Topographical variation in the calcified zone of upper femoral articular cartilage.

A series of 27 adult human femoral heads has been examined for topographical variation in 'remodelling' and other histological features of the calcified zone at the base of the articular cartilage. The specimens were obtained from necropsies; hip joints with osteoarthritic bone exposure were excluded. A tissue sample from the inferomedial aspect was compared with one from the femoral zenith, using a standard length along the articular contour at each site. Histological sections were cut in a plane vertical to that of the articular surface. A study was made of the various patterns seen within cartilage tidemarks when these were examined at high magnification in paraffin sections stained with Ehrlich's haematoxylin and eosin. Special attention was paid to the identification of tidemark segments which stained faintly and were not readily apparent. The tidemarks were mapped on a photomicrographic montage from each of the tissue samples. When a sample showed evidence of one or more extra phases of cartilage calcification, as indicated by the presence of more than one tidemark, the spatial extent of the extra calcification was quantified by linear measurement and by point counting on the photomicrographic montage. The mean of the results for the spatial extent of extra-phase calcification of the cartilage was greater for the inferomedial than for the zenith samples. However, it was also greater for samples where the articular surface showed minimal fibrillation than for samples where the surface was still intact, and it was noted that surface fibrillation was much more common in the inferomedial than in the zenith samples. Where there was more than one tidemark, the lowest sometimes showed gaps where it had been breached by an advance of ossification into the calcified cartilage. The mean value of the tangential extent of such gaps was similar at the two sites sampled. Focal contacts, where the uncalcified articular cartilage was in contiguity with calcified zone 'defects' containing tissue other than calcified hyaline cartilage, were more numerous at the femoral zenith than inferomedial to the fovea. Counts were also made of tangential shearing splits at the interface of the calcified and uncalcified cartilage. Subject to the reservation that genuine splitting may be difficult to distinguish from technical artifact, the mean number was closely similar at the two sites sampled. The interpretation of the findings is discussed in relation to remodelling changes in the cartilage base and to degenerative changes in the overlying articular cartilage.

The synovial response to intra-articular acrylic cement particles in guinea pigs.

The histology and cytology of the tissue response to intra-articular insertion of particles of acrylic bone cement containing barium sulphate has been studied in the guinea pig knee joint. Following insertion of the acrylic, fibrinous debris admixed with particles became adherent to the synovial membrane. Cell proliferation at the interface between the debris and the synovial tissue engulfed the debris, and a new layer of intimal lining cells formed over its surface. This process led to incorporation of the particles into vascularized subintimal tissue. The response to subintimal acrylic cement particles was by multinucleate giant cells (macrophage polykaryons), macrophages and fibroblasts, with a variable amount of intermingled fibrosis. After incorporation was complete, the long-term (3 months to 1 year) subintimal response acquired a basically stable histological appearance amongst which no zones of tissue necrosis were found. However, in some instances it did contain foci of neutrophil infiltration, and it is possible that such foci are a reaction to minor episodes of cell damage.

The synovial response to intra-articular Co-Cr-Mo particles in guinea pigs.

The histology and cytology of the tissue response to an intra-articular insertion of Co-Cr-Mo particles has been studied in the guinea pig knee joint. Following insertion, particles became incorporated into synovial tissue in two ways: (A) by incorporation in the intimal (surface) cell layer; (B) by growth of granulation tissue into metal-containing debris initially adherent to the synovial surface, leading to its incorporation in the subintimal tissue (i.e. beneath the surface), with subintimal fibrosis. Small particles of Co-Cr-Mo were phagocytosed by intimal cells, macrophages, multinucleate giant cells (macrophage polykaryons) and fibroblasts; large particles remained extracellular. Metal particles persisted in the synovial fluid, intimal cell layer and subintimal tissue for many months after metal insertion. As an unexpected finding, no zones of tissue necrosis were observed in the long-term (3 months to 1 year) response to Co-Cr-Mo particles incorporated in subintimal tissue. Lymphatic transport of metal particles from the knee area to inguinal lymph nodes was observed.

The tissue response to acrylic particles implanted in animal muscle.

