Growth hormone treatment of osteoporotic postmenopausal women - a one-year placebo-controlled study

Abstract

Objectives: To study the effect of 12 months of growth hormone (GH) treatment on bone markers, bone mineral density (BMD), lean body mass (LBM) and body fat mass (BF) in postmenopausal osteoporotic women. Design: Sixteen patients were randomised to a double-blind randomised placebo-controlled one-year study with daily s.c. injections of GH or placebo. After the first year 14 patients (8 placebo treated, 6 GH treated) were recruited to GH treatment during the second year. All patients were also supplemented with 0.5 g calcium per oral. Methods: Bone mineral density and body composition were assessed by dual energy X-ray absorptiometry. Biochemical bone markers were analysed by RIA or HPLC techniques. Diurnal GH profiles were performed with continuous venous blood sampling. Results: Sixteen patients started in the placebo-controlled study. In all, twelve patients completed one year and only four patients completed two years of GH treatment. At baseline 3 patients had serum insulin-like growth factor-I (S-IGF-I) levels below -2 S.D. for age. Maximal diurnal GH levels tended to correlate negatively with S-IGF-I (P = 0.076). S-IGF-I was unrelated to BMD. Serum IGF-binding protein-1 (S-IGFBP-1) correlated negatively with femoral neck BMD (r = ¹0.61, P = 0.012). The intended GH dose of 0.05 U/kg/day or a maximum of 3 U/day s.c. was reduced to 0.024 Ϯ 0.004 U/kg/day, equal to 0.5-2.7 U/day due to frequent side effects, and four patients were excluded. After one year of GH treatment BF increased slightly, LBM and BMD in total body and lumbar spine were unchanged but femoral neck BMD had decreased 3.4 Ϯ 1.6% (P < 0.05). The mean S-IGF-I increase was 32% (range ¹38-138%). Mean levels of the bone formation markers S-osteocalcin and S-procollagen type I propeptide increased maximally by 88 and 36% respectively after 9-12 months while the bone resorption markers were unchanged. In the placebo-treated group there were no significant alterations. Conclusions:The effects on S-IGF-I, bone markers and LBM were small although GH-related side effects were common. The reason for this apparent partial resistance to the anabolic effects of GH is not clear but nutritional deficits may be involved. Assessment of the effects of GH on bone mass and fracture rate requires longer study periods than one year.

Additional Beneficial Effects of Alendronate in Growth Hormone (GH)-Deficient Adults with Osteoporosis Receiving Long-Term Recombinant Human GH Replacement Therapy: A Randomized Controlled Trial

“…They result in a decrease in bone turnover, an increase in BMD, and a clear decrease in fracture risk. The effect of rhGH on BMD in non-GHD patients with postmenopausal osteoporosis is modest (22) and it is not known whether rhGH therapy decreases fracture risk in non-GHD patients.…”

Osteoporosis

“…The response to GH may differ in diverse clinical situations (ie, hypopituitarism, Shehan syndrome, postmenopause, idiopathic osteoporosis in men, children). 130,132,[154][155][156][157][158][159][160][161][162][163] In an earlier meta-analysis, fluoride, a mineral that is incorporated into bone, increased the risk of fractures when administered in high doses but reduced fractures at low doses. [164][165][166][167][168][169] Fluoride is approved as an osteoporosis therapy in Europe but not in the United States.…”

Dynamic and Structural Properties of the Skeleton in Hypoparathyroidism

“…(31,32) Hypoparathyroidism might also affect modeling and remodeling of the growing skeleton, as suggested by the finding that patients with congenital hypoparathyroidism or parathyroidectomy in childhood might not achieve normal height. (33)(34)(35) Despite scattered reports in the literature, there are no data on fracture incidence in hypoparathyroidism. This is because the epidemiology of fracture incidence is confounded by the exceedingly small numbers of patients with this disease.…”