Combined treatment of growth hormone and the bisphosphonate pamidronate, versus treatment with GH alone, in GH-deficient adults: the effects on renal phosphate handling, bone turnover and bone mineral mass.

Abstract

A potential drawback of GH replacement therapy in GH deficient (GHD) patients is the initial decrease in bone mass. The present study investigates the effects of the addition of pamidronate to GH replacement therapy in adult GHD subjects, on serum PTH and 1,25-dihydroxyvitamin D3 (1.25-(OH)2D3) levels, renal phosphate handling, bone turnover and bone mineral content (BMC). Six GHD adult patients were studied for two periods of 6 months with a wash-out period of 3 years. In the first period they were treated with conventional replacement therapy and GH. In the second study period GH treatment was identical, while after 2 weeks 150 mg pamidronate per day was added. In the first study period (GH only) there was a significant increase of phosphate reabsorption, without a change in serum PTH and 1.25-(OH)2D3 levels. This suggests a specific effect of GH or IGF-I on renal phosphate handling. This was supported by the close correlation between serum IGF-I levels and TmP/GFR (r = 0.75, P < 0.0001). When GH was administered together with pamidronate, this correlation was less, but remained significant (r = 0.44, P < 0.001). The increase in bone turnover and decrease in BMC, as initially observed during GH replacement therapy alone, were attenuated by simultaneous pamidronate administration. The decline in lumbar spine BMC (measured with dual-photon absorptiometry) at 6 months was -3.1 +/- 1.5% during GH replacement therapy alone vs an increase of +3.8 +/- 2.0% during the administration of the combination of GH and pamidronate (measured with dual-energy X-ray absorptiometry). At the distal and proximal forearm the changes amounted to -0.5 +/- 3.4% vs +4.5 +/- 1.8% and -1 +/- 1.2% vs +1.2 +/- 1.1% respectively. This study shows that the addition of a bisphosphonate to GH replacement therapy in GHD adults counteracts the GH (or IGF-I) induced increase in renal phosphate reabsorption. Furthermore, it reduces GH induced bone turnover and prevents the initial decrease in bone mineral content seen during GH treatment alone, resulting in a beneficial effect on bone mineral mass. Pamidronate might therefore be an important adjunct to GH replacement therapy in adults with GHD and severe osteopenia during the early phase of GH induced stimulation of bone turnover.