External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7). Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used. Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group. RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.
We undertook a cemental unipolar proximal femoral endoprosthetic replacement in 131 patients with a mean age of 50 years (2 to 84). Primary malignant tumours were present in 54 patients and 67 had metastatic disease. In addition, eight patients had either lymphoma or myeloma and two had non-oncological disorders. The mean follow-up was 27 months (0 to 180). An acetabular revision was required later in 14 patients, 12 of whom had been under the age of 21 years at the time of insertion of their original prosthesis. The risk of acetabular revision in patients over 21 years of age was 8% at five years compared with 36% in those aged under 21 years. All the unipolar hips in this younger age group required revision within 11 years of the initial operation. We conclude that unipolar replacement should not be used in younger patients and should be avoided in patients with a life expectancy of more than five years.
Osteofibrous dysplasia is an unusual developmental condition of childhood, which almost exclusively affects the tibia. It is thought to follow a slowly progressive course and to stabilise after skeletal maturity. The possible link with adamantinoma is controversial and some authors believe that they are part of one histological process. We retrospectively reviewed 16 patients who were diagnosed as having osteofibrous dysplasia initially or on the final histological examination. Their management was diverse, depending on the severity of symptoms and the extent of the lesion. Definitive (extraperiosteal) surgery was localised ‘shark-bite’ excision for small lesions in five patients. Extensive lesions were treated by segmental excision and fibular autograft in six patients, external fixation and bone transport in four and proximal tibial replacement in one. One patient who had a fibular autograft required further excision and bone transport for recurrence. Six initially underwent curettage and all had recurrence. There were no recurrences after localised extraperiosteal excision or bone transport. There were three confirmed cases of adamantinoma. The relevant literature is reviewed. We recommend extraperiosteal excision in all cases of osteofibrous dysplasia, with segmental excision and reconstruction in more extensive lesions.
We report a case of vertebral osteochondroma of C1 causing cord compression and myelopathy in a patient with hereditary multiple exostosis. We highlight the importance of early diagnosis and the appropriate surgery in order to obtain a satisfactory outcome.
We have modified the Ponseti casting technique by using a below-knee Softcast instead of an above-knee plaster of Paris cast. Treatment was initiated as soon as possible after birth and the Pirani score was recorded at each visit. Following the manipulation techniques of Ponseti, a below-knee Softcast was applied directly over a stockinette for a snug fit and particular attention was paid to creating a deep groove above the heel to prevent slippage. If necessary, a percutaneous Achilles tenotomy was performed and casting continued until the child was fitted with Denis Browne abduction boots. Between April 2003 and May 2007 we treated 51 consecutive babies with 80 idiopathic club feet with a mean age at presentation of 4.5 weeks (4 days to 62 weeks). The initial mean Pirani score was 5.5 (3 to 6). It took a mean of 8.5 weeks (4 to 53) of weekly manipulation and casting to reach the stage of percutaneous Achilles tenotomy. A total of 20 feet (25%) did not require a tenotomy and for the 60 that did, the mean Pirani score at time of operation was 2.5 (0.5 to 3). Denis Browne boots were applied at a mean of 10 weeks (4 to 56) after presentation. The mean time from tenotomy to boots was 3.3 weeks (2 to 10). We experienced one case of cast-slippage during a period of non-attendance, which prolonged the casting process. One case of prolonged casting required repeated tenotomy, and three feet required repeated tenotomy and casting after relapsing while in Denis Browne boots. We believe the use of a below-knee Softcast in conjunction with Ponseti manipulation techniques shows promising initial results which are comparable to those using above-knee plaster of Paris casts.
