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Volume 81-B, Issue 3 May 1999

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R. K. Marti
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EDITORIAL COMMENT Pages 377 - 377
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Frank Horan
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R. A. Dickson
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JOINT DISEASES Pages 378 - 378
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L. Sedel
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OSTEOPOROSIS Pages 379 - 379
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MR N. Rushton
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Children's Orthopaedics
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K. Daly C. Bruce A. Catterall
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The surgical treatment of Perthes’ disease by femoral or innominate osteotomy is not as effective in those over the age of eight years as it is in the younger child. This has prompted the search for other types of management in those who are older. The preliminary results of the use of a lateral shelf acetabuloplasty for such cases have shown encouraging results at two years. The concern with such an operation is that it might interfere with the growth of the outer aspect of the acetabulum and so prejudice the long-term outcome. We describe a review at maturity of 26 children presenting with early disease after the age of eight years who were treated by lateral shelf acetabuloplasty. The results suggest that the outcome is improved; 22 of 27 hips were rated as Stulberg groups 1 to 3. Poor results occurred in children, particularly girls, presenting with Group-4 disease over the age of 11 years.


T. Hattori Y. Ono T. Kitakoji S. Takashi H. Iwata
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We reviewed 98 children (133 hips) with developmental dysplasia of the hip who underwent arthrography immediately after closed reduction by overhead traction. We followed the patients to skeletal maturity to investigate whether soft-tissue interposition influences acetabular development and avascular necrosis over the long term.

The shape of the limbus and the thickness of the soft-tissue interposition at the acetabular floor, as shown on arthrograms at the time of reduction, were not directly related to the final radiological results or to the incidence of avascular necrosis. Even if marked soft-tissue interposition was found on the initial arthrogram, spontaneous disappearance was noted in 71% up to the age of five years. The final radiological results showed no difference between those in which the interposition disappeared and those with none at the time of closed reduction. However, the requirement for secondary surgery at the age of five years was significantly higher in those with more than 3.5 mm of soft-tissue interposition. In the no-disappearance group (group C) further operation was necessary in 100% and the results were significantly worse at maturity according to Severin’s classification.

We suggest that the indications for open reduction should not be based solely on the arthrographic findings at the time of closed reduction.


S. Tennant C. Kinmont G. Lamb W. Gedroyc D. M. Hunt
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Conventional methods of imaging in the investigation of developmental dysplasia of the hip all have disadvantages, either in definition or in exposure to radiation. We describe a new open-configuration MR scanner which is unique in that it allows anaesthesia and access to the patient within the imaging volume for surgical procedures and application of casts. We performed 13 scans in eight anaesthetised infants. Dynamic imaging revealed two dislocated hips which were then visualised during reduction. Hip spicas were applied without removing the patient from the scanner. In one hip, an adductor tenotomy was carried out. In all patients, stressing the hips during dynamic imaging allowed an assessment of stability. This was particularly useful in two hips in which an analysis of stability in different positions facilitated the planning of femoral osteotomies. This method of imaging provides new and important information. It has great potential in the investigation of developmental dysplasia of the hip and, with ultrasound, may allow management without the need for radiography.


A. Roposch G. Steinwender W. E. Linhart
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Primary skin closure after surgery for club foot in children can be difficult especially in revision operations. Between 1990 and 1996 a soft-tissue expander was implanted in 13 feet before such procedures. Two were primary operations and 11 were revisions. A standard technique was used for implantation of the expander. Skin augmentation was successful in 11 cases. There was failure of one expander and one case of wound infection. Sufficient stable skin could be gained at an average of five weeks. Primary skin closure after surgery was achieved in 12 cases.

We conclude that soft-tissue expansion can be used successfully before extensive surgery for club foot. The method should be reserved for revision procedures and for older children. The technique is not very demanding, but requires experience to achieve successful results.


G. J. McLauchlan C. R. C. Walker B. Cowan J. E. Robb R. J. Prescott
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We tested the hypothesis that children who sustain a supracondylar fracture have a greater range of elbow hyperextension than those with a fracture of the distal radius.

Three observers made 358 measurements in 183 children (114 boys and 69 girls). There were 119 fractures of the distal radius and 64 supracondylar fractures.

