We reviewed 27 diabetic patients who sustained a tibial fracture treated with a reamed intramedullary nail and compared them with a control group who did not have diabetes. There were 23 closed fractures and four were open. Union was delayed until after six months in 12 of the 23 (52%) diabetic patients with closed fractures and ten of the 23 (43%) control patients (p = 0.768). In two patients with diabetes (9%), closed tibial fractures failed to unite and required exchange nailing, whereas all closed fractures in the control group healed without further surgery (p = 0.489). In both the diabetic and control groups with closed fractures two patients (9%) developed superficial infections. There were two (9%) deep infections in diabetic patients with closed fractures, but none in the control group (p = 0.489).

Overall, there was no significant difference in the rate of complications between the diabetic patients and the control group, but there was a tendency for more severe infections in patients with diabetes.

An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons.

The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment.

The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry.

We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008).

These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.

This study was undertaken to elucidate the mechanism of biological repair at the tendon-bone junction in a rat model. The stump of the toe flexor tendon was sutured to a drilled hole in the tibia (tendon suture group, n = 23) to investigate healing of the tendon-bone junction both radiologically and histologically. Radiological and histological findings were compared with those observed in a sham control group where the bone alone was drilled (n = 19). The biomechanical strength of the repaired junction was confirmed by pull-out testing six weeks after surgery in four rats in the tendon suture group. Callus formation was observed at the site of repair in the tendon suture group, whereas in the sham group callus formation was minimal. During the pull-out test, the repaired tendon-bone junction did not fail because the musculotendinous junction always disrupted first.

In order to understand the factors that influenced callus formation at the site of repair, four further groups were evaluated. The nature of the sutured tendon itself was investigated by analysing healing of a tendon stump after necrosis had been induced with liquid nitrogen in 16 cases. A proximal suture group (n = 16) and a partial tenotomy group (n = 16) were prepared to investigate the effects of biomechanical loading on the site of repair. Finally, a group where the periosteum had been excised at the site of repair (n = 16) was examined to study the role of the periosteum. These four groups showed less callus formation radiologically and histologically than did the tendon suture group.

In conclusion, the sutured tendon-bone junction healed and achieved mechanical strength at six weeks after suturing, showing good local callus formation. The viability of the tendon stump, mechanical loading and intact periosteum were all found to be important factors for better callus formation at a repaired tendon-bone junction.

A total of 38 patients with leprosy and localised nerve damage (11 median at the wrist and 37 posterior tibial at the ankle) were treated by 48 freeze-thawed skeletal muscle autografts ranging between 2.5 cm and 14 cm in length. Sensory recovery was noted in 34 patients (89%) and was maintained during a mean period of follow-up of 12.6 years (4 to 14). After grafting the median nerve all patients remained free of ulcers and blisters, ten demonstrated perception of texture and eight recognised weighted pins. In the posterior tibial nerve group, 24 of 30 repairs (80%) resulted in improved healing of the ulcers and 26 (87%) demonstrated discrimination of texture. Quality of life and hand and foot questionnaires showed improvement; the activities of daily living scores improved in six of seven after operations on the hand, and in 14 of 22 after procedures on the foot. Another benefit was subjective improvement in the opposite limb, probably because of the protective effect of better function in the operated side. This study demonstrates that nerve/muscle interposition grafting in leprosy results in consistent sensory recovery and high levels of patient satisfaction. Ten of 11 patients with hand operations and 22 of 25 with procedures to the foot showed sensory recovery in at least one modality.

Deficiencies of acetabular bone stock at revision hip replacement were reconstructed with two different types of allograft using impaction bone grafting and a Burch-Schneider reinforcement ring. We compared a standard frozen non-irradiated bone bank allograft (group A) with a freeze-dried irradiated bone allograft, vitalised with autologous marrow (group B). We studied 78 patients (79 hips), of whom 87% (69 hips) had type III acetabular defects according to the American Academy of Orthopaedic Surgeons classification at a mean of 31.4 months (14 to 51) after surgery. At the latest follow-up, the mean Harris hip score was 69.9 points (13.5 to 97.1) in group A and 71.0 points (11.5 to 96.5) in group B. Each hip showed evidence of trabeculation and incorporation of the allograft with no acetabular loosening.

These results suggest that the use of an acetabular reinforcement ring and a living composite of sterile allograft and autologous marrow appears to be a method of reconstructing acetabular deficiencies which gives comparable results to current forms of treatment.

We describe a 13-year-old boy with atrophic tibial pseudarthrosis associated with neurofibromatosis who had undergone nine unsuccessful operations. Eventually, union was obtained by the use of bone morphogenetic protein 7 in conjunction with intramedullary stabilisation and autologous bone graft.

Our aim was to determine whether abnormalities noted on MRI immediately after reduction for developmental dysplasia of the hip could predict the persistance of dysplasia and aid surgical planning. Scans of 13 hips in which acetabular dysplasia had resolved by the age of four years were compared with those of five which had required pelvic osteotomy for persisting dysplasia. The scans were analysed by two consultant musculoskeletal radiologists who were blinded to the outcome in each child.

