Eur Spine J DOI 10.1007/s00586-015-3937-7
ORIGINAL ARTICLE
Initial Cobb angle reduction velocity following bracing as a new predictor for curve progression in adolescent idiopathic scoliosis Saihu Mao1,3 • Benlong Shi1,3 • Leilei Xu1,3 • Zhiwei Wang2,3 • Alec Lik Hang Hung2 Tsz Ping Lam2,3 • Fiona Wai Ping Yu2,3 • Kwong Man Lee2 • Bobby Kin Wah Ng2 • Jack Chun Yiu Cheng2,3 • Zezhang Zhu1,3 • Yong Qiu1,3
•
Received: 23 January 2015 / Revised: 6 April 2015 / Accepted: 6 April 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose The initial correction rate (ICR) has been widely used as a predictor for curve progression in adolescent idiopathic scoliosis (AIS) undergoing bracing treatment. We proposed a new parameter, the initial Cobb angle reduction velocity (ARV), for prediction of curve progression. The purpose of this study was to identify whether the initial ARV was a more effective predictor than ICR for curve progression in AIS patients undergoing brace treatment, and to evaluate the ideal cut-off point of initial ARV for prediction of curve progression. Methods This was a retrospective cohort study on AIS girls receiving standardized bracing treatment regularly followed up every 3–6 months. Standardized SRS criteria for bracing study were utilized in the case selection. The demographic data, maturity status and Cobb angle of each visit were recorded. The initial ARV and ICR were identified. Patients were divided into progressive (C6°) and non-progressive (\6°) groups based on their final bracing outcome. Differences between two groups were identified and logistic regression analysis was applied to compare the predictive values of initial ARV and ICR for curve progression during bracing treatment. S. Mao, B. Shi and L. Xu contributed equally to this work. & Yong Qiu [email protected] 1
Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road No. 321, Nanjing 210008, China
2
Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong, China
3
Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing University, Nanjing, China
Results Seventy-six patients were included in the nonprogressive group and 19 in the progressive group. Significant differences between non-progressive and progressive groups were found in terms of initial ARV (12.8 ± 21.4°/year vs -5.4 ± 15.2°/year, P = 0.001) and ICR (12.1 ± 20.7 % vs -5.8 ± 18.0 %, P = 0.001). The logistic regression analysis revealed that age at initial visit (OR 1.742, P = 0.043) and initial ARV (OR 1.057, P = 0.002) had higher predictive values than ICR (P = 0.601) for curve progression in braced AIS girls. The ideal cut-off point of initial ARV was 10°/year (OR 8.959, P = 0.005) for the prediction of curve progression. Conclusions The initial Cobb angle reduction velocity serves as a better predictor for curve progression than initial correction rate in braced AIS patients with follow-up interval of 3–6 months. At the second visit following bracing prescription, those AIS patients with reduction velocity in Cobb angle lower than 10°/year have significantly higher risk of curve progression. Keywords Adolescent idiopathic scoliosis Initial Cobb angle reduction velocity Initial correction rate Curve progression Brace
Introduction Brace has been proven to be an effective conservative treatment for adolescent idiopathic scoliosis (AIS) [1, 2]. Weinstein et al. [3] proved that bracing treatment significantly decreased the progression risk in AIS patients and the benefit increased with longer hours of brace wear. Despite the overall satisfactory outcome, around 28 % of braced AIS patients still have significant curve progression despite good fitting and compliance [4]. Study also showed
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Eur Spine J
that approximately 19 % of AIS patients with progressive curve and poor response to bracing could result in surgical intervention [4]. Hence, it is of great clinical and prognostic importance to investigate in details the predictors for curve progression in braced AIS patients. Previous studies have proposed several maturity and bone indicators that are closely associated with curve progression in AIS patients including chronological age, Risser sign, age at menarche, height growth velocity, secondary sexual characteristics and bone mineral density [5– 9]. A multi-factorial model containing various indicators could provide more accurate assessment for curve progression. However, objective clinical and radiological parameters associated with curve progression are relatively lacking. One of the well-recognized predictive parameter is the initial correction rate (ICR) defined as the percentage of decrease in the Cobb angle at the second visit following brace prescription in comparison with the pre-brace Cobb angle [ICR = 100 % 9 (Angle1 - Angle2)/(Angle1)] [10]. Reports have shown that AIS patients with lower ICR have higher probability of curve progression [11–13]. To the best of our knowledge, the calculation of ICR is influenced by the pre-brace Cobb angle, initial correction magnitude and the time interval between two consecutive follow-up measurements, thus decreasing its reliability for predicting curve progression. The ideal cut-off point of ICR for predicting curve progression reported by different studies ranged from 30 to 60 % [12, 14, 15]. The wide range of cut-off threshold limited its clinical utilization. After a series of pilot investigations, we hypothesized that the initial Cobb angle reduction velocity (ARV) could have a better predictive value than the ICR in predicting curve progression of braced AIS patients due to its independence from maturity stage, initial Cobb angle and time interval between two consecutive follow-up. The aim of this study was: (1) to identify whether the initial ARV was a more effective predictor than ICR for curve progression in braced AIS patients; and (2) to propose a new reference of initial ARV for the prediction of curve progression in AIS.
