SHORT-TERM AND LONG-TERM EFFECTS OF GROWTH-HORMONE TREATMENT ON BONE TURNOVER AND BONE-MINERAL CONTENT IN ADULT GROWTH HORMONE-DEFICIENT MALES

OBJECTIVE In view of the fact that GH-deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH-deficient adult males. DESIGN We performed a 6-month randomized, double-blind, placebo-controlled study, followed by 12-24 months of GH treatment in all patients. PATIENTS Twenty adult males with GH deficiency of childhood onset were studied. MEASUREMENTS We measured serum IGF-I, serum phosphate, biochemical indices of bone turnover (serum alkaline phosphatase activity, serum osteocalcin, serum carboxyterminal propeptide of type-I procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios) and bone mineral content, measured at the forearm and the lumbar spine by single and dual-photon absorptiometry respectively. RESULTS After 3 and 6 months of GH administration, the serum levels of alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type-I procollagen, and the fasting urinary hydroxyproline/creatinine ratio were significantly increased compared to placebo-treated patients (P < 0.01 to P < 0.001). During the open study phase, the values for these indices of bone turnover remained elevated above pretreatment levels (P<0.01 to P<0.001 at 12 months), a downward trend becoming apparent after about one year of GH treatment. BMC values showed an initial decline after 3 months of GH treatment (most likely due to an expansion of the remodelling space), followed by a significant and progressive increase above pretreatment values, reaching 7.8% for total BMC at the lumbar spine (L2-L4) and 9.9% for total BMC at the forearm, after 30 months of GH administration. CONCLUSIONS The data of our study show that administration of substitutive doses of growth hormone to GH-deficient adult males activates bone turnover for a period of at least one year and suggests that this may have a beneficial effect on bone mass in these patients.