Orthopedics

Feature Article 

Preoperative Vitamin D Deficiency Is Associated With Higher Postoperative Complication Rates in Total Knee Arthroplasty

Vishal Hegde, MD; Armin Arshi, MD; Christopher Wang, BS; Zorica Buser, PhD; Jeffrey C. Wang, MD; Andrew R. Jensen, MD; John S. Adams, MD; Erik N. Zeegen, MD; Nicholas M. Bernthal, MD

Abstract

The purpose of this study was to determine the relative incidence of postoperative complications in 25-hydroxyvitamin D (25D)-deficient and -sufficient patients undergoing total knee arthroplasty (TKA). Patients who were either serum 25D deficient (25D <20 ng/mL) or 25D sufficient (25D ≥20 ng/mL) 90 days prior to primary TKA from 2007 to 2016 were identified using the Humana administrative claims registry. The incidence of postoperative medical and surgical complications was determined by querying for relevant International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Risk-adjusted odds ratios (ORs) were calculated using multivariate logistic regression with age, sex, and Charlson Comorbidity Index as covariates. In total, 868 of 6593 patients who underwent TKA from 2007 to 2016 were 25D deficient, corresponding to a 13.2% prevalence rate. On adjustment for age, sex, and Charlson Comorbidity Index, 25D-deficient patients had a higher incidence of postoperative stiffness requiring manipulation under anesthesia (OR, 1.69; 95% confidence interval [CI], 1.39–2.04; P<.001), surgical site infection requiring irrigation and debridement (OR, 1.76; 95% CI, 1.25–2.48; P=.001), and prosthesis explantation (OR, 2.97; 95% CI, 2.04–4.31; P<.001) at 1 year. Patients who were 25D deficient also had higher rates of postoperative deep venous thrombosis (OR, 1.80; 95% CI, 1.36–2.38; P<.001), myocardial infarction (OR, 2.11; 95% CI, 1.41–3.15; P<.001), and cerebrovascular accident (OR, 1.73; 95% CI, 1.17–2.57; P=.006). Thus, serum 25D levels below 20 ng/mL are associated with a higher incidence of postoperative complications and may be a perioperative modifiable risk factor in TKA. [Orthopedics. 2018; 41(4):e489–e495.]

Abstract

The purpose of this study was to determine the relative incidence of postoperative complications in 25-hydroxyvitamin D (25D)-deficient and -sufficient patients undergoing total knee arthroplasty (TKA). Patients who were either serum 25D deficient (25D <20 ng/mL) or 25D sufficient (25D ≥20 ng/mL) 90 days prior to primary TKA from 2007 to 2016 were identified using the Humana administrative claims registry. The incidence of postoperative medical and surgical complications was determined by querying for relevant International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Risk-adjusted odds ratios (ORs) were calculated using multivariate logistic regression with age, sex, and Charlson Comorbidity Index as covariates. In total, 868 of 6593 patients who underwent TKA from 2007 to 2016 were 25D deficient, corresponding to a 13.2% prevalence rate. On adjustment for age, sex, and Charlson Comorbidity Index, 25D-deficient patients had a higher incidence of postoperative stiffness requiring manipulation under anesthesia (OR, 1.69; 95% confidence interval [CI], 1.39–2.04; P<.001), surgical site infection requiring irrigation and debridement (OR, 1.76; 95% CI, 1.25–2.48; P=.001), and prosthesis explantation (OR, 2.97; 95% CI, 2.04–4.31; P<.001) at 1 year. Patients who were 25D deficient also had higher rates of postoperative deep venous thrombosis (OR, 1.80; 95% CI, 1.36–2.38; P<.001), myocardial infarction (OR, 2.11; 95% CI, 1.41–3.15; P<.001), and cerebrovascular accident (OR, 1.73; 95% CI, 1.17–2.57; P=.006). Thus, serum 25D levels below 20 ng/mL are associated with a higher incidence of postoperative complications and may be a perioperative modifiable risk factor in TKA. [Orthopedics. 2018; 41(4):e489–e495.]

