Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis

Asymmetrical growth of the vertebrae has been implicated as one possible etiologic factor in the pathogenesis of adolescent idiopathic scoliosis. The longitudinal vertebral growth derives from the endochondral ossification of the vertebral growth plate. In the present study, the growth plates from the convex and concave side of the vertebrae were characterized by the method of histology and immunohistochemistry to evaluate the growth activity, cell proliferation, and apoptosis. Normal zoned architectures were observed in the convex side of the growth plate and disorganized architectures in the concave side. The histological grades were significantly different between the convex and the concave side of the growth plate in the apex vertebrae (P < 0.05). The histological difference was also found significant statistically between end vertebrae and apex vertebrae in the concave side of vertebral growth plates (P < 0.05). The proliferative potential indexes and apoptosis indexes of chondrocytes in the proliferative and hypertrophic zone in the convex side were significantly higher than that in the concave side in the apex vertebral growth plate (P < 0.05). There was a significant difference of the proliferative potential index (proliferating cell nuclear antigen, PCNA index) between convex side and concave side at the upper end vertebra (P < 0.05). The difference of the proliferative potential index and apoptosis index were found significant statistically in the concave side of the vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). The same result was also found for the apoptosis index (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling assay, TUNEL index) in the convex side of vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). Some correlation were found between radiographic measurements and proliferation and apoptosis indexes. The difference in histological grades and cellular activity between the convex and concave side indicated that the bilateral growth plate of the vertebrae in AIS patients have different growth kinetics which may affect the curve progression.     

In vivo dynamic loading reduces bone growth without histomorphometric changes of the growth plate

This in vivo study aimed at investigating the effects of dynamic compression on the growth plate. Rats (28 days old) were divided into three dynamically loaded groups, compared with two groups (control, sham). A device was implanted on the 6th and 8th caudal vertebrae for 15 days. Controls (n = 4) did not undergo surgery. Shams (n = 4) were operated but not loaded. Dynamic groups had sinusoidal compression with a mean value of 0.2 MPa: 1.0 Hz and ±0.06 MPa (group a, n = 4); 0.1 Hz and ±0.2 MPa (group b, n = 4); 1.0 Hz and ±0.14 MPa (group c, n = 3). Growth rates (µm/day) of dynamic groups (a) and (b) were lower than shams (p < 0.01). Growth plate heights, hypertrophic cell heights and proliferative cell counts per column did not change in dynamic (a) and (b) groups compared with shams (p > 0.01). Rats from dynamic group (c) had repeated inflammations damaging tissues; consequently, their analysis was unachievable. Increasing magnitude or frequency leads to growth reduction without histomorphometric changes. However, the combined augmentation of magnitude and frequency alter drastically growth plate integrity. Appropriate loading parameters could be leveraged for developing novel growth modulation implants to treat skeletal deformities. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1129–1136, 2014.     

Histomorphometric analysis of an adolescent distal tibial physis prior to growth plate closure

Purpose  Our current understanding of the rate and pattern of physeal closure is based on roentgenographic, magnetic resonance imaging, and qualitative histological studies. The purpose of this report is to provide a detailed histomorphometric/stereological analysis of a distal tibial human growth plate in the process of physiological epiphysiodesis. Methods  A human distal tibial growth plate was sampled in three regions (anterior, central, and posterior), with each region further separated medially, in the middle, and laterally. The regions were assessed for the location and extent of bony bar formation as well as for physeal height. Companion sections from optimally fixed tissue in the distal 100 μm of the hypertrophic zone were analyzed for hypertrophic chondrocytic volumes. Results  Physis closure started in the middle of the central region of the growth plate, with 46% of the volume in this area occupied by trans-physeal bridging bone. The growth plate was also narrowed with the lowest physeal heights evident in the middle of the central and anterior regions of the physis. Disruption of the regular columns of the physis was evident with the cells arranged in clusters with intervening areas of acellularity. The average hypertrophic cell volume was 5,900 μm³ and did not significantly differ between different areas of the physis. Conclusions  This is the first characterization of closure in a human distal tibial growth plate via optimum fixation and stereological techniques. The studied physis was during the earliest phases of closure and provides stereological support that the distal tibial physis closes in a central to medial direction.     

