Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis

Abstract

A B S T R A C T In 29 women with postmenopausal osteoporosis, the proportion of total bone surface undergoing resorption or formation was evaluated by microradiography of iliac crest biopsy samples before and after shortterm (21-4 months) and long-term (26-42 months for estrogen and 9-15 months for anabolic hormone) treatment. After estrogen administration, values for boneresorbing surfaces decreased, although less prominently after long-term than after short-term therapy. The magnitude of this decrease was positively correlated with the pretreatment value for bone-resorbing surfaces (P < 0.001). When the pretreatment value for bone-resorbing surfaces was used as a covariable, estrogen and anabolic hormone appeared to be equally effective. For boneforming surfaces, short-term therapy with either hormone had no effect but long-term therapy significantly decreased the values. Serum immunoreactive parathyroid hormone (IPTH) increased significantly after estrogen therapy; the change in IPTH was inversely related to the change in serum calcium (P < 0.001, sign test). We conclude that the primary effect of sex hormones in postmenopausal osteoporosis is to decrease the increased level of bone resorption, perhaps by decreasing the responsiveness of bone to endogenous parathyroid hormone. However, this favorable effect, at least in part, is negated after long-term treatment by a secondary decrease in bone formation. Our data are consistent with the concept that the maximal benefit that can be derived from sex hormone therapy in postmenopausal osteoporosis is arrest or slowing of the progession of bone loss.

Androgen effects on bone metabolism: recent progress and controversies

“…The direct effects of androgens on bone metabolism in vivo have been extensively assessed in animal studies (largely rodents) (59)(60)(61)(62)(63)(64)(65) and clinical or epidemiological studies (5,7,8,(11)(12)(13)(14)(15). The endpoints of these studies were BMD (5, 7, 8, 11-13, 59, 64-66, 68-80), static or dynamic histomorphometry (7, 59-62, 64, 65, 67, 68, 87, 88), measurement of biochemical markers of bone formation and bone resorption (5,12,65,66,69,(81)(82)(83)(84)(85)(86)(87)(88), or biomechanical properties of bone (63).…”

“…The endpoints of these studies were BMD (5, 7, 8, 11-13, 59, 64-66, 68-80), static or dynamic histomorphometry (7, 59-62, 64, 65, 67, 68, 87, 88), measurement of biochemical markers of bone formation and bone resorption (5,12,65,66,69,(81)(82)(83)(84)(85)(86)(87)(88), or biomechanical properties of bone (63). The majority of studies were performed either in spontaneous or orchiectomy-induced hypogonadism with or without subsequent androgen replacement therapy, or androgen treatment of eugonadal male or female subjects.…”

“…Androgen deficiency results in various abnormalities of bone metabolism, including a tall eunuchoid stature due to unfused growth plates and thinner (particularly cortical) bones as well as a lower peak bone mass and accelerated bone loss due to increased bone resorption, resulting in a higher fracture risk (1). While the clinical and biochemical effects of androgens (and androgen deficiency) on bone metabolism are well appreciated (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), the cellular and molecular action(s) of androgens on bone cells have remained largely unclear.…”

Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

“…In pre-and postmenopausal women, endogenous androgen levels correlate with BMD (25,26). Furthermore, a study comparing estrogen to a synthetic androgen in postmenopausal osteoporotic women showed that both steroids were equally effective in reducing bone resorption (27). Also, a 2-year double-blind trial showed that estrogen plus a non-aromatizable androgen significantly improved BMD over estrogen alone in surgically menopausal women (28).…”

“…Also, a 2-year double-blind trial showed that estrogen plus a non-aromatizable androgen significantly improved BMD over estrogen alone in surgically menopausal women (28). Therefore, exogenous androgens promote BMD maintenance in women when used alone (27) and in conjunction with estrogen (28).…”