Materials and methods
thoracolumbar or lumbar curves) or Milwaukee (for patients with major thoracic or double major curves) bracing treatment until brace weaning [4, 16]; and (6) compliance of bracing treatment [75 %. The exclusion criteria included: (1) patients with prior treatment or any previous history of spinal surgery; and (2) with any metabolic endocrine disorders affecting skeletal growth and height [17]. The first 4 items were selected according to the Scoliosis Research Society (SRS) inclusion criteria for bracing study, except for the initial major curve magnitude, which in this series was extended to 20°–40° due to ethical consideration [18]. The compliance of bracing treatment was calculated from the actual hours of wearing recorded on a standard form by each patient under the supervision of their respective parents. Anthropometric and radiographic measurements Patients were regularly followed up every 3–6 months to monitor the change in curve magnitude, the compliance and necessary brace adjustments until the completion of bracing treatment program for a minimum of 2 years or undergoing surgical intervention. At each visit, all patients had a full-length standard X-ray of the whole spine. Additional demographic data were also recorded: chronologic age, age at menarche and standing height. The magnitude of Cobb angle was measured on the standing antero-posterior (AP) coronal X-rays. The initial ARV was defined as the Cobb angle reduction velocity at the second visit following the prescription of brace: initial ARV = (Angle1 - Angle2)/(time interval2–1). Similarly, the ICR was defined as the correction rate of Cobb angle at the second visit following the initial bracing prescription: ICR = (Angle1 - Angle2)/(Angle1). Negative values of ARV and correction rate referred to increase in Cobb angle. The Risser sign was also recorded for each visit [19]. Finally, the AIS girls were divided into two groups according to the outcome of bracing treatment at the completion of brace weaning: the progressive group consisting of patients with curve progression C6° or surgical indication; the non-progressive group including patients with curve progression \6° or curve improvement as compared with the first visit.
Subjects Statistical methods This was a retrospective cohort study approved by the ethical committee of university hospital. From our AIS bracing database, new AIS girls seen in our special clinic between 2000 and 2008 consecutively with the following inclusion criteria were reviewed: (1) age 10–14 years; (2) Risser 0–2; (3) pre-menarche or less than 1 year post-menarche; (4) initial major Cobb angle between 20° and 40°; (5) undergoing standardized Boston (for patients with
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Data were statistically analyzed with the SPSS software 17.0 (SPSS, Inc, USA). Patients’ demographics were analyzed using the descriptive statistics. Data were presented with mean ± standard deviation (SD). Differences between the progressive group and non-progressive group were investigated with the independent-sample t test. The receiver operating characteristics (ROC) curve was used to
Eur Spine J Table 1 Comparison between non-progressive (n = 76) and progressive (n = 19) groups
Non-progressive groupa
Progressive groupa
P
Age at initial visit (year)
12.4 ± 1.0
12.0 ± 1.1
0.132
Age at menarche (year)
12.3 ± 1.0
12.3 ± 1.1
0.974
154.7 ± 7.2
152.4 ± 7.8
0.249
0.7 ± 0.8
0.5 ± 0.8
0.426
27.6 ± 5.5
26.1 ± 4.1
0.263 \0.001
Height at initial visit (cm) Risser sign at initial visit Cobb angle at initial visit (°) Cobb angle at last visit (°)
24.1 ± 7.3
37.8 ± 6.5
Initial ARV (°/year)
12.8 ± 21.4
-5.4 ± 15.2
0.001
ICR (%)
12.1 ± 20.7
-5.8 ± 18.0
0.001
ARV angle reduction velocity, ICR initial correction rate a
Data were shown as mean ± standard deviation
help define the optimal cut-off point for initial ARV and ICR. Logistic regression analysis (backward) was applied to identify the high-risk indicators for curve progression, in which the outcome of brace was coded as 0 for non-progression and 1 for progression. In the first logistic regression analysis, the consecutive variables including age, Cobb angle and standing height at initial visit and menarche age were included. In the second logistic regression analysis, initial ARV was coded as 0 for C10°/year and 1 for \10°/year; ICR was coded as 0 for C30 % and 1 for \30 %. Statistically significant difference was defined as P \ 0.05.
