Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling.

Abstract

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; nandrolone-increased expression of OPG and OPG/RANKL 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.

• Authors: Li Sun, Jiangping Pan, Yuanzhen Peng, Yong Wu, Jianghua Li, Xuan Liu, Yiwen Qin, William A Bauman, Christopher Cardozo, Mone Zaidi, Weiping Qin
• Journal: The journal of spinal cord medicine (J Spinal Cord Med) Vol. 36 Issue 6 Pg. 616-22 (Nov 2013) ISSN: 1079-0268 [Print] England
• PMID: 24090150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anabolic Agents
• Nandrolone

Topics

• Anabolic Agents (pharmacology)
• Animals
• Bone Resorption (etiology, metabolism, prevention & control)
• Cell Differentiation (drug effects)
• Disease Models, Animal
• Male
• Nandrolone (pharmacology)
• Osteoblasts (cytology, drug effects, metabolism)
• Osteoclasts (cytology, drug effects, metabolism)
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Spinal Cord Injuries (complications, metabolism)
• Wnt Signaling Pathway (physiology)