Initially, the group with a supracondylar fracture appeared to have extension 1.7° greater than that of the group with fracture of the distal radius. On average, there was a maximum variation of 3° between observers. After allowing for age, gender and observer, there was no significant difference between the groups. Our study had greater than 80% power to detect a difference in hyperextension of 2° at the 5% level with the above observer variability.

When age and gender are taken into account, any variation in the amount of hyperextension at the elbow is not sufficient to explain the occurrence of a supracondylar fracture.


Upper Limb
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P. J. McMahon J. Dettling M. D. Sandusky J. E. Tibone T. Q. Lee
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Surgical treatment for traumatic, anterior glenohumeral instability requires repair of the anterior band of the inferior glenohumeral ligament, usually at the site of glenoid insertion, often combined with capsuloligamentous plication. In this study, we determined the mechanical properties of this ligament and the precise anatomy of its insertion into the glenoid in fresh-frozen glenohumeral joints of cadavers. Strength was measured by tensile testing of the glenoid-soft-tissue-humerus (G-ST-H) complex. Two other specimens of the complex were frozen in the position of apprehension, serially sectioned perpendicular to the plane containing the anterior and posterior rims of the glenoid, and stained with Toluidine Blue.

On tensile testing, eight G-ST-H complexes failed at the site of the glenoid insertion, representing a Bankart lesion, two at the insertion into the humerus, and two at the midsubstance. For those which failed at the glenoid attachment the mean yield load was 491.0 N and the mean ultimate load, 585.0 N. At the glenoid region, stress at yield was 7.8 ± 1.3 MPa and stress at failure, 9.2 ± 1.5 MPa. The permanent deformation, defined as the difference between yield and ultimate deformation, was only 2.3 ± 0.8 mm. The strain at yield was 13.0 ± 0.7% and at failure, 15.4 ± 1.2%; therefore permanent strain was only 2.4 ± 1.1%.

Histological examination showed that there were two attachments of the anterior band of the inferior glenohumeral ligament at the site of the glenoid insertion. In one, poorly organised collagen fibres inserted into the labrum. In the other, dense collagen fibres were attached to the front of the neck of the glenoid.


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Th. Fabre C. Piton G. Leclouerec F. Gervais-Delion A. Durandeau
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Operative release for entrapment of the suprascapular nerve was carried out in 35 patients. They were assessed at an average of 30 months (12 to 98) after operation using the functional shoulder score devised by Constant and Murley. The average age at the time of surgery was 40 years (17 to 67). Entrapment was due to injury in ten patients and no cause was found in three; 34 had diffuse posterolateral shoulder pain. The strength of abduction was reduced in all the patients.

The average Constant score, unadjusted for age or gender, before operative release was 47% (28 to 53). In 25 of the patients both the supraspinatus and infraspinatus muscles were atrophied and seven had isolated atrophy of the infraspinatus muscle. The average conduction time from Erb’s point to the supraspinatus muscle and to the infraspinatus muscle was 5.7 ms (2.8 to 12.8) and 7.4 ms (3.4 to 13.4), respectively. In two patients MRI revealed a ganglion in the infraspinatus fossa and, in another, a complete rupture of the rotator cuff.

The average time from the onset of symptoms to operation was ten months (3 to 36). A posterior approach was advocated. The average Constant score, after operative release, unadjusted for age or gender was 77% (35 to 91). The overall result was excellent in ten of the patients, very good in seven, good in 14, fair in two, and poor in two. The symptomatic and functional outcome in our series confirmed the usefulness and safety of operative decompression for entrapment of the suprascapular nerve.


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J. Dawson R. Fitzpatrick A. Carr
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We have developed a 12-item questionnaire for completion by patients presenting with shoulder instability. A prospective study of 92 patients was undertaken involving two assessments, approximately six months apart, performed in an outpatient department. Each patient completed the new questionnaire and the SF36 form. An orthopaedic surgeon completed the Constant shoulder score and the Rowe assessment.

The new questionnaire and the Rowe clinical score each achieved a large standardised effect size (≥0.8) and compared favourably with relevant items on the SF36. By contrast, the Constant score barely registered any effect, confirming that it may be relatively insensitive to changes in clinical status for this particular condition.