The annual volume of total knee arthroplasty (TKA) procedures in the United States is expected to reach 3.5 million by 2030.1 This increase in volume will result in more patients experiencing postoperative complications such as prosthetic joint infection, chronic pain and stiffness, and medical complications, leading to considerable interest in prevention. One area of investigation is the perioperative modification of host risk factors. Although many risk factors, such as age, metabolic syndromes, and obesity, are relatively immutable, certain patient-specific factors related to general health, nutrition, and endocrine status are modifiable and may play a role in decreasing complication rates in TKA.2

One such modifiable risk factor that has gained recent attention is vitamin D deficiency.3–5 Unlike other risk factors that have previously been studied, the promise of vitamin D stems from 3 key features. First, epidemiologic data suggest that the prevalence of deficient (<20 ng/mL) 25-hydroxyvitamin D (25D) levels can exceed 50% to 80% in the arthroplasty population.4,6–8 Second, vitamin D is known to have significant implications in inflammatory, immune, and metabolic processes, including skeletal health and function.9 This includes mechanistic and animal studies that have elucidated the effect of 25D sufficiency on the innate and adaptive immune response.10–16 Finally, serum 25D levels can be quickly repleted using a Food and Drug Administration–approved, orally administered 25D3 product.17 Thus, the prevalence of 25D deficiency in the TKA population, the well-established mechanistic links to the human immune system and skeletal health and function, and the fact that 25D levels can be returned to normal rapidly with 25D3 treatment suggest that the serum 25D level is a perioperative modifiable risk factor for patients undergoing TKA.

Complementary clinical evidence also exists suggesting that vitamin D deficiency in arthroplasty is associated with worse functional and pain outcomes,6,18–21 longer hospital stay,22 and higher perioperative complication rates.23,24 However, to date, the literature has been limited by small samples from single institutions, follow-up within a relatively short-term perioperative period, and inconsistent adjustment of confounding comorbidities. The purpose of this study was to use a large, multi-institution administrative claims database to determine (1) the prevalence of 25D deficiency in the TKA population and (2) the relative incidence of postoperative medical and surgical complications among 25D-deficient and 25D-sufficient patients undergoing TKA.

Materials and Methods

The authors performed a retrospective review of the Humana administrative claims registry through the PearlDiver Patient Record Database (PearlDiver, Colorado Springs, Colorado) to identify patients who underwent TKA. This commercially available administrative claims database consists of approximately 20 million patient records from the Humana (Louisville, Kentucky) nationwide health insurance provider. Clinical diagnoses are queried using patient billing codes, including those classified by the International Classification of Diseases, Ninth Revision, Current Procedural Terminology, and Logical Observation Identifiers Names and Codes.

Patients who underwent primary TKA between 2007 and 2016 were identified by querying for records of patients with Current Procedural Terminology code 27447 [arthroplasty, knee, condyle and plateau; medial AND lateral compartments with or without patella resurfacing (total knee arthroplasty)] as the primary index procedure, with preoperative plasma 25D (Logical Observation Identifiers Names and Codes code 1989-3) queried within 90 days prior to the index surgery. Patients were then sorted into cohorts based on the most recent 25D as either 25D deficient (25D <20 ng/mL) or 25D sufficient (25D ≥20 ng/mL). This is based on the Institute of Medicine definitions and the association of risks to bone health with 25D levels of less than 20 ng/mL.25 Demographic and baseline characteristic data included patient age (reported in 5-year groups), sex, geographic region, International Classification of Diseases, Ninth Revision–coded medical comorbidities, and Charlson Comorbidity Index (CCI). The CCI is a well-validated prospective tool to determine 1-year mortality based on 22 medical conditions.26 The aforementioned cohorts were queried to identify patients who had a series of postoperative surgical and medical complications based on Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes, respectively. Surgical complications (Table 1) included tibial and/or femoral revision, surgical site infection requiring irrigation and debridement and/or explantation of prosthesis, and stiffness requiring manipulation under anesthesia at both 3 months and 1 year after TKA. For tibial and/or femoral revisions, patients with concomitant irrigation and debridement and prosthesis explantation were excluded to identify revisions from noninfectious causes. Medical complication categories included deep venous thrombosis and pulmonary embolism within 60 days; acute renal failure within 14 days; and acute myocardial infarction and cerebrovascular accident within 30 days.

