1. The present study is an attempt to analyse and apportion significance to the role of inductive mechanisms in bone transplantation.

2. The experimental model used in the present work is that of the composite homograftautograft of cancellous bone previously described (Burwell 1964a).

3. Iliac bone was removed from hooded rats and washed free from its marrow. The bone was then treated by various physical and chemical methods (some of which have been used by other workers to prepare bank bone), namely freezing (-20 degrees Centigrade, -79 degrees Centigrade, -196 degrees Centigrade); freeze-drying (without sterilisation, sterilisation with high energy radiation, sterilisation with ß-propiolactone); decalcification (with E.D.T.A.); irradiation (in the frozen state at a dose of 4 million rads); boiling in water; immersion in merthiolate solution; extraction of organic components with ethylenediamine: and calcining at 660 degrees Centigrade. The treated bone was then impregnated with fresh autologous marrow procured from the femoral shaft of the Wistar rat into which the treated composite graft was to be implanted. The grafts were inserted intramuscularly and removed for study after two, six and twelve weeks.

4. After fixation, serial sectioning and staining, each graft was examined microscopically, and the proportion of new bone/grafted bone scored using an arbitrary scale (0-4). The mean score (and the standard error of the mean score) was then plotted for each treated composite graft and also for several types of fresh cancellous bone grafts.

5. It was found (Fig. 2) that the various treated composite grafts formed a spectrum of bone-forming capacities–the maximum scores being attained by the frozen and freeze-dried composite grafts, the lowest scores by the "deproteinised" composite grafts.

6. The reasons for these differences are discussed. It is concluded that cancellous bone, after transplantation, has the property to induce and promote osteogenesis in marrow; moreover, that this property is contained in the organic components of bone.

7. From the standpoint of inductive mechanisms, cancellous bone treated by freezing or freeze-drying seems to be the most suitable devitalised bone for grafting purposes; bone which has been boiled or merthiolated less suitable; and "deproteinised" bone the least suitable.

8. Freeze-dried bone sterilised physically (by high energy radiation) or chemically (by ß-propiolactone) did not form significantly less new bone than did freeze-dried bone which had not been sterilised.

9. Remodelling mechanisms in bone transplantation are briefly discussed and attention drawn to the deficiencies of present knowledge. The quantitative studies of other workers have indicated that freeze-dried bone may be more rapidly remodelled than is frozen bone.

10. The importance of fresh red marrow in promoting osteogenesis in bone transplantation and in the healing of certain fractures, is emphasised. It seems likely that the interrelationship of bone and marrow revealed by experiment has wider significance not only in health and in response to injury but also in causation of certain idiopathic bone disorders.

1. The effects of the insertion of pieces of fresh cancellous bone into the subcutaneous tissues of the ear upon lymph nodes and spleens have been investigated in seventy rabbits.

2. The main immunological response is found to occur in the first regional nodes draining the sites of insertion of homografts of bone, which show a considerable increase in weight compared with nodes draining autografts of bone.

3. An increased number of large and medium lymphoid cells occurs principally in the first regional node of the homografted animals, as Scothorne and McGregor (1955) observed using skin as the homografted tissue.

4. The large and medium lymphoid cell response is found in both the cortex and the medulla of the lymph nodes. In the cortex a sectoral distribution of the cellular response is observed and the name reactive cortex is given to these sectors. Evidence is presented to show that the sectoral pattern of reactivity is probably determined by the localised entry into the node of iso-antigens through lymphatic vessels draining the bed of the graft.

5. We have made a quantitative analysis of the large and medium lymphoid cell response in the reactive parts of the diffuse lymphoid tissue of the cortex. The mean maximal large and medium lymphoid cell response occurs five days after the insertion of bone homografts.

6. The origin and fate of the large and medium lymphoid cells and their role in the production of antibodies is reviewed in the light of recent work.

7. A correlation is made between the maximal production of large and medium lymphoid cells in the first regional lymph node, the invasion of the graft bed with small lymphocytes and the inhibition of new bone formation in the homografts.

