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The etiology of frequently occurring osteoporosis in Rett syndrome is unknown. Five girls, ages 9.75, 11, 12, 13.5, and 14 years, with typical Rett syndrome requiring scoliosis surgery presented an opportunity to study bone remodeling by quantitative bone histomorphometry. Anterior iliac crest bone biopsies taken 1 to 2 days after double labeling of the bone surfaces with tetracycline were submitted for histomorphometry. Bone volume was reduced, and the surface parameters of formation (osteoid surface) were normal, whereas the parameters of resorption (osteoclast surface and number) were decreased. In four girls, the rate of bone formation was reduced but could not be measured in one girl owing to poor labeling. It is possible that the slow rate of bone formation impedes the development and accumulation of peak bone mass and contributes to the decreased bone volume in Rett syndrome. Perhaps MECP2 mutations in Rett syndrome not only influence brain development but also affect bone formation.

Androgen deficiency is associated with low bone mass in humans and animals, but the remodeling alterations that lead to bone loss are unclear. Our objective was to define early responses in both cancellous and cortical bone to orchiectomy (ORX) using histomorphometry in sexually mature (4-month-old) rats. A total of 62 male rats, 4 months of age, were divided into six groups, sham operated (SH) or orchiectomized (ORX), and sacrificed 1, 2, or 4 weeks after ORX. Calcein was given 5 and 2 days before sacrifice to label mineralizing surfaces. Bone mineral density (BMD) was measured in excised femurs by dual energy X-ray absorptiometry (DEXA). Static and dynamic histomorphometry was evaluated in the cancellous bone of the proximal tibial metaphysis and lumbar vertebral bodies, and in the cortical bone of the tibial diaphysis. Osteopenia began to develop by 2 weeks after ORX, though weight gain and femur length did not change. Femoral BMD was significantly reduced and BMC decreased (NS) by 4 weeks after ORX (p < 0.05). Tibial and vertebral cancellous bone volume decreased 19% and 13%, respectively, while osteoblast and osteoclast surfaces, and numbers of osteoclasts, increased after ORX. At 2 weeks post-ORX, an increase in cancellous bone formation rate was attributable primarily to an increase in mineralizing surfaces and a smaller rise in mineral apposition rate. In contrast, cortical bone periosteal, but not endosteal, bone formation rate and mineralizing surfaces decreased. We conclude that ORX stimulates cancellous and diminishes periosteal bone turnover rapidly after ORX, with subsequent decreases in bone volume and mineral density. The clear divergence in cortical and cancellous bone responses to hypogonadism raises important questions regarding the control of bone formation and its role in defining the skeletal phenotype.

In humans, peak bone mineral density (BMD) is a highly heritable trait and a strong determinant of subsequent osteoporotic fracture risk. To identify the genetic factors responsible for variation in peak BMD, investigators have turned to animal models. In this study we examined the heritability of BMD acquisition and characterized differences in skeletal geometry, histomorphometry, and biomechanical competence between two lines of mice artificially selected for extremes of peak whole body BMD. F 2 progeny from a cross between C57BL/6 and DBA/2 inbred strains was used as the foundation population to develop lines selected for either high or low BMD. Whole body BMD was measured by dual-energy X-ray absorptiometry (DXA). By the third generation of selection, highest-scoring BMD (HiBMD) mice exhibited 14% greater peak BMD than lowest-scoring BMD (LoBMD) mice. The mean realized heritability of peak BMD was 36%.

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