Testosterone supplementation and bone parameters: a systematic review and meta-analysis study.

The role of testosterone (T) replacement therapy (TRT) in subjects with late onset hypogonadism is still the object of an intense debate. All observational studies and placebo-controlled or -uncontrolled randomized trials (RCTs) comparing the effect of TRT on different bone parameters were considered. Out of 349 articles, 36 were considered, including 3103 individuals with a mean trial duration of 66.6 weeks. TRT improves areal bone mineral density (aBMD) at the spine and femoral neck levels in observational studies, whereas placebo-controlled RTCs showed a positive effect of TRT only at lumber spine and when trials included only hypogonadal patients at baseline (total testosterone < 12 nM). The effects on aBMD were more evident in subjects with lower T levels at baseline and increased as a function of trial duration and a higher prevalence of diabetic subjects. Either T or estradiol increase at endpoint contributed to aBMD improvement. TRT was associated with a significant reduction of bone resorption markers in observational but not in controlled studies. TRT is able to inhibit bone resorption and increase bone mass, particularly at the lumbar spine level and when the duration is long enough to allow the anabolic effect of T and estrogens on bone metabolism to take place. © 2022. Italian Society of Endocrinology (SIE).