1. An immunological examination of the sera of thirty rabbits which had received primary and secondary homografts of cancellous bone into a subcutaneous site did not reveal the presence of circulating precipitins, haemagglutinins or passive haemagglutinins. These findings are consistent with the observations of Bonfiglio and his colleagues (1955).

2. Electrophoretic examination of the serum of four rabbits receiving primary and secondary homografts of bone into an intramuscular site did not reveal any change in the serum protein fractions.

3. A search for auto-antibodies produced by primary and secondary autografts of cancellous bone was unsuccessful in fifteen rabbits.

4. The multiple injections of saline extracts of bone into four rabbits did not evoke the production of demonstrable circulating antibodies, results which are in accord with the findings of Bonfiglio and colleagues (1955) and Curtiss and colleagues (1959).

5. For the first time the production of classical antibodies in response to injections of extracts of heterologous bone has been recorded. The repeated injections of a saline extract of rabbit bone intraperitoneally into ten mice produced demonstrable precipitins and passive haemagglutinins both to protein and polysaccharide fractions present in the bone extracts.

6. Knowledge concerning the production of humoral antibodies to transplants and extracts of bone has been reviewed.

1. This is a preliminary report of an attempt to determine an objective reference point or "point of motion" during flexion and extension of the lumbar spine.

2. The method described uses superimposition of lateral radiographs taken in flexion and extension with the patient standing.

3. In seventy-eight radiographically normal subjects with no symptoms a "point of motion" was determined for each of the lowest three disc levels. At each level these points clustered within a specific zone approximately 2·5 centimetres square. Sixty-four per cent fell within a square centimetre.

4. In a comparative study of twenty-four patients with confirmed pathology, the "point of motion" fell outside the larger zone at the level of pathological change in 65 per cent of the disc levels.

5. The determination of the "point of motion" is a special technique for studying spinal motion. Its role as a diagnostic and prognostic aid in assessing patients with back pain is the subject of continuing study.

1. The rates of vascularisation in 119 autogenous, homogenous and heterogenous bone grafts, placed in the femoral medullary cavity and under the renal capsule of rabbits, were studied.

2. Substantial differences have been found in the speed of vascular penetration and arrangement among autografts, homografts and heterografts : penetration of the heterogenous implant was six or more times slower. Moreover, large areas of the homografts and heterografts were often totally excluded from the circulation for as long as the research was continued (up to three months). Revascularisation of the cortical bone was slower and less profuse than in cancellous bone, keeping always the same respective proportion between the three types of bone we have described. The results on the kidney were much less constant, and I attribute this to the vascular peculiarities of the bed.

3. Vascular patterns peculiar to the time of implantation and type of graft are described.

4. Suggestive, even if not totally convincing, evidence was found of recanalisation of old vessels inside the graft by advancing vessels from the bed.

5. There is striking correlation between the rate of vascular penetration of the bone implants and their ultimate "take" or incorporation in the bed.

1 . Current theories of the etiology of chondromalacia patellae do not explain satisfactorily either its great frequency or its common site of origin on the medial patellar facet.

2. The etiology can be more logically explained by the presence of a ridge on the upper anterior border of the cartilage of the medial femoral condyle, in most knees. This ridge, consisting of cartilage, or cartilage and bone, varies considerably in height and, in normal knee joint movement, causes considerable friction on the medial patellar facet.

3. The degenerative changes were found to be greater in the presence of the larger ridges, and–because of longer wear and tear–in the older patients.

4. This study indicates that chondromalacia was more severe in women than in men, and in patients overweight. Although the activity of the individual and the power of the quadriceps mechanism must play an extremely important part in this condition, it was not possible to assess this.

5. Two factors previously considered to be important in the etiology of this condition, namely, the length of the patellar tendon and Wiberg's Type III patellar shape, have not been confirmed in this study.

6. Resulting from the present investigation certain precautions are suggested in rehabilitation after operations on the knee, and a surgical method for discouraging the progress of this common, and sometimes disabling, condition has been devised.

