Objectives

Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM.

Objectives

Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes.

We reviewed a consecutive series of 241 uncemented, porous-coated anatomic (PCA) hip replacements at an average follow-up of five years (2 to 9). Of these, 32 had failed (13%), 26 at the acetabular component (11%) and six at the femoral component (2%). Acetabular failure was associated with local osteolysis and excessive polyethylene wear in 20 cases: in these histological examination showed giant macrophages incorporating numerous particles of high-density polyethylene. The femoral failures were related to a poor intramedullary fit with subsequent subsidence. Using the recommendation for revision as the end point, the cumulative survival rate for prostheses was 91% at six years (95% CI +/- 6%), 73% (+/- 11%) at seven years, and 57% (+/- 20%) at eight years. The result of uncemented PCA hip replacement is satisfactory up to six years, but then increasing failure of the acetabular component appears to be due to polyethylene wear, leading to osteolysis, loosening and component migration. At first, failure is often asymptomatic; routine follow-up of uncemented hip replacement is essential, especially after five years

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

To investigate the effect of instability on the remodelling of a minor articular surface offset, we created a 0.5 mm coronal step-off of the medial femoral condyle in 12 New Zealand white rabbits and transected the anterior cruciate ligament (ACL). A control group of 12 rabbits had only ACL resection and the opposite knee was used as the non-operated control. The osteoarthritic changes at 6, 12 and 24 weeks after surgery were evaluated histologically. In addition, changes in the immunological detection of 3-B-3(-) and 7-D-4 chondroitin-6-sulphate epitopes were determined because of the previous association of such changes with repair of cartilage and early osteoarthritis. In the instability/step-off group there was rapidly progressing focal degeneration of cartilage on the high side of the defect, not seen in previous step-off studies in stable knees. The rest of the femoral condyles and the tibial plateaux of the instability/step-off group had moderate osteoarthritis similar to that of the instability group. 3-B-3(-) was detectable in the early and the intermediate stages of osteoarthritis but no staining was seen in the severely damaged cartilage zones. Immunoreactivity with 7-D-4 increased as degeneration progressed. Our findings have shown that even a minor surface offset may induce rapid degeneration of cartilage when the stability of the knee is compromised

We have investigated the effect of currents induced by electromagnetic fields on the healing of the tibia of sheep after osteotomy, using objective and quantifiable criteria wherever possible. A battery-powered, induction apparatus was developed and was enclosed within the cast applied to the limb, so that the treated fractures received pulsed magnetic fields for 24 hours a day while the animals were freely mobile. In all, 13 sheep were treated and 13 were used as controls. The response was assessed by radiography of the limb and of the excised bone, by histology, including measurement of the areas of callus, fibrocallus and cortical bone, and by measurement of the uptake and extraction of bone-seeking mineral. All the bones healed and no statistically significant differences between the treated animals and the controls were discovered except (at only P less than 0.05) in the uptake of bone-seeking mineral; this increased more rapidly in treated animals over the two to three weeks after osteotomy, although at six weeks the uptake in both groups was the same

The features are described of seven cases of "juxtacortical" chondrosarcoma, the term introduced by Jaffe for a rare but distinct entity and now accepted in the World Health Organisation classification as preferable to the term "periosteal" chondrosarcoma. In all cases the lesion involved the shaft of a long bone, most often the femur, and in two cases two different long bones were affected. Six of the seven patients were male and all were in the second decade. The characteristic appearance was that of a small tumour adjacent to the cortex with areas of spotty calcification often accompanied by radiating bone spicules perpendicular to the bone shaft and a typical Codman's triangle. Histologically all the tumours showed a cartilaginous lobular pattern, well limited on the surface and seldom infiltrating the cortex; areas of spotty calcification and enchondral ossification were often present but tumour osteoid and bone were conspicuously absent. Despite the ominous histological aspect, the prognosis proved to be relatively favourable compared with the usual central chondrosarcoma of a similar grade of malignancy

