Should Teriparatide Be Part of Our Clinical Armamentarium in the Management of Medication-Related Osteonecrosis of the Jaw? A Systematic Review and Meta-Analysis.

BACKGROUND

Medication-related osteonecrosis of the jaw (MRONJ) is a severe and potentially debilitating drug reaction. Adjunctive treatments including pentoxifylline, tocopherol, and teriparatide (TPTD) have been studied, but TPTD's efficacy remains unclear.

PURPOSE: This systematic review and meta-analysis aims to consolidate and evaluate high-quality evidence on TPTD in managing MRONJ.

DATA SOURCES: An electronic search strategy was performed on 3 databases (Pubmed, Embase, and Cochrane CENTRAL). Search terms include ("Teriparatide" OR "TPTD" OR "Recombinant Parathyroid Hormone" OR "Recombinant PTH") AND ("Medication-Related Osteonecrosis of the Jaw" OR "MRONJ" OR "BRONJ"). No publication date range was utilized.

STUDY SELECTION: Inclusion criteria include randomized controlled trials, case-control studies, and cohort studies. All systematic reviews, case reports, case series, animal studies, editorials, non-English publications, or studies relating to osteoradionecrosis were excluded. Each study was screened independently, followed by final study selection after discussion with all authors.

DATA EXTRACTION AND SYNTHESIS: Primary meta-analysis used Cox proportional hazards regression with pseudo-individual-subject data reconstructed from published Kaplan-Meier curves (Guyot method) and a Tierney events + P value derivation for one study without Kaplan-Meier data. A sensitivity analysis pooled odds ratios (ORs) at the 6-month clinical response endpoint.

MAIN OUTCOMES AND MEASURES: Primary outcomes include improvement in MRONJ clinical staging. Secondary outcomes include time to improvement, adverse effects, radiographic evaluation, and presence of serum markers.

RESULTS

After review of 162 studies, 5 (3.1%) studies were included in the systematic review with 3 (1.9%) studies included in the meta-analysis (n = 101 subjects). A three-study Cox hazard ratio (HR) meta-analysis yielded a pooled HR of 5.35 (95% CI, 3.14 to 9.13, P < .0001, I2 = 0%) favoring TPTD. Subgroup analyses by dosing regimen showed directionally consistent effects (daily pooled HR = 12.52; 95% CI, 5.75 to 27.23; weekly pooled HR = 8.09; 95% CI, 3.59 to 18.26; both I2 = 0%), and an OR-based sensitivity analysis at the 6-month binary healing endpoint was directionally concordant (pooled OR = 14.26; 95% CI, 2.83 to 71.77).

CONCLUSIONS AND RELEVANCE: Adjunctive TPTD shows improvement of MRONJ staging and time to healing compared to conventional treatments alone, but the magnitude of the impact remains unclear. Additional evidence, including studies evaluating dosing regimens and subject segmentation by MRONJ staging, is warranted.