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The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 9 | Pages 1217 - 1222
1 Sep 2009
King RJ Makrides P Gill JA Karthikeyan S Krikler SJ Griffin DR

We have developed a novel method of calculating the radiological magnification of the hip using two separate radio-opaque markers. We recruited 74 patients undergoing radiological assessment following total hip replacement. Both the new double marker and a conventional single marker were used by the radiographer at the time of x-ray. The predicted magnification according to each marker was calculated, as was the true radiological magnification of the components. The correlation between true and predicted magnification was good using the double marker (r = 0.90, n = 74, p < 0.001), but only moderate for the single marker (r = 0.50, n = 63, p < 0.001). The median error was significantly less for the double marker than for the single (1.1% vs 4.8%, p < 0.001). The double marker method demonstrated excellent validity (intraclass correlation coefficient = 0.89), in contrast to the single marker (0.32).

The double marker method appears to be superior to the single marker method when used in the clinical environment.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 7 | Pages 918 - 921
1 Jul 2009
Finestone A Milgrom C Radeva-Petrova DR Rath E Barchilon V Beyth S Jaber S Safran O

We undertook a prospective study in 51 male patients aged between 17 and 27 years to ascertain whether immobilisation after primary traumatic anterior dislocation of the shoulder in external rotation was more effective than immobilisation in internal rotation in preventing recurrent dislocation in a physically active population.

Of the 51 patients, 24 were randomised to be treated by a traditional brace in internal rotation and 27 were immobilised in external rotation of 15° to 20°. After immobilisation, the patients undertook a standard regime of physiotherapy and were then assessed clinically for evidence of instability. When reviewed at a mean of 33.4 months (24 to 48) ten from the external rotation group (37%) and ten from the internal rotation group (41.7%) had sustained a futher dislocation. There was no statistically significant difference (p = 0.74) between the groups.

Our findings show that external rotation bracing may not be as effective as previously reported in preventing recurrent anterior dislocation of the shoulder.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 230 - 230
1 May 2009
Bell T Bourne RB MacDonald SJ McCalden RW Naudie DR Ralley F
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The purpose of this study was to evaluate the impact of dalteparin use on transfusion rates and blood loss in patients undergoing primary total joint arthroplasty at our center.

We prospectively studied the transfusion patterns of 1642 patients who underwent primary total hip or knee arthroplasty between January 2004 and December 2005 by five arthroplasty surgeons. The influence of daltaperin use, release of tourniquet in total knee arthroplasty, and the turnover of house staff were analyzed using SPSS V14.0 statistical software.

We identified seven hundred and three total hip and nine hundred and thirty-nine knee arthroplasty patients. The mean haemoglobin drop was statistically significant between 2004 and 2005 (p< 0.001). This was seen in both hip (p=0.014) and knee (p< 0.001) patients. Subgroup analysis of total knee arthroplasty revealed a significant difference in haemoglobin drop between surgeons who released the tourniquet prior to closure compared to release at the end of the case (p=0.005). In addition, there were significant monthly differences that corresponded with the turnover of house staff (p=0.039). Overall, no statistically significant increase in allogeneic transfusion rates was observed between years, months, and individual surgeons.

The use of dalteparin was found to be associated with a significantly increased haemoglobin drop in primary total joint replacement when compared to warfarin. However, the use of dalteparin was not associated with an increase in allogeneic transfusions at our center. The results also suggest that there may be an advantage to releasing the tourniquet and achieving hemostasis prior to closure in knee arthroplasty. Finally, the results emphasise the importance of educating new house staff on methods to reduce intra-operative blood loss and transfusion rates.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 2 | Pages 190 - 195
1 Feb 2009
Robertson DD Armfield DR Towers JD Irrgang JJ Maloney WJ Harner CD

We describe injuries to the posterior root of the medial meniscus in patients with spontaneous osteonecrosis of the medial compartment of the knee. We identified 30 consecutive patients with spontaneous osteonecrosis of the medial femoral condyle. The radiographs and MR imaging were reviewed. We found tears of the posterior root of the medial meniscus in 24 patients (80%). Of these, 15 were complete and nine were partial. Complete tears were associated with > 3 mm of meniscal extrusion. Neither the presence of a root tear nor the volume of the osteonecrotic lesion were associated with age, body mass index (BMI), gender, side affected, or knee alignment. The grade of osteoarthritis was associated with BMI.

