Bisphosphonates are synthetic compounds that are taken up preferentially by the skeleton and suppress osteoclast-mediated bone resorption. There are structural differences among the various bisphosphonates that account for considerable differences in antiresorptive potencies and in activity/toxicity ratios. Bisphosphonates are given to patients with established vertebral osteoporosis, either intermittently or continuously, but controlled, long-term data are only available for intermittent regimens. They decrease the rate of bone loss, increase spinal bone mineral density (BMD), and stabilize BMD for at least 4 years of treatment without any significant side effects. This increase in bone mass is not due to redistribution of calcium in the skeleton, as at sites with predominantly cortical bone, BMD values either do not change or increase with treatment. Bisphosphonates also appear to decrease the frequency of new vertebral fractures in some patients with established osteoporosis, but this effect needs to be verified. Other issues that need to be addressed include the optimal mode and dose of administration and hence the choice of bisphosphonate, the duration of treatment, the changes in bone metabolism following treatment arrest, and finally the efficacy of bisphosphonates in the prevention of hip fractures.
