Keith D. K. Luk

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.

Effects of short anterior lumbar interbody fusion on biomechanics of neighboring unfused segments

Study Design Segmental mobility and intradiscal pressure were measured and the data compared in six cadaveric lumbar spine specimens before and after in vitro simulated single level L4‐5 and double level L4‐5‐S1 anterior interbody fusions. Objective The experimental objective was to study the biomechanical effects of single level L4‐5 and double level L4‐5‐S1 anterior interbody fusions on the neighboring unfused segments. Summary of Background Data The relationship between the local rigidity created by fusion mass and accelerated degeneration reported at the neighboring unfused intervertebral discs is not clear. Methods Six cadaveric lumbar spine specimens were biomechanically tested in flexion and extension. Segmental mobility and intradiscal pressure of the specimens were measured before and after in vitro simulation of single level L4‐5 and double level L4‐5‐S1 anterior interbody fusions. Results The mobility of the motion segments immediately above and below an L4‐5 fusion was increased in flexion. When the L5‐S1 segment was also fused, the loss of segmental motion in both flexion and extension at the L4‐5 and L5‐S1 were compensated for by increased motion in all levels above the fusion. In both flexion and extension, the intradiscal pressures of all unfused intervertebral discs were increased after a single level L4‐5 fusion and this increase was even more marked after a double level L4‐5‐S1 fusion. Conclusions There is no evidence that the neighboring unfused segments are loaded beyond their physiological limits due to the fusion. However, the neighboring unfused segments have to work more frequently toward the extremes of their functional ranges of motion after fusion and these effects will be more marked after a double level L4‐5‐S1 fusion.

Strontium Promotes Osteogenic Differentiation of Mesenchymal Stem Cells Through the Ras/MAPK Signaling Pathway

Strontium ralenate is a new anti-osteoporosis agent. The cellular and molecular mechanism underlying the anabolic effect of strontium on bone remains to be elucidated. Osteoblasts, the main bone forming cells are known to be derived from bone marrow mesenchymal stem cells (MSCs). The present study therefore aimed to investigate the possible effects of strontium on MSCs and signaling pathways possibly involved. It was firstly demonstrated that strontium treatment significantly increased osteoblast-related gene expression and alkaline phosphatase (ALP) of osteogenic-differentiating MSCs. Accompanying the enhanced osteogenic differentiation, the increased phosphorylation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 was detected in strontium-treated MSCs. PD98059 and SB203580, selective inhibitors of ERK1/2 kinase and p38, attenuated the effect of strontium on osteogenesis. Furthermore, it was demonstrated that Rat Sarcoma viral oncogene homolog (RAS), an upstream regulator of ERK1/2 and p38, was activated by strontium treatment and siRNA-mediated Ras knockdown inhibited strontium-stimulated expression of osteogenic markers. Finally, the transcriptional activity and phosphorylation level of Runx2 was significantly increased in response to strontium treatment in MSCs. PD98059 and Ras siRNA inhibited the effect of strontium on Runx2 activation. Taken together, these results indicated that strontium can promote osteogenic differentiation of MSCs through activating the Ras/MAPK signaling pathway and the downstream transcription factor Runx2.

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.

A Genetic Locus for Adolescent Idiopathic Scoliosis Linked to Chromosome 19p13.3

Adolescent idiopathic scoliosis (AIS) is one of the most common orthopedic disorders, affecting up to 4% of schoolchildren worldwide. We studied seven unrelated multiplex families of southern Chinese descent with AIS, consisting of 25 affected members. A genomewide scan with >400 fluorescent microsatellite markers was performed. Multipoint linkage analysis by GENEHUNTER revealed significant linkage of the abnormal phenotype to the distal short arm of chromosome 19, with both a maximum multipoint LOD score and a nonparametric LOD score of 4.93. Two-point linkage analysis by MLINK gave a LOD score of 3.63 (recombination fraction theta[m=f]=0.00) at D19S216. Further high-density mapping and informative recombinations defined the AIS critical region in the vicinity of D19S216, flanked by D19S894 and D19S1034, spanning 5.2 cM on the sex-averaged genetic map on chromosome 19p13.3.

A novel injectable bioactive bone cement for spinal surgery: A developmental and preclinical study

The injection of bone cement by minimally invasive techniques for the treatment of vertebral body fractures or for stabilization of an osteoporotic vertebral body is regarded as promising in spinal surgery. The purpose of this study was to develop a novel injectable bioactive bone cement to address such concerns. The cement was composed mainly of strontium-containing hydroxyapatite (Sr-HA) filler and Bisphenol A Diglycidylether Dimethacrylate (D-GMA) resin. The Sr-HA filler was prepared by precipitation and calcination, then analyzed with Fourier transform infrared (FTIR) spectra and X-ray diffraction (XRD) patterns. Samples of strontium-containing hydroxyapatite cement (SrHAC) were formed by a combination of powder filler and resin matrix, with the setting time and peak temperature recorded. Cell relative growth rate (RGR), Tetrazolium bromide (MTT), and haemolysis tests were used to detect initial in vitro biocompatibility of the new cement. In vitro spinal biomechanical testing and morphological observation after bone cement injection were performed on pig spines. Results indicate that the setting time and peak temperature of the cement was 15 min and 55 degrees C, respectively. Cytotoxicity of the cement was class 1 (no cytotoxicity) and haemolysis was 1% (no haemolysis). Stiffness after cement injection and fatigue loading were 112% and 95% of the intact bone, respectively, which is similar to that of natural bone. Radiopacity of SrHAC allowed easy radiographic imaging. The use of SrHAC cement is, thus, promising in spinal surgery.

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.

Mechanical properties and in vitro response of strontium-containing hydroxyapatite/polyetheretherketone composites.

Strontium-containing hydroxyapatite/polyetheretherketone (Sr-HA/PEEK) composites were developed as alternative materials for load-bearing orthopaedic applications. The amount of strontium-containing hydroxyapatite (Sr-HA) incorporated into polyetheretherketone (PEEK) polymer matrix ranged from 15 to 30 vol% and the composites were successfully fabricated by compression molding technique. This study presents the mechanical properties and in vitro human osteoblast-like cell (MG-63) response of the composite material developed. The bending modulus and strength of Sr-HA/PEEK composites were tailored to mimic human cortical bone. PEEK reinforced with 25 and 30 vol% Sr-HA exhibited bending modulus of 9.6 and 10.6 GPa, respectively; alternatively, the bending strengths of the composites were 93.8 and 89.1 MPa, respectively. Based on the qualitative comparison of apatite formation in SBF and quantitative measurement of MG-63-mediated mineralization in vitro, the Sr-HA/PEEK composite was proven to outperform HA/PEEK in providing bioactivity. However, no difference was found in the trend of cell proliferation and alkaline phosphatase activity between different composites. Strontium, in the form of strontium-containing hydroxyapatite (Sr-HA), was confirmed to enhance bioactivity in the PEEK composites.