Effect of hyaluronic acid on the prevention of medication-related osteonecrosis of the jaw in a bisphosphonate-treated rat model

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BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) remains a major clinical concern due to its complex pathogenesis and low treatment success rates. Hyaluronic acid (HA), a widely used biomaterial, has demonstrated regenerative and angiogenic potential. AIM: This study investigated the effects of HA on the onset of MRONJ following tooth extraction in bisphosphonate (BP)-treated rats. METHODS: Twenty-four adult male Wistar albino rats were randomly allocated to three groups: control (saline), medication control (zoledronic acid: ZA), and experimental (ZA + HA). Animals received ZA (0.06 mg/kg, intraperitoneally, weekly for 4 weeks), followed by extraction of the lower left first molar. In the ZA + HA group, HA gel was locally applied into the socket. Rats were euthanized 28 days postoperatively. Socket healing was evaluated using micro-computed tomography (micro-CT) parameters [bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)] and histomorphometric analysis of bone formation and osteocyte lacunae. RESULTS: Micro-CT analysis showed that rats in the ZA + HA and control groups exhibited significantly higher BV/TV, BS/BV, Tb.Th, and Tb.N and lower Tb.Sp compared with the ZA group (p < 0.05). Histomorphometric analysis confirmed reduced bone formation and a greater number of empty osteocyte lacunae in the ZA group, whereas the ZA + HA group demonstrated bone regeneration comparable to controls. CONCLUSION: Local application of HA may inhibit the onset of MRONJ and enhance post-extraction bone healing in BP-exposed bone.