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.

Osteoclast profile of medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis

“…However, it was also demonstrated in vivo that radiation exposure might elicit a pro-resorptive state that is associated with high numbers of osteoclasts [63]. Comparative osteoclast counts in jaw bone sections of ORN and MRONJ (BP) patients have already been described in literature [64]. In accordance with the data of the present study, they found lower numbers of osteoclasts in ORN specimens than in MRONJ (BP) specimens (Fig.…”

“…In accordance with the data of the present study, they found lower numbers of osteoclasts in ORN specimens than in MRONJ (BP) specimens (Fig. 2b) [64]. However, contrary to the present study, they demonstrated significantly higher numbers of osteoclasts in both types of osteonecrosis when compared with a control group [64].…”

“…2b) [64]. However, contrary to the present study, they demonstrated significantly higher numbers of osteoclasts in both types of osteonecrosis when compared with a control group [64]. In accordance with the mentioned literature we found ORN lesions to feature homogenous necrosis extension patterns, whereas MRONJ (BP) lesions showed residual nests of vital bone [44, 64].…”

Actinomycosis of the jaws—histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis

“…The subgroups are briefly described in the following paragraphs. It should be mentioned that several of the patients belonging to group I or II were already described in previous studies [11][12][13][14].…”

A review of the clinical implications of bisphosphonates in dentistry

“…The presence of bacteria, and Actinomyces species in particular, are frequently observed in cultures and histology from ONJ lesion specimens. 20 Hyperbaric oxygen therapy (HBO) has proven beneficial clinically to enhance ORN wound healing and to prevent ORN before surgery in irradiated jaws. HBO produces reactive oxygen and nitrogen species, thereby promoting fibroplasia and angiogenesis by the increase in tissue oxygen gradients and modulating oxygen-sensitive signalling processes critical to osteoclast function.…”