Results Ninety-five consecutive AIS girls fulfilling the aforementioned criteria were selected and retrospectively reviewed, of which 76 patients belonged to the non-progressive group and 19 to the progressive group, respectively. As for the curve pattern, there were 60 major thoracic curves and 35 single thoracolumbar or lumbar curves. There is no difference in curve pattern between 2 groups. The average time interval between initial to second visits was 3.7 ± 0.7 months and the average bracing period lasted 35.4 ± 11.7 months. The median follow-up periods were 33 months for progression group and 30 months for nonprogression group, respectively. Comparison between the non-progressive and progressive groups Differences between the non-progressive and progressive groups were summarized in Table 1. The chronologic age, standing height and Risser sign at the first visit as well as the age at menarche were not significantly different between two groups (P [ 0.05). The average Cobb angles at the initial visit were similar with 27.6 ± 5.5° and
26.1 ± 4.1° for non-progressive and progressive groups, respectively (P = 0.263). At the last visit, significant difference in the Cobb angles was found with averaged 24.1 ± 7.3° and 37.8 ± 6.5° for the non-progressive vs progressive groups, respectively (P \ 0.001). In addition, the results revealed significant difference between nonprogressive and progressive groups in terms of initial ARV (12.8 ± 21.4°/year vs -5.4 ± 15.2°/year, P = 0.001) and ICR (12.1 ± 20.7 % vs -5.8 ± 18.0 %, P = 0.001). Logistic regression analysis of indicators for curve progression Logistic regression analysis was performed to analyze the covariate effects of initial ARV and ICR on curve progression. The results demonstrated that age at initial visit (OR 1.742, P = 0.043) and initial ARV (OR 1.057, P = 0.002) had significant predictive values for curve progression in braced AIS girls (Table 2). In contrast, the ICR (P = 0.601) could not be retained in the model. According to the ROC curve, initial ARV was significantly associated with the outcome of brace treatment. Combining the results of our study and the convenience of clinical practice, the cut-off point for initial ARV was set at 10°/year, at which the diagnostic ability reached the ideal balance between sensitivity and specificity. According to the literature [14], the cut-off point for ICR was set as 30 % in the present study. To evaluate whether the cut-off point of initial ARV was ideal, we further performed another logistic regression analysis. The results revealed that initial ARV lower than 10°/year (OR 8.959, P = 0.005. Table 3) correlated significantly with higher risk of curve progression which was not observed for the ICR with P = 0.271. Even if the ideal cut-off points for ICR were set from 40 to 60 % as were reported by other studies [12, 14, 15], the P values of ICR were still not statistically significant.
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Eur Spine J Table 2 Logistic regression analysis of indicators for bracing outcome (n = 95) Coefficient
Odds ratio
P value
Constant
-1.193
3.300
\0.001
Age at initial visit
-0.555
1.742
0.043
Initial ARV
-0.050
1.057
0.002
ARV angle reduction velocity; outcome of brace was coded as 0 for non-progression and 1 for progression
Table 3 Logistic regression analysis for ideal cut-off point of initial ARV (n = 95)
Constant Initial ARV
Coefficient
Odds ratio
P value
-2.970
19.608
\0.001
2.193
8.959
0.005
ARV angle reduction velocity; outcome of brace was coded as 0 for non-progression and 1 for progression; initial ARV was coded as 0 for C10°/year and 1 for \10°/year; ICR was coded as 0 for C30 % and 1 for \30 %
Discussion It has been widely accepted that the initial curve response was significantly associated with the final bracing outcome in AIS patients [12, 13]. Upadhyay et al. [20] found that an increase of maximum 5° or more from the pre-brace measurements indicated failure bracing outcome in AIS patients. The conclusion of Upadhyay et al. [20] was further modified by several subsequent studies, which demonstrated that the lower ICR after bracing prescription was more predictive for the brace failure [12, 14]. Gepstein et al. [14] showed that the success rates of Charleston brace were 71 and 88 % for those AIS patients with ICRs \30 and[30 %, respectively. Landauer et al. [12] found ICR of \40 % correlated with worse final bracing outcome. A study performed by Olafsson et al. [15] demonstrated that, in patients with idiopathic scoliosis, the curve was permanently reduced with an average of 7.2° when the ICR was [50 %. Therefore, AIS patients with lower initial curve correction rate had higher probability of failed bracing treatment. However, the ICR has its own limitation for the prediction of curve progression in AIS. The rate would be influenced by the initial Cobb magnitude, which means same reduction of Cobb magnitude in different individuals indicates different ICR. It is also influenced by the time interval between two consecutive follow-ups which often vary considerably. To avoid these deviations, we believe that the initial ARV could serve as a better and more reliable predictor for bracing outcome than the ICR and initial correction magnitude, since it is independent from
