Treatment with growth hormone and IGF-I in growing rats increases bone mineral content but not bone mineral density

Abstract

Human growth hormone (hGH) and insulin-like growth factor I (IGF-I) both stimulate bone formation and have been proposed as therapeutic agents for osteoporosis. We examined the effect of hGH and IGF-I alone and in combination on bone size, bone mineral content (BMC), and bone mineral density (BMD) in 10- to 12-week old growing female Sprague-Dawley rats. Sixty rats were assigned to treatment with either placebo, hGH, IGF-I, or both for 4 weeks. After 4 weeks, the right femurs and tibias were excised, and ex vivo BMC and the area of the tibia and femur were measured by dual-energy X-ray absorptiometry (DXA); volume of these bones was measured by Archimedes' principle. In addition, proximal tibial bone density was measured directly by peripheral quantitative computerized tomography (pQCT). Bone length, area, and volume in all treated groups was greater than controls. Areal bone density by DXA (BMC/area) was higher in IGF-treated rats and lower in GH-treated rats than in controls. Volumetric bone density (BMC/volume) was lower in treated groups than in controls. Measurements by pQCT confirmed that true bone density was lower in all treated groups than in controls. We conclude that treatment with hGH or IGF-I increased bone size and mineral content but decreased bone density in growing rats. Because areal correction of BMC did not adequately correct for the increased bone volume in IGF-treated rats, results of areal bone density by DXA should be interpreted with caution when treatment causes a disparity in bone size between groups.

The relationship between the GH/IGF-I axis and serum markers of bone turnover metabolism in healthy children

“…This relationship has also been investigated later in life but only in a cohort of elite athletes and in adults with acromegaly, in whom serum IGF-I levels were found to be an independent predictor of bone turnover and metabolism (45,46). IGF-I can stimulate bone remodelling when administered exogenously to mice, rats and humans or when overexpressed in bone (13,47,48). IGFBP-3 is the most abundant of the IGF-BPs in the human circulation and is thought to play an important role in mediating and modulating the biological actions of the IGF system.…”

“…Serum IGF-I and IGFBP-3 concentrations and circulating free IGF-I concentration are related to growth hormone (GH) secretion, although they are also influenced by other factors, including genetic and nutritional factors (11). GH increases the levels of markers of both bone formation and bone resorption (12), and the IGF system appears to be one of the most important factors affecting bone remodelling when administered exogenously to mice and rats or when overexpressed in bone (13). Bone remodelling markers may provide an early indication of the height velocity response to growth-promoting treatment.…”

Combined Treatment With GH and IGF-I: Additive Effect on Cortical Bone Mass But Not on Linear Bone Growth in Female Rats

“…Indeed, in healthy volunteers, combined treatment with recombinant human (rh)GH and rhIGF-I was reported to stimulate bone formation in an additive fashion as measured by procollagen type I (PICP) levels in serum (7,8). However, in normal adult rats, the combined treatment with rhGH and rhIGF-I had no additive effect on bone mineral content (9).…”

Perda clínica de inserção periodontal em uma população brasileira com deficiência isolada do hormônio do crescimento

“…Estudos em animais mostram que o GH aumenta a formação de tecidos duros in vivo (osso (Rosen et al, 1995), dentina (Young et al, 1993), esmalte ) e cemento (Clayden et al, 1994)), assim como as proteínas morfogenéticas.…”

“…Os receptores do GH são expressos nestes tecidos e medeiam resposta local ao crescimento (Li et al, 1998). Além disso, os cementoblastos, osteoblastos e células do ligamento periodontal respondem ao estímulo do GH tanto através do aumento no número destas células, bem como da expressão das proteínas ósseas morfogenéticas BMP-2 e BMP-4, do receptor da proteína óssea morfogenética tipo I, da fosfatase alcalina óssea, da osteocalcina e da osteopontina Rosen et al, 1995;Ohlsson et al, 1998;Li et al, 2001). …”