1. Surveys of a working community, of a group of elderly people, and of an urban population show an incidence of Dupuytren's contracture among men varying from 0·1 per cent in the age group fifteen to twenty-four, to 18·1 per cent in those aged seventy-five and over; and among women from 0·5 per cent in the age group forty-five to fifty-four, to 9 per cent over seventy-five. It is estimated that in the population aged fifteen and over in Lancashire and Cheshire there will be 4·2 per cent of the men and 1·4 per cent of the women with some degree of palmar contracture.

2. There appears to be no relationship between the type of occupation and the incidence or severity of contracture in men, except that among those engaged in light manual work the proportion of mildly affected hands is higher, and of bilateral contracture lower, than among either non-manual or heavy manual workers.

3. Evidence is provided that rheumatoid arthritis, past polyarthritis, osteoarthritis, cervical spondylosis and Paget's disease occur no more often in those with Dupuytren's contracture than in other members of the community.

4. Examination of the patients in an epileptic colony confirms a strong association between Dupuytren's contracture and epilepsy. Knuckle-pads, plantar nodules and periarthritis of the shoulder are all more frequent in epileptic than in non-epileptic patients with Dupuytren's contracture. Epileptics also show a higher proportion with bilateral contractures and a greater tendency to a symmetrical pattern of contracture in the two hands. A strong constitutional factor, probably genetic, thus operates in persons with both diseases.

Nevertheless, the frequency of a positive family history of contracture is lower in the epileptic cases, and reasons for this are discussed.

5. From the limited material available in the literature there would appear to be an inverse relationship between the population of certain countries and the prevalence in them of Dupuytren's contracture. The possible significance of this is briefly discussed.

Disc degeneration starts as an avascular necrosis. In the lower lumbar area the discs deteriorate early because of mechanical stresses. During certain early periods of degenerative changes a mechanical disorder between the annulus and the posterior longitudinal ligament may cause tiredness and pain. When the disc is completely degenerated and has lost its physical properties backache disappears.

Results are given of a study of four cases of osteogenesis imperfecta using biophysical methods comprising microradiography, microscopy using polarised light, and x-ray diffraction. Rebuilding of bone tissue was infrequent in the material studied and has been shown to occur in an abnormal manner. The mineralisation of the bone is more uniform than is found in normal bone. The collagen has an abnormal organisation and is sparse. The ultrastructure of bone salts and their orientation are as in normal bone.

1. Histochemical studies have been made of the distribution of alkaline phosphatase, glycogen and acid mucopolysaccharides in normal growing bones (mice, rats and men) and also in forty cases of pathological bone processes (neoplastic and dystrophic).

2. The study of normal material confirmed that alkaline phosphatase is plentiful in calcification of cartilage and even more plentiful in bone formation (whether enchondral or direct).

3. It was observed that glycogen increased in the cartilage areas about to be calcified, and that it disappeared in those calcified. It seemed that osteoblasts did not always contain glycogen.

4. In the pathological material (tumours and dystrophic processes) there was great phosphatase activity in the osteogenic areas and also in the cartilage about to be calcified. Whereas glycogen was plentiful in some cases of neoplastic or reactive osteogenesis, it was absent from others.

5. In every area of normal or pathological ossification, the presence of phosphatase seems to be a rule; glycogen is often but not always present.

6. It appears that alkaline phosphatase plays an important role in the formation of the protein matrix of bone, but is not associated with the elaboration of the mucoprotein cartilage matrix.

We believe it is premature to draw any definite conclusion on the behaviour and role of the metachromatic substances in the processes of calcification and ossification.

The histochemical study of alkaline phosphatase has shown that this is a valuable method in the detection of reactionary or pathological osteogenic processes which in some cases are difficult to demonstrate with the usual histological methods.

Blood flow in intact tendons in dogs was measured using 57Co-labelled microspheres and compared with the simultaneous clearance of a diffusible radionuclide, 85Sr, by the same tendons. Clearance was significantly greater than flow in all tendons, indicating that diffusion from surrounding tissues may be important in the nutrition of normal tendons.

1. The family history of, and associated congenital abnormalities in, patients with talipes equinovarus, talipes calcaneo-valgus and metatarsus varus living in Devonshire has been studied.

2. The chances of any individual having one of these deformities is approximately one per 1,000 in each case.

3. If one child in a family has the deformity, the chances of a second having it are one in thirty-five for talipes equinovarus and one in twenty for talipes calcaneo-valgus and metatarsus varus.