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both the initial Cobb magnitude and time interval between two consecutive visits. Previous studies [17, 21] demonstrated that the curve progression in AIS patients was significantly associated with their growth potential. The AIS patients with younger chronologic age [22], Risser stage 0 [23], delayed onset of menarche [24] and larger curve magnitude [22] were proven to have higher risk of failed bracing outcome. In the present study, there was no significant difference between progressive and non-progressive groups in terms of chronologic age, age at menarche, Cobb angle of main curve, Risser sign and standing height at the initial visit. The comparison analysis also revealed that, compared with non-progressive AIS patients, progressive AIS patients had significantly lower initial ARV and lower ICR (P \ 0.05). Therefore, the results implied that the initial curve response, represented by initial ARV and ICR, was significantly associated with the risk of curve progression. The conclusion matched with many previous studies [12, 20]. Logistic regression analysis was performed to compare further the predictive values of both initial ARV and ICR for curve progression in AIS patients with follow-up period at 3- to 6-month interval. The result (Table 2) demonstrated that the initial ARV, together with the age at initial visit, showed a closer correlation with the occurrence of curve progression than ICR, which supported our hypothesis. Upadhyay et al. [20] summarized that the response to application of a brace in AIS patients was influenced by several factors including spinal flexibility, Cobb magnitude, curve structure, curve pattern and apex of major curve. Among of them, Upadhyay et al. [20] believed that correction of Cobb angles mainly yielded the information related to the flexibility of the curvature. Therefore, similar to the ICR, the initial ARV mainly represents the flexibility of spine [20]. Similar to ICR, the cut-off point for initial ARV should be determined for accurate stratification and prognostication of the bracing outcome. We proposed that the ideal cut-off point of initial ARV of 10°/year which was evaluated with another logistic regression analysis. This regression result (Table 3) showed that the initial ARV entered the model well but not for the ICR even with the cut-off point set from 30 to 60 %. Hence, a reduction velocity of Cobb angle lower than 10°/year at the second visit following the bracing treatment indicates a higher risk of curve progression. On the other hand, we had to admit that high initial ARV did not always coincide with a successful bracing outcome, which was analogous to the ICR demonstrated by Upadhyay et al. [20]. These results strongly implied that multiple-dimensional indicators should be applied for the prediction of curve progression in AIS patients to get a more satisfying predictive model. Nevertheless, based on the results of our study, AIS
Eur Spine J
patients with low ARV (\10°/year) under bracing treatment suffered from bad spine flexibilities and high risks of curve progression. These high-risk AIS patients should be strictly braced and carefully monitored to avoid the irreversible brace failure. The limitations of the current study lies in that the initial growth potential of the included AIS patients might not be totally unified, which was quite difficult though there was no significant difference between progressive and nonprogressive groups in the maturity status at initial visit. Besides, our study was also limited by its retrospective nature and the relatively small sample size. Notably, the current study mainly focused on the curve progression during bracing treatment; however, the curve progression post brace weaning was not included. In addition, scoliosis is actually a 3-D spinal deformity, while the Cobb angle is a 2-D measurement instead of 3-D character of scoliosis, and thus minor deformity aggravation as to vertebral translation, rotation or disc wedging may not be accurately and timely reflected if only the 2-D Cobb angle was monitored. The solution is to create a reliable 3-D parameter, which is not available currently, or use multi-dimensional 2-D measurements. Further studies were warranted. Nevertheless, we are likely to be the first group to propose and validate that the initial ARV in AIS patients could serve as a new predictor significantly better than the ICR for curve progression with the ideal cut-off point of 10°/year.
Conclusion In summary, the initial Cobb angle reduction velocity could serve as a good predictor for curve progression in braced AIS patients with the follow-up period ranging from 3 to 6 months. Bracing outcome is more correlated with the initial Cobb angle reduction velocity than initial correction rate. At the second visit following the prescription of bracing treatment, the reduction velocity of Cobb angle lower than 10°/year indicates higher risk of curve progression in AIS patients. Acknowledgments This work was financially supported by the National Natural Science Foundation of China (81301603). Conflict of interest
None.
References 1. Lonstein JE, Winter RB (1994) The Milwaukee brace for the treatment of adolescent idiopathic scoliosis. A review of one thousand and twenty patients. J Bone Joint Surg Am 76:1207–1221
2. Sanders JO, Newton PO, Browne RH, Katz DE, Birch JG, Herring JA (2014) Bracing for idiopathic scoliosis: how many patients require treatment to prevent one surgery? J Bone Joint Surg Am 96:649–653. doi:10.2106/jbjs.m.00290 3. Weinstein SL, Dolan LA, Wright JG, Dobbs MB (2013) Effects of bracing in adolescents with idiopathic scoliosis. New Engl J Med 369:1512–1521. doi:10.1056/NEJMoa1307337 4. Xu L, Qiu X, Sun X, Mao S, Liu Z, Qiao J, Qiu Y (2011) Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 20:1757–1764. doi:10.1007/s00586-011-1874-7 5. Dhar S, Dangerfield PH, Dorgan JC, Klenerman L (1993) Correlation between bone age and Risser’s sign in adolescent idiopathic scoliosis. Spine 18:14–19 6. Song KM, Little DG (2000) Peak height velocity as a maturity indicator for males with idiopathic scoliosis. J Pediatr Orthop 20:286–288 7. Wever DJ, Tonseth KA, Veldhuizen AG, Cool JC, van Horn JR (2000) Curve progression and spinal growth in brace treated