Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects

OBJECTIVES Prolonged GH deficiency induces alterations in bone metabolism and structure. Trials in GH deficient adults (GHDA) employing high dose GH replacement therapy produced conflicting results, and caused several adverse effects. This prompted us to study the effects of rhGH treatment on bone metabolism and structure at lowest doses so far used. DESIGN Nine GHDA (7 males and 2 females, aged 25-34 years) were studied before, after 12 months of rhGH treatment (70 mu g/kg/week, divided into 3 injections, administered s.c. at 2000 h on Monday, Wednesday and Friday, respectively) and after 12 months off therapy. MEASUREMENTS Serum IGF-I, IGFBP-3, bone-gla-protein (BGP), procollagen-III (PIIINP), PTH and vitamin D, and bone mineral density (BMD) at proximal (Prox) and ultradistal (Dist) sites of the radius were measured. RESULTS Before treatment, IGF-I, IGFBP-3, BGP and PIIINP levels, as well as both Prox and Dist BMD, were significantly lower than in controls. GH therapy normalized all these parameters, except for the Dist value, which nonetheless increased. No significant changes in PTH and vitamin D variation were seen. After 12 months off therapy all parameters returned to pretreatment levels. CONCLUSIONS Our results suggest that 12 months of rhGH treatment at the lowest doses so far used normalizes bone metabolism and cortical bone density, and improves trabecular bone density without causing adverse events.