Effects of Recombinant Human Growth Hormone Therapy on Bone Mineral Density in Adults With Growth Hormone Deficiency: A Meta-Analysis

Objective: GH deficiency is associated with decreased bone mineral density (BMD) and increased fracture risk. Because the effects of recombinant human GH (rhGH) therapy on BMD and bone mineral content have not been systematically investigated, we conducted a meta-analysis of pertinent studies. Design: A thorough search of the literature (MEDLINE, EMBASE, and the Cochrane Register) was performed. Relevant studies were divided and analyzed according to their design (randomized/controlled or prospective/retrospective) and duration of rhGH therapy (<12 months and >12 months). Results: Administration of rhGH led to a significant increase in lumbar spine (LS) and femoral neck (FN) BMD in randomized/controlled studies of more than 1 year [weighted mean difference (95% confidence interval)] of 0.038 g/cm(2) (0.011-0.065) and 0.021 g/cm(2) (0.006-0.037) at the LS and FN, respectively, and a nonsignificant drop at the same sites in studies of shorter duration. In prospective studies, a significant increase in the LS and FN BMD was obtained. On meta-regression, a negative association was observed between the change in LS and FN BMD and subjects' age and a positive association between the BMD change and treatment duration. In a subgroup analysis, the increase in LS and FN BMD was significant in men [0.048 g/cm(2) (0.033-0.064) and 0.051 g/cm(2) (0.003-0.098), respectively] but not in women. Conclusion: This meta-analysis suggests a beneficial effect of rhGH replacement on BMD in adults with GH deficiency. This effect is affected by gender, age, and treatment duration. Larger studies are needed to evaluate the effect of rhGH on fracture risk.