Endoprosthetic replacement of the proximal femur may be required to treat primary bone tumours or destructive metastases either with impending or established pathological fracture. Modular prostheses are available off the shelf and can be adapted to most reconstructive situations for this purpose. We have assessed the clinical and functional outcome of using the METS (Stanmore Implants Worldwide) modular tumour prosthesis to reconstruct the proximal femur in 100 consecutive patients between 2001 and 2006. We compared the results with the published series for patients managed with modular and custom-made endoprosthetic replacements for the same conditions. There were 52 males and 48 females with a mean age of 56.3 years (16 to 84) and a mean follow-up of 24.6 months (0 to 60). In 65 patients the procedure was undertaken for metastases, in 25 for a primary bone tumour, and in ten for other malignant conditions. A total of 46 patients presented with a pathological fracture, and 19 presented with failed fixation of a previous pathological fracture. The overall patient survival was 63.6% at one year and 23.1% at five years, and was significantly better for patients with a primary bone tumour than for those with metastatic tumour (82.3% vs 53.3%, respectively at one year (p = 0.003)). There were six early dislocations of which five could be treated by closed reduction. No patient needed revision surgery for dislocation. Revision surgery was required by six (6%) patients, five for pain caused by acetabular wear and one for tumour progression. Amputation was needed in four patients for local recurrence or infection. The estimated five-year implant survival with revision as the endpoint was 90.7%. The mean Toronto Extremity Salvage score was 61% (51% to 95%). The implant survival and complications resulting from the use of the modular system were comparable to the published series of both custom-made and other modular proximal femoral implants. We conclude that at intermediate follow-up the modular tumour prosthesis for proximal femur replacement provides versatility, a low incidence of implant-related complications and acceptable function for patients with metastatic tumours, pathological fractures and failed fixation of the proximal femur. It also functions as well as a custom-made endoprosthetic replacement.
Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results.
Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A2, nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome.
The incidence of deep-vein thrombosis and the need for thromboprophylaxis following isolated trauma below the knee is uncertain. We have investigated this with a prospective randomised double-blind controlled trial using low molecular weight heparin with saline injection as placebo in patients aged between 18 and 75 years who had sustained an isolated fracture below the knee which required operative fixation. All patients had surgery within 48 hours of injury and were randomised to receive either the placebo or low molecular weight heparin for 14 days, after which they underwent bilateral lower limb venography, interpreted by three independent radiologists. Further follow-up was undertaken at two, six, eight and 12 weeks. A total of 238 patients fulfilled all the inclusion criteria, with 127 in the low molecular weight heparin group and 111 in the placebo group, all of whom underwent bilateral venography. There was no statistically significant difference in the incidence of deep-vein thrombosis between those patients treated with low molecular weight heparin or the placebo (p = 0.22). The number of deep-vein thromboses in the two groups was 11 (8.7%) and 14 (12.6%), respectively. Age and the type of fracture were significantly associated with the rate of deep-vein thrombosis (p = 0.001 and p = 0.009, respectively) but gender, comorbidities and the body mass index were not. The overall incidence of deep-vein thrombosis in this series was 11%. There was no clinical or statistical significant reduction in the incidence of deep-vein thrombosis with the use of thromboprophylaxis. However, we accept that owing to a cessation of funding, recruitment to this trial had to be ended prior to establishing the necessary sample size. Our results cannot, therefore, categorically exclude the possibility that low molecular weight heparin treatment could be beneficial. We recommend a further multicentre trial be undertaken to resolve this matter.
Dysplasia epiphysealis hemimelica of the left proximal femur was diagnosed in an eight-month-old girl. At the age of 18 months, radiographs of the hip and MRI showed overgrowth and loss of containment of the femoral head. She underwent resection of the superior portion of the head and neck of the femur at the age of 2.5 years. Six months later further radiographs and an MR scan show that the mass has increased in size and that hip containment has been lost. Further plain radiographs have shown that the left knee, ankle and spine were involved. To the authors’ knowledge, this is the first report of dysplasia epiphysealis hemimelica involving both the lower limb and the spine. A review of the literature is presented.
A 48-year old man presented with back pain that was resistant to treatment. An MR scan showed spondylolisthesis at L4-5 and narrowing of the exit foraminae. He had a posterior fusion which did not relieve his symptoms. He continued to have back pain and developed subcutaneous nodules in both forearms. Biopsy from the skin revealed cutaneous sarcoidosis, and one from the lumbar spine showed sarcoidosis granuloma between the bone trabeculae. A CT scan of the abdomen and chest revealed axillary lymphadenopathy, mediastinal enlarged nodes, apical nodular nodes and splenomegaly. The patient was started on large doses of methotrexate and steroids. His angiotensin-converting enzyme and calcium levels returned to normal and the back pain resolved.