Queried Surgical Complications Following Total Knee Arthroplasty

Table 1:

Queried Surgical Complications Following Total Knee Arthroplasty

Statistical Analysis

Inferential statistics comparing the baseline age, sex, regional, and comorbidity distributions of the two 25D-stratified cohorts were performed using chi-square analysis. A 2-tailed Student's t test was used to compare the baseline CCI of the 2 cohorts. Statistical significance was defined as P<.05. Using the PearlDiver statistical analysis package, multivariate logistic regression with patient age, sex, and CCI as covariates was performed to calculate adjusted odds ratios (ORs), 95% confidence intervals (CIs), and associated P values for each complication category with 25D-deficient patients treated as the exposed group. All other statistical analyses were performed using SPSS version 21 software (IBM Corp, Armonk, New York).

Results

In total, 868 25D-deficient patients (25D <20 ng/mL) who underwent primary TKA were identified in the Humana database between 2007 and 2016. The comparison group consisted of 5725 25D-sufficient patients (25D ≥20 ng/mL) who underwent TKA during the same period (Table 2). This corresponds to a 25D deficiency rate of 13.2% in the TKA population who underwent preoperative serum 25D testing. In total, 157,340 patients underwent primary TKA during this period, corresponding to a 4.2% rate of preoperative 25D measurement. For the 25D-deficient cohort, the median and mode ages were both in the 65 to 69 years group; for the 25D-sufficient cohort, the median and mode ages were both in the 70 to 74 years group (Table 2). The age distributions were not statistically equivalent between the 25D-deficient and the 25D-sufficient cohorts (P<.001). Females comprised 77.3% of the 25D-deficient cohort and 75.5% of the 25D-sufficient cohort; the distribution of sex was equivalent between the 2 groups (P=.113). Most cases came from the South (25D deficient, 79.0%; 25D sufficient, 77.7%). The 25D-deficient cohort had a significantly higher incidence of comorbid diabetes mellitus (P=.039) and obesity (P=.010) and a significantly lower incidence of comorbid peripheral vascular disease (P<.001) and chronic kidney disease (P=.012) (Table 3). The 25D-deficient patients also had a higher average CCI than their nondeficient counterparts (P<.001).

Age, Sex, Regional, and Charlson Comorbidity Index Distribution of Vitamin D–Deficient and Vitamin D–Sufficient Patients

Table 2:

Age, Sex, Regional, and Charlson Comorbidity Index Distribution of Vitamin D–Deficient and Vitamin D–Sufficient Patients

Baseline Medical Comorbidity Distribution of Vitamin D–Deficient and Vitamin D–Sufficient Patients

Table 3:

Baseline Medical Comorbidity Distribution of Vitamin D–Deficient and Vitamin D–Sufficient Patients

The incidence of queried surgical complications is listed in Table 4. On adjustment for baseline age, sex, and comorbidities using multivariate logistic regression, surgical site infection requiring irrigation and debridement (OR, 1.76; 95% CI, 1.25–2.48; P=.001) and explantation of prosthesis (OR, 2.97; 95% CI, 2.04–4.31; P<.001) had a higher incidence postoperatively among the 25D-deficient cohort at 1 year; the incidence of surgical site infection requiring irrigation and debridement was also higher among 25D-deficient patients at 3 months (OR, 2.11; 95% CI, 1.48–3.00; P<.001). The 25D-deficient patients had a significantly higher incidence of postoperative stiffness requiring manipulation under anesthesia at both 3 months (OR, 1.66; 95% CI, 1.34–2.07; P<.001) and 1 year (OR, 1.69; 95% CI, 1.39–2.04; P<.001). Rates of noninfectious component revision were less than 1.5% and statistically comparable between the 2 cohorts with risk adjustment.

