René M. Castelein

The pathogenesis of adolescent idiopathic scoliosis: review of the literature.

Study Design. Review of the literature on the pathogenesis of adolescent idiopathic scoliosis (AIS). Objective. To discuss the different theories that have appeared on this subject. Summary of Background Data. The pathogenesis of AIS, a condition exclusive to humans, has been the subject of many studies. Over the years, practically every structure of the body has been mentioned in the pathogenesis of AIS; however, the cause of this spinal deformity remains little understood. The pathogenesis of this condition is termed multifactorial. Methods. PubMed and Google Scholar electronic databases were searched focused on parameters concerning the pathogenesis of adolescent idiopathic scoliosis. The search was limited to the English language. Results. No single causative factor for the development of idiopathic scoliosis has been identified, it is thus termed multifactorial. AIS is a complex genetic disorder. The fully erect posture, which is unique to humans, seems to be a prerequisite for the development of AIS. Conclusion. Although any or all of the mentioned factors in this review may play a certain role in the initiation and progression of AIS at a certain stage, the presented material suggests that in the observed deformation, genetics, and the unique mechanics of the fully upright human spine play a decisive role.

Differences in male and female spino-pelvic alignment in asymptomatic young adults: a three-dimensional analysis using upright low-dose digital biplanar X-rays.

Study Design. A three-dimensional analysis of spino-pelvic alignment in 60 asymptomatic young adult males and females. Objectives. To analyze the differences in sagittal spino-pelvic alignment in a group of asymptomatic young adult males and females and describe gender specific reference values. Summary of Background Data. Several spinal disorders like idiopathic scoliosis and Scheuermanns disease have a well-known sex-related prevalence ratio. As spino-pelvic alignment plays an important role in spinal biomechanics, it is imperative to analyze possible differences between the male and female spino-pelvic alignment. Furthermore, in spinal fusion surgery, normal sagittal balance should be recreated as closely as possible. Methods. An innovative biplanar ultra low-dose radiographic technique was used to obtain three-dimensional reconstructions of the spine (T1–L5), sacrum, and pelvis in a freestanding position of 30 asymptomatic young male and 30 young female adults. Values were calculated for thoracic kyphosis (T4–T12), lumbar lordosis (L1–S1), total and regional lumbopelvic lordosis (PRT12, PRL2, PRL4, and PRL5), sagittal plumb line of T1, T4, and T9 (HAT1, HAT4, and HAT9), T1–L5 sagittal spinal inclination, T9 sagittal offset, and pelvic parameters (pelvic tilt, sacral slope, and pelvic incidence). In addition, vertebral inclination in the sagittal plane of each vertebra was measured. Differences in spino-pelvic alignment between the sexes were analyzed. Results. The female spine was more dorsally inclined (11° vs. 8°; P = 0.003). High thoracic and thoracolumbar vertebrae were more dorsally inclined in women than in men. Thoracic kyphosis, lumbar lordosis, regional lumbopelvic lordosis, sagittal plumb lines, T9 sagittal offset, and pelvic parameters were not statistically different between the sexes. Conclusion. These results indicate that the female spine is definitely different from the male spine. The spine as whole and individual vertebrae in certain regions of the normal spine is more backwardly inclined in females than in males. Based on our previous research this signifies that these spinal regions are subjected to different biomechanical loading conditions. These vertebral segments are possibly less rotationally stable in females than in males.

Analysis of preexistent vertebral rotation in the normal spine

Study Design. A newly developed CT measurement method was used to investigate axial rotation from T2 to L5 in the normal, nonscoliotic spine. Objectives. To identify a preexistent rotational pattern in the normal, nonscoliotic spine. Summary of Background Data. The data available on axial rotation measurements in the normal spine are scant and limited to only a few vertebrae. Systematic analysis of the thoracic and lumbar vertebrae of the normal spine, based on computed tomography has, to our knowledge, not been performed. Methods. CT scans of the thorax and abdomen of 50 persons without clinical or radiologic evidence of scoliosis were used to measure vertebral axial rotation from T2 to L5 with a newly developed semiautomatic computerized method. Results. The results of the present study showed a predominant rotation to the left of the high thoracic vertebrae, and to the right of the mid and lower thoracic vertebrae in the normal, nonscoliotic spine, which differed significantly from an equal right-left distribution. This rotational pattern is present in both males and females. Conclusion. The normal, nonscoliotic spine demonstrates a preexistent pattern of vertebral rotation that corresponds to what is seen in the most prevalent types of thoracic idiopathic scoliosis.

