The influence of gender on the short and long-term effects of growth hormone replacement on bone metabolism and bone mineral density in hypopituitaryadults: a 5-year study

OBJECTIVES The objectives of this study were to investigate the effects of GH replacement therapy in hypopituitary adults with growth hormone deficien cy (GHD) on activation of bone remodelling during dose titration and an BMD over a median of 58 months of continuous therapy. STUDY DESIGN Open label study in adult patients with GHD. rhGH was commence d at dose of 0.8 IU subcutaneously daily (0.4 IU If hypertensive or glucose tolerance impaired) with subsequent dose titration based on 2 weekly measu rement of serum IGF-I until levels reached the target range (between the me dian and upper end of the age related reference range). In patients previou sly commenced on GH using weight based regimens the dose of GH was adjusted during clinical follow-up in order to maintain serum IGF-I in the target r ange. PATIENTS Initial effects of GH on bone remodelling during dose titration we re studied In 17 patients (8F). Long-term effects of GH were determined in a separate group of 13 GHD adults (6F) over a median period of 58 months (r ange 44-72). MEASUREMENTS Osteoblastic activity was estimated by measuring serum bone sp ecific alkaline phosphatase (S-BAP). BMD was determined at both lumbar spin e (L2-L4) and femoral neck by dual energy X-ray absorptiometry (DEXA). RESULTS During dose titration a significant increment in S-BAP was observed by 10 weeks in females but occurred later in males (12-26 weeks). In the l ong term treatment group there was a significant increment in S-BAP compare d to baseline (P = 0.013) after 6 months GH treatment. After long-term GH t reatment (median 58 months) S-BAP levels decreased and were no longer stati stically significantly different from baseline at the end of the study peri od. A similar response was observed in male and female patients. There were no significant differences in baseline BMD between male and female patient s at either lumbar spine or femoral neck in the long term treatment group. No significant changes were observed in BMD after 6 months GH treatment: in either lumbar spine or femoral neck but BMD Increased over the remainder o f the study at both sites (P = 0.023 and P = 0.03 respectively). When analy sed by gender male patients showed a clear positive change in BMD after lon ger-term replacement in both lumbar spine and femoral neck (P = 0.01 and P = 0.02 respectively) but female patients showed no significant changes. Qua litatively similar results were observed when analysing changes in BMD expr essed as Z scores. CONCLUSION This study demonstrates an earlier onset of GH activation of bon e remodelling as reflected by S-BAP in females compared to males and confir ms that long-term GH treatment in hypopituitary adults with GH deficiency i ncreases or preserves BMD both at lumbar spine and femoral neck. However ma le patients seem to derive the greater benefits in BMD from long-term GH re placement; in females BMD appears simply to be stabilized rather than incre ased. This constitutes a genuine gender difference in susceptibility given that serum IGF-I was in the upper part of the reference range in all subjec ts.