1 . Twenty patients with fibrous dysplasia, confirmed histologically, are reported and discussed in regard to classification, etiology, pathogenesis and treatment. The various fibrous or fibrocystic lesions of bone are characterised briefly for purpose of contrast, and the position of fibrous dysplasia in this heterogeneous collection is suggested. 2. The classification of fibrous dysplasia based on the degree of skeletal involvement is used, and the diagnostic, therapeutic and prognostic implications of this classification emphasised. The authors endorse the opinion that fibrous dysplasia is a developmental defect. Clinical, histological and radiographic evidence is presented to point to the distinct evolution of the monostotic lesions, to which a positive and aggressive approach is recommended

1. Hereditary multiple exostosis has been studied in fifty-six patients and their relatives. In most cases previous records were available and the progress of the disease could be traced over many years. 2. The characteristic lesions are described and the complications encountered in the present series of cases are noted. The disease is inherited in approximately two-thirds of the cases and invariably produces detectable lesions in the heterozygote. 3. The cartilage-capped exostoses are confined to the endochondral skeleton where their incidence is closely related to the growth potential of the sites involved. 4. An attempt has been made to explain the curious distribution of the exostoses, and the likely theories of the pathogenesis of the disease are discussed

The pathogenesis of longitudinal reduction deformities of the limbs, or dysmelia, is still a matter of debate. Their morphological pattern was defined from a large collection of radiographs of children with dysmelia following the thalidomide disaster. We compared radiographs of 378 of these limbs with the sclerotomes which are areas of segmental sensory innervation of the limb skeleton defined by the radiation of referred pain. The pattern of dysmelia matched the sclerotomes closely in 279 limbs (73.5%). The principles of skeletal reduction in dysmelia are explained by the arrangement of the sclerotomes. The congruence between two separate and independent data sets shows that both patterns are expressions of the underlying segmental sensory innervation of the skeleton, and that the sensory nervous system is involved in the process of limb morphogenesis and teratogenesis

Congenital dislocation of the peroneal tendons is a rare and infrequently reported deformity of the foot in the neonate. Four cases of this deformity associated with a congenital calcaneovalgus deformity of the foot have been treated and followed to the resolution of both of the deformities. The calcaneovalgus foot proved more resistant to correction and required more prolonged and aggressive treatment than was usual when it was found as an isolated deformity. All four patients demonstrated other stigmata of intra-uterine malposition and oligohydramnios or both. Our anatomical studies suggested that the superior peroneal retinacular ligament was the critical stabilising structure for the peroneal tendons. A concept of the pathogenesis of this deformity is discussed and a proven regimen for its treatment presented

We studied the pathogenesis, incidence and consequences of avascular necrosis in 184 children treated for congenital dislocation of the hip. Of 210 hips, 99 (47%) had some evidence of avascular necrosis (total 81, partial 18). The incidence was not influenced by the age at reduction, the duration of traction or the use of adductor tenotomy. Patients treated by closed reduction without preliminary traction did not have a higher incidence of avascular necrosis. At long-term clinical and radiological review of 81 hips, early avascular necrosis significantly increased the chance of a poor outcome but did not predispose to acetabular dysplasia. If review includes minor forms of avascular necrosis, then this condition is common after closed reduction. Its presence is an important determinant of long-term radiological and clinical outcome

We have reviewed 41 patients with pustulotic arthro-osteopathy (PAO), all having both the typical skin rash of pustulosis palmaris et plantaris and bone lesions. The most common bones affected were the clavicle, sternum and ribs. Changes in the clavicle started, not as an enthesopathy, but with periosteal bone formation, indicative of a bone marrow disorder. About 30% of the patients also had lesions in the spine, sacroiliac region or the peripheral joints. Bone and joint lesions followed a variable and intermittent clinical course over a long period of time. Biopsies in eight cases showed similar inflammatory changes in skin, bone and synovium, with infiltration of lymphocytes and polymorphonuclear leucocytes. This suggests that there is a common pathogenesis in the three tissues

1. A genetic and orthopaedic analysis of a family of seventy members exhibiting the nail-patella syndrome is described. 2. The disorder is found to be determined by a simple dominant autosomal gene with complete penetrance, but displaying variable expressivity and great pleomorphism. 3. In the family reported all ten of the affected individuals whose blood was typed belonged to group O, demonstrating the adjacent chromosomal position of the nail-patella gene and the ABO blood group locus. 4. The pathogenesis is one of hypoplasia of the nail beds, but hyperplasia in mesodermal tissue as shown by the formation of iliac horns. 5. The skeletal changes are ascribed to a functional disturbance in the development of the traction epiphyses rather than to a primary teratogenic effect

1. The so-called adamantinoma of long bones is a clinico-pathological entity, the pathogenesis of which is still in doubt. The case for its being a synovial sarcoma showing epithelial differentiation is in our view unconvincing. 2. The tumour is slowly growing, and of low grade malignancy. Apparent cure has been effected in a third of the total cases recorded by amputation or resection of the diseased bone. 3. These means, however, have not prevented metastases to the lungs and skeleton in a similar number. 4. A case is presented in which a metastasis appeared in the chest twenty-two years after amputation of the leg. This was sensitive to telecobalt irradiation, and is the first case in which a distant metastasis has been proved microscopically

Aims

Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres.

