The specific aim is to document the status of the trabecular bone remodelling system in adult female baboons, before and after ovariectomy, using a serial tetracycline labeling and biopsy technique which enables longitudinal study of the changes in bone remodeling parameters in individual animals. The resulting data will enable the design and evaluation of therapies which counter specific bone turnover abnormalities caused by loss of ovarian function, and will establish methodology with wide application for the study of skeletal diseases of aging in nonhuman primate models. The study has direct applicability to the understanding of the mechanisms resulting in bone loss, and ultimately the clinical syndrome of osteoporosis, in post-menopausal women, a major health problem in the United States. Ten young, skeletally-mature female baboons will be tetracyline-labeled and have serial iliac crest, rib and tail biopsies before and after ovariectomy. Ovariectomy mimics the hormonal changes of menopause without the confounding variable of aging. Biopsy samples will be embedded in methyl methacrylate, sectioned, and evaluated using an IBM personal computer-based digitizing system for determination of static and dynamic histomorphometric descriptors of bone remodeling processes. The experimental design includes features which control for prior biopsy effects and will yield data on specific changes in bone remodelling parmeters induced by ovariectomy in trabecular bone. Cortical bone will also be evaluated, and ovariectomy effects documented. The animals will be sacrificed 2 to 3.5 years after ovariectomy and clinically significant skeletal sites (lumbar vertebrae, femoral neck, distal radius) evaluated as for biopsies. Serum levels of relevant elements, hormones, and enzymes will be monitored throughout the course of the study.
| Jerome, C P; Carlson, C S; Register, T C et al. (1994) Bone functional changes in intact, ovariectomized, and ovariectomized, hormone-supplemented adult cynomolgus monkeys (Macaca fascicularis) evaluated by serum markers and dynamic histomorphometry. J Bone Miner Res 9:527-40 |
| Jayo, M J; Weaver, D S; Adams, M R et al. (1990) Effects on bone of surgical menopause and estrogen therapy with or without progesterone replacement in cynomolgus monkeys. Am J Obstet Gynecol 163:614-8 |
| Jerome, C P (1989) Estimation of the bone mineral density variation associated with changes in turnover rate. Calcif Tissue Int 44:406-10 |
| Jerome, C P; Kimmel, D B; McAlister, J A et al. (1986) Effects of ovariectomy on iliac trabecular bone in baboons (Papio anubis). Calcif Tissue Int 39:206-8 |
