Osteonecrosis of the jaw risk factors
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In the past few years, thousands of cases of ONJ in patients on bisphosphonate therapy have been diagnosed usually following lack of healing after a dental extraction but also in cases of spontaneous exposure of the cortical bone tissue through the gingiva and mucosa. The recent increase of such cases has been linked with a major emphasis on the therapeutic use of bisphosphonates for osteoporosis, especially since hormone replacement therapy has been shown to increase the risk of breast cancer, clots and cardiovascular disease in women following the 2003 findings of the U.S. Women’s Health Initiative study. Two classes of bisphosphonates are presently prescribed:
- Non-nitrogen containing bisphosphonates such as etidronate (Didronel®, Procter & Gamble Pharmaceuticals)
- Nitrogen containing such as alendronate (Fosamax®, Merck), pamidronate (Aredia®, Novartis), zoledronate (Zometa®, Novartis), risedronate (Actonel®, Procter & Gamble) and ibandronate (Boniva®, Roche Laboratories).
The nitrogen containing bisphosphonates are the most potent inhibitors and no case of ONJ associated with etidronate has been reported yet. The main pharmacological action of bisphosphonates is inhibition of the osteoclast driven bone resorption. This is achieved by shortening osteoclast lifespan via apoptosis and by inhibiting osteoclast activity and recruitment on the bone surface (61). When a bisphosphonate binds to bone mineral, osteoclast resorb both bone and the bound bisphosphonate. During bone formation, if any, bisphosphonate remaining on the surface of the bone is covered and remains there until future osteoclastic bone resorption at the site. This explains why inhibition of bone resorption continues long after bisphosphonate treatment has been discontinued.
This form of therapy has been shown to prevent loss of bone mineral density (BMD) as a result of a reduction in bone turnover. However bone health is a lot more than BMD.
In healthy bone tissue there is a homeostasis between bone resorption and bone apposition. Diseased or damaged bone is resorbed through the osteoclasts mediated process while osteoblasts form new bone to replace it, thus maintaining healthy bone density. A process commonly called remodelling.
However osteoporosis is essentially the result of a lack of new bone formation in combination with bone resorption in reactive hyperemia, related to various etiological and contributing factors, and bisphosphonates do not address these factors at all.
An individual who is already having problems with osteoporosis/ osteonecrosis of the jaws due to the effects of these etiological factors will be more susceptible to the adverse effects of bisphosphonates. In theory, by suppressing osteoclastic activity and bone resorption, any ischemic-damaged bone will be left in situ instead of being resorbed. The damaged bone will not be repaired either if the factors already inhibiting osteoblastic activity are still present. Therefore the amount of osteonecrotic tissue should be expected to increase until it reaches a level when any trauma or insult to this necrotic bone will result in extremely poor healing, exposed necrotic bone to the oral environment, development of pain, and increased risks of microbial infection, as effectively seen in bisphosphonates associated cases of ONJ.
In a systematic review of cases of bisphosphonates associated ONJ up to 2006, it was concluded that the mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. According to Woo, Hellstein and Kalmar, oversuppression of bone turnover is probably the primary mechanism for the development of this form of ONJ, although there may be contributing co-morbid factors (as discussed elsewhere in this article). It is recommended that all sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate (Fosamax®), for osteoporosis is uncertain and warrants careful monitoring.
- Fosamax does more harm then good. Accessed 21 May 2006.
- Hay KD, Bishop PA. Association of osteonecrosis of the jaws and bisphosphonate pharmacotherapy: dental implications. NZ Dent J. 2006 Mar;102(1):4-9.
- Wassertheil-Smoller S. et al. Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women The Women's Health Initiative: A Randomized Trial. JAMA. 2003;289:2673-2684. PMID: 12771114
- Rodan G, Reszka A. Osteoporosis and bisphosphonates. The Journal of Bone and Joint Surgery. 2003;85-A (Suppl. 3)8-12.
- Woo S, Hellstein J, Kalmar J (2006). "Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws". Ann Intern Med. 144 (10): 753–61. PMID 16702591.