Review of current literature and implications of RANKL inhibitors for oral health care providers.

Bisphosphonates (BPs) were the first class of drugs commonly used to prevent skeletal-related events (SRE) in patients with osteoporosis, multiple myeloma (MM), or solid tumors with metastases to bone. A new alternative class of agents, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, are now available for use in these indications and have the potential to replace intravenous BPs. This paper presents a review of the current literature on denosumab and its association with osteonecrosis of the jaw (ONJ). Denosumab is a RANKL inhibitor that has recently been approved for the prevention of SRE for the same indications as BPs except for MM. Although the overall frequency of denosumab-related ONJ may be similar or higher than estimates of the occurrence rate of bisphosphonate-related ONJ, evidence continues to support appropriate planning and preventive care can reduce the likelihood of adverse effects, including osteonecrosis.

The effects of osteoclast modifiers on the oral cavity: a review for prescribers.

PURPOSE OF REVIEW: Osteonecrosis of the jaw associated with therapeutic osteoclast modifiers is a rare but serious event. The consequences of osteonecrosis can be devastating despite current treatment. With the increase in diversity of agents and significant increase in the prevalence of osteoclast modifiers prescribed by oncologists understanding diagnosis and management of osteoclast modifiers-related osteonecrosis of the jaws (OMRONJ) is necessary. The risk of osteonecrosis when osteoclast modifiers are used for management of osteoporosis is much less than osteoclast modifiers used in the oncology setting. A basic understanding of the oral exam and current management will lead to more effective communication and more effective prevention of devastating OMRONJ. RECENT FINDINGS: An indistinguishable rate of ONJ seen with new therapeutic agents is becoming apparent and relevant preventive therapy and counseling of the patient is indicated. Currently there is no comprehensive clinical guideline that unifies oncologists and oral health providers in the prevention and management of OMRONJ. SUMMARY: Communication and proper planning with each patient's provider is the most effective strategy to prevent OMRONJ. A team composed of an oncologist, oral and maxillofacial surgeon and dentist competent in managing this condition is necessary. An understanding of the cause and development of OMRONJ can give the prescriber an improved perspective to communicate with oral health professional colleagues. Current guidelines emphasize the need for dental management prior to the use of osteoclast modifiers for the prevention and management of osteonecrosis of the jaw.

Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series.

BACKGROUND: Studies of the use of pentoxifylline and α-tocopherol in osteoradionecrosis of the jaw have suggested their efficacy in this condition. We report an initial case series of pentoxifylline and α-tocopherol for patients with bisphosphonate-associated osteonecrosis (BON). METHODS: Six cases referred for management of BON were provided pentoxifylline and α-tocopherol in addition to antimicrobial therapy, and followed for a mean of 10 months. RESULTS: A 74% decrease in area of bony exposure and symptom control was achieved in these cases. DISCUSSION: Pentoxifylline with α-tocopherol may represent a strategy for management of BON. Controlled trials in cases of BON appear warranted.

Doxepin rinse for management of mucositis pain in patients with cancer: one week follow-up of topical therapy.

This study assessed the effectiveness of oral doxepin rinse for mucositis-related pain management in patients following 1 week of repeated dosing. Patients with oral mucositis due to head and neck radiation therapy or hematopoietic stem cell transplant (HSCT) were recruited to participate in a 1-week follow-up study. Subjects who gave informed consent rinsed with doxepin (5 ml) during the initial visit and were then told to use doxepin rinse over the next week as needed, three to six times per day, and return for a follow-up visit. At each visit, mucositis was scored using the Oral Mucositis Assessment Scale and oral pain was assessed using a visual analogue scale before and after rinsing. The use of a systemic analgesic was recorded, and side effects were documented. At the follow-up visit, subjects were also asked to retrospectively report average pain scores they experienced over the past week, 5 and 15 minutes following rinse. Nine subjects were enrolled in the study. Statistically significant reductions in pain scores were reported for 2 hours following doxepin rinse during the initial visit (p < .05). Patients recalled that their pain significantly dropped within 5 minutes of rinsing over the week of repeated dosing (p < .05). At the follow-up visit, subjects reported statistically significant pain reduction 5 minutes after doxepin rinsing (p < .05). These results indicate that doxepin rinsing continues to produce reduced intensity of pain levels over a 1-week span of repeated dosing.

A survey of National Cancer Institute-designated comprehensive cancer centers' oral health supportive care practices and resources in the USA.

