Prevalence of medication related osteonecrosis of the jaw in patients treated with sequential antiresorptive drugs: systematic review and meta-analysis

Background: Antiresorptive drugs (ARD) are associated with a known serious adverse event, known as medication-related osteonecrosis of the jaws (MRONJ). Transition from one ARD to another has become common clinical practice with the advent of more potent or safer agents; however, the influence of sequential antiresorptive therapy as a risk factor for MRONJ has not been established. Objectives: To investigate the prevalence of MRONJ in oncology or osteoporosis patients treated with two or more sequential ARDs as opposed to a single antiresorptive drug. Material and methods: Systematic electronic literature searches were conducted using Ovid MEDLINE, Ovid EMBASE, and Cochrane Central Register of Controlled Trials. Two review authors retrieved studies using pre-determined eligibility criteria and conducted quality assessment and data extraction. Fixed or random-effects meta-analysis models were used to summarize relative estimates for prevalence of MRONJ. Results: A total of 483 titles and abstracts were screened, and 18 full texts were retrieved for review. Twelve studies were included in the final qualitative and quantitative synthesis. Random effects meta-analysis models revealed a weighted pooled MRONJ prevalence of 19% (95% CI 10–27%) for sequential pamidronate-zoledronate therapy, 10% (95% CI 3–22%) for sequential ibandronate-zoledronate therapy. Pooled weighted prevalence of MRONJ was 13% (95% CI 3–22%) for sequential bisphosphonate-denosumab therapy while bisphosphonates only was 5% (95% CI 0–9%) and denosumab only was 4% (95% CI 3–5%). Conclusions: The present systematic review suggests an increased prevalence of MRONJ associated with sequential ARD therapy for pamidronate-zoledronate and bisphosphonate-denosumab administration when compared to single ARD therapy.