Influence of pre- and peri-natal nutrition on skeletal acquisition and maintenance.

Early life nutrition has substantial influences on postnatal health, with both under- and overnutrition linked with permanent metabolic changes that alter reproductive and immune function and significantly increase metabolic disease risk in offspring. Since perinatal nutrition depends in part on maternal metabolic condition, maternal diet during gestation and lactation is a risk factor for adult metabolic disease. Such developmental responses may be adaptive, but might also result from constraints on, or pathological changes to, normal physiology. The rising prevalence of both obesity and osteoporosis, and the identification of links among bone, fat, brain, and gut, suggest that obesity and osteoporosis may be related, and moreover that their roots may lie in early life. Here we focus on evidence for how maternal diet during gestation and lactation affects metabolism and skeletal acquisition in humans and in animal models. We consider the effects of overall caloric restriction, and macronutrient imbalances including high fat, high sucrose, and low protein, compared to normal diet. We then discuss potential mechanisms underlying the skeletal responses, including perinatal developmental programming via disruption of the perinatal leptin surge and/or epigenetic changes, to highlight unanswered questions and identify the most critical areas for future research.