The economic impact of infection and/or nonunion on long-bone shaft fractures: a systematic review

Abstract

Background:

Long-bone fractures are a major cause of morbidity worldwide. These injuries are often complicated by infection or nonunion, which significantly affect patient quality of life and economic costs. Although studies have quantified the impact of these fractures, there is not a comprehensive review summarizing their economic and lifestyle costs.

Study Objective:

This review summarized the impact of long-bone fracture infection and nonunion on health-related quality of life, as measured by utility scores, and both direct and indirect economic costs.

Methods:

A systematic review was conducted using the following databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. The search included terms related to long-bone fractures, infection, nonunion, cost, and utility. The search yielded 1267 articles, and after deduplication, 1144 were screened, yielding 116 articles for full-text review. Screening was conducted using Covidence and extraction using REDCap.

Results:

Twenty-two articles met inclusion criteria, with the majority being from the United States and Europe. Most articles were retrospective studies, predominantly regarding the tibia. Fifteen articles contained cost data and 8 contained utility data, with 1 article containing both. Ten cost articles and 1 utility article contained infection data. 8 cost and all utility articles contained nonunion data. Infection ranged from 1.5 to 8.0 times the cost of an uncomplicated fracture. Nonunion ranged from 2.6 to 4.3 times the cost of an uncomplicated fracture. Utility data were variable and ranged from 0.62 to 0.66 for infection and 0.48–0.85 for nonunion.

Conclusions:

Infection and nonunion after long-bone fractures are associated with large decreases in health-related quality of life and incur substantial costs to both patients and health care systems. The data presented in this review quantify these impacts and may serve useful for future economic analyses. In addition, this study highlights the dearth of high-quality literature on this important topic.

1. Introduction

Long-bone fractures are a significant cause of morbidity and mortality globally.¹ The rate of nonunion after all fractures is estimated to be 1.9% with higher rates in tibia, fibula, radius, ulna, and humerus fractures.² It is estimated that around 5% of fractures treated with internal fixation will result in infection.³ These complications can be devastating for patients, both in terms of their physical function and financially.^4,5

Postfracture surgery sequelae such as infection and nonunion can be detrimental to patients' quality of life (QoL).^4,6 Fracture-related infection (FRI) and nonunion can also have significant economic impact on hospital systems and patients' personal finances. These complications often require longer hospitalizations as well as more outpatient visits and prescriptions, which all drive up the direct costs to both the health care system and the patient.^4,7 Furthermore, patients often experience high indirect costs from missed work and decreased productivity.^4,5

Owing to the substantial impact of these injuries, many studies have investigated the direct and indirect economic impact as well as quality of life consequences of FRIs and fracture nonunions. However, to date there has not been a comprehensive review summarizing these findings. These data are critically important for research prioritization and form the basis from which economic analysis and future interventions, aimed at better understanding and reducing these complications, will be assessed. This systematic review aimed to summarize the impact of infection and nonunion on health-related quality of life, as measured by utility scores, and both direct and indirect economic costs after long-bone diaphyseal fractures.

2. Methods

A thorough electronic database search was conducted between December 2020 and January 2021 of the following 4 databases: PubMed, EMBASE, Web of Science, and the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Methodology Register). The search terms and search strategy were developed by 2 members of the research team (M.U., D.S.) and a research librarian (E.W.). The search strategy was developed based on the following concepts: fracture AND (infection OR nonunion) AND (cost OR utility).

To be included in the analysis, articles must have been written in English, published between 1970 and 2019, and must have reported on costs, cost estimates, expenditure, and/or utility scores related to long-bone fractures that include either nonunion, fracture-related infection, or deep surgical site infection as complications. Studies that examined fractures of bones other than the humerus, radius/ulna, femur, or tibia; did not include nonunion or fracture-related infections as complications; or were noncost burden studies were excluded.

The database search yielded 1267 articles, and 123 duplicates were removed prior to title and abstract screening using the Covidence software.⁸ One thousand one hundred forty-four titles and abstracts were screened by 2 independent reviewers. Conflicts were resolved by consensus. After title and abstract screening, 116 articles were eligible for full-text review. Full-text review yielded a total of 22 articles for data extraction. Figure 1 illustrates the article review process.⁹

Figure 1.

A PRISMA diagram representing the systematic screening stages involved in the systematic review.

