Jaw-dropping update

No pun intended but is there perhaps something sinister in this month’s title? My favorite topic to write about besides oral biofilms is BIONJ (oral and intravenous bisphosphonate-induced osteonecrosis of the jaws). When I first started writing about it in 2009, researchers and others hadn’t even agreed on an abbreviation. Some authors/associations referred to it as BRONJ, and others call it BON. There was a clear lack of understanding among medical and dental specialists about the disease mechanism and associated risk factors.

Back in 2009, thanks to Dr. Robert Marx, an oral and maxillofacial surgeon affiliated with the University of Miami, I discovered that BIONJ isn’t a new disease. Instead, it is the same incurable necrosis as the infamous “phossy jaw” that showed up in young matchstick employees who worked in close proximity to heated phosphate vapors during the Victorian era in England. These workers were paid a pittance for a menial job that could rot away portions of a mandible.

BIONJ was first reported by Marx and Stern in 2002.1 Marx described it as exposed, nonhealing bone that worsened with debridement. At that time, all of the patients in the 2002 report were being given pamidronate (Aredia, Novartis) to control malignant tumor deposits in bone.¹ Since then, nearly all associations of dental specialists, many medical specialist organizations, and some medical drug companies have published position papers on this topic.

BIONJ is characterized by exposure of bone in the jaws (maxilla and mandible) that persists for more than eight weeks in a patient who is currently or has taken a bisphosphonate and who has no history of radiation therapy to the jaws.¹ Recent reports have identified femur fractures caused by long-term use (six years or more) of alendronate (Fosamax, Merck).¹ This necrosis originates in the alveolar bone and may extend to the basilar bone and ramus.¹ Sometimes, early subclinical signs such as sclerosis of the lamina dura, loss of the lamina dura, and/or widening of the periodontal ligament space have been observed, especially in molars.1

According to Marx, the strongest evidence to date of a cause-and-effect relationship between bisphosphonates and osteonecrosis of the jaws is based on a study conducted by Novartis to gain marketing approval by the U.S. Food and Drug administration. (FDA). This randomized, controlled, and double-blinded study assigned patients with bone metastasis (cancer cells relocate to bone) to chemotherapy alone or chemotherapy plus a steroid regimen plus an intravenous bisphosphonate (Aredia or Zometa). Patients who presented with the same malignancies but without bone metastasis were given chemotherapy and a steroid regimen but they were not given intravenous bisphosphonates. Only those patients who received an intravenous bisphosphonate developed exposed bone.1

Marx prefaces his book (and, by the way, it’s a second edition) by stating that “the battle lines have been drawn.” The ongoing battle is between independent investigators (scientists) and companies (including paid consultants) who disagree about the toxicity of bisphosphonates. Who wins and who loses when a battle like this is waged? (It reminds me of the ongoing battle about access to care between organized dentistry and dental hygiene.) Sadly, the patient, who becomes a victim of politics, may be the loser in the end.

Novartis and Merck claim that their drugs do not cause BIONJ.¹

Marx, on the other hand, reports that the Novartis drugs (Zometa, 4 mg intravenously once monthly to treat cancer metastasis to bone or hypercalcemia of malignancy, and Reclast, 5 mg intravenously once yearly to treat osteoporosis) are the “most toxic intravenous preparations that produce the majority of cases of intravenous-induced osteonecrosis of the jaws (BIONJ).”1 “The Merck drug Fosamax (alendronate), 70 mg orally once weekly, is the most toxic oral preparation and produces the vast majority of oral BIONJ and has been noted to also cause spontaneous femur fractures — the very entity it is designed to prevent — with long-term use.”1 The greater potency of zolendronate (Zometa) coupled with an intravenous route enhances toxicity, and the higher dose of alendronate (Fosamax) enhances toxicity compared to other oral preparations like risedronate (Actonel) and ibandronate (Boniva). Fosamax (70 mg/wk) is actually twice the dose of Actonel (35 mg/wk) and Boniva (150 mg/month which equals 35 mg/wk).

As you read this updated information, doesn’t it make your jaw drop in disbelief? It reminds me of the Celebrex fiasco. Patients taking Celebrex at higher doses are more likely to suffer heart attacks and strokes than those who took older and cheaper painkillers. Stay tuned as we continue to explore BIONJ in future issues of RDH and discuss the strength of the evidence.

References:

1. Marx RE. (2011) Oral and Intravenous Bisphosphonate-Induced Osteonecrosis of the Jaws (2nd.ed.). Quintessence Publishing Co., Inc.

Lynne Slim, RDH, BSDH, MSDH, is an award-winning writer who has published extensively in dental/dental hygiene journals. Lynne is the CEO of Perio C Dent, a dental practice management company that specializes in the incorporation of conservative periodontal therapy into the hygiene department of dental practices. Lynne is also the owner and moderator of the periotherapist yahoo group: www.yahoogroups.com/group/periotherapist. Lynne speaks on the topic of conservative periodontal therapy and other dental hygiene-related topics. She can be reached at [email protected] or www. periocdent.com.