Skeletal Effects of Aging, Menopause and Dietary Restriction in Rhesus Macaques





R.J. Colman

Wisconsin Regional Primate Research Center
University of Wisconsin, Madison
1220 Capitol Court
Madison, WI 53715




Because the pathophysiology of human bone loss is not completely understood, use of animal models, especially nonhuman primates is necessary. To further define this model, we explored the impact of age, natural menopause and lumbar spine osteoarthritis (OA) on the skeleton in 44 male (10-34 years of age) and 46 female (10-30 years of age) rhesus macaques (Macaca mulatta). Additionally, as dietary restriction (DR) retards many aspects of aging, its impact upon age-related skeletal changes was explored in 30 male (15 control [C], 15 restricted [R]) rhesus macaques. In the first study, bone mineral content (BMC) and density (BMD) were evaluated once per animal by dual-energy x-ray absorptiometry (DXA), and degree of OA was determined by standard radiographs. Serum parameters of bone turnover and skeletal relevance were measured in fasting blood samples. Bone mass at the lateral spine and distal radius in males was lower with advancing age (p<0.01). Postmenopausal females had lower bone mass of the total body, distal radius, posterior-anterior and lateral lumbar spine than premenopausal animals (p<0.05). Osteocalcin and ICTP levels decreased with age in males (p<0.01), and osteocalcin increased following menopause in females (p<0.01). With advancing age, OA became very common, causing increased DXA-measured bone mass. These data suggest that male rhesus monkeys sustain age-related bone loss in the absence of nutritional and gonadal steroid deficiencies and that female rhesus monkeys show decreased bone mass and increased skeletal turnover following natural menopause. In the DR study, bone mass, bone turnover, serum markers of skeletal relevance and degree of OA were examined. The animals (8-14 years at study onset) have been followed through 108 months of moderate (30%) DR which reduced body weight by 12 months (p<0.05). This difference was maintained through 108 months (p<0.001). Calcium, phosphorus, alkaline phosphatase, testosterone, FSH, and turnover markers were not different between R and C groups. Total body BMC was lower (p<0.01) in R compared to C animals. Lumbar spine BMC and BMD were lower (p < 0.01) in R animals from 72-108 months. Lumbar spine OA prevalence was lower in R than C groups (42% compared to 92%). Regression analysis of total body BMC (TBBMC) vs. body weight revealed no slope or group difference between C and R groups. In humans, lower body weight is associated with lower peak bone mass. It is not known whether extrapolation of such human data to monkeys is appropriate. However, doing so predicted TBBMC to be ~21% lower in the R group, comparable to the 23% observed at 108 months. As such, the lower bone mass observed in DR monkeys reflects lower body weight, not pathological osteopenia. To conclude, rhesus macaques appear to be an excellent model for estrogen-depletion bone loss in women, following both ovariectomy and natural menopause, and to replicate age-related skeletal changes in men. In addition, DR did not cause deleterious endocrine effects, afforded protection against OA, and produced appropriately lower bone mass.




Key words: Bone mass, aging, menopause, dietary restriction, rhesus monkey







Problems or questions regarding this site should be directed to webmaster@americanaging.org