A total of 22 patients with a tibial avulsion fracture involving the insertion of the posterior cruciate ligament (PCL) with grade II or III posterior laxity were reduced and fixed arthroscopically using routine anterior and double posteromedial portals. A double-strand Ethibond suture was inserted into the joint and wrapped around the PCL from anterior to posterior to secure the ligament above the avulsed bony fragment. Two tibial bone tunnels were created using the PCL reconstruction guide, aiming at the medial and lateral borders of the tibial bed. The ends of the suture were pulled out through the bone tunnels and tied over the tibial cortex between the openings of the tunnels to reduce and secure the bony fragment. Satisfactory reduction of the fracture was checked arthroscopically and radiographically.

The patients were followed-up for a mean of 24.5 months (19 to 28). Bone union occurred six weeks post-operatively. At final follow-up, all patients had a negative posterior drawer test and a full range of movement. KT-1000 arthrometer examination showed that the mean post-operative side-to-side difference improved from 10.9 mm (standard deviation (sd) 0.7) pre-operatively to 1.5 mm (sd 0.6) (p = 0.001). The mean Tegner and the International Knee Documentation Committee scores improved significantly (p = 0.001). The mean Lysholm score at final follow-up was 92.0 (85 to 96).

We conclude that this technique is convenient, reliable and minimally invasive and successfully restores the stability and function of the knee.

Cite this article: Bone Joint J 2015;97-B:1220–5.

Introduction:

Wear debris from articulating joint implants is inevitable. Small debris particles are phagocytosed by macrophages. Larger particles initiate the fusion of many macrophages into multi-nucleated giant cells for particle encasement. Macrophages are recruited into inflamed tissues from the circulating monocyte population. Approximately 10% of white blood cells are monocytes which after release from the bone marrow circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating MRP8/14 (S100A8/A9) is a measure of monocyte recruitment, part of the monocyte-endothelial docking complex, and shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of debris production.

Introduction:

The risk factors for degenerative joint disease are well established: increasing age, obesity, joint abnormalities, trauma and overuse, together with female gender, ethnic and genetic factors. That obesity is a significant risk factor for developing osteoarthritis in non-weight-bearing as well as weight-bearing and joints was one of the first indications that the risk was nor purely that of aberrant biomechanical loading. Low grade chronic systemic inflammation is a component of each of ageing and obesity, atherosclerosis and diabetes, culminating in Metabolic Syndrome. In our study of 1684 patients with joint degeneration 85% were overweight or obese and 65% older than 65 years with 62% being both, 73% of patients were taking medications for serious, ‘non-orthopaedic’ health problems such as cardiovascular or respiratory disease, obesity or NIDDM. Monocytes are a major component of chronic inflammation, approximately 10% of white blood cells are monocytes which circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating S100A8/A9 (MRP8/14) is a measure of monocyte recruitment being shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of chronic inflammatory status.

Purpose

Internal fixation of fractures in the presence of osteopenia has been associated with a failure rate as high as 25%. Enhancing bone formation and osseointegration of orthopaedic hardware is a priority when treating patients with impaired bone regenerative capacity. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications in implant integration. This study was designed to determine if FGF 18 promotes bone formation and osseointegration in the osteopenic FGFR3−/− mouse and to examine its effect on bone marrow derived mesenchymal stem cells (MSCs).

Introduction: Long-term treatment of chronic muscu-loskeletal pain with opioids often causes a cluster of unpleasant side effects such as constipation, dizziness and cognitive impairment and is likely to lead to tolerance and to hyperalgesia, which is clinically important but not yet well researched. In this study we investigated the development of hyperalgesia after long-term treatment with opioids in patients with chronic low back pain (cLBP). The goal of this prospective longitudinal study was to investigate the long-term (> 1.5 years) effects of opioid analgetics on thermal sensation and pain thresholds and to follow the changes in pain sensitivity for 6 months during opioid withdrawal.

