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Treatment in Conjunction with Bisphosphonate Therapy
Q:What is the protocol for treating patients taking oral bisphosphonates for osteoporosis?
A:Treatment phases are related to prevention and treatment of sequelae associated with the administration of bisphosphonates. The prevention phase starts before prescribing IV or oral bisphosphonates. A thorough oral and skeletal examination should be carried out, and all necessary invasive procedures completed prior to the start of administration. Extraction of necessary teeth, removal of bony exostoses and tori, reduction of sharp mylohyoid ridges, implant therapy, periodontal surgery, and apicoectomies should all be completed with a view to eliminating the necessity for bony invasive procedures after initiation of therapy. Therapy should be delayed until the extraction/surgical site has at least been completely covered with mucosa. Mandibular sequelae outnumber maxillary sequelae 2:1 and most commonly start in areas where the mucosa is at its thinnest. Oral prophylaxis and conservative restorative dentistry must be done, and should be continued indefinitely. Edentulous patients should be examined for trauma to edges and vestibules from ill-fitting dentures, and all areas of mucosal trauma under the dentures should be relieved. The risk of devastating sequelae increases exponentially after 3 years of therapy.
Patients who have started bisphosphonate therapy are at risk of sequelae such as bisphosphonate-related osteonecrosis of the jaws (BRONJ). Treatment must be modified for this phase of prevention. Carious teeth should be cut down and root canals done on remaining roots, rather than extraction. Oral bisphosphonate regimens carry a much lower risk of development of serious sequelae than IV administration. Dental implants may be placed conservatively in this group but should be avoided in the IV administration group. Patients in this group should have informed consent to dentoalveolar procedures, given the risk of BRONJ.
AAOMS reports other factors to be considered. Serious sequelae (BRONJ) increase in risk 9% for each decade of age, and Caucasians are at greater risk than any other race. Cancer risk is ranked as follows: multiple myeloma > breast cancer > all other cancers, and risk is highest if there is a diagnosis of osteoporosis in addition to the cancer diagnosis.
The bottom line is that for individuals who have been on "oral bisphosphonates for less than three years, and have no clinical risk factors, no alteration or delay in the planned surgery is necessary."1 For those patients who have taken oral bisphosphonates for more than 3 years, therapy should be discontinued for 3 months to 6 months if their health and chronic conditions allow.
1. American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws. American Association of Oral and Maxillofacial Surgeons; 2006. Available at: http://www.aaoms.org/docs/position_papers/osteonecrosis.pdf. Accessed March 11, 2011.
A: A discussion about a clinical protocol for treating patients taking oral bisphosphonates should address the following question: Why is the patient taking oral bisphosphonates?
The overuse of bisphosphonates requires that any protocol be based on a case-by-case review and a serious communication with the medical team.1 For many patients the benefits of these drugs do not outweigh the risks. In addition, bisphosphonates have long half-lives, lasting many years in bone. The longer patients take the medications, the greater the risk of osteonecrosis.1,2
Prevention and early diagnosis can result in success with minimum cost. Patient compliance and attitude play a major role in the implementation of self-maintenance of oral health. Oral hygiene should be incorporated and established early as part of a healthy lifestyle.
Patients taking bisphosphonates and affected by plaque-induced gingival inflammation are at risk of harboring active periodontal pathogens and viruses.3 The overgrown and inflamed gingival tissue can be considered sites of active microbial and viral replication.4 However, little attention is given to gingivitis, perhaps because its danger is not taken seriously. Assuming that periodontal viruses can reside in inflammatory cells, a reduction of soft-tissue inflammation by short-interval maintenance programs of once every 6 weeks and the implementation of oral health self-maintenance is recommended.
Periodontal and dental therapy and maintenance provide a healthier oral microbial environment. The application of sea salt-water mouthrinse—one spoonful per glass of warm water, twice a day—is an antimicrobial approach that has a high degree of efficacy and tolerability. A diluted sodium hypochloride mouthrinse provides efficacy as well: one teaspoon to a 1/2-cup water, three times per week.
Early diagnosis of exposed necrotic bone can also result in success. The exposed necrotic bone can be removed by osteoplasty using rotary and hand surgical instruments. Following plasty, frequent monitoring of oral and periodontal health may reduce the risk of complications related to bacterial or human cytomegalovirus infection. Long-term prospective studies are needed to clarify the magnitude of these benefits.
1. Park-Wyllie LY, Mamdani MM, Juurlink DN, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011;305(8):783-789.
2. Dominguez LJ, Scalisi R, Barbagallo M. Therapeutic options in osteoporosis. Acta Biomed. 2010;81(suppl 1):55-65.
3. Aghaloo TL, Kang B, Sung EC, et al. Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. Published Online: February 23, 2011 (doi:10.1002/jbmr.379).
4. Nowzari H, Jorgensen MG, Aswad S, et al. Human cytomegalovirus-associated periodontitis in renal transplant patients. Transplant Proc. 2003;35(8):2949-2952.
A: Metastatic bone lesions, multiple myeloma, osteoporosis, and Paget’s disease are conditions that have been treated with bisphosphonates. Prolonged use of this class of drugs resulted in necrotic lesions of the jaw bones, primarily when administered by IV, as first described by Marx in 2003.1 Dental treatments involving jaw bone trauma might lead to the development of such lesions, but they could also develop spontaneously. These lesions seem to depress blood flow, inhibit endothelial cell function, decrease cell proliferation, and increase apoptosis.
Guidelines for prevention and treatment of BRONJ are applicable but not yet universally efficient or accepted. The labile behavior of BRONJ is understandable in light of the fact that the exact mechanism inducing the necrotic process has not been fully investigated. Duration of exposure and the way of administration are of utmost importance. More than 6 IV doses and more than 3 years of per os administration are predisposing to osteonecrosis. The observed incidence is 0.8% to 30% for the IV administration down to 0.007% to 0.01% for the per os treatment.2 Initiation of bisphosphonate treatments should be postponed for a few weeks following oral surgical interventions. Bear in mind that a cure of BRONJ is not always achieved.
Serum C-terminal telopeptide (CTx) seems to give an indication of bone turnover capacity.
Depending on the severity of the necrotic process, protocols using antiseptic mouthwashes, systemic antibiotics, analgesics, removal of necrotic sequesters, and even partial or total jaw resections have been mentioned in the literature.
1. Marx, RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61(9):1115-1117.
2. Marx RE, ed. Oral & Intravenous Bisphosphonate-Induced Osteonecrosis of the Jaws: History, Etiology, Prevention, and Treatment. Hanover Park, IL: Quintessence Publishing; 2006.
About the Authors
Robin Daniel, DDS
Oral and Maxillofacial Surgery
Hessam Nowzari, DDS, PhD
Herman Ostrow School of Dentistry of University of Southern California
Los Angeles, California
Adi A. Garfunkel, DMD
Professor of Oral Medicine
Hadassah Hebrew University