Incidence and Odds Ratio of Surgical and Medical Complications After Total Knee Arthroplasty in Vitamin D–Deficient and Vitamin D–Sufficient Patients

Table 4:

Incidence and Odds Ratio of Surgical and Medical Complications After Total Knee Arthroplasty in Vitamin D–Deficient and Vitamin D–Sufficient Patients

Regarding medical complications, 25D-deficient patients had a higher risk-adjusted incidence of postoperative deep venous thrombosis (OR, 1.80; 95% CI, 1.36–2.38; P<.001), myocardial infarction (OR, 2.11; 95% CI, 1.41–3.15; P<.001), and cerebrovascular accident (OR, 1.73; 95% CI, 1.17–2.57; P=.006). Rates of pulmonary embolism and acute renal failure were statistically comparable between the 2 cohorts.

Discussion

Vitamin D deficiency has received recent attention as a modifiable risk factor in arthroplasty for several reasons. First, epidemiologic data indicate that 50% to 80% of arthroplasty patients have insufficient or deficient 25D levels.4,6–8 Second, subnormal vitamin D balance has well-established mechanistic links to bone health and metabolism, as well as innate and adaptive immunity, all via the intracellular vitamin D receptor pathway.9,27 Finally, 25D repletion can be quickly achieved with a Food and Drug Administration–approved, cost-efficient oral supplementation prior to elective joint replacement on a population level.28 Although clinical data exist suggesting that 25D deficiency is a perioperative risk factor, these data are currently limited to small case series reporting on cohorts from single institutions. Using data over a 10-year period from the Humana administrative claims registry, the current study reports population-level data indicating that 25D deficiency is an independent risk factor for surgical and medical complications following TKA.

The rate of vitamin D deficiency (25D <20 ng/mL) in this nationwide sample of 6593 patients who underwent preoperative 25D testing was 13.2%. In the United States, Unnanuntana et al29 reported a 9.5% prevalence of 25D deficiency in their cohort of 200 patients, whereas Lavernia et al6 reported a 30% prevalence. Studies from England (24%),30 Finland (36%),31 Northern Greece (81%),8 and Germany (64%)24 have found highly variable rates of 25D deficiency in the arthroplasty population; unsurprisingly, the prevalence of 25D deficiency and insufficiency is likely endemic to certain demographics and geographic locations attributable to sun exposure, dietary supplementation, and genetic differences.9 The authors note that only 4.2% of the entire Humana TKA population had a preoperative 25D level recorded, suggesting that (1) routine 25D screening is currently uncommon in the United States and/or (2) the percentage of vitamin D–deficient patients in this population may not be representative of the US population as a whole. Taken together, the authors use these data to underscore the importance of vitamin D deficiency in populations where it is endemic, as perioperative identification and repletion in these patients may have the greatest impact on population-level complication rates and outcomes.

Predictably, 25D-deficient patients had a higher CCI than their 25D-sufficient counterparts. Multiple etiologies and intrinsic patient-specific associations and predispositions, including increased skin pigmentation, age, obesity, and malnutrition, are associated with 25D deficiency.9 The 25D-deficient patients in this study had a higher incidence of comorbid obesity (P=.010) and diabetes mellitus (P=.039). Lower 25D levels in obese patients is thought to reflect an increased volume of distribution of its fat-soluble precursor, and is of controversial clinical significance.32 Similarly, the relationship between diabetes and 25D deficiency is controversial, with some suggesting that obesity serves as a confounder and others suggesting that 25D repletion may improve glycemic control.33 The fact that 25D-deficient patients in this cohort were younger is surprising insofar as 25D deficiency is strongly correlated with age. The authors also found that 25D-deficient patients had a lower incidence of chronic kidney disease. However, it is likely that the lower incidence of deficient serum 25D values in chronic kidney disease is reflective of patients receiving chronic supplementation as part of routine screening and treatment.