Although tears of the posterior root of the medial meniscus were frequently present in patients with spontaneous osteonecrosis of the knee, this does not prove cause and effect. Further study is warranted.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 11 | Pages 1487 - 1494
1 Nov 2008
Zlowodzki M Brink O Switzer J Wingerter S Woodall J Petrisor BA Kregor PJ Bruinsma DR Bhandari M

We have studied the effect of shortening of the femoral neck and varus collapse on the functional capacity and quality of life of patients who had undergone fixation of an isolated intracapsular fracture of the hip with cancellous screws. After screening 660 patients at four university medical centres, 70 patients with a mean age of 71 years (20 to 90) met the inclusion criteria. Overall, 66% (46 of 70) of the fractures healed with > 5 mm of shortening and 39% (27 of 70) with > 5° of varus. Patients with severe shortening of the femoral neck had significantly lower short form-36 questionnaire (SF-36) physical functioning scores (no/mild (< 5 mm) vs severe shortening (> 10 mm); 74 vs 42 points, p < 0.001). A similar effect was noted with moderate shortening, suggesting a gradient effect (no/mild (< 5 mm) vs moderate shortening (5 to 10 mm); 74 vs 53 points, p = 0.011). Varus collapse correlated moderately with the occurrence of shortening (r = 0.66, p < 0.001). Shortening also resulted in a significantly lower EuroQol questionnaire (EQ5D) index scores (p = 0.05). In a regression analysis shortening of the femoral neck was the only significant variable predictive of a low SF-36 physical functioning score (p < 0.001).


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 958 - 965
1 Jul 2008
Leong JJH Leff DR Das A Aggarwal R Reilly P Atkinson HDE Emery RJ Darzi AW

The aim of this study was to validate the use of three models of fracture fixation in the assessment of technical skills. We recruited 21 subjects (six experts, seven intermediates, and eight novices) to perform three procedures: application of a dynamic compression plate on a cadaver porcine model, insertion of an unreamed tibial intramedullary nail, and application of a forearm external fixator, both on synthetic bone models. The primary outcome measures were the Objective Structural Assessment of technical skills global rating scale on video recordings of the procedures which were scored by two independent expert observers, and the hand movements of the surgeons which were analysed using the Imperial College Surgical Assessment Device.

The video scores were significantly different for the three groups in all three procedures (p < 0.05), with excellent inter-rater reliability (α = 0.88). The novice and intermediate groups specifically were significantly different in their performance with dynamic compression plate and intramedullary nails (p < 0.05). Movement analysis distinguished between the three groups in the dynamic compression plate model, but a ceiling effect was demonstrated in the intramedullary nail and external fixator procedures, where intermediates and experts performed to comparable standards (p > 0.6). A total of 85% (18 of 21) of the subjects found the dynamic compression model and 57% (12 of 21) found all the models acceptable tools of assessment.

This study has validated a low-cost, high-fidelity porcine dynamic compression plate model using video rating scores for skills assessment and movement analysis. It has also demonstrated that Synbone models for the application of and intramedullary nail and an external fixator are less sensitive and should be improved for further assessment of surgical skills in trauma. The availability of valid objective tools of assessment of surgical skills allows further studies into improving methods of training.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 442 - 445
1 Apr 2008
Amarasekera HW Costa ML Foguet P Krikler SJ Prakash U Griffin DR

We used Laser Doppler flowmetry to measure the effect on the blood flow to the femoral head/neck junction of two surgical approaches during resurfacing arthroplasty. We studied 24 hips undergoing resurfacing arthroplasty for osteoarthritis. Of these, 12 had a posterior approach and 12 a trochanteric flip approach. A Laser probe was placed under radiological control in the superolateral part of the femoral head/neck junction. The Doppler flux was measured at stages of the operation and compared with the initial flux. In both groups the main fall in blood flow occurred during the initial exposure and capsulotomy of the hip joint.

There was a greater reduction in blood flow with the posterior (40%) than with the trochanteric flip approach (11%).


