Anabolic steroid use increases intervertebral disc height and reduces vertebral subchondral bone volume in the lumbar spine in male mice

Abstract Anabolic steroids are increasingly explored for the management of musculoskeletal disease. Physiological testosterone levels support joint health, and supraphysiological levels of testosterone are linked to increased intervertebral disc (IVD) height and reports of vertebral endplate hyperconcavity. The ability of high-dose testosterone to modulate joint repair or degeneration remains speculative. The goal of this study was to determine if supraphysiological doses of testosterone promote IVD repair or alter the progression of age-associated IVD degeneration or knee osteoarthritis (OA) in the mouse. To assess injury repair, a percutaneous caudal IVD puncture was implemented at Co7/Co8 in 16.5-month-old male CD-1 mice (N=8/group). The lumbar spines of these mice were uninjured to assess age-related IVD degeneration. Mice were treated weekly with 15 mg/kg of testosterone enanthate for 6 weeks to emulate anabolic steroid use. Changes to IVDs and vertebral bones were assessed using microCT and histopathology, and the severity of knee OA was assessed by histopathology. In the caudal spine, loss of disc height induced by IVD puncture was partially rescued by testosterone with histological features associated with repair. In the lumbar spine, testosterone induced subchondral bone loss within the vertebral bodies, increased disc height, and promoted endplate hyperconcavity. Knee histopathology revealed severe OA by 18 months of age, irrespective of treatment. These findings highlight context-dependent effects of testosterone at doses modelling anabolic steroid use. Testosterone rescued disc height loss following IVD injury in the tail but did not improve age-associated IVD degeneration or knee OA. In the lumbar spine, testosterone induced vertebral subchondral bone loss, and increased disc height associated with endplate hyperconcavity resembling radiographic changes described as codfish vertebrae associated with osteoporosis and prolonged steroid therapy. Taken together, these findings suggest that both the IVD and vertebral bone respond to supraphysiological testosterone, with important differences in injury and age-associated degeneration.