A 10-year study of daily oral alendronate (Fosamax) and a 7-year study of daily oral risedronate (Actonel) indicate that both drugs maintained increases in bone mineral density (BMD) and decreases in markers of bone remodeling throughout the study period. Both drugs are now more commonly taken once weekly. Available data are insufficient to compare fracture rates with alendronate and risedronate, and fracture rates are considered the most important endpoint in osteoporosis studies. Recent reports of severe pain and jaw osteonecrosis with these drugs are disturbing.

Risedronate (Actonel - Procter & Gamble), a pyridinyl bisphosphonate, has been approved by the FDA for oral treatment of Paget's disease of bone. Characterized by excessive bone resorption, bony deformity, disorganized bone remodeling and structural weakness, Paget's disease occurs in up to 3% of people older than 55 in Europe and North America (PD Delmas and PJ Meunier, N Engl J Med, 336:558, 1997).

A once-weekly 35-mg oral formulation of the bisphosphonate risedronate (Actonel) has been approved by the FDA for prevention and treatment of postmenopausal osteoporosis. A once-weekly formulation of alendronate (Fosamax) was approved last year (Medical Letter 2001; 43:26). Bisphosphonates bind to the mineral surface of bone and decrease osteoclast activity, inhibiting the resorption phase of the bone turnover cycle. These drugs are not metabolized and remain bound to bone for several weeks.

A new enteric-coated delayed-release formulation of risedronate (Atelvia – Warner Chilcott) has been approved by the FDA for treatment of postmenopausal osteoporosis. Unlike immediate-release risedronate (Actonel) and all other oral bisphosphonates, which must be taken after an overnight fast and at least 30 minutes before eating breakfast, the new formulation is taken immediately after breakfast with at least 4 ounces of water. Then the patient must remain upright for at least 30 minutes.CLINICAL TRIAL — Approval of Atelvia was based on a 52-week non-inferiority study in more than 900...

The bisphosphonate risedronate (Actonel - Procter & Gamble) was recently approved by the FDA in a 150- mg once-monthly oral tablet for prevention and treatment of postmenopausal osteoporosis. The drug is also available for the same indication in 5-mg daily, 35-mg weekly and 75-mg twice-monthly tablets.

The In-Brief article on delayed-release risedronate in issue 1360 (Med Lett Drugs Ther 2011; 53:24) included a statement that alendronate is currently the only bisphosphonate available generically. That would have been accurate if we had added "that is FDA-approved for treatment of osteoporosis." Etidronate (Didronel, and others), which was the first bisphosphonate used to treat osteoporosis (Medical Letter 1990; 32:111) but was never approved for such use by the FDA, is also available generically. It is approved for treatment of Paget's disease and for prevention and treatment of heterotropic...

Long-term use of bisphosphonates for prevention and treatment of osteoporosis has been associated with osteonecrosis of the jaw, atypical fractures of the femur, and possibly esophageal cancer. So for how long should patients take them?

Ibandronate (Boniva - Roche/GSK), a new oral bisphosphonate, was recently approved by the FDA in a once-monthly formulation for prevention and treatment of postmenopausal osteoporosis. The drug was initially approved in 2003 as a daily tablet, but was not marketed. An intravenous formulation for use once every 3 months is under investigation.

View the Comparison Table: Some Drugs for Postmenopausal Osteoporosis

Once-a-week formulations of alendronate (Fosamax) in 35- and 70-mg tablets have now been approved by the FDA and are being heavily promoted for prevention and treatment of postmenopausal osteoporosis. A new formulation of risedronate (Actonel) for once-a-week use is under development and may be available next year.