Friday, January 6, 2012

Updating the Management of the Dental Patient at Risk for Osteonecrosis of the Jaw Bone (ONJ) While Taking Bisphosphonates or Denosumab (Prolia®) - Latest Reports from the American Dental Association

 

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Courtesy of Lexicomp:

 

The stated purpose of the 47-page report is to help dental professionals make treatment decisions based on recent and best evidence, and on expert opinion, for patients being treated with drugs to manage and prevent osteoporosis — namely the bisphosphonates and the nonbisphosphonate antiresorptive agent, denosumab (Prolia®). The report can be used as an educational tool, to assist the dental professional when discussing oral health with patients receiving these drugs and when treating these patients. This report is available at www.ada.org and can be printed from the following URL:

http://www.ada.org/sections/professionalResources/pdfs/topics_ARONJ_report.pdf

The ADA conducted a search of Medline using PubMed for literature published between May 2008 (the end date of the last advisory statement search) and February 2011. The report focuses on patients taking bisphosphonates or denosumab to manage and treat low bone mass, including osteoporosis, and not for cancer management. The report describes therapies for osteoporosis, reviews the literature for osteonecrosis of the jaw bone (ONJ), describes staging and treatment strategies for drug-induced ONJ and makes recommendations for the dental management of noncancer patients receiving antiresorptive therapy. The report is clear to emphasize that it does not represent a standard of care; the clinical recommendations should be integrated with the practitioner's professional judgment and individual patient needs and preferences. I would encourage the readers of this newsletter to access the site (see above) and review this very informative report.

To compliment the 47-page report, the ADA published the second report as an executive summary by the Council on Scientific Affairs in the November 20011 issue of the Journal of the American Dental Association entitled "Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis."

This executive summary also focuses on patients receiving bisphosphonates and other antiresorptive therapy for low bone mass rather than on patients receiving antiresorptive therapy for cancer treatment. Patients with low bone mass, namely osteoporosis, are seen routinely by general dentists and the risks and patient care are much different for patients receiving antiresorptive therapy for cancer treatment.

Highlights of the executive summary report

The executive summary report states the risk of developing ONJ in patients taking bisphosphonates or denosumab remains low, with an estimated prevalence of 0.1 % (one case out of every 1000 individuals exposed to bisphosphonates or denosumab). In their previous estimate (2008 report), the risk was 1 case out of 140,000 person years exposure to bisphosphonates. It was also stated that the benefits of using the oral bisphosphonates to prevent osteoporosis significantly outweigh the small risk of developing bisphosphonate-associated ONJ. Also, at the present time, there are no validated diagnostic techniques to determine which patients are at increased risk of developing ONJ.

The executive summary report reminds the dental professional that ONJ can occur spontaneously in patients taking these drugs. In addition, the risk of ONJ increases with specific procedures that increase bone trauma, particularly tooth extractions. Other factors that increase risk of ONJ in patients taking these drugs are age (older than 65 years), periodontitis, use of bisphosphonates for more than 2 years, smoking, denture wearing and diabetes.

The popular bisphosphonates used in the US to treat osteoporosis in postmenopausal women are alendronate (Fosamax®), alendronate/cholecalciferol (Fosamax® D), risedronate (Actonel®), ibandronate (Boniva®), and zoledronic acid (Reclast®). Denosumab (Prolia®) is not a bisphosphonate but a monoclonal antibody which inhibits bone resorption by mechanisms different from those of bisphosphonates (see previous newsletter).

The executive summary report addressed the issues of serum CTX tests and drug holidays.

Serum CTX tests

Marx et al, (Marx RE, Cillo JE Jr, and Ulloa JJ, "Oral Bisphosphonate-Induced Osteonecrosis: Risk Factors, Prediction of Risk Using Serum CTX Testing, Prevention, and Treatment," J Oral Maxillofac Surg, 2007, 65(12):2397-410) have suggested the use of a serum bone turnover marker in assessing the risk of ONJ in bisphosphonate users. The serum bone turnover marker is C-terminal telopeptide fragments from collagen (CTX) and is measured by a serum CTX test which, according to Marx, roughly correlates to the systemic suppression of bone renewal caused by the oral bisphosphonates. Marx suggested that bone turnover markers have use in assessing the risk of ONJ. Values lower than 100 pg/ml were correlated with a high risk of ONJ, values between 100 and 150 pg/ml correlated to a moderate risk, and values greater than 150 pg/ml associated with minimal or no risk. Since bisphosphonate drugs suppress osteoclastic activity, this results in suppression of bone turnover. Thus, lower serum values of the telopeptide fragments would indicate low osteoclastic activity and low bone turnover at the time of measurement. This ultimately results in bone necrosis. Thus, individuals with low CTX values while taking bisphosphonates are assumed to have jaw bones which may not be able to normally repair themselves and these individuals would have a relatively higher risk of developing ONJ compared to individuals having higher CTX serum values.

The executive summary report states that there is simply not enough evidence to recommend the use of serum tests such as serum CTX as a predictor of ONJ. This mirrors the 2008 statement which said that until objective research studies document and correlate the specificity, predictive value and reliability of the CTX test, no recommendations can be made.

