(69) Should Teriparatide Be Part of Our Clinical Armamentarium for the Management of MRONJ? A Systematic Review

Abstract:

Introduction: Medication related osteonecrosis of the jaw (MRONJ) is a severe and potentially debilitating drug reaction which results in necrosis of the maxilla and/or mandible in patients taking antiresorptive or antiangiogenic medications. In addition to standard therapies, including antibiotics and chlorhexidine, potential adjunctive treatments include pentoxyphylline, tocopherol (Vitamin E), and teriparatide (TPTD); however, limited data on the efficacy of TPTD for MRONJ exists. TPTD is recombinant human parathyroid hormone approved for treatment of post-menopausal osteoporosis. Interestingly, several trials and case reports have shown efficacy of TPTD in treating MRONJ in osteoporotic patients. Given the limited data and risk for bias, this systematic review and meta-analysis aims to consolidate and evaluate the existing high-quality evidence regarding the efficacy of adjunctive TPTD treatment in the medical management of MRONJ.

Methods: An electronic search strategy was performed in October 2024 by two researchers on three major search databases (Pubmed, Embase, Cochrane Central Register of Controlled Trials). Search terms include (“Teriparatide” OR “TPTD” OR “Recombinant Parathyroid Hormone” OR “Recombinant PTH”) AND (“Medication-Related Osteonecrosis of the Jaw” OR “MRONJ” OR “BRONJ”). Inclusion criteria includes human studies, randomized controlled trials, case control studies, cohort studies, and clinical trials. All systematic reviews, case reports, case series, animal studies, editorials, non-English publications, or studies relating to osteoradionecrosis were excluded. Primary outcomes include clinical staging improvement. Secondary outcomes include adverse effects, radiographic evaluation, and serum markers. Control or conventional treatment groups received a combination of chlorhexidine, analgesics, antibiotics, vitamin supplements, and/or limited surgical debridement, depending on the study. Meta-analysis was performed using R version 4.3.1 to evaluate odds ratio (OR) of improvement in MRONJ staging at 6 months.

Results: Initial database review resulted in 162 studies. After inclusion and exclusion criteria were met, only 5 studies were included for review with 3 studies included in the meta-analysis after full text review. No significant difference in patient age, sex, type of antiresorptive, anatomic location, MRONJ staging, or comorbidities were noted between the TPTD daily (n = 59), TPTD weekly (n = 27) or control (n = 101) groups. Adverse effects in the TPTD groups included myalgia, arthralgia, or jaw pain (n = 17), nausea or vomiting (n = 11), constipation (n = 5), and abdominal discomfort (n=3), with no significant differences between the groups. In the meta-analysis, the TPTD group, including patients who received either daily or weekly dosing (n = 59), had a 14.49 OR [3.12; 67.27] of MRONJ stage improvement at 6 months when compared to conventional treatments (n = 57) (P = .0006). Additionally, 2 studies showed a reduction in time until resolution in the daily TPTD groups when compared to conventional treatments alone (8.6 months [Yoshiga, et al, 2022]; 7.29 weeks [Kim, et al, 2023]).

Conclusion: While literature remains limited, the evidence to date supports the role of TPTD in contributing to the improvement of MRONJ staging and time to resolution when compared to conventional treatments alone. Additional evidence, including studies evaluating varying dosing regimens and patient segmentation by MRONJ staging is warranted; however, TPTD appears to have the potential to be a relatively safe and useful adjunctive treatment in the medical management of MRONJ in osteoporotic patients.

References:
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 May;80(5):920-943. doi: 10.1016/j.joms.2022.02.008. Epub 2022 Feb 21. PMID: 35300956.

R.P. Harper, E. Fung Resolution of bisphosphonate-associated osteonecrosis of the mandible: possible application for intermittent low-dose parathyroid hormone [rhPTH(1–34)] J. Oral Maxillofac. Surg., 65 (3) (2007), pp. 573-580
Figure 1. PRISMA flowchart outlining the studies identified, screened, excluded and included for review. Table 1. Clinical outcomes, including staging improvement (TPTD vs. Control), follow up duration, and mean duration until improvement.Figure 2. Comparison of odds ratio (OR) of MRONJ staging improvement between daily and weekly TPTD groups ("Any") and control groups six months following intervention.