Over the observation period, 767 young patients were seen for a first visit in scoliosis clinic for IS suspicion. Of this number, 204 were discharged or received no follow-up. Five hundred and sixty-three patients completed their follow-up to maturity in our clinic over the observation period. The clinical and demographic characteristics of the IS patients are described in Table 1. Respectively, 121, 182, and 260 patients were classified as FG1, FG2, and FG3 endophenotype. As expected, the study sample was composed of a higher percentage of females (83.8%, n = 472) when compared to males (16.2%, n = 91). The average age of the patients at first visit was 13.3-year old, and the average initial Cobb angle of the main curve was 21.2°.
Bivariate analysis on data at first visit
For each variable on initial appointment, the biological endophenotypes were compared to insure uniformity within the variable (Table 1). No differences were found between the biological endophenotypes within the clinical variables of initial Cobb angle of main curve (p = 0.179), Risser score (p = 0.085), curve type (p = 0.933), and brace treatment prescribed (p = 0.131). They were found to be initially uniformly distributed among endophenotypes, just like age, sex, and BMI (Table 1). Furthermore, the length of the follow-up, as defined as the time elapsed between the initial visit and the last visit, was the same for all patients independently of their endophenotype.
Bivariate analysis provided evidence of more severe health outcomes at maturity in IS patients classified in FG1 endophenotype compared to patients classified in FG3 endophenotype. In fact, the omnibus F test on the three endophenotype groups displayed a difference in Cobb angle of the main curve at maturity between the groups. FG3 group was the less likely to reach high Cobb angles, with an average value of 23.9° compared to 26.3° for FG2 and 27.0° for FG1 (p = 0.030). In addition, the percentage of IS patients who reached a Cobb of ≥ 45° and/or had a spinal fusion was almost two times higher in the FG1 group with 21.2%, when compared to the FG3 group with 11.2% and to the FG2 group with 18.6% (p = 0.024).
In multivariable analyses (Table 2), the linear relationship between the Cobb angle at maturity and the biological endophenotypes was borderline significant (p = 0.056 and p = 0.05) after adjusting for the following control variables in the final model (that appeared to be independently associated with the outcome): Risser sign, initial main curve Cobb angle, type of treatment, and age at maturity. The final model led to an adjusted R2 = 0.711 The initial age, initial BMI, BMI at maturity, length of the follow-up, appropriateness of the brace prescription, and length of the treatment were not associated with the outcome.
Table 3 displays the results of the logistic regression for the reach of final Cobb angle to 45° or the occurrence of surgery. The multivariable analyses indicated that IS patients classified into FG1 or FG2 endophenotype were 2 times more likely (FG1: OR = 2.181, p = 0.049) and FG2: OR = 2.141, p = 0.039) to develop a severe Cobb angle ≥ 45° or require a corrective spinal surgery than FG3 patients. The results of the severity threshold outcome were adjusted for the initial Risser score and the initial Cobb angle of main curve.
Looking more specifically at patients from that cohort who have terminated their brace treatment over the observation period (n = 138) led to a secondary analysis of the associations between brace outcomes (success/failure) and the endophenotype.
The mean Cobb angle was 37.0° ± 15.7° (median 35.0°) at the end of the treatment in the brace subsample, and it was statistically different between the biological endophenotypes. The adjusted model suggests that the endophenotype group was strongly associated with treatment success, even in the presence of the initial Cobb angle and Risser sign in the model (there was no significant effect modification of the studied association by initial Cobb angle, Risser sign, or brace type). The adjusted models were derived for girls only because of potential effect modification in the association by the sex variable, suggested by preliminary log linear analysis, and because of the small sample size for boys precluding stratification in this study. Being classified as FG3 was 9.31 [2.58–33.61] times more likely to lead to treatment success than failure in comparison to FG1 (Table 4). A similar positive association was observed for the FG2 group, but the value was not statistically significant. Based on the criterion of < 6° progression in an adjusted model, the FG3 group was 5.63 [2.11–15.05] times more likely to lead to treatment success than failure compared with the FG1 AIS group. There was no significant difference in the treatment outcomes between the FG1 and the FG2 AIS groups.