Avascular necrosis of the femoral head and talar head is a potentially disabling condition that can lead to premature arthritis in young patients. The condition involves the interruption of the blood supply to the femoral head and the talar head from various etiologies including trauma, sickle cell disease, steroid use, liver disease, alcoholism, and idiopathic.
The bone ischemia causes cell death and calcification of the marrow space in the bone. As the bone revascularizes, the dead bone is removed by new cells called osteoclasts before another type of cells called osteoblasts lay down new bone. The process of bone removal usually outpaces new bone formation leaving the bone structurally weak and vulnerable to compression fractures from physiologic stresses. These fractures cause deformation of the normal shape of the bone. This deformation is irreversible and leads to cartilage damage and arthritis.
Several surgical interventions like core decompression, bone grafting, bone marrow injection were attempted to prevent bone deformation with unsatisfactory results. Several animal studies and a few clinical studies showed that the administration of bisphosphonates can decrease the incidence of femoral head deformation. They act on osteoclasts and inhibit their weakening effect on the bone.
Treatment and prevention of osteoporosis
Treatment and prevention of osteoporosis remain the most common indication for bisphosphonate use, and a number of drugs, including etidronate, alendronate, risedronate, and Zoledronic acid and Ibandronate, have gained FDA approval for this indication. These drugs have proven useful in both the primary and secondary prevention, as well as treatment of osteoporosis and osteoporosis-related fractures. Tiludronate, alendronate, pamidronate, and risedronate are commonly used on-label in the management of Paget’s disease. Pamidronate and zoledronic acid had been FDA approved for the treatment of metastatic osteolysis and hypercalcemia of malignancy.
The list of off-label uses and indications for bisphosphonates continues to expand. Bisphosphonates have been used after post total joint arthroplasty to prevent osteolysis associated complications. Bisphosphonates have been used increasingly in the management of pediatric conditions associated with osteopenia and osteoporosis, including cerebral palsy, fibrous dysplasia, and osteogenesis imperfecta.
Oral and Intravenous Administration
Bisphosphonates are approved for oral and intravenous administration. Oral bisphosphonate can cause gastro-esophageal ulcers, intravenous bisphosphonates can cause febrile reactions, and both routes of administration can rarely cause hypocalcemia, stress fractures, severe pain, atrial fibrillation and jaw necrosis in elderly cancer patients with renal failure.
The site of action of bisphosphonates is in the bone itself and they are most effective if the drug is available in the bone before osteoclasts arrive. Systemic administration of bisphosphonates requires revascularization before they can reach the necrotic bone. Animal studies have shown that the drug can be injected directly into the necrotic bone, the drug distributes itself well in the bone, remains in the bone for a long period, and decreases the incidence of collapse. Thus a single injection of a smaller dose can avoid systemic toxicity and prevent osteoclastic bone resorption locally than when given through other routes.
Direct injection into the femoral head requires an invasive procedure that can be performed with sedation or general anesthesia. It also requires fluoroscopic guidance. It can be painful and rarely cause infection or bleeding complications. With the improper technique, the drug may not localize in the bone and enter the systemic circulation and be less effective in preventing collapse. The dose given into the bone will be equal or less than the standard systemic dose alleviating any concern of systemic toxicity.
Ibandronate and Zoledronic acid are both approved and available for intravenous injection. We have used Alendronate by the oral route, off label, for avascular necrosis with reasonable success. We expect the intraosseous injection to be safer and more effective. The procedure-related complications are minor and systemic consequences are insignificant compared to intravenous administration.