Abstract
(1) Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most often seen side effects in patients treated with nitrogen-containing bisphosphonates (BPs), a post-surgical non-healing wound condition. Since calcium phosphate (CP) compounds are able to adsorb zoledronate (ZOL) when used as a drug delivery vehicle, we aimed to verify if these ceramics might have a potential protective effect for soft tissues surrounding surgical osseous wounds. (2) Methods: The chemical reaction between ZOL and CP compounds was evaluated through ultraviolet-visible spectroscopy and elemental analysis. A primary culture of human gingival fibroblasts (HGF) was established as a model to evaluate the cytotoxicity of the association of ZOL (5–500 μM) and of ZOL/biphasic calcium phosphates (BCP). Metabolic activity, cell viability, types of cell death, the cell cycle through, and the migration ability of human gingival fibroblasts were evaluated. (3) Results: ZOL was adsorbed by biphasic calcium phosphate compounds in an aqueous solution. The HGF were sensitive to ZOL toxicity; nevertheless, ZOL/BCP showed a significant protective effect regarding metabolic activity, cell viability, and cell migration. (4) Conclusions: BCP interaction with ZOL reduces or abolishes its toxicity in HGF. This finding represents a potential solution for BRONJ in the case of patients undergoing therapy with ZOL.
Highlights
The use of bisphosphonates (BPs) has dramatically increased over the past few years
Two calcium phosphate ceramics were used; one was constituted of 99.9% beta-tricalcium phosphate (TCP; Adbone® TCP, Medbone®, Medical Devices; Leiria, Portugal), and the other was constituted of 75% hydroxyapatite (HA) and 25%
In the case of the cells treated with the combination ZOL100/biphasic calcium phosphates (BCP), there osteogenic cells, osteoblasts, osteocytes, and osteoclasts [33,34,35,36], restrict angiogenesis by inhibiting were no alterations in the various cell populations compared to the control
Summary
The use of bisphosphonates (BPs) has dramatically increased over the past few years. BPs offer substantial clinical benefit when an imbalance between osteoblast-mediated bone deposition and osteoclast-mediated bone resorption underlies physiopathology [1]. The main impact of this therapy is the prevention and treatment of cancer-related skeletal complications associated with bone metastases such as pathological fractures, spinal cord compression, tumour induced hypercalcaemia, and severe bone pain [2]. Biochemical interactions between bone microenvironment and cancer cells promote bone destruction and tumour growth [3]. In patients with advanced malignancy, tumour cells invade the bone, yielding skeletal metastases and disrupting bone homeostasis. The pharmacological effect of BPs is related to their binding to the inorganic component of bone and to their biochemical effect on cells, predominantly osteoclasts [5]. When intravenous BPs are administered, the reduction of activity and number of osteoclasts decreases bone reabsorption, diminishing the malignancy and inhibiting the growth of bone metastasis [1,6]
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