Forty-seven histologically confirmed cases of Ewing's tumour are reported, with typical age, sex and skeletal distributions. The disease-free survival curves are like those for osteosarcoma of corresponding types of bone, but with higher mortality. The two-year disease-free survival rates were 24 per cent for tumours of long bones and 5 per cent for those of other bones. Osseous metastases were most frequent, although the lung was the commonest single site involved. There were secondary deposits in lymph nodes in nine patients, possibly also in four more with mediastinal enlargement. Although initially radiosensitive, one-third of tumours recurred locally, almost always with the appearance of metastases. Neither whole bone irradiation nor high dosage alone ensures complete control of the primary tumour, and it is suggested that recently reported improved results of treatment should be attributed to adjuvant multi-drug chemotherapy. Inadequate control of the primary tumour diminishes the chance of survival and for some sites radical operation merits reconsideration

1 . Standard lumbar laminectomy was performed at multiple levels in thirty dogs, and manipulations were carried out in the spinal canal to observe their effects on periradicular adhesion formation. The canal was scarified, packed with Gelfoam, or treated with three varieties of Silastic membranes. The results were serially assessed from three days to twelve weeks by gross observation, nerve conduction studies, histological examination of transverse sections of the spine, myelin study of lumbar roots and micropaque study of the arterial supply to the roots. 2. The results were consistent biologically. The principal source of scar is dorsally in the fibrous tissue elements of the erector spinae muscle mass. This scar, the laminectomy membrane, covers the laminectomy defect and extends into the canal bilaterally to adhere to the dura and nerve roots. 3. Gelfoam does not contribute to scar formation, but instead acts as an effective interposing membrane. Silastic membranes are capable of providing protection against nerve root adhesions without interfering with the anatomical or physiological integrity of the nerves. 4. Certain clinical implications of the study are discussed

1. Forty-seven tibial nerves of rabbits were stretched, twenty-four gradually by the Instron machine and twenty-three suddenly by dropping a load. The stretched nerves were examined histologically throughout their length. 2. Nerve trunks possess a high degree of elasticity, which is mainly a feature of the epineurium. 3. The initial elongation of the nerve is due to extension of the epineurium and straightening of the funiculi and of the nerve fibres. Such elongation is "physiological" in the sense that it does not affect the nerve fibres. 4. The first structure to be ruptured during stretching is the epineurium ; this occurs when the nerve trunk has reached its limit of elasticity. 5. Before rupture of the epineurium the damage to the nerve fibres is either neurapraxia or axonotmesis, because the endoneurial sheaths and Schwann tubes remain intact. 6. Beyond the limit of elasticity very severe damage of the nerve trunk occurs; all elements of the nerve may be ruptured. If less violent force is applied, some funiculi may survive. The longitudinal extent of the lesion is always great, reaching 2 to 5 centimetres in the rabbit

1. A general picture of the histological state of the bone-cement junction, up to seven years after implantation, is presented as a result of the study of twenty-three human specimens. 2. The transmission of load from cement to bone occurs at isolated points through the medium of newly formed fibrocartilage. 3. It is clear that this fibrocartilage has been produced in response to mechanical pressure on fibrous tissue which has undergone compression between cement and underlying bone. 4. Direct contact exists between the surface of the cement and the newly formed fibrocartilage at these sites of load transmission. 5. Load-bearing fibrocartilage frequently shows areas of ossification extending into it from the underlying bone. 6. Where soft tissues in contact with cement are too thick or too delicate for load transmission a thin layer of giant-cell cytoplasm coats the cement surface. 7. No collections of giant cells to form granulomatous or caseating areas have been seen. 8. Fat storage, indicating the absence of chemical irritation, can occur within ten microns of the cement surface