The histology and ultrastructure of the tissue response to particles of acrylic bone cement have been studied in rat and guinea pig muscle. Initially the implant formed an avascular zone of extracellular particles which rapidly became infiltrated by neutrophils. The particle zone was then progressively incorporated into new tissue by an ingrowth of small blood vessels accompanied by macrophages, multinucleate giant cells and some fibroblasts'. Acrylic particles were phagocytosed into macrophages and giant cells. The giant cells often had a characteristic ring form. After vascularization and incorporation was complete, the macrophage and giant cell accumulation acquired a basically stable histological appearance over study periods of up to 2 yrs. A large majority of these cells appeared viable, and no zones of tissue necrosis were seen. However, occasional individual shrunken necrotic cells of unidentified origin and occasional individual tiny foci of nuclear debris were sometimes observed, sparsely distributed amongst the response, and a minor degree of neutrophil reaction was noted amongst some, but by no means all, of the long-term implants. The interpretation of morphological assessment for tissue toxicity is discussed. No evidence was obtained for the induction of cell-mediated hypersensitivity or of neoplasia by the cement particle preparations used.

A study of sarcogenicity associated with Co-Cr-Mo particles implanted in animal muscle.

A study has been made of the sarcogenicity of particles of cobalt-chromium-molybdenum alloy. The particles were implanted as a dry powder into a surgical incision into the dorsal paraspinal muscle of adult female rats and guinea pigs. Two preparations were used. In one, the particles had a size range of 100-250 micrometers. This preparation was implanted into 51 Wistar rats. In the other, the particles had a size range of 0.5-50 micrometers, 85% being in the range 0.5-5 micrometers. This preparation was implanted into 61 Wistar rats, 53 hooded rats, and 46 Dunkin Hartley guinea pigs. Sham operations were carried out on a control group of 50 Wistar rats. No malignant neoplasms developed at the test or control operation sites during the time periods for which the animals survived. This negative finding contrasts with that from a previous study by Health, Freeman and Swanson, who observed sarcomas in rats at sites of intramuscular injection of cobalt-chromium-molybdenum particles suspended in horse serum. Possible explanations for this difference in results are discussed.

An investigation of radiological, clinical and pathological correlations in osteoarthrosis of the hip.

Seventy per cent of cases of osteoarthrosis of the hip are regarded as being 'idiopathic' in type. Idiopathic osteoarthrosis of the hip is twice as common in females as in males. Osteoarthrosis of the hands shows a definite association with idiopathic osteoarthrosis of the hip, especially in women. Osteoarthrosis of the knees is found in over half the cases of idiopathic osteoarthrosis of the hip and of the hands, although there are sex differences in the distribution of hand and knee osteoarthrosis in these cases. Hand osteoarthrosis is not related to hand laterality, although osteoarthritic changes are likely to be more severe in the dominant hand when there is osteoarthrosis of both hands. No convincing evidence was found of a relationship between the various slab radiograph patterns from femoral heads and idiopathic osteoarthrosis of the hip. There was no definite association between idiopathic osteoarthrosis and the presence of various tissue antigens. The identification of a group of patients with idiopathic osteoarthrosis suggests a generalised cartilage abnormality, with the development of osteoarthrosis being possible related to subsequent stress changes.

Effect of calcitonin treatment on osteoclast counts in Paget's disease of bone.

Histological and biochemical changes during calcitonin treatment have been studied in 15 patients with Paget's disease of bone. For each patient, osteoclast counts were made by the same observer on serial needle biopsies of diseased bone from the posterosuperior iliac spine. Serial estimations were also made of the serum alkaline phosphatase and urinary hydroxyproline excretion. A total of 66 biopsies was examined (ranging from two to seven per patient). Osteoclast populations and the biochemical measurements were log normally distributed. During calcitonin treatment there was a statistically significant decrease in: (1) the total osteoclast count per square millimetre; (2) the number per square millimetre of osteoclasts in resorption cavities on the trabecular surface; (3) the relative proportion of osteoclasts sited in resorption cavities compared with total osteoclasts; (4) the serum alkaline phosphatase level; (5) 24-hour urinary hydroxyproline excretion. On stopping treatment there was a statistically significant increase in all of these histological and biochemical values except that the proportion of osteoclasts in resorption cavities remained low. The trabecular cement line pattern remained abnormal during and after treatment in all biopsies examined, and complete suppression of osteoclast activity was not observed. One of the patients developed a Paget's osteosarcoma while on calcitonin therapy.