The postreduction scans highlighted a number of anatomical abnormalities secondary to developmental dysplasia of the hip, but statistical analysis showed that none were predictive of persisting acetabular dysplasia in the older child, suggesting that the factors which determine the long-term outcome were not visible on these images.

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells.

Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal.

Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis.

Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of molecular diagnosis has allowed investigation of the role of genetic variations in the inflammatory response to post-traumatic complications and particularly to sepsis.

This review examines the current evidence for the genetic predisposition to adverse outcome after trauma. While there is evidence supporting the involvement of different polymorphic variants of genes in determining the post-traumatic course and the development of complications, larger-scale studies are needed to improve the understanding of how genetic variability influences the responses to post-traumatic complications and pharmacotherapy.

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures.

A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks.

In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect.

Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.

The role of bone-graft extenders in impaction revision surgery is becoming increasingly important. Tricalcium phosphate and hydroxyapatite have been shown to be both biocompatible and osteoconductive, yet many surgeons remain reluctant to use them. The difficulty in handling bone-graft extenders can be partly alleviated by using porous particles and adding clotted blood.

In an in vitro model we measured the cohesive properties of various impaction graft mixes. Several factors were evaluated including the use of pure bone graft compared with mixes with extender, washing the bone and the addition of clotted blood.

Our findings showed that pure allograft bone particles had significantly higher cohesion than when mixed with extender (p < 0.001). Washing had no effect on cohesion. The addition of clotted blood significantly increased the cohesion of both pure bone (p < 0.019) and mixes with pure bone and with porous graft extender (p < 0.044).

Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects.

We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n = 10) and those without (n = 15), and also a control group with an isolated fracture of a long bone (n = 12). The level of transforming growth factor-beta (TGF-β), was measured at five time points after injury (days 1, 5, 10, 42 and 84).

The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p < 0.001 vs other time points). The other groups peaked at day 42 and had a decrease at day 84 after injury (p ≤ 0.001).

Our findings suggest that TGF-β may have a role in the increased bone turnover and attendant complications seen in patients with acute injuries to the spinal cord.

Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.

Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments.

Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis.

The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.

Our aim was to investigate the relationship between urinary excretion of deoxypyridinoline (DPD) as a marker of bone resorption, and Perthes’ disease. There were 39 children with Perthes’ disease in the florid stage who collected first-morning urine samples at regular intervals of at least three months. The level of urinary DPD was analysed by chemiluminescence immunoassay and was correlated with the radiological stage of the disease as classified by Waldenström, and the severity of epiphyseal involvement according to the classification systems of Catterall and Herring. The urinary DPD levels of a group of 44 healthy children were used as a control.

The median urinary DPD/creatinine (CREA) ratio was significantly reduced (p < 0.0001) in the condensation stage and increased to slightly elevated values at the final stage (p = 0.05) when compared with that of the control group. Herring-C patients showed significantly lower median DPD/CREA ratios than Herring-B patients (p = 0.03). The significantly decreased median DPD/CREA ratio in early Perthes’ disease indicated a reduced bone turnover and supports the theory of a systemic aetiology. Urinary levels of DPD may therefore be used to monitor the course of Perthes’ disease.

Osteonecrosis of the knee comprises two separate disorders, primary spontaneous osteonecrosis which is often a self-limiting condition and secondary osteonecrosis which is associated with risk factors and a poor prognosis. In a series of 61 knees (38 patients) we analysed secondary osteonecrosis of the knee treated by a new technique using multiple small percutaneous 3 mm drillings.

Total knee replacement was avoided in 59 knees (97%) at a mean follow-up of 3 years (2 to 4). Of the 61 knees, 56 (92%) had a successful clinical outcome, defined as a Knee Society score greater than 80 points. The procedure was successful in all 24 knees with small lesions compared with 32 of 37 knees (86%) with large lesions. All the procedures were performed as day cases and there were no complications. This technique appears to have a low morbidity, relieves symptoms and delays more invasive surgery.

We compared the biological characteristics of extrinsic fibroblasts infiltrating the patellar tendon with those of normal, intrinsic fibroblasts in the normal tendon in vitro. Infiltrative fibroblasts were isolated from the patellar tendons of rabbits six weeks after an in situ freeze-thaw treatment which killed the intrinsic fibroblasts. These intrinsic cells were also isolated from the patellar tendons of rabbits which had not been so treated.

Proliferation and invasive migration into the patellar tendon was significantly slower for infiltrative fibroblasts than for normal tendon fibroblasts. Flow-cytometric analysis indicated that expression of α5β1 integrin at the cell surface was significantly lower in infiltrative fibroblasts than in normal tendon fibroblasts. The findings suggest that cellular proliferation and invasive migration of fibroblasts into the patellar tendon after necrosis are inferior to those of the normal fibroblasts. The inferior intrinsic properties of infiltrative fibroblasts may contribute to a slow remodelling process in the grafted tendon after ligament reconstruction.