|dc.description.abstract||Humeral shaft fractures comprise 1% of adult fractures, with isolated, closed injuries usually managed non-operatively in the first instance.
However, there is limited data regarding the modern epidemiology of these injuries and understanding of longer-term patient-reported outcomes is incomplete. There is also uncertainty regarding a broader role for initial operative fixation, and studies comparing operative and non-operative management would inform discussions regarding the optimal treatment. Nonunion complicates 15-20% of non-operatively managed fractures, and methods for the early identification of patients at increased risk would help mitigate the morbidity associated with this complication. The aims of this thesis were to investigate the epidemiology, outcomes and predictors of nonunion following a humeral shaft fracture.
A retrospective database of 898 patients with acute humeral shaft fractures sustained over a 10-year period was developed and analysed to determine the modern epidemiology and explore variation in patient and injury characteristics. All living, cognitively-intact patients with complete radiographic follow-up were sent a postal survey, to assess longer-term patient-reported outcomes and factors associated with an adverse outcome. Comparison of operative versus non-operative management was undertaken through a systematic review and meta-analysis of published prospective randomised controlled trials (RCTs), and then a single-centre prospective RCT (the HU-FIX Study). The primary outcome measure for these studies was the abbreviated (QuickDASH) or full Disabilities of the Arm, Shoulder and Hand (DASH) score. Secondary outcome measures included union/nonunion and health-related quality of life (HRQoL). Using EuroQol-5 Dimension (EQ-5D) data obtained during the longer-term outcomes study, a retrospective cost-utility analysis was performed to estimate the cost-effectiveness of routine operative fixation. Techniques for the early prediction of nonunion were investigated through a large retrospective study of baseline risk factors, a retrospective analysis of radiographic callus formation at six-weeks post-injury, and a prospective pilot study of freehand ultrasound assessment of humeral shaft fracture healing.
The incidence of humeral shaft fractures was 12.6/100,000/year (typical fractures 11.2/100,000/year, pathological fractures 1.1/100,000/year, periprosthetic fractures 0.4/100,000/year). For typical fractures (n=798), peak incidence was bimodal in men and unimodal in older women (Type G distribution). Fractures involving the proximal- (31%) and middle-thirds (48%) were more likely to occur in older, female patients with comorbidities after a fall from standing (all p<0.001), suggesting these should be considered as fragility fractures.
Retrospective analysis of 291 patients at a mean of five years (minimum one year) found that overall patient-reported outcomes were comparable to healthy, age-matched populations (mean QuickDASH 20.8, mean EQ-5D 0.730). However, union after nonunion surgery was independently associated with inferior upper limb function (QuickDASH difference 8.1, p=0.019) and HRQoL (EQ-5D difference -0.102, p=0.028) compared with union after initial operative/non-operative management.
Meta-analysis of four previously published prospective RCTs (292 patients) found that surgery was associated with superior upper limb function at six months (DASH difference 7.6, p=0.01; Constant-Murley difference 8.0, p=0.003), with no difference at one year (DASH, p=0.30; Constant-Murley, p=0.33). No differences in HRQoL or pain scores were found at any timepoint. However, surgery was associated with a lower risk of nonunion (OR 0.13, p=0.004) and the number-needed-to-treat (NNT) to avoid one nonunion was seven.
The HU-FIX Study included 64 patients randomly allocated to either operative or non-operative management. At the primary outcome timepoint (three months), the median DASH score for the operative group was superior (20.8 vs. 39.2, p=0.013), but this was not sustained at six months or one year. Overall, eight patients (12.7%) developed a nonunion, one (4%) managed operatively and seven (20%) managed non-operatively (OR 6.75, p=0.066). There were early advantages of operative management (in terms of shoulder/elbow motion, pain/satisfaction scores, HRQoL and return to sport), but no differences between the groups at one year.
Retrospective cost-utility analysis of 215 patients at a mean of five years demonstrated that routine operative fixation, in order to reduce the rate of nonunion following non-operative management, was associated with additional treatment costs (£1,542/patient, compared with routine non-operative management) but conferred a potential EQ-5D benefit of 0.120/patient. The incremental cost-effectiveness ratio of routine fixation was £12,850/QALY gained, suggesting this strategy would be cost-effective according to the NICE threshold (<£20,000/QALY gained).
Retrospective analysis of 662 patients found that pre-injury non-steroidal anti-inflammatory drugs (aOR 20.58, p=0.009) and glenohumeral arthritis (aOR 2.44, p=0.043) were associated with an increased risk of nonunion following non-operative management. However, non-operative management itself was associated with an increased risk of nonunion compared with initial surgery and was the strongest risk factor for this complication (aOR 9.91, p<0.001). Based upon these findings, five patients would need to undergo initial surgery to avoid one nonunion.
Retrospective analysis of 60 patients led to the development of the Radiographic Union Score for HUmeral fractures (RUSHU), a novel assessment tool that demonstrated substantial inter-observer agreement (intraclass correlation coefficient [ICC] 0.79). At six weeks post-injury, a RUSHU<8 was highly predictive of nonunion (sensitivity 75%, specificity 80%, positive predictive value (PPV) 65%, negative predictive value (NPV) 86%). Based on a PPV of 65%, if all patients with a RUSHU<8 underwent fixation the NNT to avoid one nonunion would be 1.5. Moreover, selective fixation based on a RUSHU<8 would be associated with estimated cost savings of £415/patient (compared with routine non-operative management), as well as conferring an overall EQ-5D utility benefit.
Prospective ultrasound assessment of 12 patients suggested this modality had substantial inter-observer reliability (ICC 0.76). Absence of sonographic callus (SC) at six weeks demonstrated sensitivity 50%, specificity 100%, PPV 100% and NPV 91% in nonunion prediction (overall accuracy 92%). Absence of sonographic bridging callus (SBC) at six weeks demonstrated sensitivity 100%, specificity 70%, PPV 40% and NPV 100% (overall accuracy 75%). Of three patients at risk of nonunion (RUSHU<8), one had SBC on six-week ultrasound (that subsequently united) and the others had non-bridging or absent SC (both developed nonunion).
The association between proximal- and middle-third humeral shaft fractures and fragility highlights the importance of balancing the risks and benefits of surgery in this patient group. Nonunion impairs longer-term patient-reported function and HRQoL, even after successful nonunion surgery. Initial surgery may confer early functional benefits, but these are not sustained beyond six months. The most significant advantage of surgery may lie in the substantially lower risk of nonunion. Routine fixation for patients with humeral shaft fractures is cost-effective at five years, as the additional costs are offset by reducing the impact of nonunion on HRQoL. Strategies to target early operative intervention to patients at increased risk of nonunion represent a pragmatic option. Identifying patients using baseline characteristics alone appears challenging, but both radiographic (RUSHU) and ultrasound assessment at six weeks appear to be reliable and accurate in predicting subsequent nonunion risk.||en