Epidemiological aspects of rheumatoid arthritis patients affected by oral bisphosphonate-related osteonecrosis of the jaws

Bisphosphonates (BPs) are stable synthetic analogs of inorganic pyrophosphate that suppress osteoclast-mediated bone resorption [1]. In this way, they have been widely used to stabilize bone loss in patients with rheumatoid arthritis (RA), especially those who develop osteoporosis, which is a common feature in this rheumatic disease [2]. However, since 2003, great concern has been generated regarding the side-effects of these drugs through increasing reports, worldwide, of a bisphosphonate-related osteonecrosis that affect the jaws (BRONJ).There are many hypotheses regarding BRONJ pathogenesis, but none of them is completely accepted. Although there have been reports with no obvious co-morbidity factors [3,4], it is reasonable to believe that co-factors may play a relevant role in the development of these lesions, especially in patients taking oral BPs. Among these co-factors, RA has been included as a relevant risk factor for BRONJ; however, until now the relationship between these diseases has not been fully explained.Due to the greater number of patients taking oral BPs for the treatment of RA and osteoporosis, it is very important for risks to be assessed. Thus, the purpose of this extended literature review is to evaluate relevant issues of patients with RA who developed oral BRONJ, including demographic, clinical, and treatment aspects, with the goal of establishing comparative associations with patients without RA who developed oral BRONJ.We performed a computerized search to identify all papers published in English from January 2003 to September 2011 in PUBMED/MEDLINE, Scopus, and Cochrane databases. Case reports, case series, and retrospective studies were included, while short communications and letters to the Editor were excluded. The studies were approved by the Ethics in Human Research Committee and were in compliance with the ethical principles of the Helsinki Declaration. Literature reviews and systematic reviews also were considered with the objectiv