The research team used REDCap (Research Electronic Data Capture) for data extraction.^10,11 The data extraction form elicited the following data from each article to address our research aim: study setting, study population, participant demographics, baseline characteristics, study methodology, recruitment, study completion rates, as well as utility scores and all costs associated with uncomplicated and complicated fractures. Utility scores are values that patients assign to their overall health state and the values usually range from 0 to 1, with 0 being equal to death and 1 being equal to perfect health.¹² While there are multiple different methods to estimate utility, we included studies using the following measurement systems: Quality-Adjusted Life Years (QALY), time trade-off (TTO), EuroQol-5 dimension (EQ-5D), and the more general system of Health State Utility Values (HSUV).^12–14 Costs associated with infection and nonunion were categorized as direct and indirect costs. Direct costs reflect expenditures that occur within the health care system (costs of hospitalization, surgery, outpatient visits, medications, and rehab) whereas indirect costs reflect societal costs that occur outside the health care system, such as lost economic output due to disability or mortality.¹⁵ Each of these has an equally weighted propensity to affect overall costs. All data/each outcome value is comparatively and appropriately weighted, incorporating geo–socio–economical differences into the allocation of the cost estimate value.

Data were summarized using tables without data synthesis. Median and range was reported for each complication and its associated utility and cost. To allow cost comparisons across different currencies, costs were standardized to February 2022 USD using the consumer price index and current exchange rate, respectively.

3. Results

There were 22 articles that met inclusion criteria. The articles were published from 1997 to 2021. Most articles were conducted in the United States (9), followed by the United Kingdom (4), Belgium (3), and Italy (3). Most articles were retrospective cohort studies (14), followed by case series (4), prospective cohort studies (2), and randomized controlled trials (2). Sample size ranged from 6 to 24,336, with the median value being 212. Most articles had data regarding the tibia (20), followed by the femur (6) and the humerus (5).

There were 15 articles that contained cost data (Table 1), 8 articles contained utility data (Table 2), and 1 article contained both cost and utility data (Calori et al). Of articles containing cost data, 10 articles had infection data (Table 3), 8 articles had nonunion data (Table 4), and 3 articles had both infection and nonunion data. Of articles containing utility data, all of the articles had nonunion data and 1 article had both infection and nonunion data (Gitajn et al) (Table 5).

TABLE 1.

