Abnormal lacuno‐canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis

Abstract

Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity occurring during peripubertal growth period that affects 1–4% of adolescents globally without clear etiopathogenetic mechanism. Low bone mineral density is an independent and significant prognostic factor for curve progression. Currently, the cause underlying low bone mass in AIS remains elusive. Osteocytes play an important role in bone metabolism and mineral homeostasis, but its role in AIS has not been studied. In the present study, iliac bone tissues were harvested from 21 patients with AIS (mean age of 14.3 ± 2.20 yr old) with a mean Cobb angle of 55.6 ± 10.61° and 13 non-AIS controls (mean age of 16.5 ± 4.79 yr old) intraoperatively. Acid-etched scanning electron microscopy (SEM) images of AIS demonstrated abnormal osteocytes that were more rounded and cobblestone-like in shape and were aligned in irregular clusters with shorter and disorganized canaliculi. Further quantitative analysis with FITC-Imaris technique showed a significant reduction in the canalicular number and length as well as an increase in lacunar volume and area in AIS. SEM with energy-dispersive X-ray spectroscopy analysis demonstrated a lower calcium-to-phosphorus ratio at the perilacunar/canalicular region. Moreover, microindentaion results revealed lower values of Vickers hardness and elastic modulus in AIS when compared with controls. In addition, in the parallel study of 99 AIS (27 with severe Cobb angle of 65.8 ± 14.1° and 72 with mild Cobb angle of 26.6 ± 9.1°) with different curve severity, the serum osteocalcin level was found to be significantly and negatively associated with the Cobb angle. In summary, the findings in this series of studies demonstrated the potential link of abnormal osteocyte lacuno-canalicular network structure and function to the observed abnormal bone mineralization in AIS, which may shed light on etiopathogenesis of AIS.—Chen, H., Zhang, J., Wang, Y., Cheuk, K.-Y., Hung, A. L. H., Lam, T.-P., Qiu, Y., Feng, J. Q., Lee, W. Y. W., Cheng, J. C. Y. Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

Association between Bone Turnover Markers, Leptin and Nutritional Status in Girls with Adolescent Idiopathic Scoliosis (AIS)

“…Similar findings are recently studied by Chen et al who showed that OC was significantly and negatively related to the Cobb's angle [32]. We also found a significant negative OC correlation vs.…”

Association between Bone Turnover Markers, Leptin, and Nutritional Status in Girls with Adolescent Idiopathic Scoliosis (AIS)

“…Similar findings have recently been studied by Chen et al who showed that OC level was significantly lower in the group with the severe AIS (Cobb's angle ≥ 45 • ) compared to the mild subgroup. However, C-terminal telopeptides (CTx) used as a bone resorption marker in this study was insignificantly lower in mild and severe compared to control group [39]. Significant positive correlation of both OC and NTx with Cobb's angle were found by Berglund et al but in the group of patients with scoliosis related to fibrous dysplasia and McCune Albright Syndrome which are related to very high level of bone turnover [40].…”

Large-scale quantification of human osteocyte lacunar morphological biomarkers as assessed by ultra-high-resolution desktop micro-computed tomography

“…A visual example of this scanning protocol and resulting images can be seen in To determine the optimal beam energy, three samples of trabecular bone were scanned at three beam energies: 55, 70, and 90kVp. These samples used for beam energy optimization originated from a separate study [38]; however, they were also human bone biopsies from the iliac crest and were considered to be comparable with our biopsy group. We aimed to maximize the image signal-to-noise ratio (SNR) just as previous studies relating to other anatomical bone sites had done [39].…”