Pinealectomy in a broiler chicken model impairs endochondral ossification and induces rapid cancellous bone loss

Background contextAdolescent idiopathic scoliosis (AIS) in humans is a lateral curvature of the spine often associated with osteopenia. It has recently been accepted that the development of AIS is closely associated with spinal overgrowth. Pinealectomy (PNX) in a chicken model consistently induces scoliosis with anatomic features similar to human AIS; however, the mechanism of PNX inducing scoliosis is poorly understood.PurposeThis experimental study attempts to improve the understanding of the mechanisms underlying the onset of scoliosis in a PNX broiler chicken model.MethodsA histomorphometric study was performed to analyze longitudinal bone growth and cancellous bone remodeling before the development of scoliosis. Static and dynamic parameters in cancellous bone and chondro-osseous junction of the 7th thoracic vertebral body at 9 days after hatching were compared between PNX chickens (n=9) and control chickens with no surgery (n=5).ResultsPNX resulted in a rapid and marked loss of cancellous bone volume (7.9±0.9% vs. 14.2±1.8%, mean±SD, p<.0005) and profoundly disrupted trabecular structure with increases in dynamic formative parameters, such as mineralizing surface, mineralization apposition rate, and adjusted appositional rate. In the chondro-osseous junction, activated osteoclasts phagocytized degenerating chondrocytes, leaving a minimal amount of cartilage matrix and activated osteoblasts, losing their scaffolding for bone formation, and directly covering the hypertrophic zone cells. The osteoid surface and thickness in the chondro-osseous junction were significantly increased in PNX chickens (43.1±14.2% vs. 11.6±5.7% and 4.1±0.2μm vs. 2.9±0.4 μm). In the subjacent cartilage regions being protected from further resorption, abundant labeled cartilage remained with higher cellularity.ConclusionsIt is known that fast-growing birds have a unique paradigm of rapid bone elongation with minimal metaphyseal bone production. A bone-forming surface exists at the front of cartilage ossification in the growth plate; therefore, papillae of hypertrophic chondrocytes become included between the trabeculae of metaphyseal bone and the overall thickness of the growth plate increases considerably in addition to distal expansion. Our results indicate that the unique mechanism for rapid bone elongation in chicken is more pronounced after PNX. PNX also induces high turnover osteoporosis, which may also contribute to the development of scoliosis in the chicken.     

Changes of selenium,copper, and zinc content in hair and serum of patients with idiopathic scoliosis

Our work aimed at extending the search for abnormalities of trace elements in patients with idiopathic scoliosis to the content of zinc (Zn), copper (Cu), and selenium (Se) in these subject's hair and serum. A total of 59 patients (54 girls and 4 boys) with idiopathic scoliosis, aged 13 on the average (range, 10–18 years), were examined. The degree of spine curvature deformity ranged between 12° and 82°. The hair of scoliotic patients under examination showed significantly increased content of zinc 263 ± 108 µg/g (p < 0.01) and copper 46.2 ± 37.1 µg/g (p < 0.01), and decreased content of selenium 0.194 ± 0.114 µg/g (p < 0.01) in comparison with the control group. In scoliotic patients, the Cu/Zn ratio in hair (0.186 ± 0.139) did not differ significantly from the values found in the probands of the control group (0.115 ± 0.09). The Cu/Se ratio in this group of patients (254.9 ± 215.9) was significantly higher (p < 0.001) due to a higher Cu value and a lower Se value in comparison with the controls (47.9 ± 23.7). In comparison with controls, the serum selenium concentration in the group of scoliotic patients was significantly decreased p < 0.05 (0.74 ± 0.13 µmol/L and 0.98 ± 0.12 µmol/L). Various changes in the content of trace elements in biological samples taken from patients with idiopathic scoliosis are not accidental. What might bring about a shift in our knowledge is speciation of various forms of trace elements in the organism in relation to idiopathic scoliosis. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1279–1282, 2008     

Oxygen dynamics at paraspinal muscles during exertion using near-infrared spectroscopy in patients with degenerative lumbar scoliosis

 Oxygen dynamics were measured in both sides of the paraspinal muscles of patients with degenerative lumbar scoliosis. The objective was to investigate the extent of stress by measuring the changes in oxygenation and blood flow volume using near-infrared spectroscopy. There were 44 patients with degenerative lumbar scoliosis (7 men, 37 women) and 11 controls with no scoliosis (2 men, 9 women). The measured recovery time for deoxyhemoglobin indicated the recovery from energy deficit after exercise. The average recovery time of the 11 control subjects was 2.4 ± 0.7 s on the right and 2.4 ± 0.8 s on the left. Among the 44 patients the average recovery time was 3.8 ± 1.8 s on the convex side and 2.1 ± 1.1 s on the concave side. There was a significant difference between the two groups. The recovery time on the concave side in patients was faster than that on the convex side. The results of the current study support the theory that stretching the muscles at the convex side results in chronic increases in the intramuscular compartment and reduced muscular blood flow. Received: May 23, 2002 / Accepted: October 29, 2002 Offprint requests to: M. Miyake, Department of Orthopaedic Surgery, Eiko Hospital, 1381 Takuma, Takuma-cho, Mitoyo-gun, Kagawa 769-1101, Japan     