BACKGROUND: The oral complications and morbidity resulting from overall cancer therapy utilizing radiation, chemotherapy, and/or stem cell transplantation can have significant impact on a patient's health, quality of life, cost of care, and cancer management. There has been minimal health services research focusing on the status of medically necessary, oral supportive services at US cancer centers. METHODS: A pre-tested, survey questionnaire was distributed to the directors of National Cancer Institute (NCI)-designated comprehensive cancer centers to assess each institution's resource availability and clinical practices, as it relates to the prevention and management of oral complications during cancer treatment. RESULTS: Sixteen of the 39 comprehensive cancer centers responded to the survey. Of the respondents, 56% of the centers did not have a dental department. The sites of delivery of oral supportive care services range from the provision of in-house dental care to community-based, private practice sites. No standard protocols were in place for either oral preventive care or for supportive services for oral complications during or after cancer therapy. Fifty percent of the responding comprehensive cancer centers reported orally focused research and/or clinical trial activities. CONCLUSIONS: Comprehensive cancer care must include an oral care component, particularly for those cancer patients who are at high risk for oral complications. This requires a functional team of oral care providers collaborating closely within the oncology team. Considering the number of cancer patients receiving aggressive oncologic treatment that may result in oral toxicity, the impact of oral conditions on a compromised host, and the potential lack of appropriate resources and healthcare personnel to manage these complications, future research efforts are needed to identify the strengths and weaknesses of present oral supportive care delivery systems at both NCI-designated cancer centers and community-based oncology practices.

Oral doxepin rinse: the analgesic effect and duration of pain reduction in patients with oral mucositis due to cancer therapy.

This research expands on our prior study, in which we assessed pain reduction after topical doxepin rinse in patients with oral mucositis resulting from cancer and cancer therapy. We continued to enroll patients with painful oral mucositis attributable solely to cancer therapy and performed further analysis on the duration of pain reduction. Fifty-one patients with oral mucositis were enrolled. Mucositis was scored and oral pain was assessed with a visual analog scale before doxepin oral rinse (5 mg/mL) and at regular intervals up to 4 h after rinsing. Of those who reported pain reduction, 95% did so within 15 min of rinsing with doxepin. In the total sample, the average patient reported a 70% maximum decrease in pain (P < 0.0001). Recurrence of pain was slow and at the conclusion of the study 19 patients (37%) still reported a reduction from baseline pain. With this censored data we used Cox-proportional hazards to determine what variables best explained longer duration of pain reduction. Our final model determined that more severe baseline pain, worse mucosal erythema score, or a larger relative maximum reduction in pain were all associated with a slower rate of pain recurrence after oral rinsing (all P < 0.01).

Cancer-related oral health care services and resources: a survey of oral and dental care in Canadian cancer centres.

PURPOSE: Prevention and management of oral complications of cancer and cancer therapy will improve oral function and quality of life, and reduce morbidity and the cost of care. Oral assessment, and oral and dental care have been strongly recommended before cancer therapy and should be continued during and after cancer therapy. The purpose of this survey was to assess the resources available for oral care in Canadian cancer centres. METHODS: Provincial cancer centres were assessed by questionnaire to determine the resources available for oral care in these facilities. RESULTS: Wide variability in oral and dental care of patients with cancer across Canada and a lack of documented standards of care were reported. Very few cancer centres had institutionally supported dental staff to support the oral care of patients with cancer, and few had dental treatment capability on site. The majority of centres managed oral care needs in the community with the patient's prior dentist. CONCLUSIONS: We recommend that national guidelines be developed for medically necessary oral and dental care for patients with cancer.

The efficacy of pilocarpine and bethanechol upon saliva production in cancer patients with hyposalivation following radiation therapy.

PURPOSE: Pilocarpine and bethanechol have been reported as potentially effective sialogogues for xerostomic patients. The purpose of the present study was to compare the efficacy of bethanechol to that of pilocarpine in patients with dry mouth following cancer therapy. STUDY DESIGN: Patients with documented hyposalivation were provided pilocarpine or bethanechol for 2-3 weeks in an open-label randomized crossover study. Baseline and weekly whole resting saliva (WRS) and whole stimulated saliva (WSS) were obtained for 5 minutes. Subjective response and side effects were recorded. RESULTS: Forty-two xerostomic patients who had received radiation therapy to the head and neck participated. The increase in the WRS and WSS with each medication independently was limited. Statistically significant increase in WRS was seen for both medications when all patients using either agent were analyzed, but no statistically significant increase in WSS was found.Twenty-seven patients completed the crossover protocol. No significant difference in the effect was noted between each of the 2 drugs whether they were prescribed as the first or second drug in the crossover. Statistically significant improvement in subjective report of saliva production/mouth wetness was seen for patients on either medication. This study suggests that subjective improvement in symptoms of dry mouth may be related to resting saliva production, and not to stimulated saliva production. No statistically significant differences in adverse side effects were reported between the medications prescribed. The most common side effects were minor and included frequent urination, dizziness, and increased sweating. CONCLUSIONS: The findings indicate that head and neck radiation-treated patients with established hyposalivation will respond minimally to systemic sialagogues and while they may experience an increase in resting saliva little change in stimulated saliva may occur. It is not known whether relatively small increases in saliva are beneficial in maintaining oral health; however, subjective improvement suggests improved quality of life. While it is not known if prolonged use of a sialagogue will have increased effects, the limited increase in saliva seen following the second drug of the crossover suggests that prolonged use of a sialagogue may further increase saliva production.