Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Postmenopausal osteoporosis is a debilitating condition which affects 25% of Caucasian women. To date, neither prophylaxis nor treatment have met with any great success. Calcium supplementation (CaSuppl) has been widely advocated in the prevention and treatment of osteoporosis despite the paucity of scientific evidence suggesting that calcium has any beneficial effect. We have employed an oophorectomised rat model to investigate the effects of oestrogen deficiency on the skeleton and bone marrow. In this laboratory approach it was also possible to examine the effects of calcium in this model.;Adult female rats were either oophorectomised or sham operated, and fed either a basal or CaSuppl diet for 6 weeks before and after surgery.;Trabecular bone volume (TBV) was quantified in the tibia, bone calcium content (BCC) in the femoral heads, and cortical and medullary areas in the femoral midshaft. Oophorectomy resulted in decreased TBV, decreased BCC, expansion of the marrow space and thinning of the cortices. Thus, this model of osteoporosis appeared to mimic the human condition in terms of the skeletal changes. With CaSuppl TBV, BCC, and cortical bone were increased in oophorectomised animals, such that, although oophorectomy still induced mineral loss, the effects were minimized.;Oophorectomy resulted in decreased plasma calcium, and 1,25-dihydroxyvitamin D. Casuppl increased these in both oophorectomised and sham operated rats, and increased plasma parathyroid hormone in oophorectomised rats only.;In experiments designed to investigate possible relationships between the source of osteoprogenitors and the induced osteopenia, bone marrow mononuclear cells (BC) were harvested from tibiae and proliferative capacity (PC) was assessed both with and without mitogenic stimulation. Oophorectomy resulted in a 4-fold increase in the basal PC of BC. With mitogenic stimulation PC was enhanced, however, cells from oophorectomised rats had a 3-fold greater response. CaSuppl suppressed the increase in basal and mitogen stimulated PC induced by oophorectomy.;To conclude, in a model of postmenopausal osteoporosis, calcium supplementation appeared to protect against ovarian hormone deficiency, and the data described herein have led to planning of future research protocols which may yield new insights into the pathophysiology of osteoporosis at the cellular level.



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