idiopathic scoliosis. Clin Orthop Relat Res 377:169–179 8. Mao SH, Li HB, Jiang J, Sun X, Cheng JC, Qiu Y (2011) An updated analysis of pubertal linear growth characteristics and age at menarche in ethnic Chinese. Am J Hum Biol Off J Hum Biol Counc 23:132–137. doi:10.1002/ajhb.21116 9. Yu WS, Chan KY, Yu FW, Yeung HY, Ng BK, Lee KM, Lam TP, Cheng JC (2013) Abnormal bone quality versus low bone mineral density in adolescent idiopathic scoliosis: a case-control study with in vivo high-resolution peripheral quantitative computed tomography. Spine J Off J N Am Spine Soc 13:1493–1499. doi:10.1016/j.spinee.2013.05.018 10. Peltonen J, Poussa M, Ylikoski M (1988) Three-year results of bracing in scoliosis. Acta Orthop Scand 59:487–490 11. Carr WA, Moe JH, Winter RB, Lonstein JE (1980) Treatment of idiopathic scoliosis in the Milwaukee brace. J Bone Joint Surg Am 62:599–612 12. Landauer F, Wimmer C, Behensky H (2003) Estimating the final outcome of brace treatment for idiopathic thoracic scoliosis at 6-month follow-up. Pediatr Rehabil 6:201–207. doi:10.1080/ 13638490310001636817 13. Vijvermans V, Fabry G, Nijs J (2004) Factors determining the final outcome of treatment of idiopathic scoliosis with the Boston brace: a longitudinal study. J Pediatr Orthop B 13:143–149 14. Gepstein R, Leitner Y, Zohar E, Angel I, Shabat S, Pekarsky I, Friesem T, Folman Y, Katz A, Fredman B (2002) Effectiveness of the Charleston bending brace in the treatment of single-curve idiopathic scoliosis. J Pediatr Orthop 22:84–87 15. Olafsson Y, Saraste H, Soderlund V, Hoffsten M (1995) Boston brace in the treatment of idiopathic scoliosis. J Pediatr Orthop 15:524–527 16. Nachemson AL, Peterson LE (1995) Effectiveness of treatment with a brace in girls who have adolescent idiopathic scoliosis. A prospective, controlled study based on data from the Brace Study of the Scoliosis Research Society. J Bone Joint Surg Am 77:815–822 17. Sanders JO, Browne RH, McConnell SJ, Margraf SA, Cooney TE, Finegold DN (2007) Maturity assessment and curve progression in girls with idiopathic scoliosis. J Bone Joint Surg Am 89:64–73. doi:10.2106/jbjs.f.00067 18. Richards BS, Bernstein RM, D’Amato CR, Thompson GH (2005) Standardization of criteria for adolescent idiopathic scoliosis brace studies: SRS Committee on Bracing and Nonoperative Management. Spine 30:2068–2075 (discussion 2076–2067) 19. Risser JC (1958) The Iliac apophysis; an invaluable sign in the management of scoliosis. Clin Orthop 11:111–119
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Eur Spine J 20. Upadhyay SS, Nelson IW, Ho EK, Hsu LC, Leong JC (1995) New prognostic factors to predict the final outcome of brace treatment in adolescent idiopathic scoliosis. Spine 20:537–545 21. Sanders JO (2007) Maturity indicators in spinal deformity. J Bone Joint Surg Am 89(Suppl 1):14–20. doi:10.2106/jbjs.f.00318 22. Emans JB, Kaelin A, Bancel P, Hall JE, Miller ME (1986) The Boston bracing system for idiopathic scoliosis. Follow-up results in 295 patients. Spine 11:792–801 23. Nault ML, Parent S, Phan P, Roy-Beaudry M, Labelle H, Rivard M (2010) A modified Risser grading system predicts the curve
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acceleration phase of female adolescent idiopathic scoliosis. J Bone Joint Surg Am 92:1073–1081. doi:10.2106/jbjs.h.01759 24. Mao SH, Jiang J, Sun X, Zhao Q, Qian BP, Liu Z, Shu H, Qiu Y (2011) Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 20:260–265. doi:10.1007/ s00586-010-1649-6
ORIGINAL ARTICLE
Initial Cobb angle reduction velocity following bracing as a new predictor for curve progression in adolescent idiopathic scoliosis Saihu Mao1,3 • Benlong Shi1,3 • Leilei Xu1,3 • Zhiwei Wang2,3 • Alec Lik Hang Hung2 Tsz Ping Lam2,3 • Fiona Wai Ping Yu2,3 • Kwong Man Lee2 • Bobby Kin Wah Ng2 • Jack Chun Yiu Cheng2,3 • Zezhang Zhu1,3 • Yong Qiu1,3
•
Received: 23 January 2015 / Revised: 6 April 2015 / Accepted: 6 April 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose The initial correction rate (ICR) has been widely used as a predictor for curve progression in adolescent idiopathic scoliosis (AIS) undergoing bracing treatment. We proposed a new parameter, the initial Cobb angle reduction velocity (ARV), for prediction of curve progression. The purpose of this study was to identify whether the initial ARV was a more effective predictor than ICR for curve progression in AIS patients undergoing brace treatment, and to evaluate the ideal cut-off point of initial ARV for prediction of curve progression. Methods This was a retrospective cohort study on AIS girls receiving standardized bracing treatment regularly followed up every 3–6 months. Standardized SRS criteria for bracing study were utilized in the case selection. The demographic data, maturity status and Cobb angle of each visit were recorded. The initial ARV and ICR were identified. Patients were divided into progressive (C6°) and non-progressive (\6°) groups based on their final bracing outcome. Differences between two groups were identified and logistic regression analysis was applied to compare the predictive values of initial ARV and ICR for curve progression during bracing treatment. S. Mao, B. Shi and L. Xu contributed equally to this work. & Yong Qiu [email protected] 1
Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road No. 321, Nanjing 210008, China
2
Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong, China
3
Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing University, Nanjing, China
