REDUCED BONE-MINERAL DENSITY IN ADULTS WITH GROWTH-HORMONE (GH) DEFICIENCY - INCREASED BONE TURNOVER DURING 12 MONTHS OF GH SUBSTITUTION THERAPY

To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therap y, 68 adults (25 females and 43 males) aged 22-61 (mean 44.2 +/- 1.2) years with GH deficiency (GHD) were studied, Fifty-eight patients had panhypopituitarism, three had isolated GHD and in seven patients at le ast one additional pituitary function was affected. Twenty-one patient s had childhood onset GHD, The patients were randomized to receive eit her GH in daily injections (0.125 IU . kg(-1). week(-1) for the first 4 weeks and subsequently 0.25 IU . kg(-1). week(-1)) or placebo for 6 months, The trial continued as an open study with GH treatment for 6 o r 12 months, with data presented as compiled data of 12 months of GH t reatment in 64 patients. Bone mineral density (BMD) was measured by du al energy x-ray absorptiometry and bone turnover was assessed by serum markers of bone metabolism (osteocalcin, procollagen I peptide, cross linked telopeptide of type I collagen and alkaline phosphatase activit y), In women with adult onset GHD (N = 19) and in men with childhood o nset GHD (N = 15), total body, spine and hip BMD was significantly red uced at baseline compared to Swedish age- and sex-matched control mate rial. In men with adult onset of GHD (N = 28), BMD did not differ from male controls, During the placebo-controlled period, GH induced decre ased total body and spine BMD, probably due to an expansion of the rem odelling space, whereas all serum markers of bone turnover increased. Compiled GH data showed similar results after 6 months of treatment. A fter 12 months of GH treatment, BMD did not differ from basal values e xcept for total body BMD, which was lower, whereas the serum markers o f bone metabolism were still increased as compared to basat values. Tw o-thirds of the patients experienced fluid retention with peripheral o edema and arthralgias on the higher GH dosage. One obese patient devel oped non-insulin-dependent diabetes mellitus and was withdrawn from th e study. These results demonstrate that GHD has negative effects on BM D and that GH substitution induces increased bone turnover. Continued long-term observations will reveal if there is a positive effect of GH substitution on bone mass in the adult GHD patient.