턱얼굴(구강악안면)외과 (Maxillofacial Surgery-Oral Surgery)
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  A Central Role for Nurses in Jaw Necrosis  http://www.face.or.kr  
   Pf Yang  (http://www.face.or.kr/) 2009-04-17 14:05:00, 조회 : 4,691

http://www.oncologynursingnews.com/A-Central-Role-for-Nurses-in-Jaw-Necrosis/article/130168/

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A Central Role for Nurses in Jaw Necrosis
Rosemary Frei, MScApril 10 2009
Oncology nurses, take note: You play a critical role in reducing the incidence and effects of a potentially serious adverse event that strikes a significant portion of oncology patients. People taking bisphosphonates—indicated for osteoporosis and osteopenia, bone metastases from multiple myeloma and solid tumors such as breast cancer, and also Paget's disease—can develop bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Exposed bone in the affected patient's mouth fails to heal, almost always after a tooth extraction or other invasive dental procedure. BRONJ affects less than 0.01% of people taking oral bisphosphonates, but up to 12% of those taking the more potent intravenous (IV) form. Other risk factors include a history of inflammatory dental disease, older age, and smoking.

BRONJ first gained widespread attention in September 2004, when Novartis modified the labeling of its IV bisphosphonates pamidronate (Aredia) and zoledronic acid (Zometa) to note the possibility of the development of BRONJ. This was followed in 2005 by a broadening of this warning to all bisphosphonates, both IV and oral. But it is only in the last year or two that the word has percolated through to a large number of healthcare professionals.

Unfortunately, this wasn't soon enough for oncology patient James Murphy. He was put on zoledronate (Zometa) in October 2003 for pubic-bone metastases from renal cancer. In November 2006 he had a tooth extraction followed later by a periodontal procedure, and developed swollen and bleeding gums together with pain in both places where work had been done.

“I don't know what my doctors or dentists knew at the time about avoiding extractions or periodontal procedures in people on Zometa, but I don't recall being cautioned about it,” says Mr Murphy, who lives on Long Island in New York. “My renal oncologist was monitoring me for Zometa dental side affects, and stopped the medication in February 2007 when he became aware of the bleeding from my gums. Then, the dental surgeon who had done my tooth extraction put me on antibiotics to try to stop the bleeding, swelling, and pain. When that provided only temporary relief he referred me to Dr Estilo at Memorial Sloan-Kettering Cancer Center in November 2007.”

Cherry Estilo, DMD, associate attending dentist at New York's Sloan-Kettering and assistant professor of dentistry, oral, and maxillofacial surgery at Weill Cornell Medical College, also in New York, explained to Mr Murphy that a piece of jaw bone had died and would eventually work its way through the gum. And that's exactly what happened: The piece of bone gradually—and, fortunately, painlessly—worked its way through his gums until one day it came out completely.

“I couldn't believe how big it was: the thickness of 2 or 3 quarters, and about the length of a quarter,” remembers Mr Murphy. The same thing happened later on the other side of his mouth, where another piece of bone had necrotized following the periodontal procedure. Mr Murphy, who is now 66 years old, has few regrets .about the experience, except he wishes someone had told him sooner that this could occur.

What Can Nurses Do?
The fact is, now that BRONJ is well characterized, nurses form an indispensable link to patients in alerting them to the possibility of this adverse event, and advising them to have any necessary dental work done before starting on a bisphosphonate.

“Oncology nurses need to focus on patient education, to make the patients aware of this potential side effect by recognizing the signs and symptoms of osteonecrosis of the jaw,” affirms Marlene McGuire, RN, MA, APNBC, an adult nurse practitioner in the Bridge Program of the Cancer Institute of New Jersey, New Brunswick. “They should tell patients who are about to receive this treatment, especially IV bisphosphonates, to have a dental examination before they go on the therapy. And nurses should regularly ask patients who are on therapy whether they're developing any dental issues such as loose teeth, swelling or bleeding of the gums, a feeling of heaviness in their jaw, or any other signs of bisphosphonate- related oral pain.”

