The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism

Objective. The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with biosynthetic human GH in hypopituitary adults on aspects of calcium homeostatis, bone metabolism and bone mineral mass. Patients. Forty hypopituitary adults (21 females and 19 males; aged 19-67 years). Design. A prospective randomized double-blind placebo-controlled trial lasting for 6 months. Protocol. Following baseline assessments, GH was given in a daily dose of 0.02-0.05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. Measurements. Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. Results. Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I increased significantly on GH treatment (mean±SD) (GH:276±197 vs P:88±50 μg/l, P < 0.0001 at 6 months). Plasma calcium increased slightly but significantly In the GH-treated group (2.23±0.11-2.29 ±011 mmol/l, P<0.05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2.29±011; P, 2.26±0.09 mmol/l). Plasma phosphate increased on GH (GH: 1.02±0.23-1.32±019; P: 0.99±0.16-0.96±012 mmol/l over the 6 months of treatment, P<0.001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104±32 vs P: 69±32 U/l, P<0.01, osteocalcin: GH: 17.2±8.0 vs P: 5.3±3.2 μg/l, P<0.001 and P1CP:GH: 207±152 vs P: 93±31 μg/l, P<0.01). There was no difference in the intact parathyroid hormone level (GH: 31±14 vs P:31±15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. Conclusion. In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.