Results Seventy-six patients were included in the nonprogressive group and 19 in the progressive group. Significant differences between non-progressive and progressive groups were found in terms of initial ARV (12.8 ± 21.4°/year vs -5.4 ± 15.2°/year, P = 0.001) and ICR (12.1 ± 20.7 % vs -5.8 ± 18.0 %, P = 0.001). The logistic regression analysis revealed that age at initial visit (OR 1.742, P = 0.043) and initial ARV (OR 1.057, P = 0.002) had higher predictive values than ICR (P = 0.601) for curve progression in braced AIS girls. The ideal cut-off point of initial ARV was 10°/year (OR 8.959, P = 0.005) for the prediction of curve progression. Conclusions The initial Cobb angle reduction velocity serves as a better predictor for curve progression than initial correction rate in braced AIS patients with follow-up interval of 3–6 months. At the second visit following bracing prescription, those AIS patients with reduction velocity in Cobb angle lower than 10°/year have significantly higher risk of curve progression. Keywords Adolescent idiopathic scoliosis Initial Cobb angle reduction velocity Initial correction rate Curve progression Brace
Introduction Brace has been proven to be an effective conservative treatment for adolescent idiopathic scoliosis (AIS) [1, 2]. Weinstein et al. [3] proved that bracing treatment significantly decreased the progression risk in AIS patients and the benefit increased with longer hours of brace wear. Despite the overall satisfactory outcome, around 28 % of braced AIS patients still have significant curve progression despite good fitting and compliance [4]. Study also showed
123
Eur Spine J
that approximately 19 % of AIS patients with progressive curve and poor response to bracing could result in surgical intervention [4]. Hence, it is of great clinical and prognostic importance to investigate in details the predictors for curve progression in braced AIS patients. Previous studies have proposed several maturity and bone indicators that are closely associated with curve progression in AIS patients including chronological age, Risser sign, age at menarche, height growth velocity, secondary sexual characteristics and bone mineral density [5– 9]. A multi-factorial model containing various indicators could provide more accurate assessment for curve progression. However, objective clinical and radiological parameters associated with curve progression are relatively lacking. One of the well-recognized predictive parameter is the initial correction rate (ICR) defined as the percentage of decrease in the Cobb angle at the second visit following brace prescription in comparison with the pre-brace Cobb angle [ICR = 100 % 9 (Angle1 - Angle2)/(Angle1)] [10]. Reports have shown that AIS patients with lower ICR have higher probability of curve progression [11–13]. To the best of our knowledge, the calculation of ICR is influenced by the pre-brace Cobb angle, initial correction magnitude and the time interval between two consecutive follow-up measurements, thus decreasing its reliability for predicting curve progression. The ideal cut-off point of ICR for predicting curve progression reported by different studies ranged from 30 to 60 % [12, 14, 15]. The wide range of cut-off threshold limited its clinical utilization. After a series of pilot investigations, we hypothesized that the initial Cobb angle reduction velocity (ARV) could have a better predictive value than the ICR in predicting curve progression of braced AIS patients due to its independence from maturity stage, initial Cobb angle and time interval between two consecutive follow-up. The aim of this study was: (1) to identify whether the initial ARV was a more effective predictor than ICR for curve progression in braced AIS patients; and (2) to propose a new reference of initial ARV for the prediction of curve progression in AIS.
Materials and methods
thoracolumbar or lumbar curves) or Milwaukee (for patients with major thoracic or double major curves) bracing treatment until brace weaning [4, 16]; and (6) compliance of bracing treatment [75 %. The exclusion criteria included: (1) patients with prior treatment or any previous history of spinal surgery; and (2) with any metabolic endocrine disorders affecting skeletal growth and height [17]. The first 4 items were selected according to the Scoliosis Research Society (SRS) inclusion criteria for bracing study, except for the initial major curve magnitude, which in this series was extended to 20°–40° due to ethical consideration [18]. The compliance of bracing treatment was calculated from the actual hours of wearing recorded on a standard form by each patient under the supervision of their respective parents. Anthropometric and radiographic measurements Patients were regularly followed up every 3–6 months to monitor the change in curve magnitude, the compliance and necessary brace adjustments until the completion of bracing treatment program for a minimum of 2 years or undergoing surgical intervention. At each visit, all patients had a full-length standard X-ray of the whole spine. Additional demographic data were also recorded: chronologic age, age at menarche and standing height. The magnitude of Cobb angle was measured on the standing antero-posterior (AP) coronal X-rays. The initial ARV was defined as the Cobb angle reduction velocity at the second visit following the prescription of brace: initial ARV = (Angle1 - Angle2)/(time interval2–1). Similarly, the ICR was defined as the correction rate of Cobb angle at the second visit following the initial bracing prescription: ICR = (Angle1 - Angle2)/(Angle1). Negative values of ARV and correction rate referred to increase in Cobb angle. The Risser sign was also recorded for each visit [19]. Finally, the AIS girls were divided into two groups according to the outcome of bracing treatment at the completion of brace weaning: the progressive group consisting of patients with curve progression C6° or surgical indication; the non-progressive group including patients with curve progression \6° or curve improvement as compared with the first visit.
