The Role of Sex and Gender in Transgender Bone and Other Musculoskeletal Health.

ABSTRACT: Musculoskeletal changes occur with gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS) used in the care of transgender adolescents and adults. Survey results have shown that orthopaedic surgeons desire to care for transgender individuals but express concern over a knowledge deficit. This article reviews the physiology and pathophysiology that may occur with GAHT and GAS. Transgender women have lower bone mineral density (BMD) prior to GAHT than cisgender men. Limited fracture data would suggest that transgender women >50 years of age have fracture rates similar to those of cisgender women. Transgender men have normal BMD prior to GAHT and are not at an increased risk for fracture compared with cisgender women. The use of puberty-blocking medications in the care of transgender youth does result in a decline in BMD, which returns to baseline with GAHT, but the effect of delaying puberty on maximal BMD and the lifetime fracture risk are unknown. At present, dual x-ray absorptiometry (DXA) is used to measure BMD and assess fracture risk. Attention should be paid to using the appropriate reference group in the interpretation of DXA for transgender individuals. Promote musculoskeletal health by ensuring appropriate calcium, vitamin D, weight-bearing activity, and a healthy lifestyle. Adherence to GAHT needs to be encouraged to avoid bone loss. Data with regard to therapy for osteoporosis in transgender patients have been lacking, but, at present, use of available therapies is expected to be effective. Information with regard to differences in other musculoskeletal health issues such as joint injuries has been lacking in transgender individuals.

Which Drug Next? Sequential Therapy for Osteoporosis.

The proliferation of drugs with unique modes of action for treating osteoporosis has been most welcome. Fear of complications, even though rare, associated with long-term bisphosphonates (BPs) changed prescribing patterns. The BPs are stored in bone for years. Drugs not stored in bone; for example, abaloparatide, teriparatide, denosumab, and romosozumab have expanded our armamentarium for treating osteoporosis but have brought new challenges. Bone accrued during treatment with the last 3 drugs, and perhaps abaloparatide, is lost rapidly after their withdrawal due to rebound increase in bone resorption. Treatment with these drugs must be followed by administration of an antiresorptive agent. The article by Kendler et al. (1) in this issue of JCEM reports alendronate preserves bone accrued during administration of denosumab.

Osteoporosis associated with excess glucocorticoids.

Excess glucocorticoids, whether endogenous or exogenous, can cause osteoporosis and fractures. Even low doses of oral glucocorticoids and mild endogenous hypercortisolism may be associated with bone loss. Patients treated with glucocorticoids, however, often are not evaluated and treated for this problem. Patients on chronic glucocorticoids or initiating these drugs should have their bone density measured and appropriate laboratory studies. They should be treated with adequate calcium and vitamin D, and antiresorptive therapy (particularly bisphosphonates) should be considered.