Patient outcomes in idiopathic scoliosis are associated with biological endophenotypes: 2020 SOSORT award winner

Abstract

Purpose Bracing is the treatment of choice for idiopathic scoliosis (IS), unfortunately factors underlying brace response remain unknown. Clinicians are currently unable to identify patients who may benefit from bracing, and therefore, better molecular stratification is critically needed. The aim of this study is to evaluate IS patient outcomes at skeletal maturity in relation to biological endophenotypes, and determine specific endophenotypes associated to differential bracing outcomes. This is a retrospective cohort with secondary cross-sectional comparative studies. Methods Clinical and radiological data were collected from 563 IS patients, stratified into biological endophenotypes (FG1, FG2, FG3) based on a cell-based test. Measured outcomes were maximum Cobb angle at skeletal maturity, and if severe, spinal deformity (≥ 45°) or surgery was attained. Treatment success/failure was determined by standard progression thresholds (Cobb ≥ 45° or surgery; Cobb angle progression ≥ 6°). Multivariable analyses were performed to evaluate associations between endophenotypes and clinical outcome. Results Higher Cobb angles at maturity for FG1 and FG2 patients were observed (p = 0.056 and p = 0.05), with increased likelihood of ≥ 45° and/or surgery for FG1 (OR = 2.181 [1.002-4.749] and FG2 (OR = 2.141 [1.038-4.413]) compared to FG3. FG3 was 9.31 [2.58-33.61] and 5. 63 [2.11-15.05] times more likely for bracing success at treatment termination and based on the < 6° progression criterion, respectively, compared to FG1. Conclusion Associations between biological endophenotypes and outcomes suggest differences in progression and/or bracing response among IS patients. Outcomes were most favorable in FG3 patients. The results pave the way for establishing personalized treatments, distinguishing who may benefit or not from treatment.

Altered mechanotransduction in adolescent idiopathic scoliosis osteoblasts: an exploratory in vitro study

“…A compromised actin dynamics in the context of AIS, can also affect ciliogenesis, resulting in a wide variation in ciliary lengths and a systemic mechanotransduction impairment 22 . From a clinical point of view, our results could explain the differential bracing outcomes among AIS patients as recently demonstrated by the works of Beauséjour et al, 48 .…”