The questionnaire provides a measurement of outcome for shoulder instability which is short, practical, reliable, valid and sensitive to changes of clinical importance.


Hip
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B. M. Wroblewski P. A. Fleming P. D. Siney
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We reviewed 261 patients with 320 Charnley low-friction arthroplasties who had a mean follow-up of 22 years 10 months (20 to 30). Of these, 93.9% considered the operation to be a success; 82.3% were free from pain and 11.6% had occasional discomfort. Satisfactory function was achieved in 59.6% and 62% had an excellent range of movement.

The clinical results did not correlate well with the radiological appearance; radiologically loose components did not affect the clinical outcome. The main long-term problem was wear and loosening of the UHMWPE cup. Our findings suggest that the radiological appearance of the arthroplasty is a more reliable indication of the state of the arthroplasty than the clinical results.


R. Pradhan
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In total hip replacement, orientation of the cup is critical to the stability of the prosthesis. A new method to determine the angle of planar anteversion is described. A simple mathematical formula uses the measurements taken from anteroposterior radiographs to calculate the planar anteversion without reference to tables or charts.

An experimental study in vitro has shown the efficacy of the formula in giving results which are within a clinically acceptable range.


M. Kioschos E. D. Shaw R. K. Beals
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Hip disease occurs in between 8% and 28% of patients with Down’s syndrome, many of whom develop disabling pain. We have carried out total hip replacement in six adult patients (9 hips) with severe arthritis of the hip. The mean follow-up was 7.75 years (2 to 14). At the latest review, all had relief of pain and full hip function. Increasing longevity and a high incidence of hip disease in these patients suggest a greater role for total hip arthroplasty in the future.


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C. P. Scott P. A. Higham J. H. Dumbleton
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We used 99 strains of organisms representative of orthopaedic infections to examine the effectiveness of a bone cement containing tobramycin, employing a modified in vitro Kirby-Bauer susceptibility model. The spectrum was broad, including Gram-positive and Gram-negative aerobic organisms, anaerobes and mycobacteria. Simplex P with added tobramycin was effective against most of the strains, including those which are resistant to typical systemic levels of tobramycin. Although direct correlation between in vitro and in vivo results is difficult, the study showed that tobramycin is stable to the exothermic polymerisation of the cement, and that it is released from the surface of the cement at concentrations high enough to inhibit the growth of most organisms which may be encountered after joint arthroplasty.


G. Magyar T. L. Ahl P. Vibe S. Toksvig-Larsen A. Lindstrand
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We describe the results of 50 operations carried out on 46 patients with medial osteoarthritis of the knee of Ahlbäck grade 1 to 3. Patients were randomised either to a closed-wedge high tibial osteotomy (HTO) or an open-wedge procedure based on the hemicallotasis technique (HCO). Their median age was 55 years (38 to 68). The preoperative median hip-knee-ankle (HKA) angle was 171° (164 to 176) in the HTO group and 173° (165 to 179) in the HCO group. After six weeks, the median HKA angle was 185° (176 to 194) in the HTO group and 184° (181 to 188) in the HCO group. In the HTO group, seven patients were within the range of 182° to 186° compared with 21 in the HCO group (p < 0.001). One year later, ten HTO patients were within this range while the HKA angulation in the HCO group was unchanged. At two years the numbers were 11 and 18, respectively.

We evaluated the clinical results on the Hospital for Special Surgery, Lysholm and Wallgren-Tegner activity scores, and patients completed part of the Nottingham Health Profile questionnaire. An impartial observer at the two-year follow-up concluded that all scores had improved, but found no clinical differences between the groups.


G. Magyar S. Toksvig-Larsen A. Lindstrand
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We studied the complications after open-wedge osteotomy by hemicallotasis in 308 consecutive patients, most of whom had osteoarthritis of the knee. The participating surgeons, who worked at 17 hospitals, used their discretion in selecting patients, operating techniques and external fixators. The general complications included 11 cases of deep-vein thrombosis (4%), six of nonunion (2%) and one of septic arthritis of the knee. There were technical complications in 13 patients (4%). In 157 patients (51%) pin-site infections were recorded; of these, 96% were minor and responded to wound toilet and antibiotic treatment. A total of 18 revision procedures was carried out.


