Jeannie:

Apologies for the protracted delay in getting back to you, was away and then catching up on some urgent obligations  - but I will have a full response and guidance tomorrow.  Thanks for your patience.

edge@evidencewatch.com

Jeannie:

I answer your excellent queries below, and in addition throw the discussion to a broader level to benefit a wider audience of concern, raising I think some critical issues not previously raised to date.

ONJ Risk and Pathogenesis in General

Osteonecrosis of the Jaw (ONJ) is mostly a disease of long-term intravenous bisphosphonate treatment, strongly correlated with the aminobisphosphonates (nitrogen-containing) agents pamidronate (Aredia) and zoledronic acid (Zometa), although there has been some extremely low and sporadic incidence with the oral bisphosphonates except clodronate (Bonefos), the latter being non-nitrogen-containing but not yet available in the U.S.   As to incidence, the reported incidence of ONJ in patients on bisphosphonates ranges from 1 - 11% (The Canadian Task Force on Osteonecrosis of the Jaw) in different studies, varying by type of bisphosphonate, patient population, and surveillance time-frame .  A primary etiological mechanism of ONJ is that surgical injury / trauma to the bone and oral mucosa expose the usually germ-free oral tissues to oral flora, predisposing  to ONJ as a result of reduced bone blood perfusion, reduced bone metabolism rates, increased osteoclast and osteoblast apoptosis, and defective mucosal barrier caused by what's known as increased keratinocyte apoptosis, all promoted by bisphosphonate use.  

ONJ Risk in Breast Cancer Populations

However, the specific breast cancer population, incidence is estimated at about 1.2% (MD Anderson ONJ Retrospective Analysis) to 3% (as per Beck and colleagues in Tuebingen (ASCO 2007).  In this BC-context, the number of treatment cycles were significant risk factors for the development of ONJ, with mean number of treatment cycles being 27 ±18 cycles (median: 21 cycles, range 6-62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1-67 months). 

More particularly, in patients on oral bisphosphonates as opposed to parenteral (iv) bisphosphonates, the mean duration of alendronate use before developing ONJ was 4.1 years (Noam Yarom and colleagues in Tel Avid).   And risk of developing ONJ also depends critically on the duration and dose of therapy, with cumulative ONJ risk of ~3% after 2 years but rising to up to 11% after 4 years of exposure.  These findings are not likely to be substantially different for other oral bisphosphonates like risedronate (Actonel).

The Issue of ONJ with Oral Bisphosphonates

Almost all (~94%) cases of ONJ occur in patients receiving intravenous bisphosphonate as compared to oral bisphosphonates.  And note that administration interval appears to modulate risk: out of over 7,000 women with postmenopausal osteoporosis treated with one yearly zolendronic acid (Zometa) or placebo,  only one on zoledronic acid experienced ONJ, and this was no different from those treated with placebo (as per The Health Outcomes Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial Research Group, Jon Grbic and colleagues reporting).  Additional risk factors include (1) prior radiation treatment to the head and neck, (2) periodontal disease or poorly fitting dentures, and most especially, (3) dental procedures involving bone surgery, especially tooth extraction, although root canal treatment seems to be a secure treatment option for patients receiving BP, as suggested by the case-control study of risk factors in beast cancer patients just reported this year by Athanassios Kyrgidis and colleagues in Greece.

Clinical Decisions

But in the final analysis, the low incidence of ONJ must be assessed in the context of the clinical benefit of bisphosphonates, in particular therapy in reducing hip, vertebral and nonvertebral fractures in this at-risk population, and also of the potential anti-metastatic activity.

As to guidelines for ONJ prevention specific to the oral bisphosphonates,   according to the AAOMS guidelines it has been helpful in mitigating risk of ONJ for patients who have been exposed to oral bisphosphonate therapy beyond three years and who require dentoalveolar surgery to have their oral bisphosphonate agent discontinued for at least three months prior to the planned surgery, as Henry Bone and colleagues for the Alendronate Phase III Osteoporosis Treatment Study Group have found that osteoclastic function begins to increase within months following withdrawal of oral bisphosphonate medications in osteoporotic women. 

