Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw.

Siri Paulo,Carlos Miguel Marto,Mafalda Laranjo,Maria Filomena Botelho,Eunice Carrilho,João Casalta-Lopes,Arménio Serra,Lina Carvalho,Manuel Marques Ferreira,Ana Coelho,Anabela Paula,João Martins,Ana Margarida Abrantes

doi:10.3390/ma13081955

Abstract

Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypothesis, a reproducible in vivo model of BRONJ in Wistar rats was used. This model directly relates chronic bisphosphonate administration with the development of osteonecrosis of the jaw after tooth extraction. BCP granules were placed in the alveolus immediately after tooth extraction in the test group. The animals were evaluated through nuclear medicine, radiology, macroscopic observation, and histologic analysis. Encouragingly, calcium phosphate ceramics were able to limit zoledronate toxicity in vivo and to favor healing, which was evidenced by medical imaging (nuclear medicine and radiology), macroscopically, and through histology. The studied therapeutic option presented itself as a potential solution to prevent the development of maxillary osteonecrosis.

Highlights

The survival of cancer patients increased substantially due to the availability and efficiency of treatments
Fourteen days after tooth extraction, there was a significant increase in animal models of Bisphosphonate-related osteonecrosis of the jaw (BRONJ) to
The experimental model used of the present study supports that experimental groups with zoledronate administration, in which extractions were performed, demonstrate an inability of soft tissues coverage, accompanied by underlying bone exposure, suggesting that the soft tissue toxicity may contribute to the establishment of maxillary osteonecrosis

Summary

Introduction

The survival of cancer patients increased substantially due to the availability and efficiency of treatments. Certain therapies determine co-morbidities and side effects, as is the case of the osteonecrosis of the jaw. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a post-surgical lesion, in which bone exposure in the maxillofacial region persists for more than. The lack of epidemiological studies, BRONJ incidence is reported from 0.8–12%, being more frequent in patients with bone metastasis who underwent intravenous nitrogenous bisphosphonate therapy [4,5]. The incidence peak in these patients is explained because bisphosphonates are effective drugs, widespread in the treatment of hypercalcemia secondary to malignancy, skeletal-related events connected with bone metastases, lytic lesion related to multiple myeloma, osteoporosis, osteopenia, and Paget’s disease, among others [6,7]. Other factors—such as the intravenous administration of the drugs, infection, and genetic predisposition—can promote the disease occurrence [8]

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