Drug holiday concept

A "drug holiday" is a discontinuance of the bisphosphonate drug for a length of time thought to achieve a reduction of risk of ONJ. It has been suggested by various researchers that one consider interrupting bisphosphonate treatment for 3-4 weeks prior to surgery and restarting after bone healing. This suggestion has not been supported by the ADA. According to the ADA, no study results to date have confirmed that drug holidays are effective in preventing ONJ without increasing the skeletally-related risks of low bone mass during treatment.

The executive summary report, like the 2008 report, goes on to make recommendations for the management of dental care of patients receiving oral bisphosphonate therapy or denosumab therapy and subdividing their recommendations according to general dentistry, oral and maxillofacial surgery, restorative dentistry and prosthodontics, orthodontics, implant placement and maintenance, management of periodontal disease and endodontics. The following are the key points from their recommendations.

General dentistry: The dental professional should not modify routine dental treatment because of the use of the osteoporotic drugs. Dental patients taking a bisphosphonate or denosumab should be informed that there is a very low risk of developing ONJ. The highest prevalence estimate in a large sample is about 0.1%. The low risk of developing ONJ can be minimized but not eliminated. The dentist is reminded that there is no validated diagnostic technique available to determine if patients are at increased risk of developing ONJ. Also, discontinuing oral bisphosphonate therapy may not eliminate or reduce the risk of developing ONJ. An oral health program consisting of sound oral hygiene practices and regular dental care may be the optimal approach for lowering risk of developing ONJ.

The executive summary report suggests a major goal in the prevention of ONJ is limiting the possibility of extensive or multifocal involvement. This is consistent with the 2008 report which said it may be prudent to proceed conservatively in bisphosphonate patients, to gain some insight as to how the patient will heal before putting multiple quadrants at risk. The 2011 summary recommends a patient with active dental or periodontal disease should be treated, despite the risk of developing ONJ, because the risks and consequences of no treatment likely outweigh the risks of developing ONJ. Leaving active dental disease untreated can lead to complications that may require more extensive and risky treatments. In certain situations, the dentist should consider obtaining written acknowledgement for consent of a chosen course of dental treatment after a discussion of the benefits, risks and treatment options.

Oral and maxillofacial surgery: Patients undergoing surgery should be informed of the risk of developing ONJ. The clinician should discuss with the patient alternative treatment plans including endodontic treatment followed by removal of the clinical crown allowing the roots to exfoliate rather than extraction, and provision of bridges and partial dentures instead of implant placement. Before and after any surgical procedures involving bone, the patient should rinse with chlorhexidine using the common regimen of twice daily rinse for 4-8 weeks after surgery. In addition, antibiotic prophylaxis, starting one day before and extending 3-7 days after dental procedures, may be effective in preventing ONJ.

Restorative dentistry and prosthodontics: There is no evidence that malocclusion or masticatory forces increase the risk of developing ONJ. All routine restorative procedures may be conducted in a patient taking oral bisphosphonates.

Orthodontics: Case reports have indicated inhibited tooth movement in patients receiving bisphosphonates. Patients should be advised of this potential complication. The duration of orthodontic treatment may be longer and uniform tooth movement may be compromised in the patient exposed to bisphosphonates and denosumab.

Implant placement and maintenance: Bisphosphonate treatment is not a contraindication for dental implant placement. Studies to date have shown similar success rates in implant placement in patients with or without bisphosphonate exposure (success 95% or greater). Dentists can inform patients that the risk of developing ONJ as a result of exposure to the bisphosphonates and denosumab is low and that success rates for implants placed in patients receiving bisphosphonate treatment is no different in the short term (less than 10 years) from the success rates for implants placed in patients without a history of bisphosphonate exposure. The executive summary report mentions the lack of data regarding effects of implant placement in patients taking oral bisphosphonates. However, the report also states that the patient may be at increased risk of developing ONJ when extensive implant placement is necessary.

Management of periodontal disease: Patients receiving bisphosphonates or denosumab who have active periodontal disease should receive appropriate forms of nonsurgical therapy. Also, as in the 2008 report, there is still no evidence that periodontal procedures such as guided tissue regeneration or bone replacement grafts increase or decrease the risk of ONJ or the success of implant treatment.

Endodontics: As stated in the 2008 report, endodontic treatment is preferable to surgical manipulation if a tooth is salvageable. The present report updates that statement with the fact that limited evidence shows that periapical healing after endodontic therapy is similar regardless of whether or not patient has a history of bisphosphonate use.

References

The full 47-page report is:

Hellstein JW, Adler RA, Edwards B, et al, for the American Dental Association Council on Scientific Affairs Expert Panel on Antiresorptive Agents, "Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis: Recommendations from the American Dental Association Council on Scientific Affairs."http://www.ada.org/sections/professionalResources/pdfs/topics_ARONJ_report.pdf Accessed Nov 25, 2011.

2011 executive summary:

Hellstein JW, Adler RA, Edwards B, et al, "Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis," Executive Summary of Recommendations from the American Dental Association Council on Scientific Affairs, J Am Dent Assoc, 2011, 142(11):1243-51.

2008 report:

Edwards BJ, Hellstein JW, Jacobson PL, et al, American Dental Association Council on Scientific Affairs Expert Panel on Bisphosphonate-Associated Osteonecrosis of the Jaw, "Updated Recommendations for the Management and Care of Patients Receiving Oral Bisphosphonate Therapy: An Advisory Statement from the American Dental Association Council on Scientific Affairs," JADA, 2008,139(12):1674-7.


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