Subjects Statistical methods This was a retrospective cohort study approved by the ethical committee of university hospital. From our AIS bracing database, new AIS girls seen in our special clinic between 2000 and 2008 consecutively with the following inclusion criteria were reviewed: (1) age 10–14 years; (2) Risser 0–2; (3) pre-menarche or less than 1 year post-menarche; (4) initial major Cobb angle between 20° and 40°; (5) undergoing standardized Boston (for patients with
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Data were statistically analyzed with the SPSS software 17.0 (SPSS, Inc, USA). Patients’ demographics were analyzed using the descriptive statistics. Data were presented with mean ± standard deviation (SD). Differences between the progressive group and non-progressive group were investigated with the independent-sample t test. The receiver operating characteristics (ROC) curve was used to
Eur Spine J Table 1 Comparison between non-progressive (n = 76) and progressive (n = 19) groups
Non-progressive groupa
Progressive groupa
P
Age at initial visit (year)
12.4 ± 1.0
12.0 ± 1.1
0.132
Age at menarche (year)
12.3 ± 1.0
12.3 ± 1.1
0.974
154.7 ± 7.2
152.4 ± 7.8
0.249
0.7 ± 0.8
0.5 ± 0.8
0.426
27.6 ± 5.5
26.1 ± 4.1
0.263 \0.001
Height at initial visit (cm) Risser sign at initial visit Cobb angle at initial visit (°) Cobb angle at last visit (°)
24.1 ± 7.3
37.8 ± 6.5
Initial ARV (°/year)
12.8 ± 21.4
-5.4 ± 15.2
0.001
ICR (%)
12.1 ± 20.7
-5.8 ± 18.0
0.001
ARV angle reduction velocity, ICR initial correction rate a
Data were shown as mean ± standard deviation
help define the optimal cut-off point for initial ARV and ICR. Logistic regression analysis (backward) was applied to identify the high-risk indicators for curve progression, in which the outcome of brace was coded as 0 for non-progression and 1 for progression. In the first logistic regression analysis, the consecutive variables including age, Cobb angle and standing height at initial visit and menarche age were included. In the second logistic regression analysis, initial ARV was coded as 0 for C10°/year and 1 for \10°/year; ICR was coded as 0 for C30 % and 1 for \30 %. Statistically significant difference was defined as P \ 0.05.
Results Ninety-five consecutive AIS girls fulfilling the aforementioned criteria were selected and retrospectively reviewed, of which 76 patients belonged to the non-progressive group and 19 to the progressive group, respectively. As for the curve pattern, there were 60 major thoracic curves and 35 single thoracolumbar or lumbar curves. There is no difference in curve pattern between 2 groups. The average time interval between initial to second visits was 3.7 ± 0.7 months and the average bracing period lasted 35.4 ± 11.7 months. The median follow-up periods were 33 months for progression group and 30 months for nonprogression group, respectively. Comparison between the non-progressive and progressive groups Differences between the non-progressive and progressive groups were summarized in Table 1. The chronologic age, standing height and Risser sign at the first visit as well as the age at menarche were not significantly different between two groups (P [ 0.05). The average Cobb angles at the initial visit were similar with 27.6 ± 5.5° and
26.1 ± 4.1° for non-progressive and progressive groups, respectively (P = 0.263). At the last visit, significant difference in the Cobb angles was found with averaged 24.1 ± 7.3° and 37.8 ± 6.5° for the non-progressive vs progressive groups, respectively (P \ 0.001). In addition, the results revealed significant difference between nonprogressive and progressive groups in terms of initial ARV (12.8 ± 21.4°/year vs -5.4 ± 15.2°/year, P = 0.001) and ICR (12.1 ± 20.7 % vs -5.8 ± 18.0 %, P = 0.001). Logistic regression analysis of indicators for curve progression Logistic regression analysis was performed to analyze the covariate effects of initial ARV and ICR on curve progression. The results demonstrated that age at initial visit (OR 1.742, P = 0.043) and initial ARV (OR 1.057, P = 0.002) had significant predictive values for curve progression in braced AIS girls (Table 2). In contrast, the ICR (P = 0.601) could not be retained in the model. According to the ROC curve, initial ARV was significantly associated with the outcome of brace treatment. Combining the results of our study and the convenience of clinical practice, the cut-off point for initial ARV was set at 10°/year, at which the diagnostic ability reached the ideal balance between sensitivity and specificity. According to the literature [14], the cut-off point for ICR was set as 30 % in the present study. To evaluate whether the cut-off point of initial ARV was ideal, we further performed another logistic regression analysis. The results revealed that initial ARV lower than 10°/year (OR 8.959, P = 0.005. Table 3) correlated significantly with higher risk of curve progression which was not observed for the ICR with P = 0.271. Even if the ideal cut-off points for ICR were set from 40 to 60 % as were reported by other studies [12, 14, 15], the P values of ICR were still not statistically significant.