1. An investigation was made of the tolerance of the cells in the femoral head in rabbits for ischaemia brought about by transecting the ligament of the femoral head and applying a ligature around the femoral neck. The animals were killed two, six, twelve, twenty-four and seventy-two hours after operation. 2. In the cells of the bone marrow and in the osteoblasts distinct histological signs of disintegration were present six hours after operation. Pyknosis of the osteocyte nuclei was found after twenty-four hours' ischaemia; sometimes vacuolar clarifications could be observed in these pyknotic nuclei. After three days of ischaemia the staining affinity for Feulgen and haematoxylin of a number of osteocyte nuclei had visibly decreased. 3. The Feulgen-DNA content of the osteocyte nuclei-as measured in individual nuclei by means of an integrated microdensitometer-was significantly reduced as compared with similar nuclei from the control side as early as after six hours of ischaemia. This DNA loss was progressive with the period of ischaemia. From these facts, the conclusion was reached that in the femoral head of the rabbit the period of reversible damage for osteocytes must have ended within six hours

1. A case of essential osteolysis is presented, occurring in a young man of eighteen with no known family history and developing progressively from early childhood. The condition was radiologically evident in the elbows, hands and feet, and was accompanied by atrophy of the cancellous bone of the epiphyses of the shoulders and knees. It was also associated with certain abnormalities of the skull and vertebrae. The patient died from a nephropathy of late onset. 2. Examination of the left foot revealed on the radiologically "lysed" bony extremities a very slow process of erosion affecting essentially the epiphysial and metaphysial cortical bone, of a non-inflammatory nature and accompanied by disappearance of the hyaline cartilage. The extremities not radiologically "lysed" showed signs of erosion that were histologically similar but not macroscopically evident; they were accompanied by regressive changes in the hyaline cartilage. 3. There were no signs of renal osteodystrophy or of Sudeck's dystrophy. 4. Post-mortem tests revealed an increase in the seromucoids and failed to reveal the presence of proline in the serum or of proline and hydroxyproline in the urine. 5. The authors discuss the place of this condition among osteolyses in general

1. In five out of eleven cases of osteoclastoma it was found that osteoclasts were present inside clearly defined blood vessels either within the tumours or in the tissues immediately surrounding the tumours. In two further cases it was found that osteoclasts protruded into the vessels although they were not lying free within the vessels. 2. The possible modes of entry of these cells into the blood stream are discussed. Although accidental dissemination of osteoclasts into damaged blood vessels could not be excluded, it was felt that the process was equally likely to be related to some inherent property of the osteoclasts. From further observations it is suggested that osteoclasts are capable of local destruction of the connective tissues of the vessel walls, probably by enzyme action. Such an action might be analogous to the processes by which, in the opinion of many, osteoclasts bring about the resorption of bone. 3. There did not seem to be any relationship between the finding of intravascular osteoclasts and the malignancy of the tumour, assessing the latter either on histological or clinical grounds. The finding of intravascular osteoclasts does not therefore appear to be of any prognostic significance

Children with a mucopolysaccharidosis or mucolipidosis suffer progressive disability of the hands, particularly in relation to dysfunction of the median nerve. This is an increasing problem because bone-marrow transplantation has dramatically improved survival without apparently changing the musculoskeletal manifestations. We have reviewed 48 children with these syndromes who required carpal tunnel decompression, recording symptoms, signs, radiological, electrophysiological and operative findings, histology and upper-limb function. In these children the carpal tunnel syndrome differs from that seen in adults. Symptoms are rare but signs such as decreased sweating, pulp atrophy, thenar wasting and manual clumsiness are much more common. At operation, the flexor retinaculum was thickened and a mass of white tenosynovium engulfed the flexor tendons. Most patients had some definite nerve constriction with a thickened epineurium. Functional improvement was seen after early decompression, with some benefit from simultaneous tendon release. Regular physiotherapy helped to maintain increased hand movement. We describe our assessment protocol, the physiotherapy and operative regime and the standard functional review which helps to maximise function in the hands and upper limbs of these children

