Bisphosphonates
Bisphosphonates include Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate), Reoclast (zolendronate).
These drugs are anologues of pyrophosphate and bind to hydroxyapatite crystals in bone, preventing resorption by osteoclasts. Large, randomized, controlled trials (with oral daily alendronate and risedronate and IV zolendronate) have demonstrated significant reductions in vertebral and hip fractures in post-menopausal women with osteoporosis. Oral and IV ibandronate has demonstrated only vertebral fracture reduction. There is also randomized controlled trial data for significantly improved BMD in men and women taking glucorticoids. A randomized controlled trial of men with osteoporosis, taking alendronate had a significant reduction in risk of vertebral fracture. Alendronate and risedronate are FDA indicated for use in osteopenia (defined as patients with T scores between -1.5 and -2.5); however, cost effectiveness in this group remains controversial, as fracture data does not exist.
Long-term safety and efficacy studies (>10 years for alendronate) have showed safety and continued improvement in BMD. There is evidence from the Fracture Intervention Trial that despite stopping alendronate for five years after taking it for five years, markers of bone remodeling remained low and fracture protection persisted. (18) The FLEX and HORIZON trials looked at bone loss and fracture in groups taken off alendronate and risendronate after set treament periods. They found that the groups that did the worst (fractured) were the groups with the worst bone density at the end of the treatment phase. The authors suggested not giving a drug holiday to patients with T <-2.5 or T< -1.5 but with vertebral fracture while on treatment.
There is a theoretical risk of osteonecrosis of the jaw (ONJ) with bisphosphonate use; however, the benefit in fracture reduction for patients with osteoporosis seems to outweigh this risk. The majority of cases of ONJ have occured in patients with cancer, taking high doses of IV bisphosphonates for hypercalcemia. Some experts recommend cessation of therapy for several months around the time of invasive jaw surgery.
Oral bisphosphonates are associated with risk of pill esophagitis. It is recommended that they be taken on an empty stomach (as multiple foods inhibit absorption) and that patients remain in an upright position for 20 - 30 minutes after swallowing the pill. One study of 72 patients who stopped alendronate because of GI side effects, found that on rechallenge, 15% of the drug group, and 17% of the placebo group stopped again because of GI side effects. (17)
Atypical fractures of the femoral shaft associated with minimal trauma have been rarely seen with longterm use of bisphosphonates. These fractures are thought to occur because of long term suppression of bone remodeling. These fractures are often preceded by groin or thigh pain. When patients on bisphosphonates develop this kind of discomfort, obtain X-rays of both femurs to look for evidence of stress fracture.
Bisphosphonate Dosing
Alendronate (Fosamax): 10mg po daily, 70mg po weekely, 35mg po weekly (osteopenia)
Risendronate (Actonel): 5mg po daily, 35mg po weekly
Ibandronate (Boniva): 2.5mg po daily, 150mg po monthly, 3mg IV q 3 months*
Zolendronate (Reclast): 5mg IV yearly*