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Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting.
There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.
Aseptic loosening of the acetabular component continues to be the most common indication for revision of total hip replacements in younger patients. Early in the evolution of the cemented hip, arthroplasty surgeons switched from removal to retention of the acetabular subchondral bone plate, theorising that unfavourable mechanical forces were the cause of loosening at the bone-cement interface.
It is now known that the cause of aseptic loosening is probably biological rather than mechanical and removing the subchondral bone plate may enhance biological fixation of cement to bone. With this in mind, perhaps it is time to revive removal of the subchondral bone as a standard part of acetabular preparation.
We investigated factors that were thought to be associated with an increased incidence of squeaking of ceramic-on-ceramic total hip replacements. Between June 1997 and December 2008 the three senior authors implanted 2406 primary total hip replacements with a ceramic-on-ceramic bearing surface. The mean follow-up was 10.6 years. The diagnosis was primary osteoarthritis in each case, and no patient had undergone previous surgery to the hip. We identified 74 squeaking hips (73 patients) giving an incidence of 3.1% at a mean follow-up of 9.5 years (4.1 to 13.3).
Taller, heavier and younger patients were significantly more likely to have hips that squeaked. Squeaking hips had a significantly higher range of post-operative internal (p = 0.001) and external rotation (p = 0.003) compared with silent hips. Patients with squeaking hips had significantly higher activity levels (p = 0.009). A squeaking hip was not associated with a significant difference in patient satisfaction (p = 0.24) or Harris hip score (p = 0.34). Four implant position factors enabled good prediction of squeaking. These were high acetabular component inclination, high femoral offset, lateralisation of the hip centre and either high or low acetabular component anteversion.
This is the largest study to date to examine patient factors and implant position factors that predispose to squeaking of a ceramic-on-ceramic hip. The results suggest that factors which increase the mechanical forces across the hip joint and factors which increase the risk of neck-to-rim impingement, and therefore edge-loading, are those that predispose to squeaking.
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.
There have been comparatively few studies of the incidence of osteolysis and the survival of hybrid and cementless total hip replacements (THRs) in patients younger than 50 years of age. We prospectively reviewed 78 patients (109 hips) with a hybrid THR having a mean age of 43.4 years (21 to 50) and 79 patients (110 hips) with a cementless THR with a mean age of 46.8 years (21 to 49). The patients were evaluated clinically using the Harris hip score, the Western Ontario and McMaster Universities (WOMAC) osteoarthritis score and the University of California, Los Angeles (UCLA) activity score. Radiographs and CT scans were assessed for loosening and osteolysis. The mean follow-up was for 18.4 years (16 to 19) in both groups.
The mean post-operative Harris hip scores (91 points
Although the long-term fixation of the acetabular metallic shell and the cemented and cementless femoral components was outstanding, wear and peri-acetabular osteolysis constitute the major challenges of THR in young patients.
We conducted a longitudinal study including patients with the same type of primary hybrid total hip replacement and evaluated patient activity and femoral osteolysis at either five or ten years post-operatively. Activity was measured using the University of California, Los Angeles scale. The primary outcome was the radiological assessment of femoral osteolysis. Secondary outcomes were revision of the femoral component for aseptic loosening and the patients’ quality of life. Of 503 hip replacements in 433 patients with a mean age of 67.7 years (30 to 91), 241 (48%) were seen at five and 262 (52%) at ten years post-operatively. Osteolytic lesions were identified in nine of 166 total hip replacements (5.4%) in patients with low activity, 21 of 279 (7.5%) with moderate activity, and 14 of 58 (24.1%) patients with high activity. The risk of osteolysis increased with participation in a greater number of sporting activities. In multivariate logistic regression adjusting for age, gender, body mass index and the inclination angle of the acetabular component, the adjusted odds ratio for osteolysis comparing high
In conclusion, of patients engaged in high activity, 24% had developed femoral osteolysis five to ten years post-operatively.
This prospective study assessed the effect of social deprivation on the Oxford hip score at one year after total hip replacement. An analysis of 1312 patients undergoing 1359 primary total hip replacements for symptomatic osteoarthritis was performed over a 35-month period. Social deprivation was assessed using the Carstairs index. Those patients who were most deprived underwent surgery at an earlier age (p = 0.04), had more comorbidities (p = 0.02), increased severity of symptoms at presentation (p = 0.001), and were not as satisfied with their outcome (p = 0.03) compared with more affluent patients. There was a significant improvement in Oxford scores at 12 months relative to pre-operative scores for all socioeconomic categories (p < 0.001). Social deprivation was a significant independent predictor of mean improvement in Oxford scores at 12 months, after adjusting for confounding variables (p = 0.001). Deprivation was also associated with an increased risk of dislocation (odds ratio 5.3, p < 0.001) and mortality at 90 days (odds ratio 3.2, p = 0.02).