4. The male relatives of the female patients with talipes equinovarus are at particular risk.

5. It is suggested that the cause of club foot is partly genetic and partly environmental, from a factor acting on the foetus in the uterus.

6. The classification of associated congenital abnormalities leads to the suggestion that the genetic factor in talipes equinovarus and talipes calcaneo-valgus relates to defective formation of connective tissue.

1. The appearance of decalcified bone matrix in the electron microscope is described.

2. In the matrix two types of collagen fibril have been distinguished. Differences observed are in solubility, x-ray diffraction pattern and appearance. In infant bone the form which appears as fine fibrils predominates. In adult bone the form which appears as tubular fibrils of larger diameter predominates.

3. In bones from elderly subjects the chemical reaction employed to convert collagen into eucollagen sometimes hydrolyses fatty acid esters, and lines due to the free fatty acid are found on the x-ray diffraction patterns of the insoluble residue after citrate extraction.

4. In ancient bones and fossils the stable tubular form of collagen survives, but not the fine fibrils.

5. When decalcified, the matrix in osteoporotic bones loses its architecture and fibrillar form. Under conditions in which only a small fraction is dissolved from normal bone most of the collagen in osteoporotic bone disperses in citric acid. The insoluble residue then gives a modified x-ray diffraction pattern.

6. Evidence has been produced to suggest that the immediate cause of many forms of osteoporosis is some local factor affecting the osteocytes, rather than a general chemical effect.

Sarcoma complicating Paget's disease is uncommon; ninety-five cases have been collected and seven further cases are now reported. Sarcoma probably complicates less than 2 per cent of all cases of Paget's disease. There is a relatively high incidence in males, especially in the sixth decade, whereas bone sarcoma over the age of fifty years without osteitis deformans is rare. Injury is prominent in the history of many cases.

Comparison of Paget's sarcoma, "ordinary" bone sarcoma and the bones affected by uncomplicated osteitis deformans reveals some important differences. As to the type of tumour, osteogenic sarcoma is the commonest, but fibrosarcoma and round-cell sarcoma are also frequent.

The serum phosphatase is a most useful prognostic guide in a disease with a generally poor prognosis. Magnesium metabolism in relation to bone sarcoma requires further study.

Prophvlaxis is based on a clinical suspicion of this complication in Paget's disease, and measures are outlined which may be of assistance.

Sarcoma in Paget's bone is highly lethal, but Nature in striking down these old people may have provided us with facts which will ultimately solve problems common to all sarcomas of bone.

1. The process of repair after fracture of the humerus of the growing rat has been studied by histological, histochemical and biochemical methods.

2. Both periosteal and surrounding mesenchymal cells take part in the process of repair.

3. The primary framework of collagen bridging the gap is mainly formed by the mesenchymal cells, while calcification and ossification of the framework is largely a function of the periosteum.

4. The mucopolysaccharide content rises rapidly in the first week after injury, and is followed by a rise in the collagen content during the second week. The deposition of calcium phosphate during the third and fourth weeks causes an apparent fall in the collagen content during that period. The collagen content tends to return to normal during the phase of remodelling in the fifth and sixth weeks.

5. The tensile strength of the healing bone bears a close relation to its collagen content.

A saw blade was made from two standard oscillating blades which were fixed to each other with channels between, so that cooling fluid could be directed to the saw teeth. The blade was connected to a standard arthroscopy pump which delivered a flow of 80 ml/min through the blade. The performance of this blade was compared with that of a standard saw blade, cutting ox-bone in the laboratory. Irrigation of the standard saw blade with saline delivered by a syringe only slightly diminished the maximum temperature. Pumped irrigation was more effective but required large volumes of fluid. The heat generated by the internally cooled saw blade was negligible and the temperatures achieved (19 degrees C to 34 degrees C) fell well below the critical level for bone death (44 degrees C to 47 degrees C).

1. The use of the Metals Research Macrotome for cutting 100 μ thick sections of fresh, unfixed specimens of arthritic human femoral heads and normal goat condyles is described.

