Should edentulous patients with dentures who are starting Zometa (intravenous zoledronic acid) for metastatic osseous disease obtain a dental clearance prior to treatment initiation?

Comment by InpharmD Researcher

Current clinical guidelines recommend pretreatment dental evaluation for patients with cancer initiating antiresorptive therapy, including edentulous patients who wear dentures. The evaluation should include assessment of denture stability, fit, and areas of mucosal trauma, as denture use and ill-fitting dentures have been identified as risk factors for medication-related osteonecrosis of the jaw (MRONJ). Guidelines also recommend optimizing oral health before treatment when medically feasible, with coordination between the dentist and treating oncologist. Ongoing dental follow-up, appropriate denture care, and patient education are also recommended throughout treatment. These recommendations are further supported by evidence from clinical trials, as presented in Tables 1-5. These studies provide further evidence demonstrating the risk of MRONJ due to Zometa (intravenous zoledronic acid); comparisons between patients who received preventative dental management versus those who did not yielded strong evidence supporting the effectiveness of preventive dental management in reducing BRONJ. Several authors concluded that comprehensive dental examination is recommended prior to initiation of therapy.

PubMed and Google Scholar were searched using combinations of the following terms: zoledronic acid, Zometa, bone-modifying agents, antiresorptive therapy, medication-related osteonecrosis of the jaw, MRONJ, dental evaluation, dental clearance, pretreatment dental screening, edentulous patients, dentures, and denture-related trauma.

Background

The 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology/American Society of Clinical Oncology (MASCC/ISOO/ASCO) clinical practice guideline on medication-related osteonecrosis of the jaw (MRONJ) evaluated evidence from 132 publications to develop recommendations for the prevention and management of MRONJ in patients with cancer receiving bone-modifying agents (BMAs). For patients initiating BMAs in nonurgent settings, the guideline recommends a comprehensive dental, periodontal, and radiographic examination when feasible, followed by development of a dental care plan coordinated between the dentist and oncologist. Routine dental follow-up is recommended approximately every 6 months after treatment initiation. The guideline identifies denture use as a risk factor for MRONJ and specifically recommends addressing ill-fitting dentures as a modifiable risk factor. Preventive oral care and patient education are emphasized for both dentate and edentulous patients, beginning before BMA initiation and continuing throughout treatment. For patients with dentures, the recommended oral care plan includes brushing and rinsing dentures after meals and at bedtime, removing dentures for at least 8 hours daily, and soaking them in a rinsing solution. [1]

A 2022 update from the American Association of Oral and Maxillofacial Surgeons (AAOMS) on MRONJ reviewed available literature and updated recommendations for prevention and management in patients receiving antiresorptive therapy. AAOMS emphasized the importance of pretreatment dental screening and recommended a comprehensive dental examination, including physical and radiographic assessment, before initiating antiresorptive therapy for malignant disease. Dental health should be optimized before treatment when systemic conditions permit, with decisions regarding treatment initiation made in collaboration with the treating physician and dentist. Clinical assessment should include consideration of edentulism and denture stability. Denture use was associated with an increased risk of MRONJ among cancer patients receiving zoledronate (odds ratio [OR] 4.9; 95% confidence interval [CI] 1.2–20.1), while another study involving 1,621 cancer patients receiving intravenous bisphosphonates reported a twofold increased risk among denture wearers. AAOMS specifically recommends examining patients with full or partial dentures for mucosal trauma, particularly along the lingual flange region, and emphasizes patient education regarding dental hygiene, regular dental evaluations, and reporting any pain, swelling, or exposed bone. [2]

Background References: [1] Yarom N, Shapiro CL, Peterson DE, et al. Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline. J Clin Oncol. 2019;37(25):2270-2290. doi:10.1200/JCO.19.01186
[2] Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg. 2022;80(5):920-943. doi:10.1016/j.joms.2022.02.008
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Should edentulous patients with dentures who are starting Zometa (intravenous zoledronic acid) for metastatic osseous disease obtain a dental clearance prior to treatment initiation?

Level of evidence

A - Multiple high-quality studies with consistent results  Read more→


Please see Tables 1-5 for your response.