Outcome, risk of dislocation and early mortality after a total hip replacement are affected by the socioeconomic status of the patient
The Oxford unicompartmental knee replacement (UKR) was designed to minimise wear utilising a fully-congruent, mobile, polyethylene bearing. Wear of polyethylene is a significant cause of revision surgery in UKR in the first decade, and the incidence increases in the second decade. Our study used model-based radiostereometric analysis to measure the combined wear of the upper and lower bearing surfaces in 13 medial-compartment Oxford UKRs at a mean of 20.9 years (17.2 to 25.9) post-operatively.
The mean linear penetration of the polyethylene bearing was 1.04 mm (0.307 to 2.15), with a mean annual wear rate of 0.045 mm/year (0.016 to 0.099). The annual wear rate of the phase-2 bearings (mean 0.022 mm/year) was significantly less (p = 0.01) than that of phase-1 bearings (mean 0.07 mm/year).
The linear wear rate of the Oxford UKR remains very low into the third decade. We believe that phase-2 bearings had lower wear rates than phase-1 implants because of the improved bearing design and surgical technique which decreased the incidence of impingement. We conclude that the design of the Oxford UKR gives low rates of wear in the long term.
There has been debate about the role of unicompartmental knee replacement in the presence of radiologically identifiable degenerative changes of the patellofemoral joint. We studied 195 knees in 163 patients in whom an Oxford unicompartmental knee replacement had been performed for medial osteoarthritis between January 2004 and July 2007. The mean age of the patients was 66 years (51 to 93). The degree of degenerative change of the patellofemoral joint was assessed using Jones’ criteria. Functional outcome was assessed at a mean of 3.4 years (2 to 7) post-operatively, using the Oxford knee score and the Short-form 12 score.
Degenerative changes of the patellofemoral joint were seen pre-operatively in 125 knees (64%) on the skyline radiographs. There was no statistically significant difference in the Oxford knee or Short-form 12 scores between those patients who had patellofemoral osteoarthritis pre-operatively and those who did not (p = 0.22 and 0.54, respectively).
These results support the opinion expressed at the designer’s hospital that degenerative changes of the patellofemoral joint in isolation should not be considered to be a contraindication to medial Oxford unicompartmental knee replacement.
Between April 2004 and July 2007, we performed 241 primary total knee replacements in 204 patients using the e.motion posterior cruciate-retaining, multidirectional mobile-bearing prosthesis. Of these, 100 were carried out using an image-free navigation system, and the remaining 141 with the conventional technique. We conducted a retrospective study from the prospectively collected data of these patients to assess the early results of this new mobile-bearing design.
At a mean follow-up of 49 months (32 to 71), 18 knees (7.5%) had mechanical complications of which 13 required revision. Three of these had a peri-prosthetic fracture, and were removed from the study. The indication for revision in the remaining ten was loosening of the femoral component in two, tibiofemoral dislocation in three, disassociation of the polyethylene liner in four, and a broken polyethyene liner in one. There were eight further mechanically unstable knees which presented with recurrent disassociation of the polyethylene liner. There was no significant difference in the incidence of mechanical instability between the navigation-assisted procedures (8 of 99, 8.1%) and the conventionally implanted knees (10 of 139, 7.2%).
In our view, the relatively high rate of mechanical complications and revision within 30 months precludes the further use of new design of knee replacement.
The low contact stress patellofemoral replacement consists of a trochlear component and a modular patellar component which has a metal-backed mobile polyethylene bearing. We present the early results of the use of this prosthesis for established isolated patellofemoral arthritis in 51 consecutive patellofemoral replacements in 35 patients. The mean follow-up was 25 months (5 to 60). The estimated survival rate at three years was 63% (95% confidence interval 47 to 80) with revision as the endpoint and 46% (95% confidence interval 30 to 63) with revision and ongoing moderate or severe pain as the endpoint.
The early results of the use of the low contact stress patellofemoral replacement are disappointing with a high rate of revision. We cannot therefore recommend its use.
