title: Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in patients with infected osteoradionecrosis and bisphosphonate-associated osteonecrosis--a paradoxical observation?
abstract: Erosion of the bone is a common problem in patients suffering from infected osteoradionecrosis (IORN) or bisphosphonate-associated osteonecrosis (BON). Besides inflammatory mechanisms and infectious agents, osteoclasts were recently suggested to be specifically involved in the osteolytic mechanisms. We therefore investigated the immunohistochemical labeling of the cysteine proteinase cathepsin K, which plays a central role in osteoclast-mediated bone resorption, in tissue specimens of patients with BON (n=9; four male, five female; mean age=69.2 years) and IORN (n=10; nine male, one female; mean age=60.5 years), and compared the results with control specimens (n=8; six male, two female; mean age=60 years). In all cases, osteoclasts were the predominant cell type expressing cathepsin K. For semiquantitative analysis, we therefore defined osteoclasts as multinuclear giant cells attached to the bone and expressing cathepsin K. Significantly higher numbers of osteoclasts were found for both types of osteonecrosis when compared with the control group (BON+IORN vs controls: P=0.0000036). Within the pathological lesions, IORN cases exhibited significantly less osteoclasts than BON (P=0.00097). Our study verified increased numbers of osteoclasts in patients suffering from BON and IORN. Although it is known that bisphosphonates (and to a lesser extent, irradiation, too) decrease osteoclast function, these findings suggest a critical involvement of osteoclasts in the mechanisms of bone destruction in the respective lesions.
authors.affiliation: Institute of Pathology, Johannes Gutenberg-University of Mainz, Langenbeckstr. 1, 55101, Mainz, Germany. hansen@pathologie.klinik.uni-mainz.de
authors.forename: Torsten
authors.initials: T
authors.lastname: Hansen
authors.forename: C James
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.forename: Christian
authors.initials: C
authors.lastname: Walter
authors.forename: Martin
authors.initials: M
authors.lastname: Kunkel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000201:enzymology* / Q000473:pathology; D010020:Osteonecrosis / Q000139:chemically induced / Q000201:enzymology*; D010025:Osteoradionecrosis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K