Articles Containing Cost Data

Number	Paper Title	First Author	Year	Journal	Study Type	Country	Sample Size	Study Population	Bones Involved	Time Horizon
1	Fracture-related infection in long-bone fractures: A comprehensive analysis of the economic impact and influence on quality of life	Iliaens et al.	2021	Injury	Retrospective cohort	Belgium	30 (15 controls)	Adults who were treated for a single fracture of the humeral, femoral, or tibial shaft	Humerus, femur, and tibia	4 y
2	The economic burden of infections following intramedullary nailing for a tibial shaft fracture in England	Galvain et al.	2020	BMJ Open	Retrospective cohort	England	805	Adult patients with tibial shaft fractures	Tibia	2 y
3	Complications in type III open tibial shaft fractures treated with open reduction and internal fixation	Chitnis et al.	2019	Journal of Comparative Effectiveness Research	Retrospective cohort	United States	580	Patients aged 18–64 years with type III tibial shaft fractures requiring ORIF	Tibia	2 y
4	Complications and its impact in patients with closed and open tibial shaft fractures requiring open reduction and internal fixation	Chitnis et al.	2019	Journal of Comparative Effectiveness Research	Retrospective cohort	United States	24,336	Adults with open or closed tibial shaft fractures requiring ORIF	Tibia	2 y
5	Health Care Costs of Post-traumatic Osteomyelitis in China: Current Situation and Influencing Factors	Jiang et al.	2019	Journal of Surgical Research	Retrospective cohort	China	278	Inpatients who had received surgical interventions for extremity post-traumatic OM	Humerus, radius, ulna, femur, and tibia	3 y
6	Incidence, Costs, and Predictors of Nonunion, Delayed Union and Mal-Union Following Long-Bone Fracture	Ekegren et al.	2018	International Journal of Environmental Research and Public Health	Retrospective cohort	Australia	315	Patients with a proximal or shaft of humerus, proximal, distal or shaft of femur, or shaft of tibia fracture	Tibia, femur, and humerus	Not specified
7	Economics of open tibial fractures: the pivotal role of length-of-stay and infection	Hoekstra et al.	2017	Health Economics Review	Retrospective cohort	Belgium	358	Adult patients with acute OTA/AO type 41, 42, and 43 fractures	Tibia	2 y
8	Infection after fracture fixation of the tibia: Analysis of health care utilization and related costs	Metsemakers et al.	2017	Injury	Retrospective cohort	Belgium	358	Adult patients with acute OTA/AO type 41, 42, and 43 fractures	Tibia	2 y
9	The management of tibial fracture nonunion using the Taylor Spatial Frame	Khunda et al.	2016	Journal of Orthopaedics	Case series	England	40	Complex tibial nonunions treated with Taylor Spatial Frames	Tibia	Average 2.2 y
10	The cost of infection in severe open tibial fractures treated with a free flap	Olesen et al.	2016	International Orthopaedics	Retrospective cohort	Denmark	45	Patients with open tibia fractures covered with free vascularized flaps	Tibia	2 y
11	Tibia shaft fractures: costly burden of nonunions	Antonova et al.	2013	BMC Musculoskeletal Disorders	Retrospective cohort	United States	853	Adult patients with tibial shaft fractures	Tibia	2 y
12	Cost-effectiveness of tibial nonunion treatment: A comparison between rhBMP-7 and autologous bone graft in 2 Italian centers	Calori et al.	2013	Injury	Retrospective cohort	Italy	54	Patients who underwent surgery for tibial nonunion, either with rhBMP-7 or ABG	Tibia	1 y
13	A health economic analysis of the use of rhBMP-2 in Gustilo–Anderson grade III open tibial fractures for the United Kingdom, Germany, and France	Alt et al.	2009	Injury	Randomized control trial	United Kingdom, Germany, and France	122	Patients who underwent surgery for with grade III open tibial fractures with 1.5 mg/mL rhBMP-2. There were 3 study cohorts from the United Kingdom, Germany, and France, respectively.	Tibia	1 y
14	Management of complex tibial and femoral nonunion using the Ilizarov technique, and its cost implications	Patil et al.	2006	Journal of Bone and Joint Surgery	Retrospective cohort	United Kingdom	40	Adult patients with complex tibial and femoral nonunions	Tibia and femur	Not specified
15	An Analysis of the Actual Cost of Tibial Nonunions	Beaver et al.	1997	The Journal of the Louisiana State Medical Society	Case series	United States	11	Adults with a tibial shaft fracture subsequently presenting with a tibial nonunion	Tibia	Average follow-up was 2.6 y

TABLE 2.

Articles Containing Utility Data

Number	Paper Title	First Author	Year	Journal	Study Type	Country	Sample Size	Study Population	Bones Involved	Time Horizon
3	Deficits in preference-based health-related quality of life after complications associated with tibial fracture	Gitajn et al.	2018	The Bone & Joint Journal	Randomized control trial	United States, Canada, Australia, Norway, and India	2138	Adults with open fracture of limb requiring operative fixation Adults with tibial shaft fracture amenable to ORIF with IM nail	Tibia	1 y
4	The Devastating Effects of Tibial Nonunion on Health-Related Quality of Life	Brinker et al.	2013	The Journal of Bone and Joint Surgery	Prospective cohort	United States	237	Adults with tibial shift fracture nonunions	Tibia	0.25–20.3 y
5	Outcomes of Tibial Nonunion in Older Adults Following Treatment Using the Ilizarov Method	Brinker et al.	2007	Journal of Orthopedic Trauma	Case series	United States	23	Patients age ≥60 y with a tibial nonunion	Tibia	Average 3.2 y (1.5–5.1 y)
6	Debilitating Effects of Femoral Nonunion on Health-Related Quality of Life	Brinker et al.	2017	Journal of Orthopaedic Trauma	Retrospective cohort	United States	187	Patients with nonunions of the femur, excluding those involving the hip or knee articular surfaces	Femur	Average 2.4 y (0.25–31.4 y)
10	Time Trade-Off as a Measure of Health-Related Quality of Life: Long Bone Nonunions Have a Devastating Impact	Schottel et al.	2015	The Journal of Bone and Joint Surgery	Retrospective cohort	United States	832	Patients ≥17 y with clavicular, humeral, forearm (radial or ulnar), femoral, and/or tibial or fibular nonunions	Clavicle, humerus, forearm (radius or ulna), femur, and/or tibia or fibula	Not specified
11	The use of a gentamicin-coated titanium nail, combined with RIA system, in the management of non-unions of open tibial fractures: A single center prospective study	Vicenti et al.	2020	Injury	Prospective cohort	Italy	17	Adults with nonunion after open tibial shaft fracture previously treated with a circular external fixator	Tibia	1 y
15	Humeral shaft nonunion in the elderly: Results with cortical graft plus stem cells	Toro et al.	2019	Injury	Case series	Italy	6	Patients >65 y with diagnosis of humeral shaft nonunion with use of cortical allograft and stem cell	Humerus	Average 1.2 y (0.3–2 y)
16	Cost-effectiveness of tibial nonunion treatment: A comparison between rhBMP-7 and autologous bone graft in 2 Italian centers	Calori et al.	2013	Injury	Retrospective cohort	Italy	54	Patients who underwent surgery for tibial nonunion, either with rhBMP-7 or ABG	Tibia	1 y