This study found that 25D deficiency was an independent risk factor for surgical site infection requiring reoperation including irrigation and debridement (OR, 1.76) and explantation of the prosthesis (OR, 2.97) at 1 year. Several smaller clinical studies have previously correlated periprosthetic joint infections with 25D deficiency. Maier et al24 reported that 86% of patients undergoing revision surgery for periprosthetic joint infection after primary total hip, knee, and shoulder arthroplasty had 25D level of less than 20 ng/mL. Traven et al23 reported that low serum 25D level was associated with an increased risk of 90-day complications among patients undergoing revision TKA, including re-revision for periprosthetic infections. Yet the current study is the first to report an increased risk of periprosthetic joint infection among the primary TKA population.

In addition, 25D-deficient patients have a significantly higher incidence of postoperative stiffness requiring manipulation under anesthesia (OR, 1.69) within 1 year. Several studies have correlated 25D deficiency with poor preoperative and postoperative functional and pain outcomes, which at an extreme may lead to stiffness and pain requiring manipulation in an operative setting.5,6,18–21,29 Maniar et al21 found that vitamin D–deficient patients had lower preoperative Western Ontario and McMaster Universities Osteoarthritis Index scores at baseline. After treatment with postoperative oral vitamin D supplementation, these patients were able to achieve functional outcome scores at 3 months comparable to those of vitamin D–sufficient patients. Conversely, Unnanuntana et al5,29 reported no difference in attainment of in-hospital functional milestones or short-term functional outcomes in 25D-deficient vs 25D-sufficient patients. Although they concluded that 25D deficiency should not delay arthroplasty, perioperative correction should be performed because of the known effects on bone quality.

The statistically higher incidences of deep venous thrombosis, myocardial infarction, and cerebrovascular accident noted in this study have not been previously reported specifically in the arthroplasty literature. Deficiency of 25D was independently correlated with coronary artery disease in data from the Framingham Heart Study.34 The posited mechanism involves decreased ligand activation of vitamin D receptor–directed anti-inflammatory myocardium and vascular pericytes.33 There is also limited literature correlating vitamin D status with venous thromboembolism rates, which may potentially be related to levels of plasma inflammatory mediators (P-selectin and high-sensitivity C-reactive protein).35

To the authors' knowledge, the current study is the first evaluating the prevalence of 25D deficiency among arthroplasty patients and the associated perioperative complication rates in a large cohort of patients across multiple institutions. However, such a study design has several limitations. First, the PearlDiver Humana database has limited granularity and, because of privacy concerns, provides aggregate rather than individual patient data. Because the database is searched by Current Procedural Terminology, International Classification of Diseases, Ninth Revision, and Logical Observation Identifiers Names and Codes codes, the available data on baseline health characteristics and complications are less comprehensive than those available through conventional chart review. Although this is partially mitigated by multivariate logistic regression controlling for CCI, this database design remains susceptible to source data biases and errors from miscoding. Second, the study design defined 25D deficiency using a serum 25D level of less than 20 ng/mL, which includes vitamin D deficiency (25D <12 ng/mL) and insufficiency (25D <20 ng/mL) as defined by the Institute of Medicine.25 Although this establishes the relationship between low serum 25D and complications in TKA, it does not establish a stepwise relationship or cut-off for which vitamin D becomes critically important. A 3-tiered study design was attempted but provided insufficient sample sizes for multivariate logistic regression because of the limitations of the PearlDiver Humana database. Furthermore, although this was beyond the scope and intent of the study, the database provides no information on functional or patient-reported outcomes. Finally, the authors note that only 4.2% of the entire Humana TKA population had preoperative 25D recorded. Indeed, it is unlikely that this was a random sampling of patients undergoing TKA, but rather a selected group of patients who were screened because of a higher pretest probability of 25D deficiency and who may already be receiving oral supplementation. Although a sampling bias, this provides important insight into the role of preoperative vitamin D repletion; those patients who were preoperatively repleted to greater than 20 ng/mL would have been included in the 25D-sufficient group. Yet there was still a significant difference between the 25D-deficient and 25D-sufficient groups, indicating that unsuccessful supplementation resulting in 25D levels remaining less than 20 ng/mL may still predispose patients to a worse complication profile. The authors believe that this strengthens the potential argument for preoperative 25D repletion.