Horizontal splitting in patellar articular cartilage.

Horizontal splits at the interface between the uncalcified and the calcified layers of the articular cartilage have been found in 31 of 50 transverse slabs of left patellae from a random series of 50 necropsy subjects aged 18 to 96 years, Evidence is presented that the splits are not due to autolysis nor to technical artefact, and it is here suggested that they result from shearing damage at the uncalcified-calcified cartilage interface during life.

Effect of age on thickness of adult patellar articular cartilage.

The thickness of left patellar articular cartilages after formalin fixation was studied in a series of autopsies on 82 subjects aged 25-96 years. For each specimen the minimal uncalcified cartilage thickness in a transverse patellar slab was determined separately for a 'lateral' segment and a 'central and medial' segment. In the women the cartilage from subjects more than 50 years old showed progressive thinning with increasing age. This was due to lesions causing disintegration of the tissue and not to matrix shrinkage. It had a strong potential to progress to full-thickness cartilage loss in the older women, and to give an appearance indistinguishable from osteoarthrosis as seen in surgical excision specimens. This progression towards patellofemoral osteoarthrosis in the elderly affects the female population generally, and not just a special subgroup; however, the incidence of clinical symptoms from this cause is not known. In men progressive thinning with age of patellar cartilage in subjects more than 50 years old was less severe, especially so in the case of the 'lateral' segment; a site of full-thickness uncalcified cartilage loss on the left patella at autopsy was seen only occasionally in the older men.

The state of knee meniscal fibrocartilage in Liverpool necropsies.

The state of the fibrocartilaginous menisci of the adult knee joint has been studied at necropsies in the city of Liverpool on a random series of 94 white Europeans (55 men, 39 women) aged 21 to 94 yr. The left lateral meniscus was selected for particular attention; in 20 of the subjects the left medial meniscus was also examined. The gross and histological appearance of the superior and inferior surfaces of the lateral meniscus and of its free inner edge is described and illustrated at various ages. The findings from necropsy specimens indicate that the fibrocartilage of the adult meniscus is susceptible to a focal process of matrix fraying and splitting which has several features similar to those seen in fibrillation of hyaline articular cartilage. Certain differences in detail between meniscal and hyaline cartilage in the pattern of cell changes at sites of overt splitting are, however, apparent. The implications of the findings are discussed in terms of an hypothesis that cartilage fibrillation represents a disruption of the collagen framework, and that "wear", of the matrix due to mechanical factors plays a major part in its development.

Cartilage fibrillation on the lateral tibial plateau in Liverpool necropsies.

A study has been made of the state at necropsy of the hyaline articular cartilage of the left tibial plateaux, with particular reference to the lateral plateau, in 47 adult white Europeans (24 men; 23 women) aged 21-88 years. The surface morphology and topographical distribution of the lesions is described for the bare area of the lateral plateau and its meniscus-covered segments, and quantitative point-counting data are presented for the amount, according to age, of overt fibrillation on the bare area. A variety of cartilage lesions was encountered: macroscopically apparent ' parallel linear' minimal fibrillation; other patterns of minimal fibrillation; 'ravines'; overt fibrillation; localized incomplete defects of the cartilage; and full-thickness cartilage loss with bone exposure. Sites of superficial fraying and splitting of the hyaline articular cartilage are a normal finding on adult human tibial plateaux. Especially in younger adults, such sites are often accompanied by large areas of cartilage surface which are still intact. On the lateral plateau, the bare area and the meniscus-covered posterior segment are more susceptible to overt fibrillation than are the meniscus-covered lateral and anterior segments. In contrast to the findings in other synovial joints, the peripheral rim of the upper tibial cartilage sheet is not particularly susceptible to overt fibrillation. Tangential extension of the changes on the lateral plateau leads to widespread involvement of the bare area and the meniscus-covered posterior segment in older subjects. However, vertical progression of the changes, sufficient to give full-thickness cartilage loss with tibio-femoral bone exposure, was seen in only a minority of persons aged over 80 years.

Hair sampling for chromium content following Charnley hip arthroplasty.

