Sequential histomorphometric changes in cancellous bone from ovariohysterectomized dogs

Abstract

To evaluate potential pharmacologic agents for the prevention or treatment of the bone loss associated with ovarian insufficiency, a predictable animal model is needed. To assess the potential utility of the ovariohysterectomized dog as a model of this condition, we characterized the sequential histomorphometric changes in canine cancellous bone in response to the loss of ovarian function. A group of 25 adult beagle dogs were ovariohysterectomized and terminated at 1, 3, 6, and 10 months following surgery. Iliac biopsies were performed following double‐fluorochrome labeling at the time of surgery and at termination. Static and dynamic histomorphometry was performed on undecalcified sections. By 3 months postovariohysterectomy, there was activation of cancellous bone remodeling as indicated by significant increases in mineralizing surface and bone formation rate. Increases in osteoid surface, mineralizing surface, and bone formation rate were also apparent at 1 month postovariohysterectomy, and although not statistically significant, these trends suggest the skeletal response to acute loss of ovarian function was rapid. This increase in bone remodeling was transient. By 6 months, mineralizing surface and bone formation rate were depressed below presurgical levels. In addition to a reduction in bone formation, a reduction in osteoblast function characterized by reduced labeling of osteoid and a disproportionate increase in eroded surface also occurred. By 10 months postovariohysterectomy, cancellous bone remodeling was not significantly different from presurgical levels. At no time was a significant reduction in bone volume detected. These data suggest that the changes in cancellous bone remodeling in the ovariohysterectomized dog are a series of transient phenomena. The duration and/or magnitude of these changes do not appear to be sufficient to effect a sizable or significant reduction in bone volume. The brief nature of the transients in bone remodeling and the lack of a sizable bone loss in the ovariohysterectomized dog limit the utility of this model for the routine assessment of agents for either the prevention or treatment of bone disease associated with ovarian insufficiency.