Article of the Month
Carla Ripamonti, MD
Managing the care of patients with bisphosphonate-associated osteonecrosis.
An American Academy of Oral Medicine position paper
Author(s): Migliorati CA , Casiglia J, Epstein J, Jacobsen PL , Siegel MA, Woo S-B
JADA. American Dental Association 2005; 136: 1658-1668
Bone metastases, the most common cause of cancer-related pain, have been found in 70 to 85% of patients with breast, lung and prostate tumours during the course of their illness.
Bisphosphonates are potent inhibitors of osteoclastic activity and accumulate over an extended period of time in the mineralized bone matrix. Moreover, they have antiangiogenic properties and may have a direct tumoricidal activity. According to data in the literature, bisphosphonates such as pamidronate, zoledronic acid and ibandronate reduce the onset of hypercalcemia and skeletal complications (pathological fractures and spinal cord compression), as well as the need for RT and surgery for fractures in patients with bone metastases due to various cancers. These agents have all been shown useful in the management of pain. The relative benefit of the three bisphosphonates has not been established in head-to-head trials. At present, they are not considered an alternative to analgesic drugs, but ongoing studies should better define their position in this respect.
Recently, bisphosphonate-associated osteonecrosis of the jaws (ONJ) has been described by many authors ( J Oral Maxillofac Surg 2004, Annals of Oncology 2005, Cancer 2005, J Oral Pathol Med 2005, N Engl J Med 2005, J Oral Maxillofac Surg 2005, JCO 2005) and represent a serious clinical and distressing complication in cancer patients with bone metastases treated with pamidronate, zoledronate, ibandronate as well as in patients with osteoporosis treated with oral alendronate.
The exact mechanism causing ONJ is unknown. The inhibition of bone remodelling and the decreased intraosseous blood flow caused by bisphosphonates (antiangiogenic properties) are supposed to be one of the possible pathobiological mechanisms. The need for bone reconstitution and remodelling increases in the presence of physiologic micro-damage occurring daily in the oral cavity and in the presence of infections of oral bone and/or when an extraction is performed. In these conditions certain patients treated with bisphosphonates develop ONJ due to a reduced capacity of bone turnover as well to a situation of hypovascularity. Systemic and local co-morbid factors such as diabetes mellitus, stage of the disease, immunosuppression, oral pathology, poor oral hygiene, presence of oral infection or metastases and /or concomitant use of chemotherapy, corticosteroids, thalidomide, may also play a role.
The oral lesions associated with bisphosphonates are similar in appearance to those of radiation-induced osteonecrosis. In most cases the diagnosis is clinically based on pain, paraesthesia, soft-tissue swelling, exposed bone, or abscess. In most patients it appears after dental extraction.
The osteonecrosis is often progressive and may lead to extensive areas of bone exposure and dehiscence. The patients may also present symptoms linked to malnutrition.
The lesions are persistent and do not respond to conventional treatment modalities such as debridement, antibiotic therapy or hyperbaric oxygen therapy. Moreover every attempt to operate on these lesions may extend the site of the osteonecrosis and involve the whole jaw. At the moment the prevention of the ONJ is the best approach. This means that patients should undergo an accurate dental examination before beginning the treatment with bisphosphonates in order to evaluate the presence of parodontopathies, dental infection, etc. and to insure there is the necessary dental care and oral hygiene.
Among the aims of the Authors of the position paper of the American Academy of Oral Medicine is the widespread dissemination of the recommendations for the prevention and the management of patients with ONJ as well as the necessary routine dental treatment of patients receiving bisphosphonate therapy.
Why I Chose this article
Bisphosphonates are drugs which have changed the clinical history of bone metastases particularly the reduction of skeletal complications.
Clinicians are concerned with this new oral complication (ONJ) associated with the administration of various types of bisphosphonates and there is a tendency to reduce their use. The data in the literature clearly indicate that prevention is the best therapeutic approach.
Carla Ripamonti, MD
Member of the Board of Directors, IAHPC
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