Diagnostic and operative codes are routinely collected for every patient admitted to hospital in the English NHS. Data on post-operative complications following foot and ankle surgery have not previously been available in large numbers. Data on symptomatic venous thromboembolism events and mortality within 90 days were extracted for patients undergoing fixation of an ankle fracture, first metatarsal osteotomy, hindfoot fusions and total ankle replacement over a period of 42 months. For ankle fracture surgery (45 949 patients), the rates of deep-vein thrombosis (DVT), pulmonary embolism and mortality were 0.12%, 0.17% and 0.37%, respectively. For first metatarsal osteotomy (33 626 patients), DVT, pulmonary embolism and mortality rates were 0.01%, 0.02% and 0.04%, and for hindfoot fusions (7033 patients) the rates were 0.03%, 0.11% and 0.11%, respectively. The rate of pulmonary embolism in 1633 total ankle replacement patients was 0.06%, and there were no recorded DVTs and no deaths. Statistical analysis could only identify risk factors for venous thromboembolic events of increasing age and multiple comorbidities following fracture surgery.
Venous thromboembolism following foot and ankle surgery is extremely rare, but this subset of fracture patients is at a higher risk. However, there is no evidence that thromboprophylaxis reduces this risk, and these national data suggest that prophylaxis is not required in most of these patients.
Impingement syndrome in the shoulder has generally been considered to be a clinical condition of mechanical origin. However, anomalies exist between the pathology in the subacromial space and the degree of pain experienced. These may be explained by variations in the processing of nociceptive inputs between different patients. We investigated the evidence for augmented pain transmission (central sensitisation) in patients with impingement, and the relationship between pre-operative central sensitisation and the outcomes following arthroscopic subacromial decompression.
We recruited 17 patients with unilateral impingement of the shoulder and 17 age- and gender-matched controls, all of whom underwent quantitative sensory testing to detect thresholds for mechanical stimuli, distinctions between sharp and blunt punctate stimuli, and heat pain. Additionally Oxford shoulder scores to assess pain and function, and PainDETECT questionnaires to identify ‘neuropathic’ and referred symptoms were completed. Patients completed these questionnaires pre-operatively and three months post-operatively.
A significant proportion of patients awaiting subacromial decompression had referred pain radiating down the arm and had significant hyperalgesia to punctate stimulus of the skin compared with controls (unpaired
The presence of either hyperalgesia or referred pain pre-operatively resulted in a significantly worse outcome from decompression three months after surgery (unpaired
These observations confirm the presence of central sensitisation in a proportion of patients with shoulder pain associated with impingement. Also, if patients had relatively high levels of central sensitisation pre-operatively, as indicated by higher levels of punctate hyperalgesia and/or referred pain, the outcome three months after subacromial decompression was significantly worse.
There are many causes of paraspinal muscle weakness which give rise to the dropped-head syndrome. In the upper cervical spine the central portion of the spinal cord innervates the cervical paraspinal muscles. Dropped-head syndrome resulting from injury to the central spinal cord at this level has not previously been described. We report two patients who were treated acutely for this condition. Both presented with weakness in the upper limbs and paraspinal cervical musculature after a fracture of C2. Despite improvement in the strength of the upper limbs, the paraspinal muscle weakness persisted in both patients. One ultimately underwent cervicothoracic fusion to treat her dropped-head syndrome.
While the cause of the dropped-head syndrome cannot be definitively ascribed to the injuries to the spinal cord, this pattern is consistent with the known patho-anatomical mechanisms of both injury to the central spinal cord and dropped-head syndrome.
There is no published literature detailing the demographics of paediatric amputations in the United Kingdom. We performed this review of children and adolescents referred to a regional limb-fitting centre from the 1930s to the current decade who suffered amputation as a result of trauma, and compared our data with similar cohorts from other units. Of the 93 patients included, only 11 were injured in the last 20 years. Road traffic accidents accounted for 63% of traumatic amputations. Of all amputations, 81% were in the lower limb and 19% in the upper limb.
Our figures are similar to those from a United Kingdom national statistical database of amputees which showed on average four traumatic amputee referrals to each regional limb-fitting centre in the United Kingdom per ten-year period. Compared with the United States, the incidence of paediatric traumatic amputations in the United Kingdom is low.
Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.
In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.
The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.
The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).
MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).
The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.
We evaluated the effect of low-intensity pulsed ultrasound stimulation (LIPUS) on the remodelling of callus in a rabbit gap-healing model by bone morphometric analyses using three-dimensional quantitative micro-CT. A tibial osteotomy with a 2 mm gap was immobilised by rigid external fixation and LIPUS was applied using active translucent devices. A control group had sham inactive transducers applied. A region of interest of micro-CT was set at the centre of the osteotomy gap with a width of 1 mm. The morphometric parameters used for evaluation were the volume of mineralised callus (BV) and the volumetric bone mineral density of mineralised tissue (mBMD). The whole region of interest was measured and subdivided into three zones as follows: the periosteal callus zone (external), the medullary callus zone (endosteal) and the cortical gap zone (intercortical). The BV and mBMD were measured for each zone.
