Kenneth M.C. Cheung

Prevalence and Pattern of Lumbar Magnetic Resonance Imaging Changes in a Population Study of One Thousand Forty-Three Individuals

Study Design. A cross-sectional population study of magnetic resonance imaging (MRI) changes. Objective. To examine the pattern and prevalence of lumbar spine MRI changes within a southern Chinese population and their relationship with back pain. Summary of Background Data. Previous studies on MRI changes and back pain have used populations of asymptomatic individuals or patients presenting with back pain and sciatica. Thus, the prevalence and pattern of intervertebral disc degeneration within the population is not known. Methods. Lumbar spine MRIs were obtained in 1043 volunteers between 18 to 55 years of age. MRI changes including disc degeneration, herniation, anular tears (HIZ), and Schmorl’s nodes were noted by 2 independent observers. Differences were settled by consensus. Disc degeneration was graded using Schneiderman’s classification, and a total score (DDD score) was calculated by the summation of the Schneiderman’s score for each lumbar level. A K-mean clustering program was used to group individuals into different patterns of degeneration. Results. Forty percent of individuals under 30 years of age had lumbar intervertebral disc degeneration (LDD), the prevalence of LDD increasing progressively to over 90% by 50 to 55 years of age. There was a positive correlation between the DDD score and low back pain. L5–S1 and L4–L5 were the most commonly affected levels. Apart from the usual patterns of degeneration, some uncommon patternsof degeneration were identified, comprising of subjects with skip level lesions (intervening normal levels) and isolated upper or mid lumbar degeneration. Conclusion. LDD is common, and its incidence increases with age. In a population setting, there is a significant association of LDD on MRI with back pain.

A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants

Magnesium and its alloys may potentially be applied as degradable metallic materials in orthopaedic implantations due to their degradability and resemblance to human cortical bone. However, the high corrosion rate and accumulation of hydrogen gas upon degradation hinders its clinical application. In this study, we adopt a new approach to control the corrosion rate by coating a controllable polymeric membrane fabricated by polycaprolactone and dichloromethane onto magnesium alloys, in which the pore size was controlled during the manufacturing process. The addition of the polymeric membrane was found to reduce the degradation rate of magnesium, and the bulk mechanical properties were shown to be maintained upon degradation. The in-vitro studies indicated good cytocompatibility of eGFP and SaOS-2 osteoblasts with the polymer-coated samples, which was not observed for the uncoated samples. The in-vivo study indicated that the uncoated sample degraded more rapidly than that of the polymer-coated samples. Although new bone formation was found on both samples, as determined by Micro-CT, higher volumes of new bone were observed on the polymer-coated samples. Histological analysis indicated no inflammation, necrosis or hydrogen gas accumulation on either of the samples during degradation. Collectively, these data suggest that the use of polymeric membrane may be potentially applied for future clinical use.

Concise Review: The Surface Markers and Identity of Human Mesenchymal Stem Cells

The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments. Markers that associate with the stemness of MSCs await to be elucidated. A number of candidate MSC surface markers or markers possibly related to their stemness have been brought forward so far, including Stro‐1, SSEA‐4, CD271, and CD146, yet there is a large difference in their expression in various sources of MSCs. The exact identity of MSCs in vivo is not yet clear, although reports have suggested they may have a fibroblastic or pericytic origin. In this review, we revisit the reported expression of surface molecules in MSCs from various sources, aiming to assess their potential as MSC markers and define the critical panel for future investigation. We also discuss the relationship of MSCs to fibroblasts and pericytes in an attempt to shed light on their identity in vivo. Stem Cells 2014;32:1408–1419

The TRP2 Allele of COL9A2 is an Age-Dependent Risk Factor for the Development and Severity of Intervertebral Disc Degeneration