Conclusion

Among patients undergoing TKA in the United States with 25D serum sampling in the preoperative period, 13.2% are 25D deficient (25D <20 ng/mL). In addition, 25D deficiency is associated with a higher risk of postoperative complications, including surgical site infection requiring irrigation and debridement and explantation of prosthesis, stiffness requiring manipulation under anesthesia, deep venous thrombosis, and cardiocerebrovascular events. These findings support the role of serum 25D as an independent and modifiable perioperative risk factor in arthroplasty. However, although oral supplementation with 25D3 is theoretically simple, quick, and inexpensive, its efficacy in arthroplasty risk reduction has not yet been reported. Further prospective studies investigating whether a clinically significant risk reduction of these aforementioned complications can be achieved with 25D repletion are warranted.

References

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Queried Surgical Complications Following Total Knee Arthroplasty

Complication CategoryCurrent Procedural Terminology CodeDescription
Tibial/femoral revisiona27486Revision of total knee arthroplasty, with or without allograft; 1 component
27487Revision of total knee arthroplasty, with or without allograft; femoral and entire tibial component
Explantation of prosthesis27488Removal of prosthesis, including total knee prosthesis, methylmethacrylate with or without insertion of spacer, knee
Irrigation and debridement27301Incision and drainage, deep abscess, bursa, or hematoma, thigh or knee region
27303Incision, deep, with opening of bone cortex, femur or knee (eg, osteomyelitis or bone abscess)
27310Arthrotomy, knee, with exploration, drainage, or removal of foreign body (eg, infection)
29871Arthroscopy, knee, surgical; for infection, lavage, and drainage
Stiffness requiring manipulation under anesthesia27550Manipulation of knee joint under general anesthesia (includes application of traction or other fixation devices)
27552Arthroscopy, knee, surgical; with lysis of adhesions, with or without manipulation (separate procedure)

Age, Sex, Regional, and Charlson Comorbidity Index Distribution of Vitamin D–Deficient and Vitamin D–Sufficient Patients

ParameterVitamin D Deficient (<20 ng/mL) (N=868)Vitamin D Sufficient (≥20 ng/mL) (N=5725)
Age, No.
  <40 y35
  40–44 y411
  45–49 y1762
  50–54 y47144
  55–59 y87348
  60–64 y126574
  65–69 y2021371
  70–74 y1981473
  75–79 y1111035
  80–84 y57520
  85–89 y14128
  90+254
Sex, No.
  Male1971402
  Female6714323
Geographic region, No.
  Midwest115823
  Northeast538
  South6864446
  West62418
Charlson Comorbidity Index, mean±SD4.13±3.293.22±3.14

Baseline Medical Comorbidity Distribution of Vitamin D–Deficient and Vitamin D–Sufficient Patients

ComorbidityVitamin D Deficient (<20 ng/mL) (n=868)Vitamin D Sufficient (≥20 ng/mL) (n=5725)P