Dr Estilo, the oncological dentist who helped Mr Murphy, agrees, but adds nurses can go a step farther by examining patients' teeth.

“Oncology nurses and oncologists should actually look carefully at all of the teeth and areas of gum to see if there are any obvious lesions,” says Dr Estilo. “But of course, this doesn't replace a thorough oral examination by a dentist.”

How Common Is BRONJ and What Are the Risk Factors?
A significant stir has been caused in the oncology and dental communities by a paper on BRONJ prevalence by University of Southern California (USC) dental researchers (J Amer Dental Assoc. 2009;140:61-66). The investigators found that, among a large sample of nonreferred USC School of Dentistry patients, 208 were taking alendronate, and 9 (4.3%) of these individuals had symptomatic BRONJ. The 9 affected individuals had been using alendronate—an oral, nitrogen-containing form of bisphosphonate—continuously for between 1 and 10 years.

However, one of the foremost experts on BRONJ in the United States is adamant that this finding does not reflect the rate of BRONJ in the general population.

“It is a single-institutional study of the incidence of necrosis in patients who presented to their clinic. And it's an inherently biased sample because USC is a major dental school, and people who think they have BRONJ or other issues are going to present there,” declared Salvatore Ruggiero, DMD, MD, chair of the American Association of Oral and Maxillofacial Surgeons' Task Force on Bisphosphonate-Related Osteonecrosis of the Jaw. “If I did the same sort of study of the patients I see in my practice, I'd have a BRONJ incidence of 50%.” Indeed, Dr Ruggiero and the other members of the task force opted not to include a reference to the USC study in their January 2009 update of their BRONJ guidelines (see http://www.aaoms.org/docs/position_papers/ bronj_update.pdf).

“We decided that we probably shouldn't include it because it will cause more confusion,” Dr Ruggiero, who is also an associate professor in the oral and maxillofacial surgery division at the Stony Brook School of Dental Medicine, and an attending oral and maxillofacial surgeon at the Long Island Jewish Medical Center, New Hyde Park, NY, told Oncology Nursing News. “We were afraid that people would extrapolate [from] that [singleinstitution rate] to think there is a large risk.”

In their updated guidelines—to be published in April in a supplement to the Journal of Oral and Maxillofacial Surgery—Dr Ruggiero and the other members of the task force provide a listing of all the bisphosphonates currently available in the United States, together with the relative potency of each formulation (see Table 1). They also summarize the clinically relevant information produced since 1993.

The task force members define the characteristics of BRONJ as current or previous treatment with a bisphosphonate, exposed bone in the maxillofacial region that has persisted for more than 8 weeks despite treatment, and no history of radiation therapy to the jaws. Conditions that should not be confused with BRONJ include sinusitis, gingivitis, periodontitis, dental caries, and temporomandibular joint disorders.

The most reliable estimates put the prevalence of oral bisphosphonate-related BRONJ at 0.01% to 0.06%, and of IV-associated BRONJ at 0.8% to 12%. Overall, receiving IV bisphosphonates increases cancer patients' risk of developing BRONJ 2.7- to 4.2-fold, with longer use translating to higher risk. Furthermore, those who also undergo invasive dental procedures are 5 to 21 times more likely to develop BRONJ than those who do not. Other risk factors include a history of inflammatory dental disease, older age, obesity, renal dialysis, diabetes, low hemoglobin, and a smoking habit.

Can It Be Prevented?
The single most important modifiable factor in the development of BRONJ is exposure to invasive dental procedures. Therefore all patients should undergo a dental evaluation and receive all necessary treatment prior to initiating IV or even oral bisphosphonate therapy. And that's where thorough education by oncology nurses and oncologists comes in.

“Ideally, they should go to the dentist for thorough oral and dental examination before they start therapy,” says Dr Estilo of cancer patients assigned to bisphosphonate treatment. “By doing this, we can identify and appropriately treat any teeth that may ultimately require extraction.”

