Increased Lumbar Lordosis and Smaller Vertebral Cross-Sectional Area Are Associated with Spondylolysis

DIAGNOSTICS

Increased Lumbar Lordosis and Smaller Vertebral Cross-Sectional Area Are Associated With Spondylolysis

Tishya A. L. Wren, PhD, Skorn Ponrartana, MD, MPH,y Patricia C. Aggabao, BA,y Ervin Poorghasamians, BS,y David L. Skaggs, MD, MMM, and Vicente Gilsanz, MD, PhD,y,z

versus 9.3 1.6 for girls and boys, respectively (both Study Design. A cross-sectional comparison of vertebral mor- P’s 0.039). Multiple linear and logistic regression analyses phology and lumbar lordosis (LL) in adolescents with and indicated that the CSA of the vertebral body was negatively without spondylolysis. associated with LL angle and an independent predictor of the Objective. To test the hypothesis that in addition to LL, presence of spondylolysis. This was true regardless of whether vertebral cross-sectional area (CSA) is also associated with girls and boys were analyzed together or independently, and spondylolysis. Summary of Background Data. Recent data indicate that the whether LL angle was measured from L1 to L5 or S1. Conclusion. We provide evidence that patients with spondylo- CSA of the vertebral body is a determinant of LL, which has lysis have increased LL and smaller vertebral CSA. been shown to be associated with spondylolysis. Key words: lumbar lordosis, spondylolysis, vertebral cross- Methods. Using magnetic resonance imaging, we compared sectional area. the degree of LL from L1 to L5 and the CSA of the lumbar Level of Evidence: 4 vertebrae in 35 adolescents (16 females and 19 males) with Spine 2018;43:833–838 spondylolysis and 86 healthy controls (36 females and 50 males) of similar sex, age, height, and weight. Results. There were no significant differences in age, height, weight, or vertebral height between subjects with and without pondylolysis is a fracture of the pars interarticularis spondylolysis, regardless of sex. In contrast, LL angle in of the neural arch, which occurs in 6% of children 1 spondylolysis patients was 57% and 51% greater in girls and S most commonly in the lower lumbar spine. Although boys with spondylolysis; 44.1 10.48 versus 28.1 9.88 and a disease of children, this condition usually becomes symp- 34.8 5.98 versus 23.0 6.08 for girls and boys, respectively tomatic in adulthood. It is thought to be the result of (both P’s < 0.0001). Additionally, values for vertebral CSA were mechanical stresses from truncal hyperextension and is 2,3 on average, 8% and 10% smaller in females and males with often described as a fatigue or stress fracture. There is spondylolysis; 7.6 0.8 cm2 versus 8.3 1.1 cm2 and 8.4 1.6 a higher incidence of these fractures in adolescents who participate in sports that require such movements, including gymnastics, football, dance, weightlifting, etc.3,4 Accumu- From the Department of Orthopaedic Surgery, Children’s Hospital Los lating evidence also indicates that greater lumbar lordosis Angeles, Keck School of Medicine, University of Southern California, Los 5–10 y (LL) angle is a risk factor for developing spondylolysis. Angeles, CA; Department of Radiology, Children’s Hospital Los Angeles, However, beyond knowledge that physical activity, exag- Keck School of Medicine, University of Southern California, Los Angeles, 11,12 CA; and zDepartment of Pediatrics, Children’s Hospital Los Angeles, Keck gerated LL, and a family history are major risk factors, School of Medicine, University of Southern California, Los Angeles, CA. our understanding of the specific genes and phenotypes that Acknowledgment date: June 1, 2017. First revision date: July 13, 2017. confer susceptibility or resistance to the development of Acceptance date: September 14, 2017. spondylolysis is very limited. The manuscript submitted does not contain information about medical device(s)/drug(s). The cross-sectional area (CSA) of the vertebral body is an important determinant of spinal mobility; a greater range of No funds were received in support of this work. 13 Relevant financial activities outside the submitted work: board membership, motion occurs when the vertebral CSA is small. We consultancy, stocks, grants, payment for lecture, royalties. recently found a strong negative correlation between mea- Address correspondence and reprint requests to Vicente Gilsanz, MD, PhD, sures of vertebral CSA and the degree of LL in healthy Children’s Hospital Los Angeles, 4650 Sunset Boulevard, MS# 81, Los adolescents, suggesting that small vertebral CSA not only Angeles, CA 90027; E-mail: [email protected] increases spinal flexibility but also facilitates LL.14 In the DOI: 10.1097/BRS.0000000000002480 current study, we compared spinal morphology between Spine www.spinejournal.com 833 Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. DIAGNOSTICS Increased LL and Smaller Vertebral CSA Associated With Spondylolysis Wren et al adolescents with and without spondylolysis using magnetic the anterior, posterior, and midportion heights in the sagit- resonance imaging (MRI). We hypothesized that girls and tal plane and right, left, and midportion heights in the boys with spondylolysis have greater LL angle and smaller coronal