Anabolic Steroids as a Novel Therapeutic Strategy for the Prevention of Bone Loss after Spinal Cord Injury: Animal Model and Molecular Mechanism
Final rept. 30 Sep 2010-29 Sep 2012
BRONX VETERANS MEDICAL RESEARCH FOUNDATION INC (VETERANS AFFAIRS) NEW YORK
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Background Spinal cord injury SCI causes severe bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men after SCI and may exacerbate bone loss. The anabolic steroid nandrolone reduces bone loss due to microgravity or nerve transection. Objective To determine whether nandrolone reduced bone loss after SCI and, if so, to explore the mechanisms of nandrolone action. Methods Male rats with complete transection of the spinal cord were administered nandrolone combined with a physiological replacement dose of testosterone, or vehicle, beginning on day 29 after SCI and continued for 28 days Results SCI reduced distal femoral and proximal tibial bone mineral density BMD by 25 and 16, respectively, at 56 days. This bone loss was attenuated by nandrolone. In ex vivo osteoclasts cultures, SCI increased mRNA levels for tartrate-resistant acid phosphatase TRAP and calcitonin receptor nandrolone-normalized expression levels of these transcripts. In ex vivo osteoblast cultures, SCI increased receptor activator of NF-kB ligand RANKL mRNA levels but did not alter osteoprotegerin OPG mRNA expression nandroloneincreased expression of OPG and OPGRANKL ratio. SCI reduced mRNA levels of Wnt signaling-related genes Wnt3a, low-density lipoprotein receptor-related protein 5 LRP5, Fzd5, Tcf7, and ectodermal-neural cortex 1 ENC1 in osteoblasts, whereas nandrolone increased expression of each of these genes. Conclusions The results demonstrate that nandrolone reduces bone loss after SCI. A potential mechanism is suggested by our findings wherein nandrolone modulates genes for differentiation and activity of osteoclasts and osteoblasts, at least in part, through the activation of Wnt signaling.
- Anatomy and Physiology
- Medicine and Medical Research