Bone health in disorders of sex differentiation.

Sex steroids are main regulators of skeletal growth, maturation and mass in both men and women. People with disorders of sex development (DSD) may experience problems in developing normal bone growth, structure and mass, because abnormal sex steroid secretion or action may be operative. In complete androgen insensitivity syndrome several reports documented reduced bone mineral density (BMD). Reduced BMD is evident in patients with not removed or removed gonads, but it is poorer in the latter, mainly when compliance with estrogen replacement therapy is not guaranteed. Large impairment of BMD does not seem to be present in patients with partial androgen insensitivity syndrome or 5alpha-reductase-2 deficiency, providing that gonads are not removed or that substitutive therapy is optimized. In congenital adrenal hyperplasia, BMD may be impaired as a result of not optimal glucocorticoid administration. In Turner syndrome, impaired BMD may result from the combined actions of estrogen deficiency, low bone dimensions, altered bone geometry, deficient cortical bone, and trabecular bone loss. Optimal estrogen administration seems to be important in preserving bone mass and enhancing trabecular bone volume. On the whole, bone health represents a main clinical issue for the management of persons with disorders of sex differentiation, and well designed longitudinal studies should be developed to improve their bone health and well-being.