Bisphosphonates have a rapid onset of action, a sustained effect, and the clinical practice experience with the agents now spans 14 years, he said. Problems with these agents include upper gastrointestinal intolerance with the oral medications; this is usually not a problem with IV administration. An acute phase reaction can occur with the IV formulations, but generally only at the initial stage.
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Other side effects are rare, he said. Osteonecrosis of the jaw and subtrochanteric fractures are extremely rare, and reports of an association between bisphosphonate use and atrial fibrillation and esophageal cancer have not been supported by any data, Dr. Bilezikian said.
The search continues for alternate and “even better” osteoporosis drugs, he said, including newer antiresorptives, new formulations of anabolic therapy, and new approaches to combination therapy.
One promising new drug that has not yet won Food and Drug Administration approval is denosumab, a human immunoglobulin G antibody to RANKL, which controls osteoclast differentiation, activation, and survival. In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every Six Months (FREEDOM) trial, denosumab was administered as a subcutaneous injection every six months. Dr. Bilezikian, a researcher on that trial, said the agent reduced new vertebral and nonvertebral fractures and the incidence of hip fractures.2
Other agents under investigation include odanacatib, a cathepsin K inhibitor; new potential indications for parathyroid hormone (such as glucocorticoid-induced osteoporosis and fracture healing); and combination therapies. Antisclerostin antibody therapy is being developed, after research revealed that sclerostin inhibits the Wnt signaling pathway, Dr. Bilezikian said.
Calling the future bright for new drug development, Dr. Bilezikian said several challenges remain. “We have to figure out how to prove efficacy and decide how to demonstrate that these drugs improve bone strength, improve bone quality, are safe, specific to bone, and affordable.”
Kathy Holliman is a medical journalist based in New Jersey.
- Black D, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New Engl J Med. 2007;356:1809-1822
- Cummings SR, Martin JS, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. New Engl J Med. 2009;361:756-765.