Tissue structure modification in knee osteoarthritis by use of joint distraction: an open 1-year pilot study

Background Modification of joint tissue damage is challenging in late-stage osteoarthritis (OA). Few options are available for treating end-stage knee OA other than joint replacement. Objectives To examine whether joint distraction can effectively modify knee joint tissue damage and has the potential to delay prosthesis surgery. Methods 20 patients (<60 years) with tibiofemoral OA were treated surgically using joint distraction. Distraction (∼5 mm) was applied for 2 months using an external fixation frame. Tissue structure modification at 1 year of follow-up was evaluated radiographically (joint space width (JSW)), by MRI (segmentation of cartilage morphology) and by biochemical markers of collagen type II turnover, with operators blinded to time points. Clinical improvement was evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) pain score. Results Radiography demonstrated an increase in mean and minimum JSW (2.7 to 3.6 mm and 1.0 to 1.9 mm; p<0.05 and <0.01). MRI revealed an increase in cartilage thickness (2.4 to 3.0 mm; p<0.001) and a decrease of denuded bone areas (22% to 5%; p<0.001). Collagen type II levels showed a trend towards increased synthesis (+103%; p<0.06) and decreased breakdown (−11%; p<0.08). The WOMAC index increased from 45 to 77 points, and VAS pain decreased from 73 to 31 mm (both p<0.001). Conclusions Joint distraction can induce tissue structure modification in knee OA and could result in clinical benefit. No current treatment is able to induce such changes. Larger, longer and randomised studies on joint distraction are warranted.

A review of methods for evaluating the quantitative parameters of sagittal pelvic alignment

BACKGROUND CONTEXT The sagittal alignment of the pelvis represents the basic mechanism for maintaining postural equilibrium, and a number of methods were developed to assess normal and pathologic pelvic alignments from two-dimensional sagittal radiographs in terms of positional and anatomic parameters. PURPOSE To provide a complete overview of the existing methods for quantitative evaluation of sagittal pelvic alignment and summarize the relevant publications. STUDY DESIGN Review article. METHODS An Internet search for terms related to sagittal pelvic alignment was performed to obtain relevant publications, which were further supplemented by selected publications found in their lists of references. By summarizing the obtained publications, the positional and anatomic parameters of sagittal pelvic alignment were described, and their values and relationships to other parameters and features were reported. RESULTS Positional pelvic parameters relate to the position and orientation of the observed subject and are represented by the sacral slope, pelvic tilt, pelvic overhang, sacral inclination, sacrofemoral angle, sacrofemoral distance, pelvic femoral angle, pelvic angle, and sacropelvic translation. Anatomic pelvic parameters relate to the anatomy of the observed subject and are represented by the pelvisacral angle (PSA), pelvic incidence (PI), pelvic thickness (PTH), sacropelvic angle (PRS1), pelvic radius (PR), femorosacral posterior angle (FSPA), sacral table angle (STA), and sacral anatomic orientation (SAO). The review was mainly focused on the evaluation of anatomic pelvic parameters, as they can be compared among subjects and therefore among different studies. However, ambiguous results were yielded for normal and pathologic subjects, as the reported values show a relatively high variability in terms of standard deviation for every anatomic parameter, which amounts to around 10 mm for PTH and PR; 10° for PSA, PI, and SAO; 9° for PRS1 and FSPA; and 5° for STA in the case of normal subjects and is usually even higher in the case of pathologic subjects. Among anatomic pelvic parameters, PI was the most studied and therefore represents a key parameter in the complex framework of sagittal spinal alignment and related deformities. From the reviewed studies, the regression lines for PI and the corresponding age of the subjects indicate that PI tends to increase with age for normal (PI = +0.17 × age+46.40) and scoliotic (PI = +0.20 × age+50.52) subjects and decrease with age for subjects with spondylolisis or spondylolisthesis (PI = -0.26 × age+75.69). CONCLUSIONS Normative values for anatomic parameters of sagittal pelvic alignment do not exist because the variability of the measured values is relatively high even for normal subjects but can be predictive for spinal alignment and specific spinopelvic pathologies.

