Jaw Bone Samples From Bisphosphonate-Treated Patients: A Pilot Cohort Study.
Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonate treatment.


OBJECTIVE
A detailed characterization of sampled peri-necrotic jawbone from bisphosphonate-treated patients was performed at tissue and cellular level (histological analyses and gene expression).


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-kappaB 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 (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-1β was strongly up-regulated compared with controls (p = .040).


CONCLUSIONS
A 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.
Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.|Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden.
Carina
C
Cardemil
Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.|BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden.
Peter
P
Thomsen
Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.|Department of Oral and Maxillofacial Surgery, Sahlgrenska University Hospital/Molndal and Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Cecilia
C
Larsson Wexell
D000368:Aged; D000369:Aged, 80 and over; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
ONJ; bisphosphonates; gene expression; histology; inflammation; jawbone