No.FrequencyNo.Frequency
Diabetes mellitus41647.93%253044.19%.039
Hypertension74285.48%487385.12%.777
Coronary artery disease26630.65%178731.21%.736
Non-ischemic heart disease13715.78%83314.55%.339
Cerebrovascular disease778.87%4297.49%.156
Peripheral vascular disease18421.20%153026.72%<.001
Obesity35240.55%206236.02%.010
Body mass index >30 kg/m220523.62%120221.00%.492
Body mass index >40 kg/m2768.76%4347.58%.228
Chronic obstructive pulmonary disorder13615.67%96016.77%.417
Chronic kidney disease19422.35%151026.38%.012
Chronic liver disease566.45%3496.10%.684
Connective tissue disorder12614.52%83914.66%.914

Incidence and Odds Ratio of Surgical and Medical Complications After Total Knee Arthroplasty in Vitamin D–Deficient and Vitamin D–Sufficient Patients

ComplicationVitamin D Deficient (<20 ng/mL) (n=868)Vitamin D Sufficient (≥20 ng/mL) (n=5725)Adjusted Odds Ratioa (95% Confidence Interval) for Vitamin D–Deficient PatientsP


No.FrequencyNo.Frequency
Surgical
  Tibial/femoral revision (at 3 months)40.46%170.30%1.47 (0.79–2.75).226
  Tibial/femoral revision (at 1 year)121.38%571.00%1.26 (0.83–1.90).276
  Explantation of prosthesis (at 1 year)131.50%260.45%2.97 (2.04–4.31)<.001
  Surgical site infection with irrigation and debridement (at 3 months)171.96%420.73%2.11 (1.48–3.00)<.001
  Surgical site infection with irrigation and debridement (at 1 year)212.42%651.14%1.76 (1.25–2.48).001
  Stiffness requiring manipulation under anesthesia (at 3 months)171.96%520.91%1.66 (1.34–2.07)<.001
  Stiffness requiring manipulation under anesthesia (at 1 year)465.30%1923.35%1.69 (1.39–2.04)<.001
Medical
  Deep venous thrombosis131.50%480.84%1.80 (1.36–2.38)<.001
  Pulmonary embolus60.69%450.79%0.87 (0.59–1.28).475
  Acute renal failure151.73%671.17%1.24 (0.99–1.55).061
  Myocardial infarction40.46%110.19%2.11 (1.41–3.15)<.001
  Cerebrovascular accident70.81%240.42%1.73 (1.17–2.57).006
Authors

The authors are from the Department of Orthopaedic Surgery (VH, AA, ARJ, JSA, ENZ, NMB), David Geffen School of Medicine, University of California, Los Angeles, and the Department of Orthopaedic Surgery (CW, ZB, JCW), Keck School of Medicine, University of Southern California, Los Angeles, California.

Drs Hegde and Arshi contributed equally to this work and should be considered as equal first authors.

Dr Hegde, Dr Arshi, Mr Wang, Dr Jensen, Dr Adams, and Dr Zeegen have no relevant financial relationships to disclose. Dr Buser is a paid consultant for Xenco Medical. Dr Wang receives royalties from Aesculap, Biomet, Amedica, Seaspine, and Synthes; holds stock in Fziomed; and has private investments in Promethean Spine, Paradugm Spine, Benevenue, NexGen, Vertiflex, Electrocore, Surgitech, Expanding Orthopaedics, Osprey, Bone Biologics, Curative Biosciences, and Pearl-Diver. Dr Bernthal is a paid consultant for Onkos, Daiichi-Sankyo, and Zimmer Biomet.

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (grant 5K08AR069112-01).

Correspondence should be addressed to: Nicholas M. Bernthal, MD, Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, 1250 16th St, Ste 2150, Santa Monica, CA 90404 ( NBernthal@mednet.ucla.edu).

Received: December 20, 2017
Accepted: February 05, 2018
Posted Online: April 30, 2018

10.3928/01477447-20180424-04

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