The incidence of donor site pain after bone graft harvesting from the posterior iliac crest may be overestimated : A study on spine fracture patients

Study Design. A retrospective cohort study on patients with traumatic vertebral fractures who underwent fusion with iliac crest bone. Objective. To evaluate the influence of low back surgery on donor site attributed pain, we compared donor site pain between patients who underwent high and low level fusions. Summary of Background Data. The most common complication of posterior iliac crest bone graft harvesting is postoperative pain at the donor site. The incidence of donor site pain after bone graft harvesting from the posterior iliac crest is mainly reported from studies in patients who underwent low lumbar or lumbosacral surgery. The close proximity of the primary surgery to the iliac crest could interfere with the reported incidence of donor site pain. Methods. Questionnaires regarding the iliac crest morbidity were sent to patients who underwent instrumented posterolateral fusion after traumatic spinal fractures. The incidence of donor site attributed pain was compared between patients whose fusion was between T2 and L2, with patients whose fusion extended to L3 or more caudally. Results. In patients with a fusion of high levels, the donor site pain was significantly lower compared with patients with fusion of low levels (14.3% vs. 40.9%). Conclusion. Patients probably cannot differentiate between donor site pain and residual low back pain. The reported incidence of pain related to posterior iliac crest bone graft harvesting may therefore be overestimated.

Identification of orthopaedic infections using broad-range polymerase chain reaction and reverse line blot hybridization.

BACKGROUND Culture remains the gold standard in the diagnosis of bacterial infection, but molecular biological techniques have yielded promising results. In this study, we validated a combined polymerase chain reaction and reverse line blot hybridization protocol for identifying musculoskeletal infections. METHODS Samples were obtained from seventy-six patients undergoing orthopaedic surgery for various aseptic and septic indications. The diagnosis of infection was based on a review of all available clinical and culture data. In addition to routine culture for aerobic and anaerobic growth, samples were analyzed with a broad-range 16S rRNA polymerase chain reaction and subsequent reverse line blot hybridization with use of twenty-eight group, genus, and species-specific oligonucleotide probes. RESULTS An infection was diagnosed on the basis of patient data in thirty-one patients. All but one of the patients with a clinical diagnosis of infection had a positive result of the polymerase chain reaction-reverse line blot hybridization. Five of the forty-five patients in whom an infection was not suspected on the basis of patient data had at least one positive result of the polymerase chain reaction-reverse line blot hybridization. Cultures demonstrated microorganisms in twenty-five patients with an infection and in two patients in whom an infection was not suspected on the basis of the patient data. Staphylococcus aureus was the most common organism grown on culture. The species identified by the polymerase chain reaction-reverse line blot hybridization was in full accordance with that grown on culture in all but one patient. CONCLUSIONS Polymerase chain reaction-reverse line blot hybridization performed well in detecting and identifying the various bacterial species and was more sensitive than routine culture. It identified Staphylococcus aureus as the most frequently found microorganism. Five patients in whom an infection was not suspected on the basis of the patient data had a positive result of the polymerase chain reaction, which may have been caused by contamination of the samples. However, three of these patients had aseptic loosening of a total hip prosthesis, suggesting the presence of a low-grade bacterial infection that remained undetected by the culture but was detected by the polymerase chain reaction-reverse line blot hybridization. LEVEL OF EVIDENCE Diagnostic Level III.

Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels

Intervertebral disc (IVD) degeneration is associated with the increased expression of several matrix metalloproteinases (MMPs), in particular MMP‐2. However, little is known about the actual activity of MMP‐2 in healthy and degenerated discs, or what mechanisms are involved in its activation. A major activation pathway involves complex formation with MMP‐14 and a tissue inhibitor of metalloproteinases‐2 (TIMP‐2). In a series of 56 human IVDs, obtained at autopsy and graded according to the Thompson score (I–V), we analysed whether MMP‐2 activity was increased in different stages of IVD degeneration and to what extent activation was related to the production of MMP‐14 and TIMP‐2. MMP‐2 activation and production were quantified by gelatin zymography. Immunohistochemical staining of MMP‐14 and TIMP‐2 was quantified with a video overlay‐based system. A positive correlation was observed between the amount of active MMP‐2 and pro‐MMP‐2 and degeneration grade (p < 0.001, correlation coefficient (CC) 0.557; and p < 0.001, CC 0.556, respectively). MMP‐2 activity correlated positively with MMP‐14 and less strongly with TIMP‐2 (p = 0.001, CC 0.436; and p = 0.03, CC 0.288, respectively). Moreover, immunopositivity for MMP‐14 correlated to degeneration grade (p = 0.002, CC 0.398). IVD degeneration was associated with the activity of MMP‐2 and the correlation of its activation with MMP‐14 production suggests MMP‐14 activates MMP‐2 during degeneration. As MMP‐14 is capable of activating several other enzymes that are also thought to be involved in IVD degeneration, it may be a key mediator of the degenerative process. Copyright

In Vitro Release of Antibiotics from Commercial PMMA Beads and Articulating Hip Spacers

The efficacy and benefits of high-dose antibiotic cement spacers compared with beads in the treatment of an infected prosthesis have been shown. However, in clinical practice, commercial, low-dose antibiotic bone cement is often used. This study investigated the in vitro antibiotic release of hip spacers made from Refobacin-Palacos-R or Antibiotic-Simplex-P cement compared with Septopal beads. Antibiotic concentrations were measured during 6 weeks. All carriers showed a burst release, but spacers showed little additional release after the first week. Cumulative release was 27.5 +/- 2.3 mg for Palacos, 23.8 +/- 0.2 mg for Simplex, and 188.3 +/- 9.3 mg for Septopal (P < .001). Despite the efficacy of high-dose antibiotic bone cement spacers, we believe one should be cautious toward using low-dose antibiotic bone cement for spacers because this could result in an unsuccessful eradication of infection.

Hypertrophic differentiation and calcification during intervertebral disc degeneration.

BACKGROUND In degenerative intervertebral discs (IVDs) collagen type X expression and calcifications have been demonstrated, resembling advanced osteoarthritis (OA), which is associated with hypertrophic differentiation, characterized by the production of collagen type X, Runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), alkaline phosphatase (ALP) and calcifications. OBJECTIVE The aim of this study was to determine if hypertrophic differentiation occurs during IVD degeneration. METHODS IVDs from all Thompson degeneration grades were prepared for histology, extraction of nucleus pulposus (NP) and annulus fibrosis (AF) tissue (N=50) and micro-CT (N=27). The presence of collagen type X, OPG and Runx2 was determined by immunohistochemistry, with OPG levels also determined by Enzyme-linked immunosorbent assay (ELISA). The presence of calcification was determined by micro-CT, von Kossa and Alizarin Red staining. RESULTS Immunohistochemical staining for collagen type X, OPG, Runx2 appeared more intense in the NP of degenerative compared to healthy IVD samples. OPG levels correlated significantly with degeneration grade (NP: P<0.000; AF: P=0.002) and the number of microscopic calcifications (NP: P=0.002; AF: P=0.008). The extent of calcifications on micro-CT also correlated with degeneration grade (NP: P<0.001, AF: P=0.001) as did von Kossa staining (NP: P=0.015, AF: P=0.016). ALP staining was only incidentally seen in the transition zone of grades IV and V degenerated IVDs. CONCLUSION This study for the first time demonstrates that hypertrophic differentiation occurs during IVD degeneration, as shown by an increase in OPG levels, the presence of ALP activity, increased immunopositivity of Runx2 and collagen type X.