Methods: Using quantitative sensory testing (QST), we compared thermal sensation and pain thresholds on the palm of the hand and the low back bilaterally among three groups: patients with cLBP and long-term treatment with opioids (group 1, n=35); opioid-naive patients with chronic low back pain (group 2, n=34) and subjects with neither pain nor opioid intake (group 3, n=27). The effects of age, sex, pain duration, duration and dose of opioid intake, comorbidity (depression) and self-reported pain intensity assessed by QST were investigated.

All patients were allocated to a 3-week multidisciplinary functional restoration programme that emphasized biopsychosocial factors and included continuous tapering of opioid dose. During the study all patients kept records of the medication they used.

Results: Group 1 patients showed significantly delayed reaction to cold and warm stimuli on the back, compared with both group 2 and group 3. Pain thresholds for cold and heat on the hand were similar in group 1 and 2 but significantly reduced in these groups compared with group 3. Age, sex, pain duration, duration and dose of opioid intake, and self-reported pain intensity, but not depression, correlated significantly with QST results.

Discussion: The present study demonstrated that long-term opioid use significantly delayed thermal QST responses but had no measureable analgesic effects in patients with chronic low back pain. While the pain thresholds in groups 1 and 2 did not differ before opioid withdrawal, both groups 1 and 2 were more sensitive to pain than group 3 (healthy controls). This finding confirms that chronic low back pain itself might cause increased pain sensitivity, which seems not to be counteracted by opioid medication. Rather, treatment in the multidisciplinary pain therapy programme had positive effects on pain thresholds in opioid-naive patients but not in patients after opioid withdrawal. The opioid-naive patients of group 2 showed normalized pain thresholds 6 months after therapy, while the former opioid-positive patients of group 1 still had significantly decreased pain thresholds despite 6 months’ abstinence.

The thrombin-related peptide, TP508, a synthetic 23 amino acid peptide, has been shown to promote soft tissue, cartilage and fracture repair. We have previously demonstrated that two injections of TP508 have signifi-cantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to test if a single injection of TP508 in a slow-releasing preparation will have the similar effects.

Unilateral tibial osteoectomies were stabilized with M100 Orthofix lengtheners in 17 male adult NZW rabbits. After 7 days, lengthening was initiated at a rate of 1.4 mm/day for 6 days. The following treatments were given: Group 1: TP508 in saline (300ug/300ul, n=6) was injected into the osteotomy gap at day of surgery and into the lengthening gap at end of lengthening. Group 2 (Control): Dextran gel (300ul, n=6) and Group 3: 300ul Dextran gel mixed with microspheres containing 300ug TP508 (n=5), was injected into the lengthening gap at end of lengthening. All animals were terminated 2 weeks after lengthening. Bone formation was assessed by weekly radiography and the specimens were subject to pQCT, microCT and histology examinations.

On radiographies there was more bone formation in the TP508 treated groups than that of the control group at 1st week post-lengthening and complete union was seen in 50% rabbits in Group 1, 33% in Group 2, and 60% in Group 3 at termination. The mean BMD of the regenerates was significantly higher in the TP508 treated groups than that of the control group (p< 0.05). MicroCT analysis demonstrated advanced bone formation in the TP508 treated animals. For histology, the regenerates were mainly consisted of woven bone of neocortilization and callus remodelling in Groups 1 and 3, whereas in Group 2, focal defects with cartilaginous tissues were frequently seen.

In conclusion we have demonstrated that a single injection of TP508 in the form of slow releasing micro-spheres has enhanced bone consolidation during distraction osteogenesis. TP508 may therefore be applied in the slow-releasing preparation for augmenting bone formation at reduced doses, costs and risks of infections through repeated injections.

Purpose: To develop an improved understanding of the in vivo behavior of intervertebral disc (IVD) cells for determining the phenotype of a differentiated stem cell in tissue engineering applications.

Methods: Nucleus pulposus (NP) and annulus fibrosus (AF) cells were isolated from adult bovine tails while notochordal cells were extracted from fetal bovine intervertebral disc. Ten million cells (of each cell type) in 500 & #61549;l of DMEM were then injected subcutaneously in C57Bl/6 mice. After 2 weeks, the mice were sacrificed and the specimens harvested. They were examined grossly, histologically and by scanning electronic microscopy (SEM) for the evidence of IVD-like structure formation. Proteoglycan was assessed by the GAG assay and PCR for analysis of gene expression. Control tissue (from bovine NP and AF) were directly fixed in glutaraldehyde, without any isolation technique and examined in SEM.