What is the Difference in Morphologic Features of the Thoracic Pedicle Between Patients With Adolescent Idiopathic Scoliosis and Healthy Subjects? A CT-based Case-control Study

Background

Describing the morphologic features of the thoracic pedicle in patients with adolescent idiopathic scoliosis is necessary for placement of pedicle screws. Previous studies showed inadequate reliability owing to small sample size and heterogeneity of the patients surveyed.

Questions/Purposes

To use CT scans (1) to describe the morphologic features of 2718 thoracic pedicles from 60 female patients with Lenke Type 1 adolescent idiopathic scoliosis and 60 age-, sex-, and height-matched controls; and (2) to classify the pedicles in three types based on pedicle width and analyze the distribution of each type.

Methods

A total of 2718 pedicles from 60 female patients with Lenke Type 1 adolescent idiopathic scoliosis and 60 matched female controls were analyzed via CT. All patients surveyed were diagnosed with adolescent idiopathic scoliosis, Lenke Type 1, at the First Affiliated Hospital of Sun Yat-sen University, and all underwent pedicle screw fixation between January 2008 and December 2013 with preoperative radiographs and CT images on file. We routinely obtained CT scans before these procedures; all patients who underwent surgery during that period had CT scans, and all were available for analysis here. Control subjects had CT scans for other clinical indications and had no abnormal findings of the spine. The control subjects were chosen to match patients in terms of age (15 ± 2.6 years versus 15 ± 2.6 years) and sex. Height of the two groups also was matched (154 ± 9 cm versus 155 ± 10 cm; mean difference, −1.06 cm; 95% CI, −1.24 to −0.81 cm; p < 0.001). Pedicle width and length were measured from T1 to T12. The thoracic spine was classified in four regions: apical vertebra in the structural curve (AV-SC), nonapical vertebra in the structural curve (NAV-SC), apical vertebra in the nonstructural curve (AV-NSC), and nonapical vertebra in the nonstructural curve (NAV-NSC). Pedicles were classified in three types: pedicle width less than 2 mm as Type I, 2 mm to 4 mm as Type II, and greater than 4 mm as Type III. Types I and II were defined as dysplastic pedicles. Paired t test, independent samples t test, one-way ANOVA, followed by Bonferroni’s post hoc test and chi-square or Fisher’s exact tests were used for statistical comparisons between patients and controls, as appropriate.

Results

No difference was found between pedicle width on the convex side (PWv) and in controls (PWn), but pedicle width on the concave side (PWc) (4.99 ± 1.87 mm) was found to be narrower than PWv (6 ± 1.66 mm) and PWn (6 ± 1.45 mm). The variation degree of pedicle width (VDPW) was greatest in the AV-SC region (34% ± 37%), in comparison to AV-NSC (20% ± 25%) (mean difference, 14%; 95% CI, 1.15%–27%; p = 0.025), NAV-SC (17% ± 30%) (mean difference, 17%; 95% CI, 7%–27%; p < 0.001), and NAV-NSC (11% ± 24%) (mean difference, 24%; 95% CI, 13%–34%; p < 0.001). Dysplastic pedicles appeared more in patients with adolescent idiopathic scoliosis (22%; 293 of 1322) compared with controls (13%; 178 of 1396) (odds ratio [OR] = 0.51; 95% CI, 0.42–0.63; p < 0.001). In patients with adolescent idiopathic scoliosis, they commonly occurred on the concave side 34% (228 of 661) and on the AV-SC region (32%; 43 of 136).

Conclusions

Pedicle width on the concave side was narrower than pedicle width on the convex side and pedicle width in healthy control subjects. The apical vertebra in the structural curve was the most variegated region of the curve with the highest prevalence of dysplastic pedicles.

Clinical Relevance

Our study can help surgeons perform preoperative assessments in females with adolescent idiopathic scoliosis, and with preoperative and intraoperative management for difficult pedicle screw placement. In particular, our results suggest that surgeons should exercise increased vigilance when selecting pedicle screw dimensions, especially in the concave aspect of the mid-thoracic curve, to avoid cortical breeches. Future studies should evaluate other Lenke types of adolescent idiopathic scoliosis, and males with adolescent idiopathic scoliosis.