H.-U. Stäubli U. Dürrenmatt B. Porcellini W. Rauschning
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We studied the anatomy of the patellofemoral joint in the axial plane on cryosections from a cadaver knee and on MR arthrotomograms from 30 patients. The cryosections revealed differences in the geometry and anatomy of the surface of the articular cartilage and corresponding subchondral osseous contours of the patellofemoral joint. On the MR arthrotomograms the surface geometry of the cartilage matched the osseous contour of the patella in only four of the 30 knees. The articular cartilaginous surface of the intercondylar sulcus and corresponding osseous contour of the femoral trochlea matched in only seven knees.

Since MR arthrotomography can distinguish between the surface geometry of the articular cartilage and subchondral osseous anatomy of the patellofemoral joint, it allows the surgeon and the radiologist to appraise the true articulating surfaces. We therefore recommend MR arthrotomography as the imaging technique of choice.


Spine
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S. Govender E Mutasa A. H. Parbhoo
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We have treated seven patients with cryptococcal spondylitis. Five presented with a neurological deficit and one was HIV-positive. Amphotericin-B and 5-flucytosine were used in five patients and ketoconazole was given orally in the remaining two. Three patients made a complete neurological recovery. Since these lesions mimic spinal tuberculosis, which is commonly seen in our environment, we draw attention to the importance of obtaining a tissue diagnosis.


P. A. Antich A. C. Sanjuan F. M. Girvent J. D. Simò
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We describe a rare herniation of the disc at the C2/C3 level in a 73-year-old woman. It caused hemicompression of the spinal cord and led to the Brown-Sequard syndrome. The condition was diagnosed clinically and by MRI six months after onset. Discectomy and fusion gave complete neurological resolution.


R. Parthasarathy K. Sriram T. Santha R. Prabhakar P. R. Somasundaram S. Sivasubramanian
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We performed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9).

Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status.

Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30° whose kyphosis increased substantially.


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A. D. Henry J. Bohly A. Grosse
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We have reviewed 81 patients with fractures of the odontoid process treated between May 1983 and July 1997, by anterior screw fixation.

There were 29 patients with Anderson and D’Alonzo type-II fractures and 52 with type III. Roy-Camille’s classification identified the direction and instability of the fracture. Operative fixation was carried out on 48 men and 33 women with a mean age of 57 years. Associated injuries of the cervical spine were present in 15 patients, neurological signs in 13, and 18 had an Injury Severity Score of more than 15. Nine patients died and 11 were lost to follow-up. Of 61 patients, 56 (92%) achieved bony union at an average of 14.1 weeks. Two patients required a secondary posterior fusion after failure of the index operation. A full range of movement was restored in 43 patients; only six had a limitation of movement greater than 25%.

We conclude that anterior screw fixation is effective and practicable in the treatment of fractures of the dens.


P. J. Parker K. B. Tepper R. J. Brumback V. P. Novak S. M. Belkoff
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Type-I fractures of the lateral tibial plateau were simulated by osteotomy in 18 pairs of unembalmed cadaver tibiae. One fracture of each pair was fixed with two lag screws whereas the contralateral site was stabilised with three lag screws, or two lag screws plus an antiglide screw. The lateral plateau was displaced downwards using a servohydraulic materials testing machine and the resulting force and articular surface gap were recorded. Yield load was defined as the maximum load needed to create a 2.0 mm articular offset at the fracture line. The yield loads of the three-lag-screw (307 ± 240 N) and antiglide constructs (342 ± 249 N) were not significantly different from their two-screw control constructs (231 ± 227 and 289 ± 245 N, respectively). We concluded that adding an antiglide screw or a third lag screw did not provide any biomechanical advantage in stabilising these fractures.


C. M. Robinson J. O’Donnell E. Will J. F. Keating
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We made a prospective study of 208 patients with tibial fractures treated by reamed intramedullary nailing. Of these, 11 (5.3%) developed dysfunction of the peroneal nerve with no evidence of a compartment syndrome.

