We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone

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

Aims. To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods. Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results. OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion. Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803

Curettage and packing with polymethylmethacrylate cement is a routine treatment for giant-cell tumour (GCT) of bone. We performed an in vitro evaluation of the cytotoxic effect of a combination of cement and methotrexate, doxorubicin and cisplatin on primary cell cultures of stromal GCT cells obtained from five patients. Cement cylinders containing four different concentrations of each drug were prepared, and the effect of the eluted drugs was examined at three different time intervals. We found that the cytotoxic effect of eluted drugs depended on their concentration and the time interval, with even the lowest dose of each drug demonstrating an acceptable rate of cytotoxicity. Even in low doses, cytotoxic drugs mixed with polymethylmethacrylate cement could therefore be considered as effective local adjuvant treatment for GCTs

Juvenile idiopathic arthritis (JIA) is a chronic disease of childhood; it causes joint damage which may require surgical intervention, often in the young adult. The aim of this study was to describe the long-term outcome and survival of hip replacement in a group of adult patients with JIA and to determine predictors of survival for the prosthesis. In this retrospective comparative study patients were identified from the database of a regional specialist adult JIA clinic. This documented a series of 47 hip replacements performed in 25 adult patients with JIA. Surgery was performed at a mean age of 27 years (11 to 47), with a mean follow-up of 19 years (2 to 36). The mean Western Ontario and McMaster Universities osteoarthritis index questionnaire (WOMAC) score at the last follow-up was 53 (19 to 96) and the mean Health Assessment Questionnaire score was 2.25 (0 to 3). The mean pain component of the WOMAC score (60 (20 to 100)) was significantly higher than the mean functional component score (46 (0 to 97)) (p = 0.02). Kaplan-Meier survival analysis revealed a survival probability of 46.6% (95% confidence interval 37.5 to 55.7) at 19 years, with a trend towards enhanced survival with the use of a cemented acetabular component and a cementless femoral component. This was not, however, statistically significant (acetabular component, p = 0.76, femoral component, p = 0.45). Cox’s proportional hazards regression analysis showed an implant survival rate of 54.9% at 19 years at the mean of covariates. Survival of the prosthesis was significantly poorer (p = 0.001) in patients who had been taking long-term corticosteroids and significantly better (p = 0.02) in patients on methotrexate

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

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

We studied the bone mineral density (BMD) of 48 long-term survivors of highly malignant osteosarcoma who had been treated according to the chemotherapy protocols of the German- Swiss-Austrian Co-operative Osteosarcoma Study Group which include high-dose methotrexate. The mean age of the patients was 31 ± 4.2 years and the mean follow-up 16 ± 2.2 years. The BMD of the lumbar spine and of the proximal femur of the non-operated side was measured by dual- energy x-ray absorptiometry. A questionnaire was given to determine life-style factors, medical history and medication. Ten patients were osteoporotic, 21 osteopenic and 17 normal according to the WHO definition. Eighteen patients suffered fractures after receiving chemotherapy and all had significantly lower levels of BMD for all the sites measured

An increased long-term survival of patients with malignant tumours also increases the possibility of the development of skeletal metastases and pathological fractures. The management of bone metastases includes the removal of gross disease and the administration of local adjuvants. We have investigated the possibility of adding antiblastic drugs to acrylic cement. Cylinders of acrylic cement were manufactured containing three different antiblastic drugs, methotrexate, cisplatin and doxorubicin. We performed in vitro analysis on MCF-7 human breast cancer cells in order to evaluate the biological effect of the mixtures and surface analysis of the acrylic cement-cisplatin cylinders using energy-dispersive x-ray analysis (EDAX). All drugs were released in an active form from the cement. Each drug had a different effect on cell viability. Doxorubicin had the greatest effect on breast cancer cells. Surface analysis showed that antiblastic drugs were present in the form of granules. These results confirm the potential of antiblastic-loaded cement as a possible adjuvant in the local treatment of bone metastases. Further studies should be undertaken to determine whether the release of antiblastic drugs from cement is elution or if they are only released from the surface

Fifty-five cases of osteosarcoma of the extremities were treated between 1972 and 1976 by combined surgery and chemotherapy (vincristine, adriamycin and methotrexate in medium doses) for 18 months. The follow-up ranges from 30 to 80 months (mean = 48 months). Twenty-six patients remained free from any evidence of disease, two had local recurrences but no metastases and 27 had metastases (four of these also had local recurrences). In 12 patients, the metastases appeared after the end of chemotherapy. Both metastases and local recurrences were more frequent in patients who had segmental bone resection (7/8) than in those treated by more radical surgery (22/47). Comparison with an "historical" group (94 osteosarcoma patients treated by operation alone in our Institute between 1960 and 1971) showed that the percentage of patients free from evidence of disease was higher in the group who receiving chemotherapy. In addition, the appearance of metastases in this group was delayed (mean = 16 months) as compared with the historical controls (mean = 8 months). On the other hand, after the same kind of operative treatment, the rate of local recurrences and the time of their appearance was almost identical in both groups

