Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement

Background: Only few previous studies have assessed the effects of long-ter m growth hormone (GH) replacement therapy on bone mineral density (BMD) in adult patients with GH deficiency. The aim of this study was to investigate the effects of long-term GH therapy on bone metabolism and BMD. Material a nd methods: At the start of the study, 20 adults with GH deficiency were ra ndomized to receive either GH, 0.25 IU x kg per week, or placebo. After 6 m onths, patients in the placebo group were switched to GH therapy, and they received GH for a further 18 months. Of the 20 patients, 14 were male and 6 female with CH deficiency of adult-onset. The mean age of the patients at the start of the study was 40.3 +/- 10.9 years and the duration of GH defic iency was 10.6 +/- 6.4 years. Patients deficient in pituitary hormones othe r than GH had been receiving stable replacement doses of appropriate hormon es for at least 6 months before the start of the study. Rates of bone metab olism were assessed by measuring calcium, phosphate, alkaline phosphatase, calciuria, phosphaturia and osteocalcin. BMD was measured by dual Xray abso rptiometry. Body composition was calculated from measurements of bioelectri cal impedance. Results: Before GH treatment, BMD in the femoral neck was lo wer in patients than in controls. The rate of bone resorption markers incre ased significantly after 6 months and remained stable during the whole trea tment period. BMD significantly increased in L2-L4 after 12 months of treat ment with an increase of Z-score. The total BMD increase was 4.5 +/- 6.5%. BMD in the femoral neck increased after 12 months with an increase of Z-sco re after 18 months. The total increase was 10.4 +/- 18%. The total BMD incr ease was not different among patients with or without basal osteopenia. In both groups BMD in L2-L4 and in the femoral neck remained stable after 12 m onths without GH treatment. Sex, age, BMI and the time in which GH deficien cy started, before or after the end of the peak of BMD, did not correlate w ith BMD. The BMD values and their response to CH treatment did not correlat e with other associated deficiencies, and we did not find differences among BMD increase and GH dose, levels of insulin-growth factor-I, insulin growt h factor binding protein-3, and parameters of body composition. Conclusions : The results of the study support previous ones that BMD is subnormal in a dults with GH deficiency; that CH replacement therapy stimulates bone turno ver with initial biochemical changes; and that in the long term, this stimu lation results in a significant augmentation in BMD that continues to incre ase after 2 years and remains stable after 12 months of GH withdrawal.