Prolia and dental extractions: what does the evidence say about timing and drug holidays?

Drug holiday for MRONJ prevention

Based on the residual effects of bisphosphonates after long-term therapy, patients at low fracture risk after 5 years of alendronate or 3 years of zoledronic acid can undergo a drug holiday with periodic reassessment. This recommendation aims to minimize safety concerns ( 27 ). However, a retrospective population study in a Korean database showed a higher prevalence of MRONJ in the first 3 years after bisphosphonate suspension ( 28 ). Although patients with and without cancer were studied, no correlation between dosing frequency or time since bisphosphonate discontinuation and the occurrence of MRONJ was observed in either group ( 28 ). The risk of developing MRONJ is small compared with the antifracture benefits of bisphosphonates in individuals with moderate to high fracture risk using these drugs ( 29 ). So far, no evidence-based study has demonstrated efficacy of bisphosphonate drug holiday in preventing MRONJ. Denosumab has no sustained antiresorptive effect. Hence, drug holiday is not recommended with this medication, mainly due to recent concerns about a rapid increase in the risk of vertebral fractures following denosumab discontinuation ( 30 ).

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis – A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso). Madeira M, Rocha AC, Moreira CA, Aguiar ÁMM, Maeda SS, Cardoso AS, de Moura Castro CH, D'Alva CB, Silva BCC, Ferraz-de-Souza B, Lazaretti-Castro M, Bandeira F, Torres SR. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

Tooth extractions in patients with osteoporosis using antiresorptive medication

The surgical technique to be performed should be minimally invasive and should provide primary closure of the dental socket ( 23 ). Alveoloplasty may facilitate primary closure of the socket after extraction, but surgeons have full discretion in deciding whether to perform it or not ( 23 ). The development of MRONJ seems to be related to cases in which the dental alveolus is not primarily closed in the immediate postoperative period, therefore requiring more healing time ( 23 ). Careful postoperative follow-up is required until the healing process is complete, which may take longer than usual ( 46 ). Another important recommendation is the completion of an informed consent form, which should make the patient aware of the low risk of dental extraction for the development of MRONJ, and the importance of complying with the recommendations on the postoperative follow-up ( 47 ). Figure 1 shows an example of an informed consent form for patients receiving osteoporosis treatment who will undergo invasive dental treatment.

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis – A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso). Madeira M, Rocha AC, Moreira CA, Aguiar ÁMM, Maeda SS, Cardoso AS, de Moura Castro CH, D'Alva CB, Silva BCC, Ferraz-de-Souza B, Lazaretti-Castro M, Bandeira F, Torres SR. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

Discussion

Dmab drug holiday may cause rebound bone turnover and precipitate an undesirable effect of seriously compromised bone structure (20). The recent treatment guidelines for osteoporosis do not recommend Dmab discontinuation without subsequent therapy with other antiresorptive agents to prevent this rebound phenomenon (3, 4). For bone metastasis patients, a study by Jacobson et al. (21) demonstrated that 35% of patients experienced ≥1 SRE following Dmab discontinuation. A retrospective cohort study by Hasegawa et al. (40) suggested that both the administration of Dmab and the discontinuation of antiresorptive medication did not result in a significant difference in MRONJ risk among patients receiving antiresorptive medication and undergoing dental procedures. The evidence from our study of Dmab treatment in bone metastasis patients also showed no differentiation in the risk of MRONJ between discontinuing and continuing medication during dental procedures, as well as no significant difference when compared to other types of antiresorptive agents or any discontinuation protocol in terms of MRONJ risk. Furthermore, the risk of MRONJ after Dmab injection for osteoporosis treatment, where the dosage is typically much lower than in malignancy treatment, is generally considered to be very low. These patients should presume tooth extraction if necessary, whereas avoiding tooth extraction can preserve the source of odontogenic infections, which are often associated with the development of MRONJ (41, 42).

Effects of discontinuing different antiresorptive regimens on medication-related osteonecrosis of the jaw in patients undergoing dental procedures: a systematic review and network meta-analysis. © the author(s). Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

Abstract

In addition, prolonged previous antiresorptive drug intake was identified as a significant independent risk factor at the patient level. No specific type of dentoalveolar procedure showed a statistically significant association with MRONJ development. These findings confirm that surgical timing is a critical determinant of MRONJ risk in Dmab-treated osteoporotic patients. Avoiding dentoalveolar interventions during the early post-injection period, particularly within the first 3 mo, may substantially reduce risk. A delay of at least 4 mo after the last Dmab administration appears to be a clinically important preventative strategy, balancing MRONJ avoidance with the need to minimize fracture risk resulting from prolonged discontinuation of therapy. Additional prospective studies are warranted to refine surgical timing recommendations and guide individualized patient care.

The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients. © The Author(s) 2026. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

Abstract

Osteoporosis patients treated with denosumab (Dmab) remain at risk for medication-related osteonecrosis of the jaw (MRONJ), particularly after dentoalveolar surgery. Optimizing surgical timing may reduce this risk while avoiding complications related to prolonged drug interruption. This retrospective cohort study evaluated 258 osteoporotic patients receiving Dmab and examined both patient-level data and intervention-level data from 91 patients who underwent 185 dentoalveolar procedures. Multivariable logistic regression and generalized estimating equations (GEE) were applied to identify factors associated with MRONJ development. Medication-related osteonecrosis of the jaw occurred in 5.43% of the total cohort. All MRONJ cases at the intervention level were observed when dentoalveolar procedures were performed within 3 mo of a Dmab injection. A longer interval between the last Dmab dose and dentoalveolar intervention demonstrated a strong protective effect against MRONJ (OR 0.35, p = .0089). In addition, prolonged previous antiresorptive drug intake was identified as a significant independent risk factor at the patient level.

The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients. © The Author(s) 2026. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).

Conclusions

This retrospective study confirms that surgical timing is the critical determinant of MRONJ risk in osteoporotic patients taking Dmab. All MRONJ cases occurred when dentoalveolar interventions were performed within 3 mo of a Dmab injection, while an increased interval between the injection and dentoalveolar intervention, was identified as a significant protective factor. Prolonged antiresorptive drug intake was found to be a possible contributor to MRONJ development. We conclude that delaying dentoalveolar procedures for at least four months post-injection, especially after previous long term ARD intake, appears to be a crucial preventive measure, as it minimizes the risk of MRONJ without triggering the fracture risk associated with prolonged drug discontinuation.

The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients. © The Author(s) 2026. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.. Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/).