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 3 | Pages 336 - 342
1 Mar 2008
Cuff DJ Virani NA Levy J Frankle MA Derasari A Hines B Pupello DR Cancio M Mighell M

We retrospectively reviewed 21 patients (22 shoulders) who presented with deep infection after surgery to the shoulder, 17 having previously undergone hemiarthroplasty and five open repair of the rotator cuff. Nine shoulders had undergone previous surgical attempts to eradicate their infection. The diagnosis of infection was based on a combination of clinical suspicion (16 shoulders), positive frozen sections (> 5 polymorphonuclear leukocytes per high-power field) at the time of revision (15 shoulders), positive intra-operative cultures (18 shoulders) or the pre-operative radiological appearances. The patients were treated by an extensive debridement, intravenous antibiotics, and conversion to a reverse shoulder prosthesis in either a single- (10 shoulders) or a two-stage (12 shoulders) procedure.

At a mean follow-up of 43 months (25 to 66) there was no evidence of recurrent infection. All outcome measures showed statistically significant improvements. Mean abduction improved from 36.1° (sd 27.8) pre-operatively to 75.7° (sd 36.0) (p < 0.0001), the mean forward flexion from 43.1° (sd 33.5) to 79.5° (sd 43.2) (p = 0.0003), and mean external rotation from 10.2° (sd 18.7) to 25.4° (sd 23.5) (p = 0.0037). There was no statistically significant difference in any outcome between the single-stage and the two-stage group.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1293 - 1298
1 Oct 2006
Allami MK Fender D Khaw FM Sandher DR Esler C Harper WM Gregg PJ

Using the Trent regional arthroplasty register, we analysed the survival at ten years of 1198 consecutive Charnley total hip replacements carried out across a single health region of the United Kingdom in 1990. At ten years, information regarding outcome was available for 1001 hips (83.6%). The crude revision rate was 6.2% (62 of 1001) and the cumulative survival rate with revision of the components as an end-point was 93.1%. At five years, a review of this series of patients identified gross radiological failure in 25 total hip replacements which had previously been unrecognised. At ten years the outcome was known for 18 of these 25 patients (72%), of whom 13 had not undergone revision.

This is the first study to assess the survival at ten years for the primary Charnley total hip replacement performed in a broad cross-section of hospitals in the United Kingdom, as opposed to specialist centres. Our results highlight the importance of the arthroplasty register in identifying the long-term outcome of hip prostheses.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 7 | Pages 955 - 958
1 Jul 2006
Siegel HJ Connor GS Lee D Lopez-Ben R Kelly DR

We report a case of bifocal rhabdomyosarcoma involving the hand and thigh in an 11-year-old female. We highlight the importance of a thorough clinical examination and an aggressive surgical approach in which each lesion is treated as a separate primary.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 235 - 236
1 May 2006
Rafee MA Mclauchlan MGJ Gilbert DR Herlekar MD
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Background Elevated plasma levels of D-dimer have been found to be a useful screening tool in the diagnosis of deep venous thrombosis (DVT) in the general population. In the postoperative setting however their role is less clear.

In approximately 73% of NHS trusts D-dimer is a prerequisite test prior to radiological imaging to diagnose DVT.

This study evaluates the effectiveness of D-dimer as a screening tool for DVT in the postoperative period following total hip and knee arthroplasty.

Method Plasma D-dimer levels were measured pre operatively and on post-operative days 1, 3, 5, and 7 in 78 patients undergoing primary total hip or knee arthroplasty. On day 7 patients underwent bilateral duplex ultrasound scanning in order to confirm the absence of DVT.

All patients wore pneumatic foot pumps for DVT prophylaxis. Chemical thromboprophylaxis was not used. All patients were under the care of one surgeon with the same postoperative regimen.

Results D-dimer levels in the post-operative period were characterized by a double peak, on days 1 and 7. Mean day 1 value 3.63 (sd=2.72, range 0.60–14.34), mean day 7 value 2.83 (sd=1.58, range 1.10–10.30). Mean values on days 3 and 5 were 2.52 (sd=2.26, range 0.50–11.85) and 2.45 (sd=1.41, range 0.91–5.05)

Comparing D-dimer levels between hip and knee arthroplasty we found that both groups displayed the same trend in post-operative D-dimer levels (i.e. peaks at days 1 and 7); however levels were significantly higher following knee replacement (At day 7 p< 0.005)

We compared D-dimer levels of these patients with a second group of 43 patients who had a confirmed DVT following hip or knee arthroplasty. The mean D-dimer level in this group was 2.20 (sd=0.98 or range 0.80 – 4.46). This group was subdivided into two groups, those with D-dimer samples before (and including) day 7 and those after. We found a significant difference between the groups (p=0.01). Mean ≤ day 7 = 2.70. Mean > day 7 = 1.97.