The chromium content of hair has been studied by neutron activation analysis of samples from 62 patients following a Charnley unilateral or bilateral hip arthroplasty by an artificial joint of stainless steel against polyethylene, inserted three to five years previously. The patients lived in the North Wales area of the British Isles. Hair chromium content was also studied in 51 control subjects of similar age to that of the patients, from the same geographical area and often from the patients' own households. Chromium content was recorded as parts per million (ppm) of hair weighed and analyzed in the state received, without preliminary ashing or chemical "washing" of the samples in the laboratory. Fifty of the 51 control subjects showed less than 2 ppm chromium in hair; one showed 2-5 ppm; none showed more than 5 ppm. Fifty-nine of the 62 patients showed less than 2 ppm chromium in hair; three showed 2-5 ppm; none showed more than 5 ppm. Attention is drawn to certain practical aspects when collecting hair samples for chromium analysis. The use and validity of hair sampling as one method of screening for systemic chromium accumulation following implant surgery is discussed. The method may be a useful adjunct to monitoring of chromium levels in blood samples. In this preliminary study, hair sampling has given no evidence of any major risk of systemic chromium accumulation in patients using a Charnley arthroplasty for periods of up to five years; no conclusion can be made concerning periods longer than this. The findings do not exclude systemic reactions of the hypersensitivity type, since this type of reaction could develop to only small amounts of chromium.

Cartilage fibrillation at the ankle joint in Liverpool necropsies.

The articular surfaces have been examined in 45 left ankle joints from a random series of adult necropsies in the city of Liverpool. Foci of overt fibrillation, with frank splitting of the articular cartilage surface, were extremely common in the ankle joint and were often already apparent in young adults. With increasing age overt fibrillation tended on the whole to become extensive, but this tendency was partly obscured by considerable variation between individuals. It initially and especially affected the periphery of the cartilage sheets and the boundaries between the central and malleolar articulation territories. Possible explanations for this peripheral susceptibility are discussed. One or more sites on the non-peripheral parts of the lateral and medial malleolar surfaces were next in order of susceptibility. The central territory of the articulation was the least susceptible to overt fibrillation. Minimal fibrillation, with a very superficial splitting of the cartilage surface, could occur at any site on the ankle joint surfaces. With increasing age, extensive involvement of the central territory by this minimal change was much more common than extensive overt fibrillation here. The surface markings of minimal fibrillation sometimes showed a macroscopially apparent orientation en face. In one sort these were parallel to flexion-extension movement and consistent with track markings from abrasive-adhesive wear. In a second sort they were parallel to the dominant en face orientation of the superficial cartilage collagen. The topography and natural history of cartilage fibrillation at the ankle joint is discussed with reference to Liverpool data from other joints. Some of the older ankles showed peripheral segments of fibrous tissue-covered cartilage loss. This feature was attributed to "ageing" rather than osteoarthrosis. Only 1 of 20 left ankles from subjects more than 70 years old showed any region of full-thickness uncalcified cartilage loss with abrasive wear of 'osteoarthritic' type. Thus it would seem that in the majority of the Lverpool population the articular cartilage of the normal ankle joint has a high resistance to the type of vertical wear found in clinically demonstrable osteoarthrosis. The practical implications of this conclusion are discussed.

Morphological patterns of articular cartilage fibrillation.

The morphology of articular cartilage fibrillation is usually studied in sections cut vertical to the surface. The present study instead concerns the appearances seen when the surface is viewed en face. The study has been made on indian ink preparations of unfixed, hydrated tissue mounted in physiological saline and examined by stereomicroscopy at times 10 while in situ on the bone, and by transmitted light microscopy of tangential surface slices at magnifications up to times 150. The results are consistent with an hypothesis that fibrillation represents mechanically induced focal wear of the tissue. Various sorts of "minimal fibrillation" and other types of surface markings are illustrated. The en face pattern of the cartilage lesions is to some extent influenced by anatomical site, and it is suggested that it is modified by the local biomechanical environment and local character of the cartilage. Some, but not all, of the various patterns show orientation in the sense either of being predominantly unidirectional or of having two major alignments one at right-angles to the other. The differing relationships of this orientation, when present, to the direction of joint movement and to the alignment of the superficial collagen and its tensile strength, are described and discussed.