plane of the lumbar vertebrae. Since some authors vertebral CSA when compared with children of similar age, define LL as the angle between the superior endplate of L1 height, and weight. and the inferior endplate of L5 (Figure 1A),15 while others have measured the angle to the superior endplate of S1, for MATERIALS AND METHODS the purpose of this study, LL was assessed using both The Institutional Review Board for clinical investigations at methodologies. All measurements were analyzed offline Children’s Hospital Los Angeles (CHLA) approved this manually with an image processing software (Osirix; Pix- study, which was compliant with the Health Insurance meo, Bernex, Switzerland). The coefficients of variation for Portability and Accountability Act. repeated MRI measurements of LL angle, vertebral CSA, and vertebral and IVD height are between 0.8% and Study Subjects 3.0%.16 We conducted a retrospective study of all children who underwent MRI examinations of the lumbar spine for Data Analysis spondylolysis at the Department of Radiology of CHLA The data were analyzed with the t test for unpaired samples from January 2010 to June 2015. We selected 16 girls and and multiple linear and logistic regression analyses. All 19 boys between 9.2 and 14.5 years of age, who had a values are expressed as mean SD. Statistical significance normal physical examination and no history of neuromus- was considered a P < 0.05. Data analysis was performed cular disease, chronic disease, or vertebral or spinal cord with Statview software (version 5.0.1; SAS Institute, Cary, anomalies, including spondylolisthesis or scoliosis. Of the NC). 35 spondylolysis patients, 32 had the isthmic fracture at L5 and three at L4; 27 study subjects had bilateral pars frac- RESULTS tures. Since the study did not entail personal contact with the The characteristics of study subjects and controls are shown spondylolysis group, only involved secondary analyses on in Table 1. Correlations between age, height, and weight existing data, and collected information from standard of and measurements of spinal morphology for all subjects are care procedures, the CHLA Institutional Review Board provided in Table 2. approved a waiver of consent. As expected, there were no significant differences in age, height, and weight between patients and controls. There Control Subjects were also no differences in the heights of the vertebral bodies Thereafter, each patient with spondylolysis in this study was among groups. In contrast, values for LL and vertebral CSA matched with two healthy controls for sex, race, age, height, were significantly different in subjects with spondylolysis and weight. For this analysis, the ages of control subjects when compared with controls (Table 1). On average, sub- differed by less than 12 months, and neither height nor jects with spondylolysis had significantly greater degree of weight differed by more than 10%. Using this approach we LL (L1–L5) when compared with controls; 57% and 51% recruited 86 healthy controls (36 girls and 50 boys) from the greater in girls and boys with spondylolysis, respectively Division of General Pediatrics at CHLA with a normal (Figure 2A). When LL angle was measured from L1 to S1, physical examination and no history of back pain or any this difference was approximately 42% greater for both other chronic complaints or disease. Informed assent and sexes. By contrast, the CSA of the vertebral body was 8.0% permission were obtained from all participants and their and 10.4% smaller in females and males with spondylolysis, parents in the control group. respectively (Figure 2B). Multiple linear regression analysis indicated that LL MRI Determinations angle differed between sexes and was positively related All MRI examinations were performed without the use of to weight, but negatively related to vertebral CSA general anesthesia or contrast enhancement. Study subjects (Table 3). were examined using a 1.5- or 3.0-Tesla whole-body MRI Multiple logistic regression analysis indicated that the scanner (Achieva R3.2; Philips Healthcare, Cleveland, OH) presence of spondylolysis was negatively associated with with a standard 8-channel spine coil and control subjects vertebral CSA in both girls and boys (Table 4). The inclusion were assessed using a research-dedicated 3.0 Tesla whole- of LL angle as an independent variable increased the pre- body MRI scanner (Achieva R3.2, Philips Healthcare, dictive power of the model but eliminated the contribution Cleveland, Ohio) with a standard 15-channel spine coil. of vertebral CSA in both sexes (Tables 5 and 6). Axial and coronal reformations were created from the 3- dimensional isotropic sagittal T2 turbo spin echo acquisi- DISCUSSION tion for the control subjects. For the purpose of this study, Available data indicate that adolescents with prominent LL vertebral CSA was measured at the midportion of the are at higher risk for spondylolysis.5–10 We recently found vertebral body from L1 to L5 in a plane parallel to the that vertebral CSA is a structural determinant of LL, endplates (Figure 1B), and vertebral height as the average of and that a greater degree of LL in adolescent females and