Results: After 2 weeks, SEM examination of specimens from AF and NP closely resembled normal bovine AF and NP. Of special interest here was the finding that some mice injected with cells from the AF developed an organized arrangement of parallel collagen fibres while NP cells injected mice had an amorphous structure with few collagen fibers. The GAG assay showed pro-teoglycan content for each samples, ranging from 3.8 microg to 26 microg. The morphology of the specimens retrieved from notochordal cells injected mice were also amorphous punctuated with thin collagen fibrils.

Conclusions: This study demonstrates that subcutaneous injection of bovine disc cells in mice can result in formation of disc structures similar to those of the bovine IVD. We believe that the cellular communication of the bovine disc cells is maintained in the mouse leading to architectural organization of the collagen fibers with the mouse as a source of nutrients. This technology may be useful in determining the phenotype of a differentiated stem cell for tissue engineering of IVD.

Purpose: Knowledge of factors regulating the turnover, repair, and degeneration of the intervertebral disc (IVD) is lacking. Although type II collagen (CII) fragments accumulate in the degenerative IVD, little is known of how they affect the degenerative process. In this study, the effect of a CII fragment, CII-(245–270), known to be critical in arthritis was investigated on gene expression of proteinases, collagen, and proteoglycan by bovine disc cells to determine its role in matrix turnover.

Methods: Cells isolated from the nucleus pulposus (NP) and annulus fibrosus (AF) of adult bovine tails were cultured in the absence (control) or presence of the fragment. The fragment CII-(245–270) (US Biological, Massachusetts) was dissolved in culture medium to a final concentration of 1& #956;g/ml. PCR was performed and products were visualized by ethidium bromide staining.

Results: Addition of the CII-(245–270) peptide at 1& #956;g/ml to NP and AF cells enhanced expression of genes for MMP-1, cathepsin K, and aggrecan after 48 hours compared with the control. MMP-13 was also upregulated in the NP. In contrast, the effect in the AF was time dependent. Type II collagen was upregulated throughout the culture time in the NP as opposed to the AF where its expression was enhanced only on day 2.

Conclusions: We have shown that the CII-(245–270) peptide can alter gene expression of proteinases, collagen, and proteoglycan in bovine disc cells. The present study reveals the complex interrelationships of gene expression in the disc that accompany fragmentation of type II collagen. This new information suggests that increased levels of these fragments, in degenerated discs, may stimulate disc breakdown but may also attempt to protect the disc, by unknown mechanisms Funding: Other Education Grant Funding Parties: AO foundation, Switzerland

Low back pain is the primary cause of disability in individuals younger than 50 years. Potential sources of low back pain include the intervertebral disks, facet joints, vertebrae, neural structures, muscles, ligaments, and fascia. Increasing evidence is available as to the importance of cytokines in acute and particular chronic pain. Cytokines can influence transduction, conduction, and transmission of the nociceptive signal, resulting in prolonged or permanent signalling to the brain’s cognitive centres in the absence of a painful noxious or nonnoxius stimulus.

Several cytokines, including IL-1, TNFa, IL-6, and IL-10 are thought to influence nociception or pain.

To date, there have been no studies of the production of inflammatory mediators in blood from patients with low back pain. We have therefore analysed levels of the proinflammatory mediators IL-1ß, IL-6, TNF-α in sera from patients with sciatica and low back pain, and their possible relationship to pain dimensions.

In this prospective longitudinal study with a follow-up of six months, the course of serum concentration of IL-1ß, IL-6 and TNF-α was measured by Bio-Plex cytokine assay in 31 patients with acute sciatica and 41 patients with chronic low back pain. Blood samples were taken at ten fixed times during follow-up, and cytokine values were adjusted to possible influential factors and correlated to the course of pain and clinical function to evaluate the predictive role of cytokine regarding therapy outcome.