TABLE 3.

Cost Data for Infection

Number	First Author	Year	Bones Involved	Complications	Cost Type	Time Horizon	Currency Year for Study	Cost	Cost in 2022 USD	Ratio Complicated to Uncomplicated
1	Iliaens et al.	2021	Humerus, femur, and tibia	Infection	Direct, Indirect	4 y	Not specified	Direct:  €47,845 (infection)  €5983 (no infection) Indirect:  €77,909 (infection)  €19,706 (no infection)	Direct:  $54,213 (infection)  $6779 (no infection) Indirect:  $88,279 (infection)  $22,329 (no infection)	Direct:  8.0:1 Indirect:  4.0:1
2	Galvain et al.	2020	Tibia	Infection	Direct	2 y	Not specified (costs collected between 2003 and 2017; 2017/2018 software used in comparison with “NHS Reference costs” to generate costs)	£16,626 (infection) £9439 (no infection)	$24,812 (infection) $14,086 (no infection)	1.8:1
3	Chitnis et al.	2019	Tibia	Infection	Direct	2 y	2017	$140,227 (infection) $50,259 (no infection)	$162,349 (infection) $58,188 (no infection)	2.8:1
4	Chitnis et al.	2019	Tibia	Infection	Direct	2 y	2017	$82,306 (infection) $21,966 (no infection	$95,290 (infection) $25,431 (no infection)	3.8:1
5	Jiang et al.	2019	Humerus, radius, ulna, femur, and tibia	Infection	Direct	3 y	Not specified	$10,504 (post-traumatic) $2189 (nontraumatic)	$11,732 (post-traumatic) $2445 (nontraumatic)	4.8:1
7	Hoekstra et al.	2017	Tibia	Infection	Direct	2 y	Not specified (cost collected between 2009 and 2016)	€48,702 (infection) €9566 (no infection)	$63,967 (infection) $11,690 (no infection)	5.5:1
8	Metsemakers et al.	2017	Tibia	Infection	Direct	2 y	Not specified (cost collected between 2009 and 2016)	€44,468 (infection) €6855 (no infection)	$54,341 (infection) $8377 (no infection)	6.5:1
10	Olesen et al.	2016	Tibia	Infection	Direct	2 y	2014 (converted from kroner to euros)	€81,155 (infection) €49,817 (no infection)	$129,565 (infection) $79,533 (no infection)	1.6:1
13	Alt et al.	2009	Tibia	Infection	Direct, Indirect (without rhBMP-7)	1 y	2007/2008	Direct:  €399–€1259 Indirect:  €43,624–€48,146	Direct:  $781–$2465 Indirect:  $85,414–$94,268	—
15	Beaver et al.	1997	Tibia	Infected Nonunion	Direct	Average follow-up was 2.6 y	Not specified	$13,740 (infected nonunion) $9407 (noninfected nonunion)	$24,280 (infected nonunion) $16,623 (noninfected nonunion)	1.5:1 (nonunion)

TABLE 4.