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Figure 1. Comparison of MRI images of the lumbar spine of 12-year-old females with and without spondylolysis. Coned-down sagittal and axial T2 turbo spin echo images of the lumbar spine showing greater degree of LL, measured as the angle between the superior endplate of L1 and the inferior endplate of L5, and smaller vertebral CSA, measured at the level of L4, in the (A) spondylolysis patient as opposed to the (B) control. CSA indicates cross-sectional area; MRI, magnetic resonance imaging.

males was associated with smaller vertebral cross-sectional spondylolysis had 8% to 10% smaller vertebral cross-sec- dimensions.14 The current study shows that in addition to a tional dimensions when compared with controls. Logistic greater degree of LL, adolescents with spondylolysis have regression analyses indicated that the negative association significantly smaller vertebral CSA; this was true for both between vertebral CSA and spondylolysis persisted even sexes and whether LL angle was measured from L1 to L5 or after accounting for height and weight in both girls and S1 (Tables 5 and 6). On average, adolescents with boys. The addition of LL angle as an independent variable

TABLE 1. Age, Anthropometric Measurements, and MR Values of Spinal Morphology in 35 Adolescents With and 86 Without Spondylolysis Females Males Spondylolysis Control Spondylolysis Control (n ¼ 16) (n ¼ 36) P (n ¼ 19) (n ¼ 50) P Age, yr 12.6 1.6 11.9 1.4 0.080 12.6 1.6 12.1 1.8 0.386 Height, cm 154.4 11.3 152.9 9.1 0.609 157.2 15.5 152.6 13.4 0.235 Weight, kg 48.4 10.7 49.0 14.0 0.877 54.2 15.7 47.2 14.9 0.094 Vertebral height, 2.13 0.25 2.10 0.22 0.684 2.08 0.30 2.02 0.27 0.495 cm Vertebral CSA, 7.62 0.81 8.28 1.12 0.039 8.36 1.63 9.33 1.56 0.026 cm2 Lumbar lordosis 44.1 10.4 28.1 9.8 <0.0001 34.8 5.9 23.0 6.0 <0.0001 L1–L5, 8 Lumbar lordosis 52.7 9.4 37.0 12.3 <0.0001 43.5 8.3 30.6 7.6 <0.0001 L1–S1, 8 CSA indicates cross-sectional area.

