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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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. © 1996 Wiley‐Liss, Inc.

Clodronate Prevents Osteopenia and Loss of Trabecular Connectivity in Estrogen-Deficient Rats

“…Our study is in agreement with earlier findings on femoral neck width (18,19) . It has been shown recently that the rat does not have in the femoral neck modeling‐dependent bone gain by increased periosteal bone formation following OVX (14,16,18,19) . This may explain the lack of any change in neck width in our study and theirs (18,19) .…”

“…Estrogen deficiency led to a less well connected trabecular network of the femoral neck in the OVX/Veh group, as evidenced by the lower trabecular number and higher trabecular separation relative to the SHAM/Veh group, in agreement with earlier studies (15,16,18,19) . The method of trabecular interconnection used in the present study provided a negative mean value of trabecular bone pattern factor for femoral neck secondary spongiosa in the SHAM/Veh group, indicating that concave surfaces were abundant in a well‐connected trabecular network (8,12) .…”

“…2) and expressed as the mean neck width of the measured values (18) . The first measurement site nearest to the growth plate is considered to be situated intracapsularly and the other sites extracapsularly (16) . Femoral neck length (red) was defined as the perpendicular distance from the growth plate metaphyseal junction to the baseline at the junction of the neck and the greater trochanter.…”

“…These have been implemented on cancellous bone of iliac biopsy samples (8–11) and on vertebral bodies of humans (7,12) . Strut analysis of cancellous bone has been carried out in ovariectomized (OVX) rats on proximal tibia (13) and on femoral neck (14–16) . Stereological methods have also been used for estimating 3D connectivity of vertebral cancellous bone in OVX rats (17) …”

“…When the pathogenesis of bone loss in the femoral neck and the effects of drugs on it have been investigated in estrogen‐deficient rats, it has been found that the gross and histoanatomy of the hip region appear to be roughly similar in humans and rats (14–16,18,19) . ) The femoral neck is a load‐bearing skeletal site both in rats and in humans and thus suitable for biomechanical testing (16,20–23) …”