The patients with this complication were significantly younger (mean age 25.6 years) and most had closed fractures of the forced-varus type with relatively minor soft-tissue damage. The fibula was intact in three, fractured in the distal or middle third in seven, with only one fracture in the proximal third. Eight of the 11 patients showed a ‘dropped hallux’ syndrome, with weakness of extensor hallucis longus and numbness in the first web space, but no clinical involvement of extensor digitorum longus or tibialis anterior. This was confirmed by nerve-conduction studies in three of the eight patients.

There was good recovery of muscle function within three to four months in all cases, but after one year three patients still had some residual tightness of extensor hallucis longus, and two some numbness in the first web space. No patient required further treatment.


R. M. Kerry B. A. Masri C. P. Beauchamp C. P. Duncan
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We describe a U-shaped approach to the distal femur which, having divided the extensor mechanism and elevated the entire quadriceps muscle, gives excellent exposure and allows a number of reconstructive options. It was used in 14 patients, 13 of whom were followed up for a mean of 3.5 years (1 to 11). There was no case of flap necrosis, and complications related to the reconstruction were acceptable.


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R. J. Grimer S. R. Carter R. M. Tillman R. S. Sneath P. S. Walker P. S. Unwin P. C. Shewell
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We have performed endoprosthetic replacement after resection of tumours of the proximal tibia on 151 patients over a period of 20 years. During this period limb-salvage surgery was achieved in 88% of patients with tumours of the proximal tibia. Both the implant and the operative technique have been gradually modified in order to reduce complications. An initial rate of infection of 36% has been reduced to 12% by the use of a flap of the medial gastrocnemius, to which the divided patellar tendon is attached. Loosening and breakage of the implant have been further causes of failure. We found that the probability of further surgical procedures being required was 70% at ten years and the risk of amputation, 25%. The development of a new rotating hinge endoprosthesis may lower the incidence of mechanical problems.

Limb salvage for tumours of the proximal tibia is fraught with complications, but the good functional outcome in successful cases justifies its continued use.


K. S. Ayoub F. Fiorenza R. J. Grimer R. M. Tillman S. R. Carter
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We carried out extensible endoprosthetic replacement of the proximal or total humerus in 18 children aged between six and 12 years, after resection of primary bone tumours mainly for osteosarcoma and Ewing’s sarcoma. In 11 patients we performed 44 lengthening procedures, with an average of two per child annually and a mean total extension of 29.9 mm per patient. We were able to achieve lengthening of the operated limb with few complications and a mean functional rating of 79.3% according to the Enneking system. Progressive lengthening of these prostheses does not adversely affect the overall function of the arm, and superior subluxation of the head of the prosthesis has not been a problem.


G. Möller M. Priemel M. Amling M. Werner A. S. Kuhlmey G. Delling
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The Gorham-Stout Syndrome (Gorham’s massive osteolysis) is a rare condition in which spontaneous, progressive resorption of bone occurs. The aetiology is poorly understood. We report six cases of the condition and present evidence that osteolysis is due to an increased number of stimulated osteoclasts. This suggests that early potent antiresorptive therapy such as with calcitonin or bisphosphonates may prevent local progressive osteolysis.


M. Yamazaki F. Nakajima A. Ogasawara H. Moriya R. J. Majeska T. A. Einhorn
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The multifunctional adhesion molecule CD44 is a major cell-surface receptor for hyaluronic acid (HUA). Recent data suggest that it may also bind the ubiquitous bone-matrix protein, osteopontin (OPN). Because OPN has been shown to be a potentially important protein in bone remodelling, we investigated the hypothesis that OPN interactions with the CD44 receptor on bone cells participate in the regulation of the healing of fractures. We examined the spatial and temporal patterns of expression of OPN and CD44 in healing fractures of rat femora by in situ hybridisation and immunohistochemistry. We also localised HUA in the fracture callus using biotinylated HUA-binding protein.

OPN was expressed in remodelling areas of the hard callus and was found in osteocytes, osteoclasts and osteoprogenitor cells, but not in cuboidal osteoblasts which were otherwise shown to express osteocalcin. The OPN signal in osteocytes was not uniformly distributed, but was restricted to specific regions near sites where OPN mRNA-positive osteoclasts were attached to bone surfaces. In the remodelling callus, intense immunostaining for CD44 was detected in osteocyte lacunae, along canaliculi, and on the basolateral plasma membrane of osteoclasts, but not in the cuboidal osteoblasts. HUA staining was detected in fibrous tissues but little was observed in areas of hard callus where bone remodelling was progressing.