The group of patients with Confirmed DVT on or before day 7 were compared with those free of clot. There was no significant difference found between the D-dimer levels of the two groups. (p=0.37)

Conclusion The D-dimer level is never normal (< 0.4mg/l), in the week following total hip or knee replacement and so cannot exclude a DVT. The level it rises to is indistinguishable form that seen in the population with a DVT and so cannot identify those patients in whom further investigation is warranted. Requesting a D-dimer test in this population wastes time and resources and is of no benefit.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 141 - 141
1 Mar 2006
Romalde DR Romalde R Proubasta D Ignasi R Perez L Espiga M Javier T Lopez VC
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Aims: A biomechanical and clinical study was made to compare two nonunion fixation device: the AO dynamic compresiòn plate and a locked intramedullary nail.

Methods: A retrospective review was made of all patients from three major hospitals in the Barcelona area with the diagnosis of aseptic non-union of the humeral shaft. After exclusion criteria series were limited to fifty-four patients, treated between 1992 and 2002. Of these, 35 were women and 19 were men with a median age of 55 (18–91) years. Operative treatment was with plate in 74.1% and locked nail in 25.9%. Statistical analysis was made to compare consolidation rate, consolidation time and complications in both devices and to looking for possible prognostic consolidation factors. We used the Finite element Method to compare the biomechanical behaviour between plate and nail.

Results: The consolidation rate was 78.6% with nail and 70.3% in plate, but this rate has significantly improved (p< 0.05) when plate is used in hypertrophic non-union and nail in atrophic union.

The median consolidation time was 5.73 months with nail and 4.92 months in plate.

The complication rate was 21.4% with nail and 20.0% in plate.

Focus deformation is lesser with nail than plate in anterior bending, axial charge and torsion but no in lateral bending.

Six or more cortical screws beside focus with plate increase consolidation too (p< 0.05).

The consolidation rate in graft group was 70.5% versus 85.7% in group without graft.

Conclusions: Plating provides better results in hypertrophic nonunions and nailing in atrophic nonunions.

Six or more cortical screws beside focus when plate is used improves consolidation rate.

Consolidation not seems be modified by graft use.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 3 | Pages 402 - 404
1 Mar 2006
Boardman DR Middleton FR Kavanagh TG

As metal-on-metal arthroplasty becomes more widespread, concerns are being raised about the potential dangers of metal particulate debris. We present the case of a benign psoas mass secondary to the presence of such particles. The mass was excised and the hip resurfacing subsequently revised to a total hip replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 32 - 35
1 Jan 2005
Diab M Clark JM Weis MA Eyre DR

In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained en bloc during subsequent surgery which was performed for degenerative osteoarthritis in three patients at 6, 25 and 30 years after the initial augmentation procedure. In each patient, the augmentation comprised of red cancellous bone covered on its articulating surface by a distinct layer of white tissue. Microscopy of this tissue showed parallel rows of spindle-shaped cells lying between linearly arranged collagen bundles typical of joint capsule. Biochemical analysis showed type I collagen, the principal collagen of joint capsule and bone, with no significant quantity of type II collagen, the principal collagen of cartilage. While the added bone produced by acetabular augmentation was durable, histological and biochemical analyses suggested that it had not undergone cartilage metaplasia. The augmented acetabulum articulates with the head of the femur by means of an interposed hip joint capsule.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 7 | Pages 1021 - 1026
1 Sep 2004
Matsui Y Mirza SK Wu J Carter B Bellabarba C Shaffrey CI Chapman JR Eyre DR

Two collagen type IX gene polymorphisms that introduce a tryptophan residue into the protein’s triple-helical domain have been linked to an increased risk of lumbar disc disease. To determine whether a particular subset of symptomatic lumbar disease is specifically associated with these polymorphisms, we performed a prospective case-control study of 107 patients who underwent surgery of the lumbar spine. Patients were assigned to one of five clinical categories (fracture, disc degeneration, disc herniation, spinal stenosis without spondylolisthesis and spinal stenosis with spondylolisthesis) based on history, imaging results, and findings during surgery. Of the 11 tryptophan-positive patients, eight had spinal stenosis with spondylolisthesis and three had disc herniation. The presence of the tryptophan allele was significantly associated with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63 to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds ratio 6.81, 95% CI 1.47 to 41.95).