2. A technique for isolating living cells from these slices by decalcification followed by enzymic digestion is reported.

3. The microscopic appearances of the fresh slices, the decalcified slices and the isolated cells as seen by incident or transmitted fluorescent lighting, by phase-contrast microscopy, by scanning electron microscopy and by histological and cytological techniques are illustrated.

4. These techniques might be applicable to the examination of biopsy specimens of pathological bone or to basic research on bone cells.

1. Previous immunological studies have shown that homografts of fresh marrow-free iliac bone are only weakly, if at all, antigenic.

2. In view of this finding an attempt was made to produce a foreign bone graft capable of forming new bone as readily as an iliac autograft by the following method. Living cells of high osteogenic potential and of autologous type were introduced into the graft by combining homologous fresh marrow-free iliac bone with the animal's own red marrow to form a fresh composite homograft-autograft of cancellous bone.

3. Such fresh composite homograft-autografts were inserted into a muscular site in Wistar rats and removed for microscopical examination at intervals of one to seven days and at two, six and twelve weeks after transplantation.

4. It is found that bone and marrow together as a fresh composite homograft-autograft form considerably more new bone than do either of the components of the graft transplanted separately. Homografts of fresh marrow-free iliac bone form, in general, a small amount of early phase and late phase new bone. Autografts of red marrow transplanted alone to a muscular site formed new bone in thirteen to thirty experiments (43 per cent).

5. The stimulus to osteogenesis, and the cellular source of osteoblasts, in marrow autografts is discussed in the light of present knowledge. The concept is suggested that after its transplantation there develops in marrow an inductive system leading to osteoblastic differentiation and bone formation. It is proposed that the necrosis of a portion of a marrow graft liberates osteogenic substances which are taken up by primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of the marrow which are induced, thereby, to differentiate as osteoblasts.

6. The cellular source of osteoblasts in a fresh composite homograft-autograft of cancellous bone is discussed. It is deduced that the new bone is derived mainly from the contained marrow of the graft, by mechanisms similar to those leading to osteoblastic differentiation in transplanted autografts of marrow.

7. The stimulus to the greater formation of new bone by fresh composite autograft-homografts than by autografts of marrow transplanted alone is discussed. Two explanations are suggested: 1) a more extensive necrosis of marrow in a composite homograft-autograft than in marrow transplanted alone; and 2) an inductive effect of bone upon marrow.

8. The new bone formed by autografts of fresh marrow-containing iliac bone, it is concluded, is derived not only from osteoblasts on the surfaces of the grafted bone but also from primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of its marrow.

9. Mechanisms which may play a role in the histogenesis of woven bone are discussed.

10. The significance of the relation of bone and marrow is considered briefly in the light of knowledge concerning the venous patterns of bone and marrow.

1. Based on studies in seventy-five patients, a technique is described for body surface activity measurements over localised skeletal lesions up to one month after injection of the λ-emitting isotopes Ca⁴⁷ and Sr⁸⁵.

2. The activity was high over skeletal lesions like fracture, metastatic cancer, eosinophilic granuloma, chondroma, osteomyelitis and Paget's disease.

3. The high isotope uptake is interpreted as evidence of an increased rate of bone tissue turnover.

4. These findings suggest that external counting of Ca⁴⁷ and Sr⁸⁵ may be used for quantitation of the rate of formation of normal and pathological bone tissue. A special application would be localisation and delineation of metastatic cancer in cases where radiographic evidence is uncertain or non-existent.

1. The antigenicity of homologous cortical and cancellous bone has been investigated in eighty-four rabbits.

2. The primary immune responses which occur in lymph nodes draining homografts of fresh tissues (Burwell and Gowland 1961, 1962) have been used as a histological indicator of the antigenicity of fresh homologous cortical bone freed from soft tissues.

3. The secondary immune responses which occur in lymph nodes draining homografts of fresh marrow-containing iliac bone (Burwell 1962a, b) have been used also as a histological indicator of the antigenicity of homografts of 1) fresh cortical bone freed from soft tissues, 2) fresh marrow-free iliac bone, and 3) mairow-containing iliac bone treated by boiling, freezi ng, freeze-drying and merthiolate solution.

