Showing papers by "Nuffield Orthopaedic Centre published in 1997"

The Localization of Androgen Receptors in Human Bone

Abstract: Androgens have important effects on the human skeleton, and deficiency has been associated with bone loss in both males and females. The skeletal actions of androgens may be mediated directly via the androgen receptor (AR) or indirectly via the estrogen receptor after aromatization to estrogens. The presence of androgen receptors has been demonstrated in bone cells and chondrocytes in vitro, but their presence in human bone in situ has not been reported. In order to provide further evidence for a direct action of androgens on bone via androgen receptors, we have used specific monoclonal antibodies to investigate the expression of human AR in normal developing and osteophytic bone of both sexes. In the growth plates from the developing bone, androgen receptors were predominantly expressed in hypertrophic chondrocytes and in osteoblasts at sites of bone formation. They were also observed in osteocytes in the bone, and in mononuclear cells and endothelial cells of blood vessels within the bone marrow. In the...

Loss to follow-up matters

Abstract: Survival analysis of joint replacement relies on the assumption that surgical procedures in patients lost to follow-up have the same chance of failing as those in patients who continue to be assessed. Our study questions that assumption. During the 16-year follow-up of 2268 patients who had received total hip replacements 142 (6%) were lost to follow-up. The cumulative loss at 15 years was 20%. At their last assessment, patients who subsequently failed to attend for follow-up had significantly worse pain, range of movement and opinion of their progress (p < 0.001) and significantly worse radiological features than a matched control group (p < 0.01). Patients lost to follow-up have a worse outcome than those who continue to be assessed. Consequently, a survival analysis that does not take into account such patients is likely to give falsely optimistic results. It is therefore essential that vigorous attempts are made to minimise loss to follow-up, and that the rate of such loss is quoted. The overall loss to follow-up disguises the magnitude of the problem, which is best quantified by a cumulative rate of follow-up. The reliability of a study can be assessed by a loss-to-follow-up quotient, calculated by the number of failures: the lower the quotient the more reliable the data. Ideally, the quotient should be less than 1.

Changes in muscle fibre type, muscle mass and IGF-I gene expression in rabbit skeletal muscle subjected to stretch.

Abstract: The relationship between IGF-I and changes in muscle fibre phenotype in response to 6 d of stretch or disuse of the lower limb muscles of the rabbit was studied by combining in situ hybridisation and immunohistochemistry procedures. Passive stretch by plaster cast immobilisation of the muscle in its lengthened position not only induced an increase in IGF-I mRNA expression within the individual muscle fibres but also an increase in the percentage of fibres expressing neonatal and slow myosin. This change in phenotype was also found to be accompanied by a rapid and marked increase of muscle mass, total RNA content as well as IGF-I gene expression. In contrast, IGF-I appears not to be involved in muscle atrophy induced by immobilisation in the shortened position and the inactivity which results from this procedure. The level of increase in expression of IGF-I mRNA varied from fibre to fibre. By using adjacent serial sections, the fibres which expressed IGF-I mRNA at the highest levels were identified as expressing neonatal and the slow type 1 myosin. These data suggest that the expression of IGF-I within individual muscle fibres is correlated not only with hypertrophy but also with the muscle phenotypic adaptation that results from stretch and overload.

Human arthroplasty derived macrophages differentiate into osteoclastic bone resorbing cells

Abstract: Objective—In aseptic loosening, a heavy macrophage response to biomaterial wear particles is commonly found in arthroplasty tissues. The aim of this study was to discover if these cells contribute to the bone resorption of aseptic loosening by diVerentiating into osteoclasts. Methods—Macrophages were isolated from the pseudocapsule and pseudomembrane of loose cemented and uncemented hip arthroplasties at the time of revision surgery and then co-cultured on glass coverslips and dentine slices with UMR 106 rat osteoblast-like cells, both in the presence and absence of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. Macrophages isolated from the synovial membrane of patients with osteoarthritis (OA) undergoing hip replacements were similarly studied as a control group.

