Bone density and skeletal turnover in complete androgen insensitivity syndrome.

CONTEXT: Complete androgen insensitivity syndrome (CAIS) is a rare disorder caused by androgen receptor mutations. Due to malignancy concerns, patients historically underwent early gonadectomy, a practice that has come under scrutiny. Data on bone health are limited, especially considering adolescents with intact gonads and after gonadectomy.

OBJECTIVE

This work aimed to investigate bone mineral density (BMD), lean body mass (LBM), and bone turnover in CAIS with intact gonads or after gonadectomy.

METHODS

Dual-energy x-ray absorptiometry was used to assess BMD and LBM. Serum bone biomarkers and reproductive hormones were measured.

RESULTS

Seventeen individuals with CAIS were evaluated, 5 (mean age 27 years) after gonadectomy and 12 (mean age 18 years) with intact gonads. BMD Z-scores trended lower than reference standards, regardless of gonadectomy status. In participants with intact gonads, LBM was positively correlated with spinal BMD Z-score. Procollagen 1 N-terminal propeptides were higher in participants with intact gonads, while osteocalcin levels were lower. There were increased luteinizing hormone and testosterone levels, and decreased estradiol and estrone levels in those with intact gonads. In participants after gonadectomy, BMD Z-scores trended lower. LBM was positively correlated with BMD Z-score at the femoral neck and exercise score with BMD Z-score at the total hip.

CONCLUSION

These findings raise concern that low BMD represents a health risk in all individuals with CAIS, including those with intact gonads and after gonadectomy. Bone remodeling was affected negatively but there was a positive correlation between LBM and BMD. These results underscore the importance of androgens for musculoskeletal health.