Effect of testosterone use on bone mineral density in men : a systematic review and meta-analysis of randomized controlled trials

Abstract

Background The use of testosterone replacement therapy as treatment for clinical androgen deficiency has been growing in popularity. Low androgen levels are related to lower bone density in men, so testosterone might protect bone health. Bone mineral density is a biomarker for osteoporosis, which is associated with fractures. One systematic review and two previous meta-analyses have assessed the effect of testosterone replacement on bone health, one in 2005 and the other in 2006. This study provides an update focusing on the group who are increasingly using testosterone, i.e., older men. This study provides an up-to-date meta-analysis from randomized controlled trials of the effect of testosterone replacement on bone mineral density in middle-aged to older men.

Methods A search of PubMed for randomized placebo-controlled trials was conducted until May of 2015, using the search term “(androgen OR testosterone) AND bone AND men AND trial” restricted to studies in English. A bibliographic search yielded no additional trials. Studies included in this meta-analysis were chosen using the following pre-specified inclusion and exclusion criteria. Trials were included if they were randomized, lasted at least 6 months, published before May of 2015, included men over 40 years with androgen deficiency, measured bone mineral density in g/cm3, and included at least one group given testosterone alone through oral, transdermal, or intramuscular means. Trials were excluded if they were not published in English or did not report adequate data for analysis. Quality of the studies was assessed using the Jadad scale. Sensitivity analysis was done excluding low quality studies. Meta-regression was performed on pre-determined subgroups based on testosterone dosage, duration of trials, baseline testosterone status, method of testosterone administration, and glucocorticoid use.

Results The search of PubMed yielded 390 studies, of which 13 met the inclusion criteria. In an analysis of all studies, bone density of the lumbar spine increased by 0.023 g/cm3 (95% confidence interval (CI) 0.009 to 0.037) on testosterone, but bone mineral density of the femoral neck did not (0.006 g/〖cm〗^3 (95% CI -0.001 to 0.013)). Heterogeneity across studies was high. Sensitivity analysis based on trials with a higher Jadad score gave a smaller effect of testosterone on lumbar spine bone density (0.014, 95% CI 0.0004 to 0.030) but the estimate for the femoral neck (0.008, 95% CI 0.0003 to 0.016) was slightly larger. Meta-regression showed method of testosterone administration explained a large amount of heterogeneity, and that intramuscular injections were associated with the largest increase in bone mineral density when compared to oral or transdermal testosterone. Conclusions This updated meta-analysis indicates that testosterone treatment has little effect on bone mineral density, especially after taking study quality into account. The conclusions of this study are greatly limited by the lack of fracture outcome. Given the very recent warnings from regulators about adverse cardiovascular events associated with testosterone replacement, testosterone does not appear to be a good option for the prevention or treatment of osteoporosis in men.