Histo-anatomy of the proximal femur in rats: impact of ovariectomy on bone mass, structure, and stiffness.

Abstract

Hip fractures are the most devastating consequence of osteoporosis in humans. Since the ovariectomized (ovx) rat is a useful model of estrogen-deficient osteoporosis, the purposes of this study were to describe the histo-anatomical features of the rat hip and to determine changes in the proximal femur induced by ovariectomy to evaluate the use of this skeletal site for future bone studies. Changes in body mass and composition and in bone mineral content and density were determined by DEXA at 12 weeks after ovariectomy. Gross and histo-anatomy of the rat hip was studied by light microscopy and histomorphometry. Cancellous and cortical bone changes induced by ovx at the femoral midneck were determine using dynamic, static, and structural histomorphometric techniques. The stiffness of the femoral neck was determined by biomechanical testing, and the results were correlated with histological observations and the histomorphometric data. The bony structures of the rat hip, articular cartilage, and muscular and capsular attachments are very similar to the human. Rats, however, have an active growth plate and a well-vascularized periosteum covering the intracapsular portion of the femoral neck, which is different from the adult humans. Rats in the sham and ovx groups exhibited similar biological variations in the thickness of the femoral neck and epiphyseal bone and cartilaginous composition. Ovariectomy promoted periosteal modeling and induced endocortical and cancellous bone remodeling, with a net loss of bone mass due to excess bone resorption. The ovx-induced increase in resorption resulted in reduced trabecular number, thickness, and endocortico-trabecular connectivity, which likely contributed to less bone stiffness in ovx rats relative to the sham controls. There are numerous similarities in the structure and histology of the rodent and human hip. Skeletal changes induced by ovariectomy in rats, particularly those at the endocortical surface and in the cancellous bone, are very similar to changes observed in the proximal femur in osteoporotic women. In addition, ovx in the rat had compromised the biomechanical properties at the femoral neck, similar to what occurs in the postmenopausal women. Data presented here confirmed responsiveness of the proximal femur in rat to ovarian hormone deficiency, which appears to be a useful and relevant site to investigate mechanisms and interventions relative to human disease.