Cost Data for Nonunion

Number	First Author	Year	Bones Involved	Complications	Cost Type	Time Horizon	Currency Year for Study	Cost	Cost in 2022 USD	Ratio Complicated to Uncomplicated
6	Ekegren et al.	2018	Tibia, femur, and humerus	Nonunion Mal-Union Delayed Union	Direct	Not specified	Not specified	AUD $14,957 (average, not specified by bone)	$12,682 (average, not specified by bone)	—
8	Metsemakers et al.	2017	Tibia	Nonunion	Direct	2 y	Not specified (cost collected between 2009 and 2016)	€29,217 (nonunion) €6773 (union)	$35,704 (nonunion) $8277 (union)	4.3:1
9	Khunda et al.	2016	Tibia	Nonunion	Direct	Average 2.2 y	Not specified	£26,000 (treated with TSF)	$41,814 (treated with TSF)	—
11	Antonova et al.	2013	Tibia	Nonunion	Direct	2 y	2006	$53,506 (nonunion) $20,984 (union)	$75,861 (nonunion) $29,750 (union)	2.6:1
12	Calori et al.	2013	Tibia	Nonunion	Direct	1 y	2009	€8461 (rhBMP-7 group) €7666 (ABG group) mean total 8078.14	$17,688 (rhBMP-7 group) $16,025 (ABG group)	—
13	Alt et al.	2009	Tibia	Delayed fracture Healing (DFH)	Direct, Indirect (without rhBMP-7)	1 y	2007/2008	Direct: €734–€2020 Indirect: €43,624–€48,146	Direct: $1437–$3955 Indirect: $85,414–$94,268	—
14	Patil et al.	2006	Tibia and femur	Nonunion	Direct	Not specified	Estimated for the year 2004–2005	£29,204 (combined, for femur and tibia; not including BMP, ultrasound, electromagnetic induction and antibiotics)	$78,361 (combined, for femur and tibia; not including BMP, ultrasound, electromagnetic induction and antibiotics)	—
15	Beaver et al.	1997	Tibia	Infected Nonunion Noninfected Nonunion	Direct	Average follow-up was 2.6 y	Not specified	$11,333 (nonunion) $13,740 (infected nonunion) $9407 (noninfected nonunion)	$20,027 (nonunion) $24,280 (infected nonunion) $16,623 (noninfected nonunion)	—

TABLE 5.

Utility Data for Infection and/or Nonunion

Number	First Author	Year	Bones Involved	Complications	Utility Scores	Time Horizon	Utility Scores
3	Gitajn et al.	2018	Tibia	Nonunion, Infection	HSUVs QALYs, calculated from SF-6D	1 y	HSUVs:  0.649 (nonunion)  0.657 (infection, op)  0.654 (infection, non-op) QALYs:  0.624 (nonunion)  0.625 (infection, op)  0.628 (infection, non-op)
4	Brinker et al.	2013	Tibia	Nonunion	Time Trade-Off	0.25–20.3 y	Time Trade-Off: 0.64
5	Brinker et al.	2007	Tibia	Nonunion	Time Trade-Off QALYs	Average 3.2 y (1.5–5.1 y)	Time Trade-Off:  0.48 (before treatment)  0.87 (after treatment) QALYs: 5.3 (difference pretreatment to post-treatment)
6	Brinker et al.	2017	Femur	Nonunion	Time Trade-Off	Average 2.4 y (0.25–31.4 y)	Time Trade-Off: 0.62
10	Schottel et al.	2015	Clavicle, humerus, forearm (radius or ulna), femur, and/or tibia or fibula	Nonunion	Time Trade-Off	Not specified	Time Trade-Off:  Clavicle: 0.59; Humerus: 0.71;  Forearm: 0.54; femur: 0.68;  Tibia or fibula: 0.68  Mean total: 0.68
11	Vicenti et al.	2020	Tibia	Nonunion	EQ-5D	1 y	0.6 (baseline) 0.9 (1-y postop)
15	Toro et al.	2019	Humerus	Nonunion	EQ-5D	Average 1.2 y (0.3–2 y)	0.451
16	Calori et al.	2013	Tibia	Nonunion	EQ-5D QALYs	1 y	EQ-5D (1 Month Postsurgery):  0.59 (total)  0.62 (rhBMP-7)  0.52 (ABG) EQ5-D:  1 (total)  1 (rhBMP-7)  0.85 (ABG) QALY:  0.768 (rhBMP-7)  0.79 (ABG)

The mean direct cost of infection across all the relevant studies was $52,187 (range $781–$162,349). There were 2 studies with indirect costs of infection recorded, which ranged from $85,414 to $94,268. The cost of infection ranged from 1.5 to 8.0 times the cost of an uncomplicated fracture in the included studies. The mean direct cost of nonunion across all the relevant studies was $30,852 (range $1437–$78,361). There was 1 study with indirect costs of nonunion recorded, with a range of $85,414–$94,268 (Alt et al). The cost of nonunion ranged from 2.6 to 4.3 times the cost of an uncomplicated fracture.