Is dental clearance necessary before antiresorptive treatment in pediatric patients?
Design

Retrospective cohort study

N= 136
Objective To determine if there was a difference in the frequency of medication-related osteonecrosis of the jaws (MRONJ) between pediatric patients who obtained dental clearance and those who didn’t obtain dental clearance before the start of antiresorptive therapy. The secondary aim was to assess the effect of dental clearance on future dental follow-up after the start of antiresorptive treatment
Study Groups

Clearance group (n= 88)

No-clearance group (n= 48)
Inclusion Criteria Patients less than 18 years of age who received antiresorptive treatment from 2010 to 2024 at Children’s Medical Center Dallas
Exclusion Criteria Patients with less than 6 months of follow-up
Methods Patients were divided into two groups: those who received dental clearance before starting antiresorptive treatment and those who did not. Dental clearance was defined as a dental evaluation and treatment, if necessary, before the start of antiresorptive therapy. Data were collected from medical and dental records, and statistical analyses were performed to evaluate the effect of dental clearance on MRONJ and dental follow-up.
Duration 2010 to 2024
Outcome Measures

Primary: Frequency of MRONJ

Secondary: Dental follow-up after the start of antiresorptive treatment
Baseline Characteristics   Sample total (n= 136)
Age in years 8.27 ± 5.07
Male: Female 77:59
Longest follow up in years 5.35 ± 3.23
Mean dental visits per year 1.02 ± 0.93
Immunosuppressant exposure 24
Dental Extractions - Total patients 34
Dental Extractions - Total teeth extracted 108
Dental Extractions - Total permanent teeth extracted 14
Reason for antiresorptive - Osteogenesis imperfecta 38
Reason for antiresorptive - Malignancy 13
Reason for antiresorptive - Other 85
Antiresorptive medication - Pamidronate 35
Antiresorptive medication - Zoledronic acid 77
Antiresorptive medication - Denosumab 3
Antiresorptive medication - Combination 21
Results   Clearance (n= 86) No-clearance (n= 36) p-Value 95% CI
Mean dental visits per year 1.21 ± 0.96 0.55 ± 0.65 0.0002 0.31-1
Adverse Events No cases of MRONJ were observed in either group
Study Author Conclusions

No MRONJ cases were observed in the present study. In pediatric patients who receive dental clearance prior to the start of antiresorptive medications, there is an association with continued routine dental follow-up. Future multicenter studies are needed to fully discern the risk of MRONJ in the pediatric population and the necessity of dental clearance.
Critique

This study is limited by its retrospective design and sample size, given the rarity of MRONJ. Additionally, the overall exposure to antiresorptive medications among subjects may be underestimated as oral antiresorptives were not tabulated. The lack of observed MRONJ cases within the cohort precluded analysis to address the specific aim. However, the results provide meaningful data from a high-volume pediatric institution. To the authors’ knowledge, this is the first study to investigate the role of dental clearance for pediatric patients receiving antiresorptive medications.
Table 1 References:
[3] Neal TW, Mohseni S, Ratcliffe V, Schlieve T. Is dental clearance necessary before antiresorptive treatment in pediatric patients?. Oral Surg Oral Med Oral Pathol Oral Radiol. 2026;141(2):137-141. doi:10.1016/j.oooo.2025.07.015

Association of Osteonecrosis of the Jaw With Zoledronic Acid Treatment for Bone Metastases in Patients With Cancer
Design

Multicenter, prospective observational cohort study

N= 3491
Objective To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm
Study Groups All patients (N= 3491)
Inclusion Criteria Patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration
Exclusion Criteria History of ONJ or radiotherapy to the maxillofacial area; more than 1 histological tumor finding (other than treated basal cell or squamous cell skin cancer or in situ cervical cancer)
Methods Patients received zoledronic acid as clinically indicated. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. ONJ was defined using established criteria.
Duration January 30, 2009, to December 13, 2013
Outcome Measures

Primary: Cumulative incidence of confirmed ONJ

Secondary: Risk factors for ONJ
Baseline Characteristics   All patients (n= 3491)
Age, median (range), y 63.1 (22.4-93.9)
Female 1806 (51.7%)
Male 1685 (48.3%)
Race - White 2942 (86.8%)
Race - Black 368 (10.9%)
Cancer type - Breast 1120 (32.1%)
Cancer type - Multiple myeloma 580 (16.6%)
Cancer type - Prostate 702 (20.1%)
Cancer type - Lung 666 (19.1%)
Cancer type - Other 423 (12.1%)
Results   All patients (n= 3491) 3-year cumulative incidence
Confirmed ONJ 90 cases 2.8% (95% CI, 2.3%-3.5%)
Confirmed plus suspected ONJ 118 cases 3.7% (95% CI, 3.1%-4.4%)
Adverse Events Higher rate of ONJ associated with fewer total number of teeth, presence of dentures, and current smoking
Study Author Conclusions The cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.
Critique The study's large scale and prospective design are strengths, providing valuable insights into ONJ risk factors. However, limitations include lack of detailed information on antiangiogenic agents and socioeconomic factors, and potential underestimation of ONJ cases due to reliance on confirmed cases and clinically directed oral examinations
Table 2 References:
[4] Van Poznak CH, Unger JM, Darke AK, et al. Association of Osteonecrosis of the Jaw With Zoledronic Acid Treatment for Bone Metastases in Patients With Cancer. JAMA Oncol. 2021;7(2):246-254. doi:10.1001/jamaoncol.2020.6353

