differ in age or weight. In each subject, measurements were made separately on the cancellous (Cn), endocortical (Ec), and intracortical (Ct) subdivisions of the endosteal envelope. In the fracture patients, osteoblast surface was reduced substantially on each subdivision, most markedly on the Cn surface, where about 25% of the deficit was in cuboidal (type II) osteoblasts, suggesting impaired recruitment; the remaining 75% of the deficit was in intermediate (type III) cells, suggesting earlier transition from type III to type IV (flat) cells. On the Ec and Ct surfaces, the deficit was exclusively in type III cells. Mean bone formation rate was reduced by about 18% on the Cn but not on the Ec or Ct surfaces. The deficit was more significant in subjects matched for Cn BV/TV when adjusted for the inverse regression on osteocyte density and after logarithmic transformation. The difference in bone formation rate resulted from a corresponding reduction in wall thickness without a change in activation frequency. The frequency distribution of bone formation rate was more skewed to the left in the fracture patients than in the controls. Osteoclast surface was significantly lower on each subdivision. The variation in osteoblast surface, bone formation rate, and osteoclast surface was significantly greater in the fracture patients than in the controls, with more abnormally low and abnormally high values. The data suggest the following conclusions: (1) The histologic heterogeneity of postmenopausal osteoporosis is reaffirmed; (2) the different subdivisions of the endosteal envelope, although in continuity, behave differently in health and disease; (3) a combination of defective osteoblast recruitment and premature osteoblast apoptosis would account for the deficit in type II and III cells and the reductions in wall thickness and bone formation rate on the Cn surface and the previously reported osteocyte deficiency in Cn bone; (4) premature disaggregation of multinuclear to mononuclear resorbing cells could account for the osteoclast deficit; and (5) some patients with vertebral fracture have one or another disorder of bone remodeling that at present cannot be identified by noninvasive means. © 2011 American Society for Bone and Mineral Research.