Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients

Abstract

It is yet unknown whether the intravenous administration route alone can fully account for the exacerbation of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to identify the potential role of the bisphosphonate (BP) administration route as an independent prognostic factor for non-cancerous, stage III MRONJ patients. Bone samples were retrospectively obtained from two groups of osteoporosis patients who underwent surgery for the treatment of stage III MRONJ. Among the subjects, 10 had a history of only oral BP consumption and 10 of intravenous (IV) BP administration. The samples were assessed for osteoclast morphology and immunohistochemical expression of the receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and potassium calcium-activated channel subfamily N member 4 (Kcnn4). Although the osteoclasts derived from both groups exhibited no significant differences in the mean quantity, diameter, and nuclearity, significantly attenuated tartrate-resistant acid phosphatase activity was noted among the IV BP-induced MRONJ bones compared to those of the oral BP group. Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Our results indicate the potential of the BP administration route as an independent prognostic factor for advanced-stage MRONJ, regardless of the dosage or indication for which the BP was prescribed.

Medication-Related Osteonecrosis: Why the Jawbone?

“…However, compensatory stimulation of osteoclastogenesis and even increased osteoclast number could be observed at different stages of MRONJ [21]. In one study, cultures of the necrotic MRONJ lesions expressed giant, hypernucleated osteoclasts [22]. Recent studies have suggested the direct effects of anti-resorptive medications on oral immune cells [23] and periodontal ligament stem cells [24,25].…”

“…Recent studies have suggested the direct effects of anti-resorptive medications on oral immune cells [23] and periodontal ligament stem cells [24,25]. Patients receiving IV bisphosphonates have higher bone OPG and lower TRAP and RANKL expression levels, which could signify an impaired osteoclast activation by other bone cells, such as osteoblasts and osteocytes [22,26]. Experimental and clinical studies have shown that steroid therapy, nicotine smoking, and associated systemic pathologies, such as dia-betes or inflammatory joint pathology, increased the risk of MRONJ with bisphosphonate treatment [27,28].…”

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws

“…We cannot be conclusive that the differences are caused by the route of administration alone; other factors, such as differing health conditions of patients who require IV or oral bisphosphonates could also play a role. However, a recent study has found that IV administration of bisphosphonates seem to have a greater effect on osteoclastic activity-compared to oral bisphosphonates at the same dosage-that seems to "aggravate" the conditions of BRONJ [91].…”

Medication-Related Osteonecrosis of the Jaws: A Literature Review

“…Bisphosphonate administration can be done orally and intravenously. Oral administration uptake shows only 1% absorbance into the gastrointestinal tract and intravenous (IV) shows an absorption rate of over 50% [16]. The prevalence of BRONJ in osteoporosis patients with the administration of bisphosphonates is known to range from 0% to 0.04%, and some papers show a prevalence of less than 0.001% [17,18].…”