The healing of a hamstring graft to bone is the weak link in the reconstruction of a cruciate ligament using this donor material. We therefore investigated the augmentation of healing at the tendon-bone interface using calcium-phosphate cement (CPC). We performed semitendinosus autograft reconstructions of the anterior cruciate ligament on both knees of 22 New Zealand white rabbits. The interface between the grafted tendon and the bone tunnel for one knee was filled with CPC. Six rabbits were killed at the end of the first and second post-operative weeks in order to evaluate the biomechanical changes. Two rabbits were then killed sequentially at the end of weeks 1, 3, 6, 12 and 24 after operation and tissue removed for serial histological observation. Histological examination showed that the use of CPC produced early, diffuse and massive bone ingrowth. By contrast, in the non-CPC group of rabbits only a thin layer of new bone was seen. Mechanical pull-out testing at one week showed that the mean maximal tensile strength was 6.505 ± 1.333 N for the CPC group and 2.048 ± 0.950 N for the non-CPC group. At two weeks the values were 11.491 ± 2.865 N and 5.452 ± 3.955 N, respectively. Our findings indicate that CPC is a potentially promising material in clinical practice as regards its ability to reinforce the fixation of the tendon attachment to bone and to augment the overall effectiveness of tendon healing to bone

We reviewed all patients with a clinically infected foot ulcer attending a specialised neuropathic foot clinic. Neuropathy was confirmed by the inability to feel a 5.07 Semmes-Weinstein hair, areflexia and impaired vibration sense, as measured by a biothesiometer. Of 40 patients who attended the clinic over a two-year period, six with ischaemic ulcers were excluded. The remaining 34 had plain radiographs of the foot followed by a . 99m. Tc-MDP bone scan. If the latter was positive, an . 111. In-labelled WBC scan was performed with planar and/or tomographic dual-isotope studies where appropriate. Bone and WBC scans were performed in 31 patients. In ten, isotope imaging showed infection localised to the soft tissues only and conservative treatment was successful in them all. Eighteen patients were treated surgically with excision of the involved bone, which was sent for culture and histological examination. Dual-isotope scans had a sensitivity of 93% and a specificity of 83%. . 99m. Tc-MDP bone scans with the appropriate . 111. In-labelled WBC scans can reliably determine the site and extent of osteomyelitis in the neuropathic diabetic foot

The formation of a painful neuroma after operations on the medial or lateral sides of the elbow is a common problem. Our aim was to determine the relationship of the cutaneous nerves to the three usual skin incisions around the elbow. In 18 freshly frozen cadaver arms we made three standard 16 cm incisions in the skin medially, laterally, and posteriorly and explored them using loupe magnification. The number of nerves crossing each incision was determined by gross observation and their diameter measured by electronic microcallipers. In ten arms, biopsies of the nerves in each incision were sent for histological examination. We found significantly more cutaneous nerves crossing the medial and lateral incisions than the posterior. The diameter of the nerves crossing the posterior incision was significantly smaller than those crossing the lateral incision. Cutaneous nerves are at considerable risk of injury when medial or lateral incisions are used to approach the elbow, but the posterior approach carries less hazard. The routine use of the posterior incision may reduce the incidence of symptomatic paraesthesia and the formation of a painful neuroma after operation

We examined the radiographs from a prospective clinical study of fixation by pedicle screws and those from an experimental study in a sheep model. In the clinical study, instruments were removed from 21 patients after implantation for 11 to 16 months and the extraction torques of the screws were recorded. A structured protocol was used for the radiological examinations. In the experimental study, loaded pedicle screw instrumentations were implanted in the sheep for six or 12 weeks. After radiological examination the pull-out resistance and the histological characteristics were studied. In the clinical study, all screws with radiolucent zones had a significantly reduced mean extraction torque compared with screws without radiolucent zones (16 ± 10 Ncm v 403 ± 220 Ncm; p < 0.0001). In the experimental study the mean maximum pull-out resistance for the screws with radiolucent zones was significantly lower than for those with no radiolucency (243 ± 156 N v 2214 ± 578 N; p = 0.0006) and the mean bone-to-screw contact was reduced for screws with zones compared with those without zones (8 ± 9% v 55 ± 29%; p = 0.0002). Our findings showed that all screws with radiolucent zones had low extraction torques or low pull-out resistance. A radiolucent zone is a good indicator of loosening of a pedicle screw