Previous studies have shown that the activity of the cytostatic drug methotrexate (MTX) embedded in acrylic cement is not affected by thermal changes in the cement. MTX is slowly released from the cement for several months and remains biologically active throughout this period. Our aim was to determine whether MTX embedded in cement would control the local growth of a tumour. In 15 rabbits we injected 0.1 ml of VX. 2. tumour suspension into the proximal tibia. At 3, 5, 7, 10 and 14 days three animals were killed and the tibiae removed and examined histologically. With increasing growth of the VX. 2. carcinoma there was increased bone destruction and a rise in the numbers of osteoclasts, but after 14 days the numbers of osteoclasts had decreased. We then injected VX. 2. into the tibiae of another 45 rabbits. After 5 days most of the tumour was curetted out and the defect filled with cement containing either 0 g, 0.1 g, 0.5 g, 1.0 g or 2.0 g MTX/40 g cement. The rabbits were divided into three groups and killed at 3, 7 or 10 days after implantation of cement. The number of osteoclasts and the amount of bone destruction were measured in each tibia. In all three groups bone destruction and osteoclast proliferation were markedly decreased with higher doses of MTX, but bone destruction was not eliminated. Our findings show that in the higher doses used, which were not toxic to the animal, MTX-embedded cement may be of value in minimising the amount of tumour-induced osteolysis and may be a useful adjunct in the surgical management of pathological fractures

Of 41 consecutive patients with newly diagnosed osteogenic sarcoma admitted to the Children's Orthopedic Hospital and Medical Center in Seattle, Washington, between 1952 and 1977, 19 treated before 1973 did not receive adjunctive chemotherapy (histological group) whereas after 1972 22 have been so treated (chemotherapy group). Chemotherapy consisted primarily of high doses of methotrexate and adriamycin for 16 months after surgical treatment. Patients in the historical group have been observed for a minimum of nine years (six patients) or until death (13 patients). The 13 surviving patients in the chemotherapy group have been followed for a minimum of three years (median five years) and all 12 disease-free patients have been off therapy for between one and a half and five and a half years (median three years). Overall, the chemotherapy group has had a significant increase in both survival (p = 0.03) and disease-free survival (P = 0.02) compared to the historical group. In 35 patients with localised disease at diagnosis, the three-year disease-free survival and the three-year survival rates were 18 per cent and 41 per cent respectively in the historical group, and 67 per cent and 78 per cent (life table estimates) respectively in the chemotherapy group. With adjunctive chemotherapy only one of the seven patients developing pulmonary metastases did so later than nine months after diagnosis. The superior results in the chemotherapy group could not be accounted for by differences in age, sex, presence of metastases at diagnosis, histopathology, location of primary tumour, type of initial or subsequent surgical treatment, or the use of standard or computerised lung tomography. Although the use of historical controls in this study does not exclude other changes as contributing to the observed improvement in outcome, our data support the contention that adjunctive chemotherapy improves both the disease-free survival and the overall survival of patients with osteosarcoma and rarely delays the onset of recurrent or metastatic disease

Aims

Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI).

Aims

Osteonecrosis (ON) can cause considerable morbidity in young people who undergo treatment for acute lymphoblastic leukaemia (ALL). The aims of this study were to determine the operations undertaken for ON in this population in the UK, along with the timing of these operations and any sequential procedures that are used in different joints. We also explored the outcomes of those patients treated by core decompression (CD), and compared this with conservative management, in both the pre- or post-collapse stages of ON.

Aims

The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology.

Aims

The aim of this study was to identify factors that determine outcomes of treatment for patients with chondroblastic osteosarcomas (COS) of the limbs and pelvis.

Aims

Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI.

Aims

We retrospectively report our experience of managing 30 patients with a primary malignant tumour of the distal tibia; 25 were treated by limb salvage surgery and five by amputation. We compared the clinical outcomes of following the use of different methods of reconstruction.

Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for haematological malignancy in childhood. In order to describe its incidence and main risk factors and to evaluate the current treatment options, we reviewed 105 children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or acute myeloid leukaemia, or a non-Hodgkin’s lymphoma. Overall, eight children (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18 involved sites, 12 of which were in the femoral head. All these children were aged > nine years (p < 0.001). All had received steroid treatment with a mean cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed between genders and no thrombophilic disorders were identified. Their initial treatment included 11 core decompressions and two bipolar hip replacements. Later, two salvage osteotomies were done and three patients (four hips) eventually needed a total joint replacement. We conclude that AVN mostly affects the weight-bearing epiphyses. Its risk increases with age and higher steroid doses. These high-risk patients may benefit from early screening for AVN.

Cite this article: Bone Joint J 2013;95-B:1708–13.

The purpose of this study was to evaluate the natural history of rheumatoid disease of the shoulder over an eight-year period. Our hypothesis was that progression of the disease is associated with a decrease in function with time.

A total of 22 patients (44 shoulders; 17 women, 5 men, (mean age 63)) with rheumatoid arthritis were followed for eight years. All shoulders were assessed using the Constant score, anteroposterior radiographs (Larsen score, Upward-Migration-Index (UMI)) and ultrasound (US). At final follow-up, the Short Form-36, disabilities of the arm, shoulder and hand (DASH) Score, erythrocyte sedimentation rate and use of anti-rheumatic medication were determined.

The mean Constant score was 72 points (50 to 88) at baseline and 69 points (25 to 100) at final follow-up. Radiological evaluation showed progressive destruction of the peri-articular structures with time. This progression of joint and rotator cuff destruction was significantly associated with the Constant score. However, at baseline only the extent of rotator cuff disease and the UMI could predict the Constant score at final follow-up.

A plain anteroposterior radiograph of the shoulder is sufficient to assess any progression of rheumatoid disease and to predict functional outcome in the long term by using the UMI as an indicator of rotator cuff degeneration.

Cite this article: Bone Joint J 2014;96-B:1520–4.