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Jaw Bone Samples From Bisphosphonate‐Treated Patients: A Pilot Cohort Study
Author(s) -
Cardemil Carina,
Thomsen Peter,
Larsson Wexell Cecilia
Publication year - 2015
Publication title -
clinical implant dentistry and related research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.338
H-Index - 85
eISSN - 1708-8208
pISSN - 1523-0899
DOI - 10.1111/cid.12307
Subject(s) - osteonecrosis of the jaw , osteoprotegerin , medicine , rankl , bisphosphonate , pathology , tartrate resistant acid phosphatase , bone resorption , osteocalcin , cathepsin k , proinflammatory cytokine , bone marrow , dental alveolus , alkaline phosphatase , inflammation , osteoclast , osteoporosis , receptor , dentistry , chemistry , activator (genetics) , biochemistry , enzyme
Osteonecrosis of the jaw ( ONJ ) is a severe complication of bisphosphonate treatment. Purpose A 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 Methods Alveolar bone samples were collected from patients with (n = 5) and without ONJ (n = 5). Healthy patients served as controls (n = 10). Results The 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 ‐kappa B ligand [ RANKL ], osteoprotegerin [ OPG ], tartrate‐resistant acid phosphatase, and cathepsin K ), inflammation (tumor necrosis factor‐alpha, interleukin [ IL ]‐1β, and IL ‐6), angiogenesis (vascular endothelial growth factor A), and apoptosis ( C asp3, C asp8, 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 ‐1β was strongly up‐regulated compared with controls (p = .040). Conclusions A down‐regulated expression of C asp8 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.