Bone Mineral, Histomorphometry, and Body Composition in Adults with Growth Hormone Receptor Deficiency

Abstract

Growth hormone (GH) and insulin-like growth factor I (IGF-I) deficiencies have been associated with osteopenia in both children and adults. To examine the effects of growth hormone resistance on bone mineral and body composition, we studied 11 adults (mean age 30 years) with growth hormone receptor deficiency (GHRD, Laron syndrome) and 11 age-and gender-matched controls from Southern Ecuador. Bone mineral and body composition were determined by dual-energy X-ray absorptiometry. Bone physiology was assessed with biochemical markers of bone turnover and dynamic bone histomorphometry. Bone size and body composition differed markedly between subjects with GHRD and controls. Affected adults were 40 cm shorter than controls, had significantly less lean body mass, and had increased percent body fat. Bone mineral content and density (BMD) at the spine, femoral neck, and whole body were significantly lower in adults with GHRD than in controls. Mean BMD Z scores were ؊1.5 to ؊1.6 at all sites in affected women and ؊2.2 to ؊2.3 in men with GHRD. Estimated volumetric bone density (BMAD) at the spine and femoral neck, however, was not reduced in GHRD. Spine BMAD was 0.210 ؎ 0.025 versus 0.177 ؎ 0.021 for affected women versus controls ( p < 0.05) and 0.173 ؎ 0.018 versus 0.191 ؎ 0.025 for men with GHRD versus normals ( p ‫؍‬ 0.31). Urinary pyridinoline concentrations were significantly greater in adults with GHRD than in controls, while type I collagen C-telopeptide breakdown products and markers of bone formation did not differ. Differences in histomorphometry were limited to a reduction in trabecular connectivity; bone volume and formation rate were similar to controls. These data confirm the importance of the GH/IGF axis in regulating bone size and body composition. The contribution of these peptides to the acquisition and maintenance of bone mineral is less certain since volumetric bone density was preserved despite low levels of IGF-I and IGFBP-3 associated with GH resistance. (J Bone Miner Res 1998;13:415-421)

Bone homeostasis in growth hormone receptor–null mice is restored by IGF-I but independent of Stat5

“…This confirms previous reports in humans and rodents (26,32), but also demonstrates that the low cortical bone mass in GHR -/-mice relates to an early cessation of periosteal bone growth. Previous densitometry studies suggested reduced trabecular bone mass in GH deficiency (26,32), while others suggest this relates to reduced cortical width, since most mouse-bone densitometry techniques do not adequately account for altered bone size (33). Here we specifically measure trabecular bone volume histomorphometrically and observe that while cortical bone mass is reduced, trabecular bone volume is not altered in GHR -/-mice.…”

Genetic disorders in the GH–IGF-I axis in mouse and man

“…Patients with GH deficiency due to GHRHR mutations or GH insensitivity due to GHR mutations have a normal BMAD (92)(93)(94). BMAD in a patient with an IGF-I gene deletion is mildly reduced.…”

Impact of Androgens, Growth Hormone, and IGF-I on Bone and Muscle in Male Mice During Puberty

“…(4) The GH receptor (GHR) gene disrupted or knockout (GHRKO) mouse model is a model for the absence of GH signaling, (5) and in accordance to the human GH insensitivity syndrome (also called Laron syndrome), characterized by severe postnatal growth failure, elevated GH levels and greatly decreased serum IGF-I concentrations. (6) Beside the well-known effects of GH on longitudinal skeletal growth, both mice and men with inactivation of GHR signaling also have decreased cross-sectional bone area and reduced cortical thickness, (7)(8)(9)(10) which is considered to be related to the low serum IGF-I concentrations. (11,12) In addition to the well-documented role of the GH/IGF-I axis, androgens also play an essential role in male pubertal growth and radial bone expansion.…”