Developmental programming of bone deficits in growth-restricted offspring

Abstract

Recent evidence links low birthweight and poor adult bone health. We characterised bone size, mineral content, density and strength (stress strain index of bone bending strength (SSI)) in rats from weaning to 12 months. Bilateral uterine vessel ligation (Restricted) or sham surgery (Control) was performed on gestational Day 18 in rats inducing uteroplacental insufficiency. Postmortem of male and female offspring was performed at postnatal Day 35 and at 2, 4, 6 and 12 months. Femur mineral content, density and strength were measured using quantitative computed tomography (pQCT). Restricted pups were born 10%-15% lighter and remained smaller with shorter femurs than Controls (P<0.05). Male and female Restricted rats had lower trabecular bone content compared with Controls (P<0.05), without trabecular density changes. Cortical content was reduced in Restricted males (Day 35 and 6 and 12 months) and at all ages in Restricted females (P<0.05). Cortical density was lower at Day 35 in Restricted males (P<0.05). SSI was lower at Day 35 and at 6 and 12 months in Restricted males, and at all ages in Restricted females (P<0.05). Skeletal deficits were detected in Restricted offspring with gender-specific differences during juvenile and adolescent periods. Bone deficits observed at 6 months in males were greater than at 12 months, indicating that aging can exacerbate programmed bone phenotypes.