Our findings indicate that tryptophan polymorphisms predispose carriers to the development of symptomatic spinal stenosis associated with spondylolisthesis which requires surgery.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 140 - 140
1 Feb 2003
McMullan MG Glenn JV O’Hagan S Marsh DR Patrick S
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Aim: The aim of the project was to discover if bacteria were implicated in non-union of fractures of the tibia and femur, which had been treated with intramedullary nailing.

Method: 40 intramedullary nails removed from tibial and femoral fractures were retrieved for the purpose of the study. 20 of these nails were from fractures, which had successfully united and were removed for mainly anterior knee pain or discomfort at screw sites. These nails formed the control group for the project. 20 nails were removed from fractures which had failed to unite prior to further operative intervention such as exchange nailing or the application of an Ilizarov frame. These fractures had no clinical evidence of infection and formed the study group for the project. The nails were subjected to ultrasound in the research laboratory to dislodge adherent bacterial formed as biofilm from the surface of the nail. Using both standard culture techniques and non-culture techniques, any dislodged bacteria were isolated and identified. Non-culture techniques involved the use of specific monoclonal antibody labelled immunofluorescence microscopy. Isolated bacteria were tested for the sensitivities of commonly used antibiotics in orthopaedic practice according to NCCLS guidelines.

Results: We discovered that bacteria were detected in up to 70% of the nails removed from fractures, which had failed to unite, using both standard culture and non-culture techniques. Also, we discovered that bacteria were detected in up to 30% of the nails removed from fractures that had united. The organisms identified were mainly the coagulase negative staphylococcus epidermidis and the gram-positive anaerobe proprionibacterium acnes. The antibiotics gentamicin, erythromycin, cefotaxime and cefomandole performed poorly against the isolated bacteria. Vancomycin, ciproxin and fucidin however performed better.

Conclusion: Bacteria formed as biofilm on intramedullary nails may have a significant role in the development of non-union fractures treated by this method. The bacteria isolated showed worrying resistance to commonly used antibiotics in orthopaedic practice, in particular, those used as prophylaxis.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 333 - 333
1 Nov 2002
Knight MTN Ellison DR Goswami AKD Hillier VF
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Objective: To analyse the incidence and gravity of reported complications that arise in spinal surgery and assess the comparative safety, or otherwise, of Endoscopic Laser Foraminoplasty.

Design: Prospective independently analysed study of complications arising during the six weeks following Endoscopic Laser Foraminoplasty was correlated and compared to a meta-analysis of reported data on complications in conventional spinal surgery.

Subjects: Nine hundred and fifty-eight procedures performed on 716 patients

Outcome measures: Occurrence of complications.

Results: The cohort integrity of operative and review records at six weeks after surgery was 100%. Twenty four complications occurred in 23 patients: nine cases of discitis (one infective) (0.9%), one dural tear (0.1%), one deep wound infection (0.1%), two patients suffered a foot drop (one transient) (0.2%), one myocardial infarction (0.1%), one erectile dysfunction (0.1%) and one post operative panic attacks (0.1%). MRI later demonstrated eight residual disc herniations (0.8%). The overall surgical complication rate was 1.6%. Meta-analysis of conventional spinal surgery reported overall complication rates for fusion (11.8%), decompression (7.6%), discectomy (6.0%) and chemonucleolysis (9.6%).

Conclusions: The complication rate of Endoscopic Laser Foraminoplasty is significantly lower than that reported following conventional spinal surgery (P < 0.01).


The thoracoscopic technic is a minimal surgical approach that minimizes the skin, muscle and ribs trauma without altering the effectiveness of the treatment.