In the endosteal area, there was a significant increase in the density of newly formed callus which was subsequently diminished by bone resorption that overwhelmed bone formation in this area as the intramedullary canal was restored. In the intercortical area, LIPUS was considered to enhance bone formation throughout the period of observation. These findings indicate that LIPUS could shorten the time required for remodelling and enhance the mineralisation of callus.
The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing’s sarcoma. We identified 300 patients with new primary Ewing’s sarcoma diagnosed between 1980 and 2005 from the centres’ local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing’s sarcomas. Although patients with skeletal Ewing’s were younger (mean age 16.8 years) than those with extra-skeletal Ewing’s sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing’s sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not.
This large series has shown that the oncological outcomes of Ewing’s sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.
The use of allografts for the treatment of bone tumours in children is limited by nonunion and the difficulty of finding a suitable graft. Furthermore, appositional growth can’t be expected of an allograft.
We used an overlapping allograft in 11 children, with a mean age of ten years (4 to 15), with a mean follow-up of 24.1 months (20 to 33). There were five intercalary and six intra-articular resections, and the tumours were in the femur in six cases and the humerus in five. Rates of union, times to union, remodelling patterns and allograft-associated complications were evaluated.
No allograft was removed due to a complication. Of the 16 junctional sites, 15 (94%) showed union at a mean of 3.1 months (2 to 5). Remodelling between host and allograft was seen at 14 junctions at a mean of five months (4 to 7). The mean Musculoskeletal Tumor Society score was 26.5 of 30 (88.3%). One case of nonunion and another with screw protrusion required re-operation.
Overlapping allografts have the potential to shorten time to union, decrease rates of nonunion and have positive appositional growth effect.
This study evaluated the results of a physeal-sparing technique of intra-articular anterior cruciate ligament (ACL) reconstruction in skeletally immature patients, with particular reference to growth disturbance. Between 1992 and 2007, 57 children with a mean age of 12.2 years (6.8 to 14.5) underwent ACL reconstruction using the same technique. At a mean of 5.5 years (2 to 14) after surgery, 56 patients underwent clinical and radiological evaluation. At that time, 49 patients (87.5%) had reached bony maturity and 53 (95%) achieved A or B according to the IKDC 2000 classification. Four patients had stopped participation in sports because of knee symptoms, and three patients (5.4%) had a subsequent recurrent ACL injury. There was no clinical or radiological evidence of growth disturbance after a mean growth in stature of 20.0 cm (3 to 38).
This study demonstrates that ACL reconstruction sparing the physes in children is a safe technique protecting against meniscal tears and giving better results than reconstruction in adults, without causing significant growth disturbance.
The objective of this study was to determine the effectiveness of screening and successful treatment of methicillin-resistant
We screened 5933 elective orthopaedic in-patients for MRSA at pre-operative assessment. Of these, 108 (1.8%) were colonised with MRSA and 90 subsequently underwent surgery. Despite effective eradication therapy, six of these (6.7%) had an SSI within one year of surgery. Among these infections, deep sepsis occurred in four cases (4.4%) and superficial infection in two (2.2%). The responsible organism in four of the six cases was MRSA. Further analysis showed that patients undergoing surgery for joint replacement of the lower limb were at significantly increased risk of an SSI if previously colonised with MRSA.
We conclude that previously MRSA-colonised patients undergoing elective surgery are at an increased risk of an SSI compared with other elective patients, and that this risk is significant for those undergoing joint replacement of the lower limb. Furthermore, when an infection occurs, it is likely to be due to MRSA.
Congenital pseudarthrosis of the tibia remains one of the most difficult orthopaedic problems. We describe early excision and the use of the Masquelet technique to reconstruct the bone defect in a child aged 14 months. Consolidation sufficient for complete weight-bearing was achieved by seven weeks. After two and a half years, the child was asymptomatic with a fully reconstructed tibia and no leg-length discrepancy.
A 60-year-old man developed severe neuropathic pain and foot-drop in his left leg following resurfacing arthroplasty of the left hip. The pain was refractory to all analgesics for 16 months. At exploration, a PDS suture was found passing through the sciatic nerve at several points over 6 cm and terminating in a large knot. After release of the suture and neurolysis there was dramatic and rapid improvement of the neuropathic pain and of motor function.
This case represents the human equivalent of previously described nerve ligation in an animal model of neuropathic pain. It emphasises that when neuropathic pain is present after an operation, the nerve related to the symptoms must be inspected, and that removal of a suture or irritant may lead to relief of pain, even after many months.
Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An
In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone.
We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.
