Reclast Disease Interactions

Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders (e.g., periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). The manufacturers of bisphosphonates recommend discontinuation of bisphosphonate treatment for patients undergoing invasive dental procedures. Patients who develop osteonecrosis of the jaw while on bisphosphonate therapy should receive care by an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment.

The use of bisphosphonates is contraindicated for the treatment of osteoporosis in patients with hypocalcemia. These agents increase bone mineral density, a process that requires an adequate supply of calcium in the body. Following the initiation of therapy, a short-term reduction in serum calcium and phosphate levels usually occurs due to inhibition of bone resorption, especially in patients with Paget's disease, in whom the pretreatment rate of bone turnover may be greatly elevated. Hypocalcemia and other disturbances of mineral metabolism, such as vitamin D deficiency, should be treated prior to initiation of therapy. Appropriate intake of calcium and vitamin D should be ensured throughout the course of treatment.

Zoledronic acid injection is contraindicated in patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment. No dosage adjustment is required in patients with a creatinine clearance of greater than or equal to 35 mL/min. Creatinine clearance should be calculated based on actual body weight using Cockcroft-Gault formula before each zoledronic acid injection dose. Acute renal failure (ARF) has been observed in patients after a single administration. If history or physical signs suggest dehydration, zoledronic acid injection therapy should be withheld until normovolemic status has been achieved. Zoledronic acid injection should be used with caution in patients with chronic renal impairment. Consider monitoring creatinine clearance in patients at-risk for ARF who are taking concomitant medications that are primarily excreted by the kidney.

There have been reports of bronchoconstriction in aspirin-sensitive patients receiving bisphosphonates. Use of these agents in asthmatic and in aspirin-sensitive patients should be used with caution.