Altered bone mineral density in patients with complete androgen insensitivity syndrome

Androgens have major influences on the regulation of bone mineralization. Because of their unique peripheral metabolism androgens may act on bone via activation of the androgen and/or estrogen receptor. Patients with complete androgen insensitivity syndrome (cAIS) are natural models to assess androgen actions on bone. We studied bone mineral density (BMD) in 10 patients with cAIS (mean age 13.70, range 4.7-19.8 years); 3 patients were studied before gonadectomy; the others were castrated and 6 were on hormonal replacement therapy. The BMD area (aBMD) was measured by dual energy X-ray; lumbar 'apparent' volumetric density (vBMD) was calculated using the formula VBMD = aBMD x [4/(pi x width)]. In the patients, aBMD (0.72 +/- 0.16 g/ cm(2)) and VBMD (0.23 +/- 0.04 g/cm(3)) were significantly (p < 0.001)reduced in comparison with those of a control group (n = 15, age 5.0-20.5 years: aBMD 1.028 +/- 0.20 g/cm(2); vBMD 0.35 +/- 0.04 g/cm(3)). Both aBMD and vBMD were also reduced in comparison with normal values for males (aBMD -2.66 +/- 0.99 SDS, p < 0.001; vBMD -3.08 +/- 1.53 SDS, p < 0.0005) and females (aBMD -2.88 +/- 1.05 SDS, p < 0.001; VBMD -2.84 +/- 1.18 SDS, p < 0.0007). Real lumbar bone density, assessed by computed tomography in 1 patient, was also reduced (-6.2 SDS and -3.5 SDS for male and female normal values, respectively). Biochemical markers of bone metabolism were normal and not significantly different in patients and controls. Girls with cAIS did not have more fractures than controls. In conclusion, both aBMD and VBMD are reduced in cAIS patients, while bone turnover and the fracture risk seem not to be increased. Our data indicate that both androgens and estrogens may be required for acquisition of bone density during childhood.