Effects on bone of surgical menopause and estrogen therapy with or without progesterone replacement in cynomolgus monkeys

Abstract

The influence of estrogen replacement therapy on bone loss of surgically postmenopausal cynomolgus macaques was evaluated histomorphometrically using the first (L-1) lumbar vertebra and ex vivo dual photon absorptiometry of the third (L-3) lumbar vertebra. The animals were a subgroup of a larger study on the effects of estrogen replacement therapy on diet-induced coronary artery atherosclerosis. The three experimental conditions were as follows: untreated females with oophorectomy, females with oophorectomy treated with continuous estrogen replacement therapy plus cyclic progesterone, and females with oophorectomy treated with estrogen replacement therapy. Bone mineral density (grams per square centimeter) of L-3, when covaried for body mass index (body mass index, body weight/(trunk length/100)2), was significantly lower for the oophorectomy group compared with the group treated by estrogen replacement therapy plus progesterone and estrogen replacement therapy groups (p = 0.018). When covaried for body mass index, trabecular bone volume percentage of a midsagittal section of L-1 was not significantly different between groups, but the adjusted mean was greatest in the estrogen replacement therapy plus progesterone group, followed closely by the estrogen replacement therapy group, and was least in the oophorectomy group. When covaried for body mass index, trabecular plate number was significantly lower (p = 0.022) and mean trabecular plate separation was significantly higher (p = 0.033) in the oophorectomy group. Thus both estrogen replacement therapy and estrogen replacement therapy plus progesterone provided overall protection against surgical menopause-associated bone mass loss. Cynomolgus macaques are an extremely useful animal model for estrogen replacement therapy use in prevention of postmenopausal bone loss.