Between 1990 and 2001, 24 children aged between 15 months and 11 years presented with late orthopaedic sequelae after meningococcal septicaemia. The median time to presentation was 32 months (12 to 119) after the acute phase of the disease. The reasons for referral included angular deformity, limb-length discrepancy, joint contracture and problems with prosthetic fitting. Angular deformity with or without limb-length discrepancy was the most common presentation. Partial growth arrest was the cause of the angular deformity. Multiple growth-plate involvement occurred in 14 children. The lower limbs were affected much more often than the upper. Twenty-three children underwent operations for realignment of the mechanical axis and limb-length equalisation. In 15 patients with angular deformity around the knee the deformity recurred. As a result we recommend performing a realignment procedure with epiphysiodesis of the remaining growth plate when correcting angular deformities.
We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff. We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity. Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients.
The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically. Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets. Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.
Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.
We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1α, HIF-2α, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour. There was no HIF-1α and HIF-2α staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1α and HIF-2α expression was 40% and 25%, respectively. The tumour size (≥ 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1α expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1α and the MVD and a strong trend towards a correlation between HIF-1α and the PCNA index or histological grade. Our findings suggest that HIF-1α protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation.
Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 106 cells after three weeks’ tissue culture. Calcium sulphate (CaSO4) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation. This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO4 has not to our knowledge been reported in a clinical setting.
Arrest of growth of the distal radius is rare but will produce deformity of the wrist. We corrected angular deformity and shortening of the distal radius by epiphysiolysis and gradual lengthening without a corrective osteotomy.
We reviewed 25 patients in whom a MUTARS megaprosthesis with a conical fluted stem had been implanted. There were three types of stem: a standard stem was used in 17 cases (three in the proximal femur, nine in the distal femur and five proximal tibia), a custom-made proximal femoral stem in four cases and a custom-made distal femoral stem in four cases. The mean age of the patients was 40.1 years (17 to 70) and the mean follow-up was for 2.5 years (0.9 to 7.4). At follow-up two patients had died from their disease: one was alive with disease and 22 were disease-free. One of 23 prostheses had been removed for infection and another revised to a cemented stem. The mean Musculoskeletal Tumor Society score was 24.9 (12 to 30) and the mean Karnofsky index was 82% (60% to 100%). There was no radiological evidence of loosening or subsidence. Stem stress shielding was seen in 11 patients and was marked in five of these. There were five complications, rupture of the extensor mechanism of the knee after extra-articular resection in two patients, deep venous thrombosis in one, septic loosening in one, and dislocation of the hip in one. The survival rate after seven years was 87% (95% confidence interval (CI) 83 to 91) for the patients and 95% (95% CI 91 to 99) for the megaprosthesis. A longer follow-up is needed to confirm these encouraging results.
This study investigated the quality and quantity of healing of a bone defect following intramedullary reaming undertaken by two fundamentally different systems; conventional, using non-irrigated, multiple passes; or suction/irrigation, using one pass. The result of a measured re-implantation of the product of reaming was examined in one additional group. We used 24 Swiss mountain sheep with a mean tibial medullary canal diameter between 8 mm and 9 mm. An 8 mm ‘napkin ring’ defect was created at the mid-diaphysis. The wound was either surgically closed or occluded. The medullary cavity was then reamed to 11 mm. The Reamer/Irrigator/Aspirator (RIA) System was used for the reaming procedure in groups A (RIA and autofilling) and B (RIA, collected reamings filled up), whereas reaming in group C (Synream and autofilling) was performed with the Synream System. The defect was allowed to auto-fill with reamings in groups A and C, but in group B, the defect was surgically filled with collected reamings. The tibia was then stabilised with a solid locking Unreamed Humerus Nail (UHN), 9.5 mm in diameter. The animals were killed after six weeks. After the implants were removed, measurements were taken to assess the stiffness, strength and callus formation at the site of the defect. There was no significant difference between healing after conventional reaming or suction/irrigation reaming. A significant improvement in the quality of the callus was demonstrated by surgically placing captured reamings into the defect using a graft harvesting system attached to the aspirator device. This was confirmed by biomechanical testing of stiffness and strength. This study suggests it could be beneficial to fill cortical defects with reaming particles in clinical practice, if feasible.