Study Design. Low back pain (LBP) and sciatica are usually caused by degenerative disc disease (DDD). Although they are common, the etiology of these conditions is poorly understood. A large population case-control study in the Southern Chinese was performed to study genetic risk factors to DDD. Objectives. To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc. Summary of Background Data. A Finnish study found an association between LBP and sciatica with two variants of the α-chains of collagen IX, encoded by the Trp2 and Trp3 alleles, representing Gln326Trp and Arg103Trp amino acid substitutions in the COL9A2 and COL9A3 genes, respectively. Trp2 was found only in affected individuals (4%), whereas Trp3 was present in both affected (24%) and unaffected (9%) individuals. Because of the low frequency of the Trp2 allele in whites, the significance and contribution of this allele to DDD are not known. Using more objective criteria to define the disease by magnetic resonance imaging (MRI), we tested these alleles for association with DDD in a large population study. Methods. Lumbar DDD, the presence of anular tears, and disc and endplate herniations were defined by MRI in 804 Southern Chinese volunteers 18 to 55 years of age. These were correlated with the frequencies of the Trp2 and Trp3 alleles. Results. The Trp2 allele was present in 20% of the population and was associated with a fourfold increase in the risk of developing anular tears at 30 to 39 years and a 2.4-fold increase in the risk of developing DDD and endplate herniations at 40 to 49 years. Affected Trp2 individuals had more severe degeneration. The Trp3 allele was absent from the Southern Chinese population. Conclusion. This largest-ever population study using MRI to define DDD demonstrates for the first time that the Trp2 allele is a significant risk factor for the development and severity of degeneration. The association is age- dependent as it is more prevalent in some age groups than in others. The contrasting Trp allele frequencies between the Finns and the Chinese are the first indication that the genetic risk factors for DDD varies between ethnic groups.

Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease

Hirschsprungs disease (HSCR), or aganglionic megacolon, is a congenital disorder characterized by the absence of enteric ganglia in variable portions of the distal intestine. RET is a well-established susceptibility locus, although existing evidence strongly suggests additional loci contributing to sporadic HSCR. To identify these additional genetic loci, we carried out a genome-wide association study using the Affymetrix 500K marker set. We successfully genotyped 293,836 SNPs in 181 Chinese subjects with sporadic HSCR and 346 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Aside from SNPs in RET, the strongest overall associations in plausible candidate genes were found for 2 SNPs located in intron 1 of the neuregulin1 gene (NRG1) on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI95%:(1.40, 2.00), P = 1.80 × 10−8] and 1.98 [CI95%:(1.59, 2.47), P = 1.12 × 10−9], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (P = 0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotype (TT) in the presence of the NRG1 rs7835688 heterozygote, indicating that NRG1 is a modifier of HSRC penetrance. Our highly significant association findings are backed-up by the important role of NRG1 as regulator of the development of the enteric ganglia precursors. The identification of NRG1 as an additional HSCR susceptibility locus not only opens unique fields of investigation into the mechanisms underlying the HSCR pathology, but also the mechanisms by which a discrete number of loci interact with each other to cause disease.

Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population.

Study Design. Large scale, case-control study. Objective. To assess the effect of the Taq I alleles in vitamin D receptor on the risk of developing degenerative disc disease in a Southern Chinese population. Summary of Background Data. Previous studies in Finns and Japanese suggest that the Taq I polymorphism of vitamin D receptor is associated with the development of degenerative disc disease in the lumbar spine. However, sample sizes were small, and the results need to be confirmed in other populations. Method. Lumbar degenerative disc disease was defined by magnetic resonance imaging (MRI) on 804 Southern Chinese volunteers between 18 and 55 years of age. Restriction enzyme digestion of polymerase chain reaction products was used to analyze the Taq I alleles. The resulting genotypes were correlated with the presence of lumbar disc degeneration and bulge on MRI. Results. Using logistic regression analysis and adjusting for age and sex, the t allele of Taq I in vitamin D receptor gene was significantly associated with degenerative disc disease, with an odds ratio (OR) of 2.61 (95% confidence interval [CI] 1.15–5.90, P = 0.041). Further subgroup analysis showed that in individuals younger than 40 years, the OR was even higher, at 5.97 (95% CI 1.69–21.15, P = 0.002). Similarly, disc bulge was significantly associated with t allele (OR = 7.17, 95% CI 1.43–36.01, P = 0.001) in individuals younger than 40 years. Anular tears and the Schmorl nodes were not associated with the t allele of Taq I polymorphism. Conclusion. To our knowledge, this is the largest scale genetics study to date using MRI to define precisely degenerative disc disease in the Southern Chinese population. We showed that the t allele of vitamin D receptor Taq I is associated with a high risk of degenerative disc disease and disc bulge developing, especially in individuals younger than 40 years.