     

Anterior lengthening in scoliosis occurs only in the disc and is similar in different types of scoliosis

BACKGROUND CONTEXTRelative anterior spinal overgrowth was proposed as a generalized growth disturbance and a potential initiator of adolescent idiopathic scoliosis (AIS). However, anterior lengthening has also been observed in neuromuscular (NM) scoliosis and was shown to be restricted to the apical areas and located in the intervertebral discs, not in the bone. This suggests that relative anterior spinal overgrowth does not rightfully describe anterior lengthening in scoliosis, as it seems not a generalized active growth phenomenon, nor specific to AIS.PURPOSETo determine if compensatory curves in congenital scoliosis exhibit a mechanism of anterior lengthening without changes in the vertebral body, similar to curves in AIS and NM scoliosis.STUDY DESIGN/SETTINGCross-sectional.PATIENT SAMPLECT-scans were included of patients in whom a short segment congenital malformation had led to a long thoracic compensatory curve without bony abnormality. Based on data of other scoliosis types, the calculated required sample size was n=12 to detect equivalence of vertebral bodies as compared with nonscoliotic controls. Out of 143 congenital scoliosis patients, 18 fit the criteria and compared with 30 nonscoliotic controls, 30 AIS and 30 NM scoliosis patients.OUTCOME MEASURESThe anterior-posterior length discrepancy (AP%) of the total curve and for vertebral bodies and intervertebral discs separately.METHODSOf each vertebral body and intervertebral disc in the compensatory curve, the anterior and posterior length was measured on CT-scans in the exact mid-sagittal plane, corrected for deformity in all three planes. The AP% was calculated for the total compensatory curve (Cobb-to-Cobb) and for the vertebral bodies and the intervertebral discs separately. Positive AP% indicated that the anterior side was longer than the posterior side.RESULTSThe total AP% of the compensatory curve in congenital scoliosis showed lordosis (+1.8%) that differed from the kyphosis in nonscoliotic controls (−3.0%; p<.001) and was comparable to the major curve in AIS (+1.2%) and NM scoliosis (+0.5%). This anterior lengthening was not located in the bone; the vertebral body AP% showed kyphosis (−3.2%), similar to nonscoliotic controls (−3.4%) as well as AIS (−2.5%) and NM scoliosis (−4.5%; p=1.000). However, the disc AP% showed lordosis (+24.3%), which sharply contrasts to the kyphotic discs of controls (−1.5%; p<.001), but was similar to AIS (+17.5%) and NM scoliosis (+20.5%).CONCLUSIONSThe current study on compensatory curves in congenital scoliosis confirms that anterior lengthening is part of the three-dimensional deformity in different types of scoliosis and is exclusively located in the intervertebral discs. The bony vertebral bodies maintain their kyphotic shape, which indicates that there is no active anterior bony overgrowth. Anterior lengthening appears to be a passive result of any scoliotic deformity, rather than being related to the specific cause of AIS.     

The modulation of spinal growth with nitinol intervertebral stapling in an established swine model

Purpose

Anterior spinal stapling for the treatment of adolescent idiopathic scoliosis has been shown to slow progression in small curves; however, its role in larger curves remains unclear. The purpose of this study was to evaluate the effectiveness of nitinol staples to modulate spinal growth by evaluating the two-dimensional and three-dimensional morphological and histological effects of this method in a well-established porcine model.

Methods

Three immature Yucatan miniature pigs underwent intervertebral stapling. Two staples spanned each of three consecutive mid-thoracic discs and epiphyses. Monthly radiographs were obtained. Computed tomography (CT) was conducted at harvest after 6 months of growth. Measurements of wedging and height for each disc and vertebral body were conducted. Micro CT was used to compare physeal closure between stapled and non-stapled levels. Histology of the growth plate also compared the hypertrophic zone thickness for control and stapled vertebrae.

Results

After 6 months of stapled growth, the average coronal Cobb angle of the stapled segments increased by 7.7 ± 2.0° and kyphosis increased by 3.3 ± 0.6° compared to preoperative curves. Increased vertebral wedging and decreased disc height (p < 0.001) were noted in stapled regions. Overall, 26 ± 23 % of each growth plate was closed in the stapled segments, with 6 ± 8 % closure in the unstapled levels. No difference was observed regarding the hypertrophic zone height when comparing instrumented to uninstrumented levels, nor was a difference recognized when comparing right versus left regions within stapled levels alone.

Conclusions

Six months of nitinol intervertebral stapling created a mild coronal and sagittal deformity associated with reduced vertebral and disc height, and increased coronal vertebral and sagittal disc wedging.