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Eur Spine J Table 2 Logistic regression analysis of indicators for bracing outcome (n = 95) Coefficient
Odds ratio
P value
Constant
-1.193
3.300
\0.001
Age at initial visit
-0.555
1.742
0.043
Initial ARV
-0.050
1.057
0.002
ARV angle reduction velocity; outcome of brace was coded as 0 for non-progression and 1 for progression
Table 3 Logistic regression analysis for ideal cut-off point of initial ARV (n = 95)
Constant Initial ARV
Coefficient
Odds ratio
P value
-2.970
19.608
\0.001
2.193
8.959
0.005
ARV angle reduction velocity; outcome of brace was coded as 0 for non-progression and 1 for progression; initial ARV was coded as 0 for C10°/year and 1 for \10°/year; ICR was coded as 0 for C30 % and 1 for \30 %
Discussion It has been widely accepted that the initial curve response was significantly associated with the final bracing outcome in AIS patients [12, 13]. Upadhyay et al. [20] found that an increase of maximum 5° or more from the pre-brace measurements indicated failure bracing outcome in AIS patients. The conclusion of Upadhyay et al. [20] was further modified by several subsequent studies, which demonstrated that the lower ICR after bracing prescription was more predictive for the brace failure [12, 14]. Gepstein et al. [14] showed that the success rates of Charleston brace were 71 and 88 % for those AIS patients with ICRs \30 and[30 %, respectively. Landauer et al. [12] found ICR of \40 % correlated with worse final bracing outcome. A study performed by Olafsson et al. [15] demonstrated that, in patients with idiopathic scoliosis, the curve was permanently reduced with an average of 7.2° when the ICR was [50 %. Therefore, AIS patients with lower initial curve correction rate had higher probability of failed bracing treatment. However, the ICR has its own limitation for the prediction of curve progression in AIS. The rate would be influenced by the initial Cobb magnitude, which means same reduction of Cobb magnitude in different individuals indicates different ICR. It is also influenced by the time interval between two consecutive follow-ups which often vary considerably. To avoid these deviations, we believe that the initial ARV could serve as a better and more reliable predictor for bracing outcome than the ICR and initial correction magnitude, since it is independent from
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both the initial Cobb magnitude and time interval between two consecutive visits. Previous studies [17, 21] demonstrated that the curve progression in AIS patients was significantly associated with their growth potential. The AIS patients with younger chronologic age [22], Risser stage 0 [23], delayed onset of menarche [24] and larger curve magnitude [22] were proven to have higher risk of failed bracing outcome. In the present study, there was no significant difference between progressive and non-progressive groups in terms of chronologic age, age at menarche, Cobb angle of main curve, Risser sign and standing height at the initial visit. The comparison analysis also revealed that, compared with non-progressive AIS patients, progressive AIS patients had significantly lower initial ARV and lower ICR (P \ 0.05). Therefore, the results implied that the initial curve response, represented by initial ARV and ICR, was significantly associated with the risk of curve progression. The conclusion matched with many previous studies [12, 20]. Logistic regression analysis was performed to compare further the predictive values of both initial ARV and ICR for curve progression in AIS patients with follow-up period at 3- to 6-month interval. The result (Table 2) demonstrated that the initial ARV, together with the age at initial visit, showed a closer correlation with the occurrence of curve progression than ICR, which supported our hypothesis. Upadhyay et al. [20] summarized that the response to application of a brace in AIS patients was influenced by several factors including spinal flexibility, Cobb magnitude, curve structure, curve pattern and apex of major curve. Among of them, Upadhyay et al. [20] believed that correction of Cobb angles mainly yielded the information related to the flexibility of the curvature. Therefore, similar to the ICR, the initial ARV mainly represents the flexibility of spine [20]. Similar to ICR, the cut-off point for initial ARV should be determined for accurate stratification and prognostication of the bracing outcome. We proposed that the ideal cut-off point of initial ARV of 10°/year which was evaluated with another logistic regression analysis. This regression result (Table 3) showed that the initial ARV entered the model well but not for the ICR even with the cut-off point set from 30 to 60 %. Hence, a reduction velocity of Cobb angle lower than 10°/year at the second visit following the bracing treatment indicates a higher risk of curve progression. On the other hand, we had to admit that high initial ARV did not always coincide with a successful bracing outcome, which was analogous to the ICR demonstrated by Upadhyay et al. [20]. These results strongly implied that multiple-dimensional indicators should be applied for the prediction of curve progression in AIS patients to get a more satisfying predictive model. Nevertheless, based on the results of our study, AIS
Eur Spine J
patients with low ARV (\10°/year) under bracing treatment suffered from bad spine flexibilities and high risks of curve progression. These high-risk AIS patients should be strictly braced and carefully monitored to avoid the irreversible brace failure. The limitations of the current study lies in that the initial growth potential of the included AIS patients might not be totally unified, which was quite difficult though there was no significant difference between progressive and nonprogressive groups in the maturity status at initial visit. Besides, our study was also limited by its retrospective nature and the relatively small sample size. Notably, the current study mainly focused on the curve progression during bracing treatment; however, the curve progression post brace weaning was not included. In addition, scoliosis is actually a 3-D spinal deformity, while the Cobb angle is a 2-D measurement instead of 3-D character of scoliosis, and thus minor deformity aggravation as to vertebral translation, rotation or disc wedging may not be accurately and timely reflected if only the 2-D Cobb angle was monitored. The solution is to create a reliable 3-D parameter, which is not available currently, or use multi-dimensional 2-D measurements. Further studies were warranted. Nevertheless, we are likely to be the first group to propose and validate that the initial ARV in AIS patients could serve as a new predictor significantly better than the ICR for curve progression with the ideal cut-off point of 10°/year.
Conclusion In summary, the initial Cobb angle reduction velocity could serve as a good predictor for curve progression in braced AIS patients with the follow-up period ranging from 3 to 6 months. Bracing outcome is more correlated with the initial Cobb angle reduction velocity than initial correction rate. At the second visit following the prescription of bracing treatment, the reduction velocity of Cobb angle lower than 10°/year indicates higher risk of curve progression in AIS patients. Acknowledgments This work was financially supported by the National Natural Science Foundation of China (81301603). Conflict of interest
None.
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