Part 2. Review and meta‐analysis of studies on modulation of longitudinal bone growth and growth plate activity: A micro‐scale perspective

Abstract

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.

Patients with trochlear dysplasia have dysplastic medial femoral epiphyseal plates

“…The explanation for this in previous studies [19,20,33,37] is that the lack of stress stimulation to the medial condyle in the laterally dislocated patella leads to delayed development of the medial condyle, resulting in dysplasia of the medial trochlea. Thus, osteogenesis of the epiphyseal plate is afected by mechanical stress [7,33,35] and inluences the formation of trochlear morphology, which may be an important intermediate link in the development of trochlear dysplasia. It was found that there are signiicant positive correlations among the area of the medial growth plate, medial TPD, height of the medial condyle and capacity of the proximal trochlear groove, which consistent with previous indings.…”

“…Injury to the epiphysis may result in a series of potential problems, such as joint deformities, premature closure of the epiphyseal plate and traumatic arthritis [4,9,24,34]. Osteogenesis of the epiphysis can be afected by mechanical stress [7,27,39], and the distal femur growth plate may inluence trochlear morphology in terms of abnormal stress due to poor patellar trochlear engagement. Studies have already revealed the complex anatomical shape of the distal femur epiphyseal plate [6,11], while it remains unknown whether the development of the distal femoral epiphyseal plate in adolescents with trochlear dysplasia is diferent from that in normal adolescents.…”

Patient-specific finite element modeling of scoliotic curve progression using region-specific stress-modulated vertebral growth

“…However, the stress sensitivity parameters calculated in the current FE model may be considered to compensate for its limited scope. Second, due to the relative coarseness of the Risser sign (0-5, in steps of 1) to chronological age (continuous), 4 Average error in frontal vertebral wedging angle of the apical and adjacent above and below levels, between the current PS-FE models and patient X-Rays ITP ITP + 1y ITP + 2y ITP + 3y All TPs Apex + 1 (°) 2.9 ± 2.1 2.9 ± 2.4 3.0 ± 2.3 3.9 ± 3.6 3.2 ± 2.7 Apex (°) 4.1 ± 1.7 2.9 ± 1.5 3.1 ± 1.5 3.4 ± 2.0 3.4 ± 1.8 Apex − 1 (°) 2.3 ± 2.1 3.0 ± 1.8 3.5 ± 1.7 2.4 ± 1.7 2.8 ± 1.9 or even continuous scale (Collagen X biomarker levels) of skeletal maturity with chronological age, and using this relationship to more accurately scale stress sensitivity for each patient [47][48][49]. Third, IVD elastic modulus was scaled from normative data for all simulated timepoints based on spine flexibility obtained at the final timepoint (approximately 3 years after ITP), where in reality, IVD elastic modulus may vary between normative and AIS patients, and spine flexibility may not remain constant over this timespan [50].…”

“…Second, due to the relative coarseness of the Risser sign (0–5, in steps of 1) to chronological age (continuous), scaling of stress sensitivity based on a correlation between Risser sign and chronological age may contribute to error in prediction of curve progression. This limitation could be addressed by correlating a more precise (Sanders score) or even continuous scale (Collagen X biomarker levels) of skeletal maturity with chronological age, and using this relationship to more accurately scale stress sensitivity for each patient [ 47 – 49 ]. Third, IVD elastic modulus was scaled from normative data for all simulated timepoints based on spine flexibility obtained at the final timepoint (approximately 3 years after ITP), where in reality, IVD elastic modulus may vary between normative and AIS patients, and spine flexibility may not remain constant over this timespan [ 50 ].…”

What’s New in Limb Lengthening and Deformity Correction

“…Macro‐scale changes in longitudinal bone growth resulting from mechanical loading relied on load magnitude, anatomical location, and species. From the micro-scale perspective, understanding the gene and protein expressions altered by mechanical loading may be an important step toward progressively less invasive correction of skeletal deformity, including methods other than mechanical modulation 66,67 .…”