Jaw Bone Samples From Bisphosphonate-Treated Patients: A Pilot Cohort Study

Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonate treatment. PurposeA detailed characterization of sampled peri-necrotic jawbone from bisphosphonate-treated patients was performed at tissue and cellular level (histological analyses and gene expression). Materials and MethodsAlveolar bone samples were collected from patients with (n=5) and without ONJ (n=5). Healthy patients served as controls (n=10). ResultsThe histological analysis demonstrated low to moderate inflammation, displaying areas of inflammatory infiltrate in the bone marrow. Multinuclear giant cells and osteoclasts were found in both groups. Markers of bone formation (alkaline phosphatase, Col1a1, and osteocalcin), bone resorption (receptor activator of NF-kappaB ligand [RANKL], osteoprotegerin [OPG], tartrate-resistant acid phosphatase, and cathepsin K), inflammation (tumor necrosis factor-alpha, interleukin [IL]-1, and IL-6), angiogenesis (vascular endothelial growth factor A), and apoptosis (Casp3, Casp8, p53, and Smac) were evaluated. Nonparametric statistical tests were used to identify differences between the groups. In patients with ONJ, the expression level of the proinflammatory marker IL-1 was strongly up-regulated compared with controls (p=.040). ConclusionsA down-regulated expression of Casp8 compared with controls was observed (p=.014) in patients treated with bisphosphonates. The RANKL/OPG ratios were similar in the three groups. The results indicate a need to further investigate the molecular mechanisms involved in the course of ONJ related to antiresorptive treatment.