Longitudinal Cohort Study of Risk Factors in Cancer Patients of Bisphosphonate-Related Osteonecrosis of the Jaw
Design

Longitudinal cohort study

N= 1,621
Objective To calculate the incidence of and identify the risk factors for osteonecrosis of the jaw (ONJ) in patients with cancer treated with intravenous bisphosphonates (zoledronate, ibandronate, and pamidronate)
Study Groups

Multiple myeloma (n= 539)

Breast cancer (n= 1,041)

Prostate cancer (n= 41)
Inclusion Criteria Patients with breast cancer, prostate cancer, or multiple myeloma treated with intravenous bisphosphonates at Theagenio Cancer Hospital between January 2000 and October 2008, who received any intravenous BP for a minimum of 5 months
Exclusion Criteria Patients with prior history of radiation therapy to the head and neck region
Methods Patients received monthly intravenous doses of pamidronate (90 mg), zoledronate (4 mg), or ibandronate (6 mg). Data included age, sex, medical history, BP type, and doses administered. Dental examination and history review were conducted. ONJ was staged according to the American Association of Oral and Maxillofacial Surgeons guidelines
Duration January 2000 to October 2008
Outcome Measures

Primary: Incidence of ONJ

Secondary: Risk factors for ONJ development (use of dentures, history of dental extraction, having ever received zoledronate)
Baseline Characteristics   Patients With ONJ (n= 80) Patients Without ONJ (n= 1,541)
Age, years 63.6 60.0
No. of doses 22.6 17.7
Smoking habit 52.5% 53.6%
History of dental extraction 57.5% 4.4%
Use of dentures 30.0% 13.8%
Root-canal treatment 23.8% 25.0%
Having ever received Zoledronate 97.5% 70.4%
Having ever received Pamidronate 20.0% 20.4%
Having ever received Ibandronate 3.8% 34.0%
Results   Multiple Myeloma (n= 539) Breast Cancer (n= 1,041) Prostate Cancer (n= 41) All Patients (n= 1,621)
Crude ONJ incidence 8.5% 3.1% 4.9% 4.9%
Total ONJ cases 46 32 2 80
Adverse Events No specific adverse events other than ONJ were reported in the study
Study Author Conclusions The study validated dental extractions and use of dentures as risk factors for ONJ development. Ibandronate and pamidronate seem to exhibit a safer drug profile concerning ONJ complication. Before initiation of a bisphosphonate, patients should have a comprehensive dental examination.
Critique The study's strengths include a large sample size and comprehensive data collection over an extended period. However, the cohort design cannot guarantee dose matching between various malignancies and BP drug schemas administered. The study is limited by its observational nature, which may introduce selection bias and confounding factors. Randomized controlled trials are needed to validate these results.
Table 3 References:
[5] Vahtsevanos K, Kyrgidis A, Verrou E, et al. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol. 2009;27(32):5356-5362. doi:10.1200/JCO.2009.21.9584

Bisphosphonate-Related Osteonecrosis of the Jaws: A Case-Control Study of Risk Factors in Breast Cancer Patients
Design

Retrospective case-control study

N= 60
Objective To determine whether routine dental procedures can be considered as possible risk factors for the development of osteonecrosis of the jaws (ONJ) in breast cancer patients receiving bisphosphonates (BP)
Study Groups

Group A: Breast cancer patients with ONJ (n= 20)

Group B: Breast cancer controls without ONJ (n= 40)
Inclusion Criteria Age >18 years; diagnosis of breast cancer; clinically and radiographically diagnosed bone metastases; ZA treatment for a minimum period of 6 months; informed consent
Exclusion Criteria Previous radiation in the head and neck area; recent oral cavity inflammation
Methods Patients received ZA intravenously every fourth week for a minimum of 6 months. Routine dental care, smoking habits, history of tooth extraction, use of dentures, and root canal therapy were recorded. Conditional univariate and multivariate logistic regression analyses were performed to identify risk factors for ONJ
Duration October 2002 to October 2007
Outcome Measures

