: Physical exercise can strengthen the skeleton substantially, provided that one begins exercising at a young age. During skeletal growth, exercise augments weight-bearing bone structure by enhancing periosteal apposition. The largest gains in bone mass tend to be where hydrostatic pressures within extracellular fluid compartments are greatest. This finding suggests that extracellular fluid pressures or fluid shear stress on bone cells provide a stimulus for bone formation. The best exercises for building bone are those involving impact loading of the skeleton. However, recent prospective studies have shown that even impact exercise is not very effective for building bone in adults. In addition, impact exercise can increase the risk of osteoarthritis in older adults. Considering the meager benefits and potential risks of impact exercise, one might question whether it should be prescribed for prevention of osteoporosis. Instead low-impact exercises designed to improve muscle strength and balance may be preferred for prevention of fractures. The goal of the low-impact exercise strategy is to prevent falls rather than to build bone mass. Several biochemical mediators of the mechanical-loading effects on bone have been identified. Foremost among these are prostaglandins and nitric oxide. In addition, parathyroid and growth hormones provide permissive signals for bone mechanotransduction. Finally, studies of inbred strains of mice suggest that the ability of bone to respond to mechanical loads is under genetic control. The Endocrinologist 2000; 10: 164-169 Learning Objectives: * Review the mechanisms by which exercise strengthens the skeleton. * What types of exercise are best, and what is the trade-off with adverse effects of impact exercise? * Consider how hormones and certain drugs influence the actions of exercise on skeletal structure. (C) 2000 Lippincott Williams & Wilkins, Inc.