We examined soft tissue biopsies from 26 patients with symptomatic nerve root fibrosis and arachnoiditis after a previous laminectomy. Dense fibrous connective tissue was found about the nerve roots and in 14 cases (55%) fibrillar foreign material was seen within it. This material had the histochemical characteristics of cotton fibres from swabs and neurosurgical patties. In two other cases nerve root fibrosis was associated with residual radiopaque lipid thought to derive from earlier myelography. Our findings suggest that risks may be associated with the introduction of foreign material into the vertebral canal, and that microscopic fragments of surgical swabs and patties may have a role in the pathogenesis of postoperative periradicular fibrosis

We have studied core biopsy specimens from 16 femoral heads affected by idiopathic avascular necrosis at the silent stage, when there were no clinical or radiographic manifestations but scintigraphy was positive. All the specimens showed necrosis of trabeculae and of bone marrow, but the most common and characteristic feature was evidence of old and new haemorrhage in the marrow. In the areas of intramedullary haemorrhages, trabeculae and bone marrow were completely necrotic, with a transitional area of incomplete necrosis between these areas and those without haemorrhagic lesions, where the trabeculae and bone marrow were normal. There was good correlation between necrosis and haemorrhagic episodes, and it was concluded that repeated intramedullary haemorrhage at the silent stage is probably related to the pathogenesis of idiopathic avascular necrosis of the femoral head

The pathogenesis of slipped upper femoral epiphysis is unknown but the condition has been linked with various endocrine disorders. Nine patients with slipped epiphyses in association with primary juvenile hypothyroidism are presented. In all patients, slipping occurred or symptoms developed in the affected hip before the hypothyroidism was diagnosed. A generalised pathology was suggested by the absence of trauma (8 patients), by bilateral slipping (6 patients), and by obesity and short stature in all patients. All cases had delayed skeletal maturation and characteristic metaphysial changes were seen on their radiographs. The clinical diagnosis of juvenile hypothyroidism can be difficult but it merits consideration in patients who have a slipped upper femoral epiphysis in association with short stature, obesity, delay in skeletal maturity, or any one of these

1. Degenerative arthritis has been produced consistently in adult rabbits by the injection of the proteolytic plant enzyme papain into the hip joint. Arthritic changes were recognisable radiographically after six weeks. 2. A progression of changes occurred, from loss of acid mucopolysaccharide staining in the matrix, fibrillation, fissuring and erosion of articular cartilage with death of chondrocytes in the weight-bearing areas, to secondary bony changes of subchondral sclerosis, occasional cysts and osteophyte formation. 3. Synovial inflammation occurred with accumulation of cartilage and bone debris in the inferior capsule and later capsular thickening. 4. It is suggested that this arthritis is sufficiently similar to human osteoarthritis to be useful as a model for further studies of the pathogenesis of the disease and the effects of different methods of treatment

Aims

To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA).

Aims

With novel promising therapies potentially limiting progression of Dupuytren’s disease (DD), better patient stratification is needed. We aimed to quantify DD development and progression after seven years in a population-based cohort, and to identify factors predictive of disease development or progression.

We investigated the pathogenesis of soft-tissue contracture in club foot, using immunohistochemistry to study 41 biopsy specimens and 12 normal deltoid ligaments from cadavers. Five biopsy specimens were studied by electron microscopy (EM) to determine the presence of myofibroblasts. All 41 specimens of club foot stained positively for vimentin as against only one of the 12 control specimens. By contrast, there was no difference in staining for desmin or α-smooth muscle actin. EM showed some variability in the appearance of ligamentous cells. Most contained bundles of microfilaments in the cytoplasm and many had abundant pinocytotic vesicles, but no basal lamina or plasmalemmal attachment plaques. Cells of the medial ligamentous tissue in patients with club foot contain vimentin and others have myofibroblastic characteristics. Both features may contribute to recurrence after soft-tissue release

Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation. Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response. The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of collagen is not limited to bone, as well as the influence of the host’s metabolism on their concentration, produce considerable intra- and inter-individual variability in their interpretation. Despite this, the possible role of bone-turnover markers in the assessment of progression to union, the risks of delayed or nonunion and the impact of innovations to accelerate fracture healing must not be ignored

We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of an average age of 31.5 years. Defects of the annulus fibrosus were classified as peripheral, circumferential or radiating; the nucleus pulposus as normal, moderately or severely degenerate. Peripheral tears were more frequent in the anterior annulus, except in the L5-S1 disc. Circumferential tears were equally distributed between the anterior and the posterior annulus. Almost all the radiating tears were in the posterior annulus, and closely related to the presence of severe nuclear degeneration. Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogenic pain

Among 449 patients with leprosy, 40 had clinical and radiographic evidence of neuroarthropathy in 50 feet. These changes were classified into four types according to the joints first involved by major lesions: ankle (25 feet), midtarsal (15 feet), tarsometatarsal (7 feet) and subtalar (3 feet). The progression of joint destruction was different in each type, but despite the severe destructive changes seen in radiographs, the patients had relatively few complaints. The muscles innervated by the peroneal nerve were severely paralysed in ankle and midtarsal types and it seems that, over a long term, repeated trauma and/or abnormal stress may lead to these types of neuroarthropathy. Neuropathy was less severe in the tarsometatarsal type of joint degeneration; the pathogenesis in this type seemed to be mainly direct trauma to the forefoot

The pathogenesis of Perthes' disease has been related to increased intra-articular pressure secondary to a joint effusion. The pressure within the hip in different positions was measured in eight children with transient synovitis and four with the synovial stage of Perthes' disease. In the position of comfort for the hip this pressure was always less than the arteriolar blood pressure and in a supine position it did not exceed the systolic blood pressure. However, in extension with medial rotation the intra-articular pressure always became several times the systolic blood pressure. This high pressure was also recorded in the stable lateral position which occurs normally during sleep. It is concluded that in the presence of a synovial effusion in the hip, a position of extension and medial rotation causes an increase in intra-articular pressure which may compromise the blood supply to the capital epiphysis of the femur