Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain reported (avoid use in history of these symptoms in association with bisphosphonate therapy). May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) reported with oral bisphosphonates. Use with caution in dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Risk of hypocalcemia (often asymptomatic) may be associated with both oral and I.V. use. Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw (mostly in cancer, but also in postmenopausal osteoporosis and other diagnoses). Use is contraindicated when serum creatinine >5 mg/dL, (440 μM). May cause hypocalcemia or transient hypophosphatemia. Should not be given as bolus injection (may precipitate acute renal failure, severe local reactions, and thrombophlebitis).