Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, ) and, after adjusting for body weight and femoral length, smaller femoral area (2%, ), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, ) and density (4%, ) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength ( ) and stiffness ( ). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring. 1. Introduction Osteoporosis is a major public health concern in North America and affects as many as 2 million Canadians [1] and 40 million Americans [2]. The financial burden of long-term, hospital, and chronic care of osteoporosis is estimated to be $2.3 billion dollars per year in Canada [3] and greater than $15 billion dollars per year in the United States [4]. Adult bone health and risk of osteoporosis is dictated, in part, by whether individuals achieve peak bone mass by young adulthood [2, 5]. Peak bone mass is controlled by genetics as well as lifestyle factors including diet and physical activity. Epidemiological evidence suggests that many children from families with history of fractures have lower bone mass, and therefore higher risk for fractures [2]. Moreover, appropriate nutrition during pregnancy and in early childhood is essential in maintaining bone health and can alter the trajectory of achieving peak bone mass (as reviewed in [5–7]). The interest in folic acid intake during pregnancy and childhood and its effects on bone health is twofold. First, higher intake of folic acid is associated with higher bone mineral density (BMD) of postmenopausal women older than 50 [8, 9] and is associated with a lower risk of fractures in men and women older than 65 [10, 11]. Second, early diet may modulate the risk of developing diseases in
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