Normal Growth Hormone Secretory Reserve in Men with Idiopathic Osteoporosis and Reduced Circulating Levels of Insulin-Like Growth Factor-I

Abstract

Many men with idiopathic osteoporosis have reduced circulating insulin-like growth factor-I (IGF-I) levels. The major source of circulating IGF-I is GH-mediated production by the liver. The known anabolic effects of GH on the skeleton raised the possibility of GH deficiency in these men. We sought to test this hypothesis in this study. Fourteen men (mean age, 52.1 +/- 3.2 yr, range 31-68) with idiopathic osteoporosis were studied. Mean lumbar spine bone mineral density (BMD) was 0.723 g/cm2, T score -3.5; femoral neck BMD was 0.642 g/cm2, T score, -3.07; distal (1/3) radius BMD was 0.708 g/cm2, T score, -2.05. Eleven of 14 (79%) had frank reductions in serum IGF-I levels compared with age and sex-matched values (158.5 +/- 50 SD vs. 180 +/- 45 SD). GH secretion was stimulated by iv arginine infusion (30 g) over 30 min followed 1 h later by oral L-dopa (500 mg). Serum GH was measured at time (t) = -15, 0, 30, 45, 60, 90, 120, 150, and 180 min. All patients responded to at least one stimulus with the majority (n = 9) responding to both. Five patients responded either to arginine or to L-dopa but not to both. Baseline GH for the entire group was 0.77 + 0.08 ng/mL (SEM). Peak GH following arginine (t = 45-60 min) was 14.0 +/- 2.8 ng/mL, a 17.7 +/- 2.8-fold rise. Peak GH following L-dopa (t = 120-180 min) was 5.7 +/- 1.0 ng/mL, a 9.2 +/- 2.2-fold rise. No difference in maximal secretion was observed between those with low or normal IGF-I levels. Neither IGF-I nor IGF binding protein-3 concentrations changed significantly during the short period of GH stimulation. These data suggest that men with osteoporosis and reduced IGF-I levels do not appear to have a deficiency in the GH axis. Other hormonal or local factors may be important in regulating IGF-I expression. Deficiencies of IGF-I production at skeletal sites may be important in the pathogenesis of this syndrome.

BMD Is Reduced in HIV-Infected Men Irrespective of Treatment

“…Modification of the IGF system has been reported in patients infected with HIV. (20) We measured only IGF1 that has been shown to be decreased in males with idiopathic osteoporosis, (21) and we observed no changes in our HIV ϩ patients. Most of the studies of BMD in HIV ϩ patients have included only a small proportion of untreated patients or none at all.…”

Additional Beneficial Effects of Recombinant Growth Hormone in Alendronate-treated Patients with Idiopathic Osteoporosis

“…Two pa- crease in bone density and decrease fracture rate, but never allow a full recovery of bone architecture [10]. Idiopathic osteoporosis has been related to low insulin-like growth factor 1 (IGF-1) concentrations in blood [3,6] and boné [2], and to osteoblastic dysfunction, leading to limited bone formation whatever the rate of bone resorption [19]. Thus, even the patients with IO and normal serum IGF-1 could benefit from bone anabolic drugs.…”

“…Both phenomena have been related to low concentrations of insulin-like growth factor 1 (IGF-1) in serum [3,4] and boné [5], and histomorphometric analysis show decreased osteoblastic surface and function [5,6]. Rosen et al found an association of low serum IGF-1 and homozygosity for a specific allele of the IGF-1 microsatellite (192/192) in men with idiopathic osteoporosis [7].…”

“…AP, white 58 years, male, diagnosis of osteoporosis after fall and fractures of the right humerus and vertebral bodies at age forty-eight. Despite normal gonadal function, received testosterone for two years withThe reasons for the low circulating IGF-1 levels in a subset of patients with idiopathic osteoporosis remain unclear as previous studies of GH secretion in these patients have failed to identify any significant abnormalities [3,4].…”

Aspectos genéticos, influência do eixo GH/IGF1 e novas possibilidades terapêuticas na osteoporose idiopática

“…Esses trabalhos apontam para um importante papel do IGF1 circulante na aquisição do pico de massa óssea e na homeostase esquelética do indivíduo adulto. Entretanto, não parece haver defeito na secreção do GH nos homens com osteoporose idiopática, como constatado por Kurland et al (21) . Estes autores avaliaram 14 homens com osteoporose idiopática após teste de estímulo com arginina e L-dopa, encontrando um padrão secretório normal do GH, apesar de níveis séricos de IGF1 baixos, demonstrando que estes homens não eram deficientes de GH.…”