This type of surgery has been gaining importance due to its advantages: excellent lighting, visualization and magnification. It offers an acute visual control during manipulation and dissection of delicate structures. We aim to assess the anterior release and the thoracic spine arthrodesis through thoracoscopic approach and measure the effectiveness and security of anterior thoracoscopic instrumentation in an experimental study in pigs.

The study was performed on 18 pigs which weighed between 40 and 60 kg. The surgical procedures were conducted at the Hospital Italiano in Buenos Aires. A thoracoscopic surgery was performed as an access to the spine.

The quality of the anterior release ranged significantly from cases in which the incision of the common anterior vertebral ligament could not be finished to cases in which more than 75% of the anterolateral disk circumference was released. In the subjective thoracoscopic assessment of the surgeon the screws were placed successfully in all The radiographic assessment confirmed the surgeon’s presumption, all the screws had been placed correctly. The rod presented complications in several cases.

The radiographic assessment showed that 40.6% (13 patients) of the disc spaces were pseudoarthrosic or with a delayed union. The macroscopic examination confirmed this finding and raised the number of pseudoarthrosic spaces up to 46.8% (15 patients) revealing 4 discs that still had a nucleus pulposus. The data were reinforced by histologic examination.

This histologic cuts were performed using the E & O method. The fibrous ring was clearly identified in the pseudoarthrosic cases as well as the processes of the osteochondral bone formation in its different phases of maturation.

It is very important to highlight that in our experience we had found a direct relationship between the quality of the disectomy, the fusion technique and the experience of the surgeon.

The surgical technique, the rod placement on the screws needs proper positioning and depth. The radiographic and microscopic examination confirmed that the posterior longitudinal ligaments was not damaged.

The thoracoscopic instrumentations in pigs using a rod and screws of third generation is a secure technique. It is essential the development of instrumentation which allows effective thoracoscopic distraction and compression.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 235 - 235
1 Nov 2002
Atkins G Haynes DR Zannettino A Capone M Crotti T Findlay D
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We have used a culture system of human peripheral blood mononuclear cells (PBMC)as a source of osteoclast (OC) precursors and murine stromal cells to define the cytokine environment in which human OC form, and to determine the separate contributions of the stromal and haemopoietic elements. We designed a panel of reverse transcription-polymerase chain reaction (RT-PCR) primers that specifically amplify the respective murine or human mRNA species that correspond to cytokines and their receptors previously shown to promote or inhibit OC formation. Murine ST-2 cells and human PBMC were cocultured for up to 21 days in the presence of 1,25(OH) 2vitD3, dexamethasone and human macrophage-colony stimulating factor (M-CSF). OC formation was monitored by the appearance of cells that were positive for tartrate resistant acid phosphatase and able to form resorption lacunae on slices of dentine. We found that the ST-2 cells in these cultures expressed mRNA encoding a repertoire of many of the reported osteoclastogenic factors, as well as the recently described OC differentiation factor (ODF/RANKL). The stromal cells also expressed mRNA encoding osteoprotegerin (OPG), a potent inhibitor of OC formation. We found that agonists and antagonists of OC formation were expressed by both the stromal cells and the PBMC. RANK, the receptor for ODF/RANKL, was expressed only by the PBMC as were IL-1R2 and c-FMS. We identified three features of the cytokine environment that may be a characteristic of normal OC formation. Firstly, the ratio of mouse ODF:OPG mRNA was found to increase during the cocultures, consistent with a key role for ODF in the promotion by stromal cells of OC formation. Secondly, we found that mRNA encoding IL-1 and IL-17, as well as IL-6 and sIL-6R, were coordinately expressed by the PBMC. Thirdly, analysis of the culture medium showed that the PBMC secreted IL-1, IL-6 and TNF-alpha protein only in coculture with ST-2 cells during the first few days of osteoclast development. Similarly, prostaglandin E2, shown to synergise with ODF during OC development, was secreted only in cocultures. Together, these data show OC develop in a complex cytokine environment and suggest that haemopoietic cells provide signals to stromal cells during OC development. Work is in progress to extend these studies to human PBMC interacting with normal human osteoblasts.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 4 | Pages 622 - 622
1 May 2002
Bickerstaff DR