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TABLE 2. Correlations Between Age, Anthropometric Measurements, and MR Values of Spinal Morphology in 121 Adolescents With and Without Spondylolysis LL L1–S1 (8) LL L1–L5 (8) CSA (cm2) Vertical Height (cm) Weight (kg) Height (cm) Age, yr 0.17 0.13 0.38 0.78 0.57 0.78 Height, cm 0.05 0.04 0.58 0.85 0.73 Weight, kg 0.11 0.12 0.50 0.65 Vertebral height, cm 0.16 0.14 0.43 Vertebral CSA, cm2 0.43 0.42 Lumbar lordosis L1–L5, 8 0.92 P 0.05 for jrj0.18. CSA indicates cross-sectional area; LL, lumbar lordosis. increased the predictive power of the model but eliminated directly proportional to the load applied, but inversely the contribution of vertebral CSA, raising the possibility that related to its CSA.18,19 In LL, compressive loading on the the association between LL and spondylolysis results from posterior side of the curve inhibits longitudinal growth deficient vertebral cross-sectional growth. while tensile loading on the anterior side accelerates it. This Lordosis and a wide range of mobility in the lumbar spine differential remodeling stimulus promotes discrepant are unique characteristics of human bipedalism.17 A greater growth leading to posteroanterior wedging of the vertebral range of motion occurs when the disc is tall and/or the body, most prominently at the fifth lumbar vertebra, which vertebral CSA is small. For comparable disc thickness and contributes to 40% of the total anterior lumbar curvature stiffness, a smaller vertebral CSA results in greater flexion/ and is the site of the vast majority of spondylolysis cases.1,20 extension and lateral flexion.13 The smaller vertebra also Whether the small vertebral body size found in spondy- imparts a mechanical disadvantage that increases stress lolysis patients also translates to small pars interarticularis is within the vertebrae for all physical activities.18 During unknown. Several morphological characteristics of the lum- axial compression, stress within the vertebral body is bar neural arches have been proposed as risk factors for spondylolysis.21–23 While facet height, width, and orientation and interfacet distance have all been the subject of considerable interest, no data are available regarding the potential influence of the thickness of the pars interarticularis on this condition. Studies are needed to investigate the possibility that besides exaggerated lordosis and increased spinal flexibility associated with small vertebrae,13 decreased strength associated with smaller/thinner pars interarticularis is a characteristic of spondylolysis.

TABLE 3. Multiple Linear Regression Model of Sex, Height, Weight, and Vertebral CSA on Measures of LL Angle b SE PR2 A. Lumbar lordosis L1–L5 0.353 Sex: F 0.108 1.723 0.188 Height, cm 0.189 0.101 0.112 Weight, kg 0.312 0.082 0.006 Vertebral CSA, cm2 0.652 0.717 <0.0001 B. Lumbar lordosis L1–S1 0.358 Figure 2. Comparisons of LL and vertebral CSA in females and males Sex: F 0.101 1.968 0.213 with and without spondylolysis. Box plots of adolescent females and Height, cm 0.235 0.115 0.049 males with (gray) and without (white) spondylolysis showing signifi- Weight, kg 0.274 0.093 0.014 cantly (A) greater LL angle (both P’s < 0.0001) and (B) smaller verte- Vertebral CSA, cm2 0.669 0.814 <0.0001 bral CSA (both P’s 0.039) in the spondylolysis groups. CSA CSA indicates cross-sectional area; LL, lumbar lordosis; SE, standard error. indicates cross-sectional area; LL, lumbar lordosis.

