Background/Purpose: Rheumatoid Arthritis (RA) is a known risk factor for osteoporosis. There are many factors that contribute to this increased risk, including the use of glucocorticoids, systemic inflammation due to the disease process and relative physical inactivity.  Only a few studies have assessed the risk of fractures in RA. The objective of this systematic review was to assess the risk of fractures in adults with RA compared with controls from the general population.

Methods: Two authors screened citations from the following electronic databases:  MEDLINE (1946 to July 2015), EMBASE (1947 to July 2015), Cochrane Database of Systematic Reviews (2005 to July 2015) and CINAHL (1981 to July 2015). Included citations had to be written in English, only include patients greater than or equal to 18 years of age and compare fracture incidence/prevalence between RA patients and a control group.  Case control, cohort and cross-sectional studies were included. Abstracts and conference proceedings were not searched. The primary outcome was fracture incidence and/or prevalence. Two authors abstracted data using a standardized data abstraction form. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS).

Results: The searches resulted in 3451 citations, and after applying the inclusion criteria, we selected seventeen observational studies comparing fracture incidence and/or prevalence between RA and controls. Overall, the results demonstrated that the risk of fracture was elevated in RA compared to controls in 14 of the 17 studies. Thirteen studies were adjusted for glucocorticoid use and there was an increased risk of fracture with glucocorticoid use in 4/13 of these studies. Seven studies analyzed RA severity or functional impairment as a risk factor for fracture and the risk of fracture was elevated in 2/7 of these studies. Fracture ascertainment was performed by searching medical records in seven studies, analyzing spine radiographs in six studies, self-reported history in two studies and by multiple methods in two studies.  Eight studies evaluated fractures at multiple sites, whereas nine studies evaluated fractures only at a single site (spine in 6 and hip in 3).  Only two studies reported specific data on fragility fractures, whereas in the remaining studies, the fracture mechanisms were not defined. Assessment using the NOS revealed that the studies were of high quality. Scoring by NOS criteria revealed that 14/17 studies scored 4/4 on selection, all studies scored 2/2 on comparison and 13/17 studies scored 3/3 on outcome/exposure. Limitations of the studies included the following:  studies enrolled a diverse range of patient and control group populations, and generally included all types of fractures determined by various methods and involving multiple sites. Some studies only included women while others included both genders. The studies took place in different countries. These differences between the studies made it difficult to directly compare them.  Due to the marked study heterogeneity, a meta-analysis was not performed.

Conclusion: The risk of fracture in RA is elevated when compared to the general population.