In addition to this, or in lieu of should this not be viable, patients anticipating dental surgery should be optimized for health of oral flora via antibiotic and antimicrobial prophylaxis, since there is some evidence I have presented on my ONJ Watch site (Evidence-based Guidance on Osteonecrosis of the Jaw | Consumer Alert: Osteoporosis Drugs - A Pain in the Jaw?) that in cases of ONJ, a microbe, the gram positive bacterium Actinomyces, frequently an opportunistic pathogen especially of the oral cavity, attached to the necrotic bone tissue.  And given this, I also uncovered that besides oral rinsing with chlorhexidine (Peridex, Corsodyl, Savacol) and use of systemic antibiotic therapy, there is rare good news in that several non-prescription agents are also active and effective against various forms of orally resident Actinomyces:
 

1. a baking soda toothpaste containing 52% baking soda and 3% sodium percarbonate (Arm & Hammer PeroxiCare) as well as another dentifrice containing 65% baking soda (Arm & Hammer Dental Care) resulted in statistically significant reductions in the levels of Actinomyces species); and

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2. the antimicrobial mouth rinse Listerine, extraordinarily, completely eradicated a broad spectrum of oral microorganisms in 10 to 30 seconds, including Actinomyces, and may even be effective in providing some significant analgesia, probably due as the study author speculates to a decrease in oral bacteria by the antimicrobial action of Listerine, leading to lowering the inflammatory response of the host;

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3. either hydrogen or carbamide peroxide treatment at concentration of at least 3%; an excellent preparation is the OTC product Gly-Oxide which is formulation in a soothing glycerin base.

My Conclusions

Given these findings, my evidence-based perspective is that we can no longer consider bisphosphonates by themselves as the sole cause of ONJ, but must acknowledge the joint role that oral pathogens, in particular Actinomyces, play in its development, suggesting a vital positive role of anti-bacterial therapy in minimizing or remitting adverse symptoms, and possibly in also prophylactically minimizing the potential for even contracting ONJ while on bisphosphonate therapy.

So in the final analysis,

1. I would disagree that the risk of ONJ in the case of your anticipated tooth extraction is too high;

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2. the preventive strategies I have outlined above and  documented on ONJ Watch can be deployed to minimize the already low risk still further;

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3. the evidence suggests that the benefits outweigh the risks by a high order of many magnitudes;

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4. I have noted in my own research review the critical breakthrough findings of Allan Lipton at Pennsylvania State University reported at SABCS 2007 and updated in published form this year in which breast cancer recurrence was evaluated based on bone mineral density (BMD), with the potentially practice-changing finding that patients who were the most osteoporotic or osteopenic had the highest risk of recurrence, via the mechanism that accelerated bone metabolism itself might promote the growth of micrometastatic cancer.  As Paul Goss MGH Cancer center / Harvard noted in an interview, "the more quiescent bone is in the presence of cancer, the better patient outcomes will be", and bisphosphonate therapy induces higher bone quiescence, and as Allan Lipton has concluded "breaking the cycle of bone destruction and tumor growth in bone with bisphosphonates can produce profound benefits".

My Case for Bisphosphonates Administration Despite Risk

So I would conclude that in addition to

1. anti-osteoporotic benefit in fracture risk reduction,
2. therapeutic benefit against bone metastasis SREs (skeletal-related events)
3. potential anti-metastatic activity,
4. also potential anti-angiogenic / anti-VEGF activity, we now based on the evidence I marshaled must add
5. reduction of the risk of breast cancer recurrence / relapse. 

Not only do these benefits strike me as compelling, but above that they strike me as overwhelming against the small and mitigatable potential risk.  Of course each patient must ultimately decide how to proceed in consultation with their health professionals, but these are critical issues to explore in any discussion and decision process. 

Jeannie:

You're in luck - any flavor of Listerine will do as they all use the same active formulation (I agree, the original flavor is an acquired taste, one I haven't acquired). 

SoCalLisa:  Good move!

Gina:  The fellow pictured should buy his Listerine wholesale and in bulk, and may want to entertain bathing in it regularly.  I'll say a prayer.