4. It is found that whereas fresh homologous cortical bone fails usually to produce cytological evidence of a primary response in the regional lymph nodes, fresh homologous cortical bone chips inserted into the drainage areas of lymph nodes sensitised previously to donor ..tissue evoke constantly cytological evidence of a secondary response.

5. Fresh homologous marrow-free iliac bone inserted into the drainage areas of lymph nodes sensitised previously to donor tissue does not produce detectable evidence of a secondary response.

6. Homografts of boiled marrow-containing iliac bone do not elicit a secondary response in lymph nodes previously sensitised to donor tissue.

7. Previous work has shown that homografts of frozen (–20 degrees Centigrade) marrow-containing iliac bone do not evoke a primary response in lymph nodes draining such grafts. In the present work it is shown that similar frozen homografts inserted into the drainage areas of lymph nodes previously sensitised to donor tissue evoked a secondary response in three of six lymph nodes.

8. Homografts offreeze-dried marrow-containing iliac bone fail usually to evoke a secondary response in lymph nodes sensitised to donor tissue.

9. Homografts of marrow-containing iliac bone treated by immersion in merthiolate solution before being inserted into the drainage areas of lymph nodes previously sensitised to tissue from the donor elicited a secondary response in three of five lymph nodes.

10. Knowledge concerning the antigenicity offresh and treated homologous bone is discussed in the light of recent work.

1. Experiments to examine the antigenicity of homologous bone tissues in rats are reported. The tissues studied included fresh marrow-free cortical bone blocks and chips, fresh, boiled, frozen and freeze-dried marrow-containing iliac bone, fresh iliac bone devoid of marrow, and fresh red marrow.

2. The various tissues were transplanted from hooded to Wistar rats. Three weeks later a skin graft from each donor was transplanted to its respective host to detect the presence of transplantation immunity, which was indicated by the early rejection of the skin graft.

3. Homografts of fresh cortical bone evoked transplantation immunity indicating that it contained transplantation antigens which were also in the skin.

4. Homografts of fresh marrow-containing iliac bone also evoked transplantation immunity, which was shown to be caused by the red marrow.

5. Fresh iliac homografts devoid of marrow did not elicit transplantation immunity. This suggests that iliac bone tissue may not contain transplantation antigens or that the small amount of iliac bone inserted was insufficient.

6. Microscopy of the grafts, removed after three weeks, showed that the inflammatory infiltrations around the bone homografts and autografts were not very different, but that the amount of new bone formed was different. The autografts produced a lot of new bone, the homografts only a little.

7. It is suggested that the immune response evoked in the host by the foreign graft impairs the formation of new bone by fresh homografts of cortical blocks, cortical chips and marrow-containing iliac bone.

8. The impairment of new bone formation by homografts of marrow-free iliac bone is discussed. Such bone grafts fail to evoke detectable transplantation immunity. Why these grafts do not form more new homologous bone than the other homografts studied, is not clear.

9. Homografts of boiled and frozen iliac bone do not evoke any detectable change in the sensitivity of the host to donor tissue.

10. Homografts of freeze-dried marrow-containing iliac bone elicit a slight but significant prolongation of the survival of skin homografts. The implication, in terms of modern immunological theory, is that in such grafts certain tissue antigens still persist.

We report the findings from independent prospective clinical and laboratory-based joint-simulator studies of the performance of ceramic femoral heads of 22.225 mm diameter in cross-linked polyethylene (XLP) acetabular cups. We found remarkable qualitative and quantitative agreement between the clinical and simulator results for the wear characteristics with time, and confirmed that ceramic femoral heads penetrate the XLP cups at only about half the rate of otherwise comparable metal heads.

In the clinical study, 19 hips in 17 patients were followed for an average of 77 months. In the hip-joint simulator a similar prosthesis was tested for 7.3 million cycles.