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TABLE 4. Multiple Logistic Regression for Height, Weight, and Vertebral CSA on the Incidence of Spondylolysis Females b SE PR2 Males b SE PR2 Spondylolysis 0.116 Spondylolysis 0.311 Height, cm 0.058 0.044 0.188 Height, cm 0.089 0.051 0.079 Weight, kg 0.001 0.033 0.985 Weight, kg 0.066 0.041 0.108 Vertebral CSA, cm2 0.996 0.435 0.022 Vertebral CSA, cm2 1.553 0.445 0.0005 CSA indicates cross-sectional area; LL, lumbar lordosis; SE, standard error.

TABLE 5. Multiple Logistic Regression for Height, Weight, Vertebral CSA, and LL (L1–L5) on the Incidence of Spondylolysis Females b SE PR2 Males b SE PR2 Spondylolysis 0.448 Spondylolysis 0.542 Height, cm 0.069 0.067 0.300 Height, cm 0.044 0.063 0.488 Weight, kg 0.102 0.080 0.200 Weight, kg 0.016 0.057 0.782 Vertebral CSA, cm2 0.644 0.550 0.242 Vertebral CSA, cm2 0.046 0.552 0.934 Lumbar lordosis L1–L5, 8 0.209 0.066 0.002 Lumbar lordosis L1–L5, 8 0.397 0.136 0.004 CSA indicates cross-sectional area; LL, lumbar lordosis; SE, standard error.

TABLE 6. Multiple Logistic Regression for Height, Weight, Vertebral CSA, and LL (L1–S1) on the Incidence of Spondylolysis Females b SE PR2 Males b SE PR2 Spondylolysis 0.355 Spondylolysis 0.426 Height, cm 0.042 0.061 0.489 Height, cm 0.046 0.057 0.416 Weight, kg 0.080 0.069 0.245 Weight, kg 0.051 0.046 0.270 Vertebral CSA, cm2 0.383 0.530 0.470 Vertebral CSA, cm2 0.597 0.477 0.211 Lumbar lordosis L1–S1, 8 0.144 0.048 0.003 Lumbar lordosis L1–S1, 8 0.159 0.059 0.007 CSA indicates cross-sectional area; LL, lumbar lordosis; SE, standard error.

This study has several notable limitations, including LL white adolescent girls and boys of either European or measurement method and the population examined. All Hispanic descent, and the degree to which our results are subjects had to be analyzed in the supine position using a translatable to other populations remains unknown. This is uniform method of evaluation for LL; however, prior data especially pertinent since heritable predisposition to this have shown that LL in the upright position can be repro- condition is known in certain ethnic groups.1 Finally, we duced by positioning the patient supine with straightened acknowledge that we did not control for other potential lower extremities.24 Differences between the upright and determinants of spondylolysis, such as apophyseal morphol- supine scanning technologies in LL assessment has been ogy, paraspinous musculature, and physical activity.28,29 estimated as just 2.98, which is significantly smaller than In conclusion, the current study corroborates previous the difference we found between spondylolysis patients and reports suggesting an association between exaggerated LL controls.25 Moreover, MRI is slightly less sensitive than and spondylolysis as well as provides new evidence that computed tomography (CT) in depicting spondylolysis; a smaller vertebral CSA is a structural parameter of this recent study using CT as the gold standard found that MRI condition. It also raises the possibility that the association was an effective method (92% sensitivity) for detecting pars between LL and spondylolysis could result from deficient injuries. However, MRI can detect stress reactions when a vertebral cross-sectional growth. Establishing a comprehen- fracture is not visible on CT scan, allowing early treatment sive characterization of the determinants of spondylolysis of prelysis lesions,26 and many orthopedic surgeons cur- will not only require the identification of the structural rently use MRI to avoid radiation.27 parameters that contribute to the greater mechanical weak- Study subjects were not randomly recruited but patients ness of the pars interarticularis and the genes that control thought to require MRI examinations to rule out secondary them, but also the external conditions driving the stress causes for low back pain. Also, our analysis was confined to fracture. Spine www.spinejournal.com 837 Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. DIAGNOSTICS Increased LL and Smaller Vertebral CSA Associated With Spondylolysis Wren et al

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