At admission of the study and 10 days later, the proportion of TNF-α positive subjects was significant elevated among patients with low back pain compared to patients with acute sciatica. Median (SD) of serum TNF-α concentrations were significant higher in patients with chronic low back pain (n=41) than in patients with acute sciatica (n=31). In the whole period the pain of patients reduced from time to time. Elevated TNF-α serum levels are associated with a significantly improved pain in patients with chronic low back pain but not with acute sciatica. A close coherence exists between the cytokines IL-1ß, IL-6 and TNF-α together in blood of patients as with acute sciatica as with chronic low back pain. But no connection of IL-1ß, IL-6 or TNF-α and CRP in blood was observed. Neither age, sex, BMI, nicotine and alcohol consumption are not related to the serum levels of cytokines.

As far as we know, this is the first analysis of parameters predicting a major clinical connection of cytokines in blood and low back pain. Our findings indicate that elevated serum levels of the proinflammatory cytokine TNF-α are associated with a significantly improved pain in patients with chronic low back pain but not with acute sciatica. We concluded that Detection of high level of TNF-α might be a marker for more pain in patients with chronic low back pain. and TNF-α probably play an important role in the chronic process of low back pain.

The thrombin-related peptide, TP508, is a synthetic 23 amino acid peptide, which represents the receptor binding domain of thrombin. TP508 mimics thrombin by interacting with receptors on cells involved in tissue repair. TP508 has been shown to enhance revascularization of injured tissue, and promote soft tissue wound healing, cartilage repair, and fracture repair. The aim of this study is to (1) test the effect of TP508 on bone regeneration during distraction osteogenesis; (2) study the chemotactic effect of TP508 on human osteoblasts.

Unilateral tibial osteoectomies were performed and stabilized with MX100 Orthofix lengthener in 5 male adult NZW rabbits. After 7 days, distraction was initiated at rates of 1.4 mm / day for 6 days. TP508 (100 μg/ml, n=2; 10 μg/ml, n=1) or saline (300 μl, n=2) was injected into the osteotomy / lengthening gap at days 1, 7 and 14 post surgery. Animals were sacrificed at 2 weeks after leg lengthening. Bone formation in the regenerate was assessed by radiography, quantitative computed tomography (pQCT) and histology. For chemotaxis studies, MG63 cells were cultured on glass cover slips for three days, and then inverted onto a Dunn chamber slide and sealed with dental wax. Gradients of TP508 (1, 10, 100 μg/ml) were added to the outer well and plain medium to the inner well. A sequence of images of the cells between the wells was taken via a CCD camera for 9 hours at interval of 10 minutes. Movements of individual cells were tracked and statistically analysed by a specially written Macro program. The Rayleigh test for unimodal clustering was used to determine the directional chemotactic movements.

The radiographic evaluation indicated a significant increase in new bone in the distraction regenerate in the TP508 treated groups at 1 and 2 weeks. pQCT images at 2 weeks demonstrated more advanced bone formation in the TP508 treated animals compared to the control. The mean total bone mineral density (BMD) of the regenerate, obtained from 3 slices was significantly greater (p = 0.019, t-test) in the TP508 treated group (BMD = 479.20 +/− 35.57 mg/ccm) than that in the saline control group (BMD = 355 +/− 2.83 mg/ccm). The histological evaluation supported the radiographic and the pQCT results. For chemotaxis study, no directional movements of the cells were found in the controls, whereas the MG63 cells were strongly chemotactic to TP508 at 1, 10 and 100 μg/ml concentrations.

This preliminary study shows that administration of TP508 enhances bone formation during distraction osteogenesis in the rabbit. The findings also show that TP508 has a chemotactic effect on osteoblasts, consistent with the effect of TP508 on fracture repair. A large animal study is in the process to confirm these findings and explore the underlying mechanisms.

A new method of recording the three-dimensional anatomy of the proximal femur from a single anteroposterior radiograph is described. This technique shows that in Perthes' disease the femoral head and neck are in significant anteversion and true varus. This anatomical configuration may be important in the pathogenesis and treatment of this disorder.