Growth modulation is an emerging method for treatment of angular skeletal deformities such as adolescent idiopathic scoliosis (AIS). The Hueter-Volkmann law, by which growth is stimulated in tension and inhibited in compression, is widely understood, and applied in current growth-modulating interventions such as anterior vertebral body tethering (AVBT) for AIS. However, without quantification of the growth rate effects of tension or compression, the possibility of under-or overcorrection exists. A definitive mechanical growth modulation relationship relating to treatment of such skeletal deformities is yet to exist, and the mechanisms by which growth rate is regulated and altered are not fully defined. Review of current literature demonstrates that longitudinal (i.e., lengthwise) growth rate in multiple animal models depend on load magnitude, anatomical location, and species. Additionally, alterations in growth plate morphology and viability vary by loading parameters such as magnitude, frequency, and whether the load was applied persistently or intermittently. The aggregate findings of the reviewed studies will assist in work towards increasingly precise and clinically successful growth modulation methods. Part 1 of this review focuses on the effects of mechanical loading, species, age, and anatomical location on the macro-scale alterations in longitudinal bone growth, as well as factors that affect growth plate material properties. Part 2 considers the effects on micro-scale alterations in growth plate morphology such as zone heights and proportions, chondrocyte viability, and related gene and protein expression.

Finite element (FE) modeling of the spine has increasingly been applied in orthopedic precision-medicine approaches. Previously published FE models of the pediatric spine growth have made simplifications in geometry of anatomical structures, material properties, and representation of vertebral growth. To address those limitations, a comprehensive FE model of a pediatric (10-year-old) osteo-ligamentous thoracic and lumbar spine (T1-L5 with intervertebral discs (IVDs) and ligaments), ribcage, and pelvis with age- and level-specific ligament properties and orthotropic region-specific vertebral growth was developed and validated. Range of motion (ROM) measures, namely lateral bending, flexion-extension, and axial rotation, of the current 10 YO FE model were generally within reported ranges of scaled in vitro adult ROM data. Changes in T1-L5 spine height, as well as kyphosis (T2-T12) and lordosis (L1-L5) angles in the current FE model for two years of growth (from ages 10 to 12 years) were within ranges reported from corresponding pediatric clinical data. The use of such comprehensive pediatric FE models can provide clinically relevant insights into normative and pathological biomechanical responses of the spine, and also contribute to the development and optimization of clinical interventions for spine deformities.

Macro-scale changes in longitudinal bone growth resulting from mechanical loading were shown in Part 1 of this review to depend on load magnitude, anatomical location, and species. While no significant effect on longitudinal growth was observed by varying frequency and amplitude of cyclic loading, such variations, in addition to loading duration and species, were shown to affect the morphology, viability, and gene and protein expression within the growth plate. Intermittent compression regimens were shown to preserve or increase growth plate height while stimulating increased chondrocyte presence in the hypertrophic zone relative to persistent and static loading regimens. Gene and protein expressions related to matrix synthesis and degradation, as well as regulation of chondrocyte apoptosis were shown to exhibit magnitude-, frequency-, and duration-dependent responses to loading regimen. Chondrocyte viability was shown to be largely preserved within physiological bounds of magnitude, frequency, amplitude, and duration. Persistent static loading was shown to be associated with overall growth plate height in tension only, reducing it in compression, while affecting growth plate zone heights differently across species and encouraging mineralization relative to intermittent cyclic loading. Lateral loading of the growth plate, as well as microfluidic approaches are relatively understudied, and age, anatomical location, and species effects within these approaches are undefined. Understanding the micro-scale effects of varied loading regimes can assist in the development of growth modulation methods and device designs optimized for growth plate viability preservation or mineralization stimulation based on patient age and anatomical location.

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Purpose This study describes the creation of patient-specific (PS) osteo-ligamentous finite element (FE) models of the spine, ribcage, and pelvis, simulation of up to three years of region-specific, stress-modulated growth, and validation of simulated curve progression with patient clinical angle measurements. Research Question: Does the inclusion of region-specific, stress-modulated vertebral growth, in addition to scaling based on age, weight, skeletal maturity, and spine flexibility allow for clinically accurate scoliotic curve progression prediction in patient-specific FE models of the spine, ribcage, and pelvis? Methods Frontal, lateral, and lateral bending X-Rays of five AIS patients were obtained for approximately three-year timespans. PS-FE models were generated by morphing a normative template FE model with landmark points obtained from patient X-rays at the initial X-ray timepoint. Vertebral growth behavior and response to stress, as well as model material properties were made patient-specific based on several prognostic factors. Spine curvature angles from the PS–FE models were compared to the corresponding X-ray measurements. Results Average FE model errors were 6.3 ± 4.6°, 12.2 ± 6.6°, 8.9 ± 7.7°, and 5.3 ± 3.4° for thoracic Cobb, lumbar Cobb, kyphosis, and lordosis angles, respectively. Average error in prediction of vertebral wedging at the apex and adjacent levels was 3.2 ± 2.2°. Vertebral column stress ranged from 0.11 MPa in tension to 0.79 MPa in compression. Conclusion Integration of region-specific stress-modulated growth, as well as adjustment of growth and material properties based on patient-specific data yielded clinically useful prediction accuracy while maintaining physiological stress magnitudes. This framework can be further developed for PS surgical simulation.