Smoking, alcohol and the risk of dupuytren’s contracture

Abstract: We investigated the association of Dupuytren's contracture with smoking and with alcohol by a case-control study in which 222 patients having an operation for this condition were matched for age, operation date and gender with control patients having other orthopaedic operations. Fifty of the cases were also each matched with four community controls. Data were collected by postal questionnaire. Dupuytren's contracture needing operation was strongly associated with current cigarette smoking (adjusted odds ratio 2.8 (95% confidence interval (CI) 1.5 to 5.2)). The mean lifetime cigarette consumption was 16.7 pack-years for the cases compared with 12.0 pack-years for the controls (p = 0.016). Dupuytren's contracture was also associated with an Alcohol Use Disorders Test score greater than 7 (adjusted odds ratio 1.9 (95% CI 1.02 to 3.57)). Mean weekly alcohol consumption was 7.3 units for cases and 5.4 units for controls (p = 0.016). The excess risk associated with alcohol did not appear to be due to a confounding effect of smoking, or vice versa. Smoking increases the risk of developing Dupuytren's contracture and may contribute to its prevalence in alcoholics, who tend to smoke heavily.

Genetic influences in end-stage osteoarthritis: sibling risks of hip and knee replacement for idiopathic osteoarthritis

Abstract: From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95% CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%. The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.

Total hip replacement: indications for surgery and risk factors for failure

Abstract: Total hip replacement is one of the most successful and cost effective interventions in medicine.1 2 It offers reliable relief of pain and considerable improvement in function in patients suffering with osteoarthritis or inflammatory arthritis of the hip.3-7 Currently about 50 000 hip replacements are performed in the United Kingdom annually while worldwide the number is over 300 000. Two thirds of these are performed in patients over 65 years of age.8 Ninety to ninety five per cent of patients can expect to have their total hip replacement functioning at 10 years,8 and in 85% they will still be functioning at 20 years.9 Although 85% of patients undergoing total hip replacement have a diagnosis of osteoarthritis,8 inflammatory arthritis, both seropositive and seronegative, is an important indication for total hip replacement and can offer tremendous improvements in quality of life even in the very young.10 In rheumatoid arthritis it has been estimated that the cost to the community of total hip replacement will be recuperated within an average 1.5 years because of savings made on medical and social care.2 Quality of life after surgery approximates that of a healthy reference population.4 Improvements in pain, energy levels, sleep, social, and sexual function are all observed.4 7 Oxygen demands on activity are decreased and walking ability improves.5 11 Most of these improvements are seen within three months of surgery.5 These gains in quality of life allow large numbers of patients to retain their independence and function more actively in society. ### PAIN Pain is the principal indication for hip replacement and is reliably relieved as early as one week after surgery.12 Pain from an arthritic hip is classically located in the groin and buttock. Radiation into the thigh may occur and at times pain …

Biomaterial particle phagocytosis by bone-resorbing osteoclasts

Abstract: Abundant implant-derived biomaterial wear particles are generated in aseptic loosening and are deposited in periprosthetic tissues in which they are phagocytosed by mononuclear and multinucleated macrophage-like cells. It has been stated that the multinucleated cells which contain wear particles are not bone-resorbing osteoclasts. To investigate the validity of this claim we isolated human osteoclasts from giant-cell tumours of bone and rat osteoclasts from long bones. These were cultured on glass coverslips and on cortical bone slices in the presence of particles of latex, PMMA and titanium. Osteoclast phagocytosis of these particle types was shown by light microscopy, energy-dispersive X-ray analysis and SEM. Giant cells containing phagocytosed particles were seen to be associated with the formation of resorption lacunae. Osteoclasts containing particles were also calcitonin-receptor-positive and showed an inhibitory response to calcitonin. Our findings demonstrate that osteoclasts are capable of phagocytosing particles of a wide range of size, including particles of polymeric and metallic biomaterials found in periprosthetic tissues, and that after particle phagocytosis, they remain fully functional, hormone-responsive, bone-resorbing cells.

The Role of Magnetic Resonance Imaging in the Management of Peripheral Nerve Tumours

Abstract: Fourteen cases of peripheral nerve tumour which had been examined by MRI were reviewed T1-weighted images showed the tumours to be of intermediate signal and T2-weighted images showed a high signal with some heterogeneity These appearances are not specific to peripheral nerve tumours, although the diagnosis may be suggested if the lesion arises from a major nerve trunk The association with a nerve trunk may be defined by MRI, thus assisting with surgical planning Neurilemmomas, neurofibromas and malignant nerve sheath tumours could not be differentiated with certainty using MR alone The MR features of lipofibromatous hamartoma are reported

Pain levels after total hip replacement: their use as endpoints for survival analysis.

