Intrauterine growth restriction decreases endochondral ossification and bone strength in female rats

Intrauterine growth restriction (IUGR) modifications to postnatal skeletal growth may increase adult fracture, especially in females who have greater risk of osteoporosis. Little is known about the effect of IUGR on the patterns of postnatal endochondral ossification and bone development. Here for the first time we reveal bone formation, mineralization, and strength in IUGR female rats during early postnatal life and adulthood. Endochondral ossification rate of the hypertrophic zone (HZ) and hypertrophic cell length (HCL) at distal femur and proximal tibia, and primary ossification center (POC) of the whole femur and tibia were quantified at birth to day 21. Bone area (BA), bone mineral content (BMC), and bone density by dual-energy X-ray absorptiometry and bone strength determined from three-point bending were measured at days 21 and 120. IUGR femur and tibia HZ, HCL, and POC were significantly diminished at birth to day 21. IUGR decreased BA and BMC as well as femur/tibia diameter, length, stiffness, and peak load values at days 21 and 120. Our findings demonstrate a negative long-term effect of IUGR on bone size, mineral content, and strength in weanling and adult female rats. We speculate that IUGR decreases endochondral ossification responsiveness, and in turn, postnatal linear skeletal growth, mineralization, and strength in female rats.