In exceptional cases, however, bone-disease-related pain is so severe that the patient must be started on IV bisphosphonate before having a dental checkup, she admits.

Can reducing the IV bisphosphonate dosing frequency significantly reduce the rate of BRONJ? One small study suggests this may be the case. Alessandro Corso, MD, of the Hematology Clinic, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy, and his colleagues randomized 51 multiple myeloma patients to monthly IV pamidronate and another 55 to monthly treatment for 1 year followed by a reduced schedule of IV pamidronate once every 3 months for the remainder of their treatment (Leukemia. 2007;21:1545-1548). Six patients in the first group but only 1 in the second group developed BRONJ, yielding an 8-fold lower risk for BRONJ with the less-frequent dosing

A Mayo Clinic panel of hematologists, dental specialists, and nurses formulated bisphosphonate guidelines for multiple myeloma patients at their institution in 2006. Based on the then-available evidence of BRONJ risk, they completely abandoned zoledronic acid and instead began using pamidronate exclusively (Mayo Clin Proc. 2006;81[8]:1047-1053). They also started discontinuing bisphosphonates after 2 years in patients who achieved complete response and/or a plateau phase, and switching to therapy once every 3 months in those who had not responded after 2 years.

Yet Dr Ruggiero is skeptical, and notes that people at other institutions are as well. “The Mayo group made the decision to change the dosing schedule based on the premise that if once a month is not good, maybe once every 3 months is better—without any data to support it,” he pointed out. “And I've not seen any evidence since to suggest this approach is efficacious in reducing the incidence of BRONJ, other than that 1 [Italian] paper, which had a very small number of patients.”

Dr Ruggiero and the other members of the task force also updated the staging of BRONJ in their latest guidelines. They added an “at risk” category and a Stage 0 category, together with suggested treatment strategies for each stage (see Table 2).

Are Drug Holidays Safe?
One of the more poorly understood areas relating to the treatment and prevention of BRONJ is whether people who have been taking an IV bisphosphonate can benefit from a drug holiday and, if so, how long the holiday should be. The members of the task force cite 3 recent studies showing that discontinuation allows existing necrosis to stabilize, reduces the risk of additional necrosis sites, and reduces complications (see for example Ann Oncol. August 9, 2008 [Epub ahead of print]).

“If patients develop BRONJ that includes an area of exposed bone, most oncologists will probably take them off bisphosphonates,” Dr Ruggiero points out. “It depends on the patient's stage of BRONJ and risk of developing a cancer-related skeletal complication. The oncologists have to make the risk-benefit decision of whether continuing the once-monthly IV bisphosphonate therapy is warranted in the face of the BRONJ, when the bisphosphonates have an approximately 10- year half-life.”

What is still unknown, he adds, is the optimal period of discontinuation of IV bisphosphonates—either in those who have not developed BRONJ but require dental surgery, or in those who have BRONJ. This period has been defined in oral bisphosphonates: Those who have taken the oral bisphosphonates for less than 3 years and have no clinical risk factors do not need a drug holiday surrounding dental surgery. However, those who have taken the medications for more than 3 years and/or who have also taken corticosteroids can benefit from being taken off oral bisphosphonates for 3 months before and 3 months after the surgery—as long as they have no contraindications and the medication is restarted after osseous healing has taken place. For patients taking oral bisphosphonates who have developed BRONJ, 6-12 months of discontinuation can significantly speed the healing of BRONJ after the condition has been treated—again, as long as the patients have no contraindications. |

Ms McGuire of the Cancer Institute of New Jersey noted that in her experience it is a “tough balance” to determine whether, and for how long, to take patients with BRONJ off IV bisphosphonates.

“We have had a few people develop BRONJ who were on Zometa for their bone metastases; it can help alleviate their terrible pain,” she said. “So the oncologist has to work with the oral surgeons as to when the patient can return to taking the bisphosphonate. It's done on a case-by-case basis.”
   


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