Primary: Development of ONJ

Secondary: Association of routine dental procedures with ONJ
Baseline Characteristics   Group A: Patients With ONJ (n= 20) Group B: Breast Cancer Controls (n= 40)
Age, years (mean) 59.5 61.9
Doses, No. (mean) 25.0 24.5
Routine dental care 65% 40%
Smoking 80% 57.5%
History of tooth extraction 50% 7.5%
Use of dentures 40% 17.5%
Root canal treatment 20% 10%
Results   Adjusted OR 95% CI P-value
History of tooth extraction 16.4 3.4 to 79.6 0.001
Use of dentures 4.9 1.2 to 20.1 0.029
Routine dental care 0.27 0.04 to 1.9 0.197
Adverse Events Not specifically detailed in the study
Study Author Conclusions The study suggests that routine dental procedures, particularly tooth extraction and use of dentures, are significant risk factors for developing ONJ in breast cancer patients receiving BP. Early dental evaluation and regular follow-up are recommended to prevent ONJ.
Critique The study is limited by its retrospective design and potential recall bias. The sample size is relatively small, which may affect the generalizability of the findings. However, it provides valuable insights into the risk factors associated with ONJ in breast cancer patients receiving BP treatment.
Table 4 References:
[6] Kyrgidis A, Vahtsevanos K, Koloutsos G, et al. Bisphosphonate-related osteonecrosis of the jaws: a case-control study of risk factors in breast cancer patients. J Clin Oncol. 2008;26(28):4634-4638. doi:10.1200/JCO.2008.16.2768

Preventive dental management of osteonecrosis of the jaws related to zoledronic acid treatment
Design

Single-center clinical study

N= 255
Objective To evaluate the effect of preventive dental management on reducing the incidence and delaying the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients treated with intravenous zoledronic acid (ZA)
Study Groups

Group A (preventive group, n= 192)

Group B (control group, n= 63)
Inclusion Criteria Patients with cancer who received at least four intravenous doses of 4 mg ZA every 4 weeks for bone metastases due to solid tumors and had a clinical follow-up of at least 3 months
Exclusion Criteria Not explicitly stated
Methods Patients received dental treatment prior to (Group A) or after (Group B) the initiation of ZA therapy. Dental treatments performed, incidence proportion (IP), and incidence rate (IR) in both groups were analyzed using significance tests. BRONJ onset was estimated using the Kaplan–Meier estimator and log-rank test. Independent risk factors to develop BRONJ were evaluated using Cox regression analysis models
Duration June 2008 to May 2014
Outcome Measures Primary: Incidence of BRONJ Secondary: Onset of BRONJ
Baseline Characteristics   All patients (n= 255) Group A (n= 192) Group B (n= 63) p-value
Age (years), mean (SD) 61.5 (10.9) 61.6 (11.2) 60.9 (10) .063
Sex - Female 155 (60.8%) 111 (57.8%) 44 (69.8%)  
Type of cancer - Breast 109 (42.7%) 72 (37.5%) 37 (58.7%) .031
Type of cancer - Prostate 54 (21.2%) 43 (22.4%) 11 (17.5%)  
Type of cancer - Multiple myeloma 53 (20.8%) 43 (22.4%) 10 (15.9%)  
Tobacco 41 (16.1%) 35 (18.2%) 6 (9.5%) .013
Alcohol 9 (3.5%) 7 (3.6%) 2 (3.2%) .86
Results   Group A (n= 192) Group B (n= 63) p-value
BRONJ incidence proportion (IP) 7.3% 36.5% .000
BRONJ incidence rate (IR) patients/month 0.004 0.007 -
BRONJ-free survival at 3 years 97% 66% .056
Adverse Events N/A
Study Author Conclusions BRONJ occurred significantly in patients who underwent dental extractions after the initiation of ZA and did not accomplish a preventive dental program. Preventive dental treatment prior to the initiation of ZA therapy significantly reduces the risk of BRONJ and the need for dental procedures once ZA therapy has started.
Critique The study provides strong evidence for the effectiveness of preventive dental management in reducing BRONJ incidence. However, the lack of randomization and the difference in ZA doses between groups could introduce bias. The study's single-center design may limit generalizability, and the retrospective nature of data collection for group B could lead to selection bias.
Table 5 References:
[7] Coello-Suanzes JA, Rollon-Ugalde V, Castao-Seiquer A, et al. Preventive dental management of osteonecrosis of the jaws related to zoledronic acid treatment. Oral Dis. 2018;24(6):1029-1036. doi:10.1111/odi.12842