The effects of prolonged growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults*

Abstract

Short-term GH replacement in hypopituitary adults increases bone turnover; data on the consequences of longer-term GH treatment are limited. We report on the effects of 12-18 months of GH replacement treatment with biosynthetic human GH on bone metabolism and bone mass in hypopituitary adults. Patients were studied before and after GH treatment for 12 months (n = 11) and 18 months (n = 27) respectively in an open trial. GH dose was 0.04 +/- 0.01 IU/kg daily. Plasma calcium, phosphate and intact PTH concentrations, 24-hour urinary calcium excretion, 3 markers of bone formation (total alkaline phosphatase, osteocalcin and procollagen 1 carboxy terminal peptide (P1CP)) and serum concentration of carboxyterminal cross-linked telopeptide of type 1 collagen (ICTP), as a marker of bone resorption, were measured at 6-month intervals. Lumbar spine and total body bone mineral mass was measured by dual-energy X-ray absorptiometry. Small increases were observed in plasma calcium and phosphate concentrations at 12 months of GH therapy but the differences at 18 months were not statistically significant. Serum intact PTH concentration did not change. Plasma total alkaline phosphatase increased significantly on GH from 75 +/- 26 to 92 +/- 30 (P < 0.01) and 85 +/- 31 U/I (NS) at 12 and 18 months respectively. Serum osteocalcin increased from 6.5 +/- 3.7 to 15.7 +/- 6.2 (P < 0.0001) and 16.6 +/- 5.7 micrograms/I (P < 0.001) at 12 and 18 months respectively and P1CP increased significantly from 106.0 +/- 47.3 micrograms/I to 165.5 +/- 95.3 (P < 0.0001) and 177.2 +/- 72.2 micrograms/I (P < 0.01) at 12 and 18 months respectively. Plasma ICTP concentration increased also from 3.4 +/- 1.8 to 7.3 +/- 3.4 (P < 0.0001) and 7.0 +/- 2.7 micrograms/I (P < 0.003) at 12 and 18 months of GH therapy respectively. No significant change was observed in total body or lumbar spine bone mass, over the 18 months of GH treatment Replacement therapy with GH in hypopituitary adults for 6-18 months produced a sustained increase in bone turnover (both formation and resorption). Bone mass was maintained but did not increase over the study period.