Abstract: We have assessed the relative value of various outcome measures after THR, by the analysis of follow-up data from over 2000 patients. They had been reviewed clinically and radiologically six months after operation, at one year, and then every two years, some for 16 years. At each review their pain level, stiffness and opinion of progress were scored and a radiograph taken. We found that pain level was the most informative outcome as a predictor of revision and correlated well with the patients' opinions. We made a comparison between the six types of implant in the series, using survival analysis and log-rank testing with different pain levels as endpoints. This analysis revealed differences which were not detected by survival analysis using the traditional endpoint of revision. We therefore recommend the use of different levels of pain as the main outcome measures after total hip replacement.

Radio-opaque agents in bone cement increase bone resorption

Abstract: A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO 4 ) and zirconium dioxide (ZrO 2 ) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO 4 or ZrO 2 , however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO 4 were associated with 50% more bone resorption than those containing ZrO 2 . Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing is BaSO 4 likely to be associated with more osteolysis than that containing ZrO 2 .

The reliability of measurements of pelvic radiographs in infants

Abstract: We have evaluated the reliability of the measurement of radiological indicators in developmental dysplasia of the hip. Three observers each independently assessed 60 pelvic radiographs from infants aged from 3 to 36 months. Errors from the true value of a single measurement made by a single observer (E1), of the average of two measurements by a single observer (E2), and of the average of two single measurements by two different observers (E3) were established for the acetabular index of Hilgenreiner, for the assessment of superior and lateral femoral displacement and for indicators of pelvic alignment. The errors for the assessment of the acetabular index were E1 ± 5°, E2 ± 5°, and E3 ± 3.5°. There was a significant correlation between the presence of an acetabular notch on the radiograph and an increased error in measurement (p = 0.01). Yamamuro’s measurement of lateral femoral displacement was more reliable than the Hilgenreiner distance. The errors of indicators of pelvic alignment showed a correlation with the age of the infant; the quotient of pelvic rotation was more reliable after seven months of age (p

Osteoclasts are capable of particle phagocytosis and bone resorption.

Abstract: Osteoclasts are multinucleated cells specialized for the function of lacunar bone resorption. Although they are known to be capable of phagocytosis of inert particles, it is not known whether this abolishes their ability to respond to hormones or to form resorption lacunae. Human and rat osteoclasts were isolated from giant cell tumours of bone and rat long bones, respectively, and cultured on coverslips and cortical bone slices, both in the presence and in the absence of particles of latex (1 μm diameter) and polymethylmethacrylate (PMMA) (<50 μm). By light microscopy, it was evident that osteoclasts which had phagocytosed both latex and PMMA particles remained responsive to calcitonin. Osteoclast phagocytosis of particles was also evident on scanning electron microscopy, where it could also be seen that these cells were associated with the formation of resorption lacunae. These findings underline the fact that the osteoclast is a true member of the mononuclear phagocyte system and that phagocytosis does not abrogate either its hormonal response to calcitonin or its highly specialized function of bone resorption. That osteoclasts which have phagocytosed biomaterial particles such as PMMA are still able to carry out lacunar bone resorption is of interest in clinical conditions such as aseptic loosening, where a heavy foreign body particle load is often associated with extensive bone resorption. © 1997 John Wiley & Sons, Ltd.

Mri after operative reduction for developmental dysplasia of the hip

Abstract: We performed MRI on 13 infants after operative reduction for developmental dysplasia of the hip (DDH). Using an axial gradient-echo sequence, MRI accurately depicted the acetabular anatomy and confirmed adequate reduction in 12 patients. The one patient with redislocation after surgery was correctly identified. MRI can be carried out quickly, inexpensively and without risk of radiation and is the investigation of choice to confirm adequate reduction in DDH.

Synovectomy of the elbow and radial head excision in rheumatoid arthritis. Predictive factors and long-term outcome.

Abstract: We carried out a survival analysis of elbow synovectomy (ES) and excision of the radial head (RHE) performed on 171 rheumatoid elbows. The failure criteria were revision surgery (performed or desired) and/or the presence of significant or severe pain. The cumulative survival was 81% at one year which thereafter decreased by an average of 2.6% per year. The strongest predictor for success was a low preoperative range of supination-pronation when corresponding survival curves were compared. A low range of flexion-extension also predicted failure. Combining both factors gave better prediction (failure: 6.3% v 67%), but a long duration of elbow symptoms before surgery predicted failure (72%, p = 0.04). At review, there was a mean gain of 50° in supination-pronation and 11° in flexion-extension; both correlated with success. Failure correlated with recurrence of synovitis, elbow instability, ulnar neuropathy, poor general mobility and poor upper-limb function. The last was independently affected by the severity of RA in the ipsilateral shoulder. Our findings show that although the short-term result of ES and RHE in rheumatoid arthritis is good, the long-term outcome is poor except in a subgroup with more than 50% limitation of forearm rotation.