Our findings suggest that OPN, rather than HUA, is the major ligand for CD44 on bone cells in the remodelling phase of healing of fractures. They also raise the possibility that such interactions may be involved in the communication of osteocytes with each other and with osteoclasts on bone surfaces. The interactions between CD44 and OPN may have important clinical implications in the repair of skeletal tissues.


I. Catelas A. Petit R. Marchand D. J. Zukor L’H. Yahia O. L. Huk
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Although the response of macrophages to polyethylene debris has been widely studied, it has never been compared with the cellular response to ceramic debris. Our aim was to investigate the cytotoxicity of ceramic particles (Al2O3 and ZrO2) and to analyse their ability to stimulate the release of inflammatory mediators compared with that of high-density polyethylene particles (HDP). We analysed the effects of particle size, concentration and composition using an in vitro model. The J774 mouse macrophage cell line was exposed to commercial particles in the phagocytosable range (up to 4.5 μm). Al2O3 was compared with ZrO2 at 0.6 μm and with HDP at 4.5 μm. Cytotoxicity tests were performed using flow cytometry and macrophage cytokine release was measured by ELISA.

Cell mortality increased with the size and concentration of Al2O3 particles. When comparing Al2O3 and ZrO2 at 0.6 μm, we did not detect any significant difference at the concentrations analysed (up to 2500 particles per macrophage), and mortality remained very low (less than 10%). Release of TNF-α also increased with the size and concentration of Al2O3 particles, reaching 195% of control (165 pg/ml v 84 pg/ml) at 2.4 μm and 350 particles per cell (p < 0.05). Release of TNF-α was higher with HDP than with Al2O3 particles at 4.5 μm. However, we did not detect any significant difference in the release of TNF-α between Al2O3 and ZrO2 at 0.6 μm (p > 0.05). We saw no evidence of release of interleukin-1α or interleukin-1ß after exposure to ceramic or HDP particles.


R. González Santander M. A. Plasencia Arriba G. Martinez Cuadrado A. Lopez Alonso M. González-Santander Martinez F. J. Martinez Alonso M. Monteagudo M. V. Toledo Lobo
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We have studied the formation of collagen fibrils in ‘activated fibroblasts’ of tendo Achillis of rabbits. The tendon was in the process of regeneration after experimental partial tenotomy. Samples were taken from the peri-incisional region and analysed by transmission electron microscopy.

Ultrastructural examination showed the presence of a ‘fine dense granular substance’ inside the rough endoplasmic reticulum and procollagen filaments. These come together to form collagen fibrils in the dilated vacuoles of the rough endoplasmic reticulum. The possible intra- and extracellular origin of collagen fibrils is suggested. Within the cell biosynthesis of collagen fibrils take place with the formation of collagen substance which gives rise to procollagen filaments. These make contact in parallel apposition to produce striated ‘spindle-shaped bodies’ which elongate by the longitudinal attachment of more procollagen filaments and form intracellular nascent collagen fibrils.


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S. A. Corbett M. Hukkanen J. Batten I. D. McCarthy J. M. Polak S. P. F. Hughes
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Our aim was to investigate whether nitric oxide synthase (NOS) isoforms, responsible for the generation of NO, are expressed during the healing of fractures. To localise the sites of expression compared with those in normal bone we made standardised, stabilised, unilateral tibial fractures in male Wistar rats. Immunostaining was used to determine the precise tissue localisation of the different NOS isoforms. Western blotting was used to assess expression of NOS isoform protein and L-citrulline assays for studies on NOS activity. Control tissue was obtained from both the contralateral uninjured limb and limbs of normal rats.

Immunohistochemistry showed increased expression of endothelial NOS (eNOS) to be strongest in the cortical blood vessels and in osteocytes in the early phase of fracture repair. Western blot and image analysis confirmed this initial increase. Significantly elevated calcium-dependent NOS activity was observed at day 1 after fracture.

