Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy

Abstract

To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therapy, 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 least one additional pituitary function was affected. Twenty-one patients had childhood onset GHD. The patients were randomized to receive either 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 to 12 months, with data presented as compiled data of 12 months of GH treatment in 64 patients. Bone mineral density (BMD) was measured by dual 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 activity), In women with adult onset GHD (N = 19) and in men with childhood onset GHD (N = 15), total body, spine and hip BMD was significantly reduced at baseline compared to Swedish age- and sex-matched control material. In men with adult onset of GHD (N = 28), BMD did not differ from male controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women

“…In fact, long-term administration of rhGH has been shown to signi®cantly improve bone mineralization in GH de®cient adults, 34 who display reduced BMD and increased risk for fracture. 35 In the present study, a tendency of the serum markers of bone turnover (AP bone isoenzyme, serum osteocalcin and urinary hydroxyproline) to increase was observed in obese patients treated with rhGH but not in energy-restricted placebo-treated patients. Moreover, rhGH treatment appeared to prevent, in our obese women, a diet-related reduction of urinary calcium.…”

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

“…The studies which have frequently been designed as open observational follow-up to short term randomised trials, uniformly tend to show an initial significant decline of BMD or BMC at several sites during GH therapy followed by an increase in BMD from 6 months onwards (9 -16). However, total body BMD was shown to remain significantly reduced after 12 months of GH treatment (17). In a Finnish multicentre study (15) subanalysis revealed that significant treatment effects were found only in patients who were osteopenic at baseline and, further, that treatment response was significantly more pronounced in male than in female patients.…”

“…In theory, GH substitution therapy should improve bone mineralisation and reduce fracture risk in these patients. An increase of BMD and BMC following GH treatment has been reported in several (9 -16) but not all (17) open trials. However, except for one study (18,19), the verification of such findings in randomised, placebo-controlled, double blinded trials with appropriate treatment doses of GH has not been possible.…”

Bone Metabolism During Chronic Growth Hormone Deficiency – Experimental and Clinical Studies

“…15,17 Treatment of GHD patients with GH dosedependently increases bone turnover as judged by biochemical bone markers. [19][20][21][22][23][24] Due to the dynamics of bone remodelling (bone resorption preceding bone formation), increases in bone resorptive and formative markers are observed after three and six months substitution, respectively. Although the effects of GH on bone turnover are consistent and sustained during long-term substitution, the effects on bone mass have been more elusive due to short duration of treatment period.…”