ELSEVIER Bone Vol. 20, No. 4 April 1997:355-364 The Androgenic Anabolic Steroid Nandrolone Decanoate Prevents Osteopenia and Inhibits Bone Turnover in Ovariectomized Cynomolgus Monkeys C. P. JEROME, 1 R. A. POWER, 1 I. O. OBASANJO, 1 T. C. REGISTER, 1 M. GUIDRY, 1 C. S. CARLSON, 1 and D. S. WEAVER 2 I Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, and 2Department of Anthropology, Wake Forest University, Winston-Salem, NC, USA We examined the effects of nandrolone decanoate (25 mg im every 3 weeks) on bone mass, serum biomarkers, and bone histomorphometric endpoints in 52 female cynomolgus ma- caques randomized into four treatment groups: (1) sham- ovariectomized (sham); (2) ovariectomized + placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (Nan); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNan). Serum alkaline phosphatase (ALP), osteo- calcin, and tartrate-resistant acid phosphatase (TRAP) were assayed every 3 months, and X-ray densitometry of the lum- bar spine was done every 6 months. Fluorochrome-labeled iliac biopsies collected at baseline and 1 year, and lumbar vertebrae and midshaft femur collected at 2 years, were evaluated histomorphometrically. Body weight increased over 50% with administration of nandrolone. After 2 years, ovx animals had lower spinal BMC and BMD than all other groups. Ovx animals also had higher bone turnover rates than all other groups, as indicated by higher levels of the serum and urine biomarkers, and by at least twofold higher label-based bone formation rates in the femur diaphysis and in both cancellous and cortical bone of the ilium and verte- bral bodies. Nandrolone-treated animals had similar serum estradiol levels as the sham animals, presumably due to con- version of endogenous or exogenous androgens. The effects of nandrolone on bone in this experiment are consistent with estradiol action and may be attributable to the increased serum estradiol. Despite >50% higher body weight, nandro- lone-treated, ovariectomized animals did not have higher bone mass than sham animals. (Bone 20:355-364; 1997) © 1997 by Elsevier Science Inc. All rights reserved. Key Words: Nandrolone decanoate; Bone mass; Serum bone biomarkers; Bone histomorphometry; Postmenopausal osteopo- rosis; Cynomolgus macaques. Address for correspondence and reprints: Christopher Jerome, Depart- ment of Comparative Medicine, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. Introduction Estrogen replacement therapy is beneficial in the prevention and treatment of osteoporosis in women. Although the efficacy of androgen administration in treating osteoporosis is not as well defined, there is evidence suggesting that androgens may pro- tect against bone loss in both genders. Hypogonadal men have lowered bone density, and treatment with androgens appears to improve this condition. 435'22"24'31 Both serum testosterone levels and bone mass decrease with aging in men, ~4'5° although significant correlations between serum testosterone levels and bone density have not been observed in the same individualsJ 8 In women, there is also evidence for androgenic effects on bone. Hyperandrogenic amenorrheic women have higher bone den- sity than women with other forms of amenorrhea, ~7'56 and posi- tive correlations between bone density and serum testosterone levels have been reported in women. 9'59 Dihydrotestosterone in- creased bone mass in ovariectomized rats, ~3 and the treatment of orchidectomized rats with androgens protected against bone 1OSS.61 Nandrolone decanoate is a synthetic, anabolic androgen that has been tested in several clinical trials in postmenopausal, os- teoporotic women. In these trials, nandrolone increased bone mass in the radius 28"3°'46'48'49 and spine, 26"37'55 decreased meta- carpal endosteal lOSS, 16 decreased fracture rate, 28 and increased iliac BV/TV in a small number of patients biopsied. 26 The ef- fect of nandrolone on bone mass was generally attributed to inhibition of bone resorption, because nandrolone decreased urinary calcium 28'46'49 and hydroxyproline excretion. 28 Markers of bone formation were increased slightly, 26 or not at all, 3° but bone-forming (osteoid) surfaces increased in a small num- ber of patients biopsied. 26 No clinical trials have been con- ducted using nandrolone therapy in the early postmenopausal period. Ovariectomized cynomolgus macaques exhibit changes in bone mass and function similar to those occurring in women after natural or surgical menopause. Thus, macaques are an excellent animal model for studying the pathogenesis of postmenopausal osteoporosis and the effects of hormonal interventions. Although the effects of estrogen replacement therapy on bone mass and serum bone biomarkers in this model have been docu- mented, 34'36 little is known regarding the effects of androgen administration on bone in these animals. The present study was designed to examine the effects of long-term nandrolone deca- © 1997 by Elsevier Science Inc. 355 8756-3282/97/$17.00 All rights reserved. PII $8756-3282(97)00008-2