Inducible NOS (iNOS) was localised principally in endosteal osteoblasts and was also seen in chondroblasts especially in the second week of fracture healing. Western blotting showed a reduction in iNOS during the early healing period. Significantly reduced calcium-independent NOS activity was also seen. No neuronal NOS was seen in either fracture or normal tissue.

Increased eNOS in bone blood vessels is likely to mediate the increased blood flow recognised during fracture healing. eNOS expression in osteocytes may occur in response to changes in either mechanical or local fluid shear stress. The finding that eNOS is increased and iNOS reduced in early healing of fractures may be important in their successful repair.


R. L. M. Deijkers G. J. Bouma E. M. W. van der Meer-Prins P. E. Huysmans A. H. M. Taminiau F. H. J. Claas
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We analysed the cellular immune response in ten transplantations of different massive bone allografts, of which five had a poor clinical outcome. Cytotoxic T lymphocytes (CTL) and T helper lymphocytes (TH) against mismatched donor antigens were found in all patients. More importantly, CTL with a high affinity for donor antigens were found in five cases. High-affinity CTL need no CD8 molecule to stabilise the antigen binding and are strongly associated with rejection of heart and corneal transplants. Even after removal of most of the bone-marrow cells, we found high-affinity CTL and high TH frequencies. This T-cell response could be detected over a period of years.

We conclude that frozen bone allografts can induce high-affinity donor-specific CTL. The present assay allows qualification and quantification of the levels of CTL and TH in the blood. This approach may be helpful in studying the effect of the immune response on the outcome of the graft.


S. Decker W. Winkelmann B. Nies F. van Valen
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Bone tumours may recur locally even after wide surgical excision and systemic chemotherapy. Local control of growth may be accomplished by the addition of cytostatic drugs such as methotrexate (MTX) to bone cement used to fill the defect after surgery and to stabilise the reconstructive prosthesis. We have studied the elution kinetics of MTX and its solvent N-methyl-pyrrolidone (NMP) from bone cement and their biological activities in five cell lines of osteosarcoma and in osteoblasts, and compared them with the effects of the parent compounds alone and in combination.

Our findings show that MTX is released continuously over months at concentrations highly cytotoxic to osteosarcoma cells and suggest that the impregnated bone cement would be effective in the long term. Proliferating osteoblasts, however, were much less sensitive towards MTX. The dose-response relationship for NMP and experiments with MTX/NMP-mixtures show that the eluted concentrations of solvent are not toxic and do not influence the effects of MTX.

We suggest that bone cement containing MTX dissolved in NMP releases the drug in a suitable and effective way and may be of value in the treatment of bone tumours.


R. Crawford B. Puddle N. Hunt N. A. Athanasou
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We reviewed histologically the incidence and pathogenesis of the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the pseudocapsule, femoral and acetabular membranes and periprosthetic tissue at revision of 789 cases of failed total hip replacement. In 13, periprosthetic tissues were found to have deposits of CPPD crystals in areas of cartilaginous metaplasia; four also showed evidence of localised deposition of amyloid. None of the patients had a history of chondrocalcinosis in the hip or other joints. Cartilaginous metaplasia and other changes in periprosthetic tissues may predispose to the deposition of CPPD and associated localised amyloid.


Obituary
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GAE DCJ
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M. D. NORTHMORE-BALL
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Author’s reply Pages 556 - 556
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KEVIN HARDINGE
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P. QUARTEY
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Femoral stem fixation Pages 557 - 558
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J. R. LOUDON
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Authors’ reply Pages 557 - 557
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P. GRIGORIS D. L. HAMBLEN
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Authors’ reply Pages 557 - 557
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P. GRIGORIS D. L. HAMBLEN
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A. M. COLLIER S. PATIL
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S. EHRENDORFER A. READING
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E. SHERRY
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Author’s reply Pages 558 - 558
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G. SHEN
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Authors’ reply Pages 559 - 560
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P. A. ROBERTSON H. R. BLACKLEY L. D. PLANK
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P. DUPRE
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S. A. MILNER
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Authors’ reply Pages 559 - 559
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P. A. SCHAI T. S. THORNHILL R. D. SCOTT
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P. L. FRANK
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Author’s reply Pages 560 - 560
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D. JONES
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R. Lloyd Williams
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Gabriel Panayi
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Andrew Jackson
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Lord Stamp
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