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- Title
Osteomalacia: The Missing Link in the Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws?
- Authors
Bedogni, Alberto; Saia, Giorgia; Bettini, Giordana; Tronchet, Anita; Totola, Andrea; Bedogni, Giorgio; Tregnago, Paolo; Valenti, Maria Teresa; Bertoldo, Francesco; Ferronato, Giuseppe; Nocini, Pier Francesco; Blandamura, Stella; Carbonare, Luca Dalle
- Abstract
Background. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-documented adverse event from treatment with nitrogen-containing bisphosphonates (NBPs). During a preliminary histomorphometric study aimed at assessing the rate of bone remodeling in the jaws of patients with surgically resected BRONJ, we found a defect of bone mineralization (unpublished data). We hypothesized that osteomalacia could be a risk factor for BRONJ in patients taking NBPs. Therefore, we looked for static and dynamic histomorphometric evidence of osteomalacia in biopsies from subjects with and without BRONJ. Methods. This case-control study used histomorphometric analysis of bone specimens of patients using NBPs (22 patients with BRONJ and 21 patients without BRONJ) who required oral surgical interventions for the treatment/ prevention of osteonecrosis. Patients were given tetracycline hydrochloride according to a standardized protocol before taking bone biopsies from their jaws. Biopsies with evidence of osteomyelitis or necrosis at histology were excluded from the study. Osteomalacia was defined as a mineralization lag time >100 days, a corrected mean osteoid thickness >12.5 mm, and an osteoid volume >10%. Results. In all, 77% of patients with BRONJ were osteomalacic compared with 5% of patients without BRONJ, according to histomorphometry. Because osteomalacia was found almost exclusively in NBP users with BRONJ, this is likely to be a generalized process in which the use of NBPs further deteriorates mechanisms of bone repair. Conclusions. Osteomalacia represents a new and previously unreported risk factor for disease development. This finding may contribute to a better understanding of the pathogenesis of this disease and help with the development of strategies to increase the safety of NBP administration.
- Subjects
ANALYSIS of bones; OSTEONECROSIS; CONFIDENCE intervals; DIPHOSPHONATES; EPIDEMIOLOGY; FISHER exact test; HISTOLOGICAL techniques; JAWS; OSTEOMALACIA; RESEARCH funding; STATISTICS; U-statistics; LOGISTIC regression analysis; DATA analysis; CASE-control method; DATA analysis software
- Publication
Oncologist, 2012, Vol 17, Issue 8, p1114
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2012-0141