Bone loss in the ovariectomized baboonPapio ursinus: densitometry, histomorphometry and biochemistry

Abstract

To develop a non-human primate model of systemic bone loss after ovariectomy, 24 ovariectomized (OVX) and eight control (non-OVX) female baboons Papio ursinus were investigated over a period of 48 months using bone mineral density (BMD), iliac crest bone histomorphometry, bone turnover markers, and variables of calcium metabolism. Lumbar spine (L1–L4) BMD measured by dual energy X-ray absorptiometry (DXA) decreased in OVX animals in the first 12 months (−7.6%) and showed a slow trend towards recovery after 24 months. Controls showed a slow increase in spinal BMD over 4 years (+9.7%). Total hip BMD decreased slowly up to 48 months in all animals (OVX −12.6%versus controls −10%); this indicated that OVX had a limited effect on total hip BMD. Forearm BMD did not change. The significant decrease in trabecular bone volume (TBV) of the iliac crest from baseline to 12 months was followed by some recovery. Microarchitectural deterioration of trabecular bone in OVX animals was demonstrated by a decline in trabecular number and an increase in trabecular spacing. These changes were also evident on sections of whole vertebrae, proximal femora and iliac crests. Changes in iliac TBV reflected spinal but not hip BMD changes in the OVX animals. Static and dynamic histomorphometric variables indicated that bone turnover was increased for 36 months following OVX. Controls showed no changes in histomorphometric variables. Bone specific alkaline phosphatase (ALPs) in OVX animals remained elevated throughout the study; osteocalcin (OC) was significantly elevated only at 6 and 12 months, and deoxypyridinoline (Pyr-D) was elevated at 12 months but declined after 24 months. ALPs was thus more sensitive to the long-term effects of OVX than were OC or Pyr-D. Controls showed no changes in bone turnover markers. This study showed consistent deleterious changes in lumbar BMD, bone histomorphometry with microarchitectural deterioration together with altered biochemical markers of bone turnover in the first 12 months after OVX. Since these changes resemble those in post-menopausal women, the non-human primate Papio ursinus is suitable for the study of bone loss in post-menopausal women.

Cross-sectional geometry of the femoral midshaft in baboons is heritable

“…Populations of biologically relevant, genetically characterized animals, such as the baboon, an established and reliable nonhuman primate model for the genetics of many skeletal traits [30, 34–36], whose environmental exposures may be controlled and/or adequately accounted for, may facilitate more accurate detection of these effects and more precise estimation of their magnitudes. Like humans, baboons naturally undergo skeletal remodeling over a relatively long life-span.…”

“…Similarity in bone composition and microstructure results in fracture properties of bone tissue that are more similar to those of human bone than is true of other popular animal models [37]. Baboons resemble humans in their patterns of skeletal density changes and bone loss with increasing age, experience a natural menopause late in life [38] and show increased skeletal turnover upon ovariectomy [36, 39–40]. Finally, the captive baboon colony at Southwest National Primate Research Center (SNPRC)/Southwest Foundation for Biomedical Research (SFBR) displays a population-wide level of genetic variation that is absent in inbred rodent models.…”