Genetic influences in end-stage osteoarthritis

Abstract: From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95% CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%.The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.

Inhibitory and stimulatory effects of prostaglandins on osteoclast differentiation.

Abstract: The effect of prostaglandins (PGs) on osteoclast differentiation, an important point of control for bone resorption, is poorly understood. After an initial differentiation phase that lasts at least 4 days, murine monocytes, cocultured with UMR106 osteoblastic cells (in the presence of 1,25-dihydroxyvitamin D3) give rise to tartrate-resistant acid phosphatase (TRAP) positive osteoclast-like cells that are capable of lacunar bone resorption. PGE2 strongly inhibits TRAP expression and bone resorption in these cocultures. To examine further the cellular mechanisms associated with this inhibitory effect, we added PGE2 to monocyte/UMR106 cocultures at specific times before, during, and after this initial 4-day differentiation period. To determine whether this PGE2 inhibition was dependent on the type of stromal cell supporting osteoclast differentiation, we also added PGE2 to cocultures of monocytes with ST2 preadipocytic cells. Inhibition of bone resorption was greatly reduced when the addition of PGE2 to monocyte/UMR106 cocultures was delayed until the fourth day of incubation; when delayed until the seventh day, inhibition did not occur. PGE2 inhibition of bone resorption was concentration-dependent and at 10−6 M was also mediated by PGE1 and PGF2α. In contrast to its effects on monocyte/UMR106 cocultures, PGE2 stimulated bone resorption in monocyte/ST2 cocultures. Both ST2 cells and UMR106 cells were shown to express functional receptors for PGE2. These results show that PGs strongly influence the differentiation of osteoclast precursors and that this effect is dependent not only on the type and dose of PG administered, but also on the nature of the bone-derived stromal cell supporting this process.

Venous haemodynamics in both legs after total knee replacement.

Abstract: We studied the effect of total knee replacement on venous flow in 110 patients. Resting venous blood flow was measured using strain-gauge plethysmography before operation, after surgery and after discharge from hospital. There was a significant reduction in mean venous capacitance (p < 0.001) and mean venous outflow (p < 0.004) affecting only the operated leg. Both improved significantly after mobilisation in the early postoperative period, returning to preoperative levels by six days after surgery and before discharge from hospital. Our findings showed that venous stasis may contribute to deep-vein thrombosis only in the first few days after total knee replacement. This would be the most important period for the use of flow-enhancing prophylactic devices. Comparison with changes in blood flow after total hip replacement identified different patterns of altered haemodynamics suggesting that there are different mechanisms of venous stasis and thrombogenesis in hip and knee arthritis and during surgery for these conditions.

The population of users of upper limb prostheses attending the Oxford Limb Fitting Service.

Abstract: There is no central database that records the changing provision of prostheses in the United Kingdom. Experience suggests there have been some shifts in the population, particularly in the past decade. Because the detailed records of these changes are contained in the patients' medical records it is difficult to assess the substance of these data except on an individual basis; the larger picture requires the sifting of a centre's or many centres' data. This paper describes the analysis of one such set of records at the Oxford Limb Fitting Centre. It relates the profile of the population that attends the centre to the general population, and compares the information with that obtainable from other sources. The possible causes for the findings are discussed.

Synovectomy of the elbow and radial head excision in rheumatoid arthritis

Abstract: We carried out a survival analysis of elbow synovectomy (ES) and excision of the radial head (RHE) performed on 171 rheumatoid elbows. The failure criteria were revision surgery (performed or desired) and/or the presence of significant or severe pain. The cumulative survival was 81% at one year which thereafter decreased by an average of 2.6% per year. The strongest predictor for success was a low preoperative range of supination-pronation when corresponding survival curves were compared. A low range of flexion-extension also predicted failure. Combining both factors gave better prediction (failure: 6.3% v 67%), but a long duration of elbow symptoms before surgery predicted failure (72%, p = 0.04). At review, there was a mean gain of 50° in supination-pronation and 11° in flexion-extension; both correlated with success. Failure correlated with recurrence of synovitis, elbow instability, ulnar neuropathy, poor general mobility and poor upper-limb function. The last was independently affected by the severity of RA in the ipsilateral shoulder. Our findings show that although the short-term result of ES and RHE in rheumatoid arthritis is good, the long-term outcome is poor except in a subgroup with more than 50% limitation of forearm rotation.