Utility data were reported using several different instruments including QALY, time trade-off, EQ-5D, and the more general HSUV. There was one article with utility data for infection, with a median HSUV of 0.66 and QALY of 0.63 (calculated from the SF-6D utility score). For nonunion, the following were the identified ranges varied by survey instrument. The one study reporting HSUV found nonunion yielded an HSUV of 0.65. The range for studies involving QALYs was 0.73–0.768, for the time trade-off was 0.48–0.68, and the range for EQ-5D was 0.45–0.60.

4. Discussion

This systematic review aimed to identify the economic and utility costs of infection and nonunion in the setting of a long-bone fracture. We identified 22 articles for inclusion with most reporting on data collected in the United States and Europe. Most articles had data related to the tibia. Sample size and study characteristics varied widely between the studies. In addition, the impact of infection and nonunion varied between studies. The cost of infected fractures was 1.5- to 8-fold higher than uncomplicated fractures with a median utility score of 0.63. The cost of nonunion ranged from 2.6 to 4.3 that of union, with the median utility of 0.73.

To our knowledge, the current systematic review is the first of its kind to summarize the cost and utility of infection and/or nonunion of long-bone fractures. Our cost findings surrounding infection corroborate the existing literature surrounding surgical infections in orthopaedics and other fields which have shown anywhere from 2 to 8 times increased cost of care.^16–18 These costs were similar to those associated with nonunion, which could add $15,000 or more to the cost of a patient's care.¹⁹ In the context of other medical conditions, these costs outpace admissions for simple diagnosis such as community acquired pneumonia and are more comparable with more serious medical diagnoses such as heart failure or cancer.^20–22 The rising costs of care for orthopaedic-related injuries is a major barrier in an individual's ability to access quality orthopaedic care. As a result, an increased burden is placed on the health care system as patients present later in their disease/injury course with more complex interventions needed to address their issues. As a result, it is imperative to constantly interrogate these rising costs of care to identify ways to mitigate them.

This article lays the foundation for future economic analyses which may look to investigate the associated benefit and utility values that are intertwined with these costs in the form of cost-benefit or cost-utility analyses. Such future research will allow us to begin to estimate the costs and benefits associated with preventing a single infection or nonunion occurrences. Such analyses deepens our understanding of the economic burdens associated with these diseases, and also enables policy makers to make valuable comparisons across interventions, to inform best resource distribution practices.

Our findings related to utility demonstrated the significant effects of infection and nonunion on health-related quality life. The literature remains sparse; however, the more robust nonunion literature has shown that utilities associated with tibial nonunion were significantly lower when compared with other common medical conditions including congestive heart failure, type-2 diabetes mellitus, and even myocardial infarction.²³ The utility scores for nonunion were similar to more severe conditions such as stroke and emphysema.²³

The current review had strengths and some limitations. There were multiple efforts taken to decrease bias in article selection. Article review and extraction was completed by 2 independent investigators. Extraction data were corroborated by a third reviewer who organized the tables. Our review also had several limitations. Articles were restricted to manuscripts published in English. In addition, there were a low number of articles identified for several of the outcomes reported in this study and some variability in fracture types. Outcomes such as a quality of life can be quantified in heterogeneous ways which can lead to difficulty in comparisons across different metrics. Finally, the overall low-quality and heterogeneity of studies on this topic prevented a formal synthesis of data. Such heterogeneity highlights the dire need for an expansion of literature concerning these topics. Future studies should aim build on this work and bridge the gap in quality and investigate this topic at a more granular level. Topics of interest may include but are not limited to issues concerning the exploration of the costs associated with infection and nonunion individually, the exploration of costs stratified by different bone types, the establishment of incremental cost-effectiveness ratios, more stratified cost benefit analyses, and the optimization of cost effectiveness models. Such analyses will allow us to more accurately and completely understand costs associated with orthopaedic trauma care.

5. Conclusion

Infection and nonunion after long-bone fracture are associated with large decreases in health-related quality of life and incur substantial costs to both patients and health care systems. The data presented in this review quantitate these impacts and may serve as useful basis for future economic analyses evaluating interventions aimed to prevent or treat these complications. Our intention is for these values to serve as proximal price ranges for the basis of the future orthopaedic cost analysis research. At the same time, this study highlights the dearth of high-quality literature on this important topic and emphasizes the need for further investigation in this domain.