Research in animal models indicates that without estrogen, the effectiveness of exercise for increasing bone mineral in females is reduced. With decreased estrogen levels, there is an increase in the threshold at which strains are detected by bone, in turn reducing the transmission of mechanical to biochemical signals for bone formation. Studies combining estrogen replacement and exercise training in postmenopausal women have yielded mixed results but indicate that the combination of interventions may be more effective than either intervention alone for increasing bone mass. Given the continued debate over the risks and benefits of estrogen replacement, other compounds such as bisphosphonates or phytoestrogens may be preferred in combination with exercise training for optimally increasing bone mass and preventing osteoporotic fracture. Studies on animals show that the combination of bisphosphonate or phytoestrogen supplementation with exercise training is effective, but trials in humans are lacking.