Bone Health in Disorders of Sex Differentiation

Abstract

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 5α-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.

Hormonal Management of Complete Androgen Insensitivity Syndrome from Adolescence Onward

“…It may be related to a CAIS-specific sex steroid milieu characterized by a tendency to increased estrogen levels for males but clearly reduced for females (table 2) [3,4,14], leading to prolonged skeletal growth [12,15]. According to this hypothesis, the tendency to increased adult height in women with CAIS could be prevented by female-appropriate estrogen induction of puberty in adolescents without gonads [12] or some estrogen supplementation in those with intact gonads [15], but specific trials on this matter should be done to optimize management. In addition, the gene(s) on Y chromosome may contribute to the pattern of skeletal growth and maturation in CAIS [13,16].…”

“…Lumbar BMD was usually more affected than femoral BMD [15]. Impaired BMD has been related to gonadectomy not followed by appropriate HRT, even if defective AR action at bone level may contribute per se to the altered bone mineralization [15,31]. …”

“…Albeit few longitudinally followed patients are reported, the majority of the studies did not demonstrate improvements [15] – even worse BMD values under ‘classic’ HRT were found [15]. A relevant improvement has been shown in a single women with CAIS by using overphysiological doses of transdermal estrogens, but lumbar BMD remained –2.0 SDS at 5 years of follow-up [32].…”

Androgen Insensitivity Syndrome (AIS)

“…77 No defi nitive evidence shows that bone mineral density is less aff ected in women who had late gonadectomies than in women who had early gonadectomies, although those who had the procedure later in life are substantially taller than those who had early gonadectomies. 78,79 Women with complete androgen insensitivity syndrome do not seem to have an increased risk of fractures. Measurement of bone density at presentation in the case of young women with complete androgen insensitivity syndrome and at 2 yearly inter vals is a useful index of the eff ectiveness of hormone replacement (unpublished).…”

Biomaterials Applicable for Alveolar Sockets Preservation: In Vivo and In Vitro Studies

“…They help retain calcium in bones, thereby maintaining a strong bone matrix. Sex steroids not only influence the accrual of bone mass and bone mineral density but also bone growth (Manolagas et al 2002;Bertelloni et al 2010). -Growth hormone (GH) -is one of the most important regulator substances for both bone growth and bone remodelling.…”