Another report described 63 cases o

Another report described 63 cases of jaw osteonecrosis resistant to conservative measures and requiring surgical intervention in most cases. Although a majority of the cases were reported in cancer patients who had received intravenous bisphosphonate, some of the cases were reported in women who had received oral bisphosphonates for osteoporosis. Oral bisphosphonates are poorly absorbed (less than 5%). Taking them in the presence of food or calcium supplementation further reduces absorption. After absorption, bisphosphonate uptake to the primary site of action is rapid and sustained. Once attached to bone tissue, bisphosphonates are released very slowly. These drugs are not metabolized and are excreted renally. They are not recommended for use in patients with renal insufficiency. The most notable adverse effects associated with the bisphosphonates are gastrointestinal, ranging from relatively mild nausea, vomiting, and diarrhea to more severe esophageal irritation and esophagitis. Common adverse reactions reported in clinical trials include dyspepsia, abdominal pain, nausea, and esophageal reflux. Clinically significant adverse events include esophageal ulceration, erosions with bleeding, perforation, stricture, and esophagitis. Upper gastrointestinal adverse effects have been reported in up to 20% of patients. However, in some studies, the incidence is no different from that for placebo. Many gastrointestinal events are related to inappropriate administration. An evaluation of the Fracture Intervention Trial data found certain factors, including advanced age, previous upper gastrointestinal tract disease, and nonsteroidal anti-inflammatory drug use, increased the risk for gastrointestinal adverse events. In addition to appropriate administration, once-weekly administration of oral bisphosphonates may decrease the risk of adverse gastrointestinal effects. Proper drug administration is important for optimal absorption and prevention of adverse effects. Oral bisphosphonates should be taken 30 to 60 minutes prior to the first meal or food in the morning after an overnight fast with 6 to 8 oz of water (or 2 oz with the oral solution). Patients should remain upright and refrain from lying down for 30 to 60 minutes after administration. The tablets should be swallowed whole without chewing or sucking. Administration should be with water only and not combined with other fluids. Bisphosphonates should not be taken with other medications or dietary supplements. Bisphosphonates are not recommended for use in patients with esophageal abnormalities, hypocalcemia, and renal insufficiency or failure (creatinine clearance less than35 mL/minute). There is considerable interest in using injectable bisphosphonates, such as pamidronate and zoledronic acid, in patients unable to tolerate or absorb oral bisphosphonates. Zoledronic acid in particular has a potential advantage of once-yearly dosing. Currently, neither drug has received FDA approval for this indication. Ibandronate has recently been approved for this indication