Risk factors for nonunion following surgically managed, traumatic, diaphyseal fractures: a systematic review and meta-analysis

Abstract

Background There are several studies on nonunion, but there are no systematic overviews of the current evidence of risk factors for nonunion. The aim of this study was to systematically review risk factors for nonunion following surgically managed, traumatic, diaphyseal fractures. Methods Medline, Embase, Scopus, and Cochrane were searched using a search string developed with aid from a scientific librarian. The studies were screened independently by two authors using Covidence. We solely included studies with at least ten nonunions. Eligible study data were extracted, and the studies were critically appraised. We performed random-effects meta-analyses for those risk factors included in five or more studies. PROSPERO registration number: CRD42021235213. Results Of 11,738 records screened, 30 were eligible, and these included 38,465 patients. Twenty-five studies were eligible for meta-analyses. Nonunion was associated with smoking (odds ratio (OR): 1.7, 95% CI: 1.2–2.4), open fractures (OR: 2.6, 95% CI: 1.8–3.9), diabetes (OR: 1.6, 95% CI: 1.3–2.0), infection (OR: 7.0, 95% CI: 3.2–15.0), obesity (OR: 1.5, 95% CI: 1.1–1.9), increasing Gustilo classification (OR: 2.2, 95% CI: 1.4–3.7), and AO classification (OR: 2.4, 95% CI: 1.5–3.7). The studies were generally assessed to be of poor quality, mainly because of the possible risk of bias due to confounding, unclear outcome measurements, and missing data. Conclusion Establishing compelling evidence is challenging because the current studies are observational and at risk of bias. We conclude that several risk factors are associated with nonunion following surgically managed, traumatic, diaphyseal fractures and should be included as confounders in future studies.

Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors

“…Diabetes appears to be a risk factor for non-union, as shown in a meta-analysis [88]. However, larger randomized controlled trials have been surprisingly scarce.…”

“…Age itself may present a risk factor for non-unions in the clavicle [83,84,86], however the literature for the humerus is indecisive [85,87]. A recent meta-analysis was unable to include age, due to the heterogeneity of data presentation [88].…”

“…A larger systematic meta-analysis concluded sex not to be a risk factor for non-union (odds ratio [OR]: 1.0) [88].…”

“…Another systematic review and meta-analysis pooled 7516 procedures to reveal a 2.2 times higher risk of delayed healing or non-union in smokers [99]. A meta-analysis pooled 38,465 patients, and found that smoking status led to an OR of 1.7 for non-union [88]. A prospective trial including 647 patients calculated an OR of 2.4 for the development of tibial non-union in smokers [91].…”

“…Obesity has been identified as a risk factor for non-union even in pediatric patients [103,104], and was assessed with an OR of 1.5 for non-union according to a meta-analysis [88].…”