Drs Newland and Lawson are from University of Kentucky HealthCare, and Dr Adams is from University of Kentucky College of Pharmacy, Lexington, Kentucky.
Drs Newland, Lawson, and Adams have no relevant financial relationships to disclose.
Correspondence should be addressed to: Ashley M. Newland, PharmD, Department of Pharmacy Services, University of Kentucky HealthCare, 800 Rose St, H110, Lexington, KY 40536-0293 (firstname.lastname@example.org).
Cancer patients have a better prognosis now than in the past. An estimated 66% of patients diagnosed with cancer between 1996 and 2004 were alive at 5 years.1 As patients are living longer after treatment, long-term complications associated with treatment are becoming a greater issue. Avascular necrosis, also referred to as osteonecrosis, ischemic necrosis, subchondral avascular necrosis, aseptic necrosis of bone, and osteochondritis dissecans, is one such complication.2
Avascular necrosis is a disorder involving breakdown of the bone and has been reported as a complication associated with a number of different disease states and drug therapies. Joint replacement surgery may be required in cases of severe bone destruction, and avascular necrosis has been reported to be the cause for >10% of joint replacement procedures in the United States.2
Chemotherapy agents and other medications used in the treatment of malignancy have been associated with the development of avascular necrosis, including corticosteroids, bisphosphonates, asparaginase, and others (Sidebar). It is important to be aware of these potential drug causes of avascular necrosis, as early recognition and management of the disease process, including early cessation of causative therapy, is necessary to improve patient outcomes, reduce morbidity, and improve quality of life.2
Abbreviation: AVN, avascular necrosis.
Avascular necrosis is a pathological process involving death of bone and bone marrow cells secondary to compromise of the bone vasculature and blood flow. With interrupted blood flow, osteocytes and fat cells die, leading to marrow edema and changes in bone structure.3 This leads to infarction and death of bone, causing the collapse of the architectural structure of the bone and mechanical failure.2 Avascular necrosis most commonly occurs in weight-bearing joints such as the hips, knees, humeral head, and jaw.3,4 Although the exact mechanism for development of avascular necrosis is unknown, several mechanisms have been proposed, including vascular occlusion, altered lipid metabolism and fat emboli, intravascular coagulation, healing processes, and primary cell death.2 In cancer patients, hypercoagulability is thought to be an important contributing factor to develop avascular necrosis.5
Symptoms associated with avascular necrosis include pain at the injury site, swelling, and limited range of motion. Pain may start as mild but can progress rapidly to severe pain in situations involving avascular necrosis secondary to trauma. Range of motion is generally not an issue initially, but as the disease progresses, it can lead to functional limitations.
A number of causes of avascular necrosis, including local trauma, hematologic disorders, metabolic abnormalities, chronic renal failure, pancreatitis, and infectious processes such as osteomyelitis. Alcoholism and tobacco abuse have also been tied to increased risk of avascular necrosis.3
Orthopedic problems such as congenital hip dislocation, slipped capital femoral epiphysis, hereditary dysostosis, and Legg-Calve-Perthes disease have also been associated with avascular necrosis. Iatrogenic causes of avascular necrosis include radiation, hemodialysis, organ transplantation, and medications.2
Drug therapies used for the treatment of malignancies have been implicated in the occurrence of avascular necrosis, with corticosteroids being the most widely reported medication. Patients with existing risk factors for avascular necrosis who are receiving drug therapy associated with avascular necrosis are at an increased risk of developing avascular necrosis compared to patients without preexisting risk. Cancer patients commonly fit into this multiple avascular necrosis…