Testosterone replacement therapy in older men: skeletal outcomes and fracture risk

Testosterone replacement therapy (TRT) is increasingly prescribed to older men with symptomatic testosterone deficiency, yet the balance of musculoskeletal benefits and harms remains uncertain.

To synthesise current evidence on TRT-related effects on bone, muscle, falls/fractures, and tendon outcomes in older men, and to contextualise these findings within plausible mechanisms and recent regulatory positions.

We conducted a state-of-the-art narrative review of randomised controlled trials, meta-analyses, clinical guidelines, and large observational/registry-based studies assessing musculoskeletal and tendon endpoints in older men receiving TRT.

Across trials, TRT consistently increases lean mass and reduces fat mass, while improvements in strength and physical performance are generally modest and heterogeneous. Evidence indicates small-to-moderate increases in bone mineral density, particularly at the spine and hip, but robust proof of fracture prevention is lacking. In the Testosterone Trials, TRT improved several surrogate musculoskeletal measures but did not reduce falls. In the TRAVERSE fracture analysis, TRT did not lower fracture risk and a higher fracture incidence was reported in the TRT group (hazard ratio 1.43).

Observational data suggest an association between TRT initiation and tendon injury, although causal inference is limited by confounding and detection bias. A potential explanation is a temporal mismatch between relatively rapid gains in muscle capacity and slower adaptation of tendon and bone to increased loading.

In older men with confirmed hypogonadism, TRT may improve body composition and selected functional outcomes, but it should not be considered a disease-modifying strategy for preventing falls or fractures. Careful patient selection, assessment of baseline fracture/tendon risk, and structured monitoring are warranted, particularly in the context of evolving regulatory warnings regarding TRT use for age-related low testosterone.