Prediction of Correction of Scoliosis with Use of the Fulcrum Bending Radiograph

We used a new method to assess spinal flexibility in thirty patients who were to be managed operatively for adolescent idiopathic scoliosis. The method involves placing the patient in the lateral decubitus position and bent over a fulcrum (a radiolucent padded cylinder) so that the spine is passively hinged open. For thoracic curves the fulcrum is centered under the rib corresponding to the apex of the curve, and for lumbar curves the fulcrum is placed directly under the apex. The preoperative workup for the thirty patients included an anteroposterior radiograph made with the patient standing, a lateral-bending radiograph made with the patient supine, and the new fulcrum bending radiograph. All patients were treated with posterior spinal arthrodesis with segmental spinal instrumentation. The degree of flexibility obtained with the traditional and new methods was compared with the degree of correction observed on the radiograph made, with the patient standing, one week after the operation. Preoperatively, the mean Cobb angle was 58 degrees on the anteroposterior radiograph made with the patient standing, 31 degrees on the lateral-bending radiograph made with the patient supine, and 24 degrees on the fulcrum bending radiograph. The mean angle was 25 degrees on the anteroposterior radiograph made one week postoperatively, so the mean correction was 57 per cent. The difference between the mean angle on the lateral-bending radiograph and that on the postoperative radiograph was significant (p < 0.001); however, the mean angle measured on the preoperative fulcrum bending radiograph and the postoperative angle were almost identical. We found the fulcrum bending radiograph to be more predictive of the degree of flexibility and correctability than the lateral-bending radiograph in this group of patients who had segmental spinal instrumentation for correction of idiopathic scoliosis.

Genetics of disc degeneration

Low back pain from degenerative disc disease (DDD) is one of the most common disorders seen in general and orthopaedic practices. DDD has been attributed to the accumulation of environmental factors, primarily mechanical insults and injuries, imposed on the “normal” aging changes. However, recent studies have shown an association between genetic influences and disc degeneration, with risk of developing DDD quoted to be increased up to six times that of the general population. It is likely that DDD is a complex, multifactorial disease determined by the interplay between gene(s) and the environment. This review focuses on the evidence for genetic disposition, the genes or biological processes that are implicated, and the need to consolidate resources and clarify phenotype definition to take advantage of the new technologies in genetic analysis to enhance our understanding of this condition.

The association of lumbar intervertebral disc degeneration on magnetic resonance imaging with body mass index in overweight and obese adults: A population‐based study

OBJECTIVE To investigate the association of being overweight or obese with the presence, extent, and severity of lumbar disc degeneration on magnetic resonance imaging (MRI) in adults. METHODS A population-based cross-sectional study of 2,599 southern Chinese volunteers was conducted. Subjects underwent radiographic and clinical assessment, and weight and height were measured. Sagittal T2-weighted MRIs of the lumbar spine were obtained. The presence, extent, and severity of disc degeneration and additional radiographic and clinical parameters were assessed. Asian-modified body mass index (BMI) (kg/m(2) ) categories were used. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS The study included 1,040 men and 1,559 women (mean age 41.9 years). Disc degeneration was noted in 1,890 subjects (72.7%). BMI was significantly higher in subjects with disc degeneration (mean 23.3 kg/m(2) ) than in subjects without degeneration (mean 21.7 kg/m(2) ) (P < 0.001). A significant increase in the number of degenerated levels (P < 0.001), global severity of disc degeneration (P < 0.001), and end-stage disc degeneration with disc space narrowing (P < 0.001) was noted with elevated BMI, in particular in overweight and obese subjects. In the adjusted multivariate logistic regression model, there was a positive linear trend (r(2) = 0.99) between BMI and the overall presence of disc degeneration in overweight (OR 1.30 [95% CI 1.03-1.62]) and obese (OR 1.79 [95% CI 1.17-2.74]) subjects. End-stage disc degeneration with disc space narrowing was significantly more pronounced in obese subjects (adjusted OR 1.72 [95% CI 1.23-2.41] [reference normal weight]). CONCLUSION Our findings, in one of the largest studies to systematically assess lumbar disc degeneration on MRI, indicated a significant association between the presence, extent, and global severity of disc degeneration with weight in overweight and obese adults.

Association of the Asporin D14 Allele with Lumbar-Disc Degeneration in Asians

Lumbar-disc degeneration (LDD) is a polygenic disease. Susceptibility genes reported so far are mainly extracellular matrix proteins. D14 allele of asporin (ASPN) is associated with osteoarthritis (OA). Candidate-gene association studies showed that the D14 allele is also significantly associated with LDD in Chinese and Japanese individuals. Meta-analysis showed that individuals harboring a D14 allele had higher risk with a summary odds ratio of 1.70 (p = 0.000013). ASPN expression in vertebral discs increased with age and degeneration. Our results indicate ASPN is a LDD gene in Asians, and common risk factors may be considered for OA and LDD.