Both clinical and simulator results showed relatively high rates of penetration over the first 18 months or 1.5 million cycles, followed by a very much lower wear thereafter. Once an initial bedding-in of 0.2 mm to 0.4 mm had taken place the subsequent rates of penetration were very small. The initial clinical wear during bedding-in averaged 0.29 mm/year; subsequent progression was an order of magnitude lower at about 0.022 mm/year, lower than the 0.07 mm/year in metal-to-UHMWP Charnley LFAs.

Our results show the excellent tribological features of alumina-ceramic-to-XLP implants, and also confirm the value of well-designed joint simulators for the evaluation of total joint replacements.

1. The response of the first regional lymph node to a homograft of fresh iliac cancellous bone inserted subcutaneously into the rabbit's ear three weeks after the introduction of a similar graft from the same donor into the same ear has been investigated in thirty rabbits. Fifteen rabbits which received second-set autografts of cancellous bone have also been studied.

2. The insertion of second-set homografts of fresh marrow-containing cancellous bone evokes an immune secondary response in the lymph nodes draining the grafts.

3. The increase in weight of the first regional lymph nodes on the side receiving second-set homografts is more rapid and of greater magnitude than that of nodes draining first-set homografts of cancellous bone. Second-set autografts evoke weight changes in the draining nodes similar to those in nodes draining first-set autografts of cancellous bone.

4. The histological changes which occur in the lymph nodes draining the second-set homografts (secondary response) are described and compared with those occurring in lymph nodes draining first-set homografts of cancellous bone (primary response).

5. In the primary response the distribution of large and medium lymphoid cells is throughout an activated sector of the cortex of the lymph node (Burwell and Gowland 1961), but in the secondary response these cells are found peripherally within the activated sector of the node. In both the primary and the secondary responses large and medium lymphoid cells are found in the medullary trabeculae of the lymph nodes.

6. The differences between the primary response of lymph nodes draining a tissue homograft (cancellous bone) and the primary response of lymph nodes draining classical antigens, and reported by other workers, are described.

7. Knowledge concerning the inflammatory response in the tissues of the host surrounding homografts of fresh cortical and cancellous bone implanted into animals previously sensitised to tissue from the respective donor is reviewed.

8. The late phase of new bone formation by homografts of fresh cancellous bone is discussed in the light of immunological studies.

1. The antigenicity of cancellous bone has been investigated in ninety-seven rabbits.

2. The immune responses of lymph nodes draining fresh homografts of cancellous bone (Burwell and Gowland 1961b) has been used as a histological indicator of the antigenicity of components of fresh homologous cancellous bone and also of the antigenicity of homologous bone subjected to a variety of physical or chemical treatments.

3. The principal antigenic component of a fresh homograft of iliac cancellous bone is the nucleated cells of the red marrow.

4. Homologous marrow-free cancellous bone does not usually produce cytological evidence of an immune response in the lymph node draining the graft, unless new homograft bone formation occurs.

5. The treatment of marrow-containing cancellous bone by boiling, freezing at - 20 degrees Centigrade, freeze-drying, irradiation or by merthiolate solution impairs the transplantation antigenicity of the tissue as a homograft.

6. The immersion of cancellous bone in a glycerol-serum-Ringer solution which is then slowly cooled to - 79 degrees Centigrade, stored for one week and then rapidly thawed, allows considerable preservation of the antigenicity of the red marrow.

7. Knowledge concerning the antigenicity of fresh and treated homologous bone is discussed.

8. Evidence is presented to show that the large and medium lymphoid cell response of lymph nodes draining homografts is due principally to the T-antigens, rather than H-antigens, of the grafts.

9. The changes which occur in the first regional lymph nodes draining tissue homografts may provide another test system to assess the transplantation antigenicity of foreign tissues or extracts of foreign tissues other than bone.

Aims. To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity. Methods. Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation. Results. Overall, 17 studies (566 feet) were included: 13 studies used clinical grading criteria to report a postoperative ‘success’ of 87% (75% to 100%), 14 reported on orthotic use with 88% reduced postoperative use, and one study reported on ankle kinematics improvements. Ten studies reported post-surgical complications at a rate of 11/390 feet (2.8%), but 84 feet (14.8%) had recurrent varus (68 feet, 12%) or occurrence of valgus (16 feet, 2.8%). Only one study included a patient-reported outcome measure (pain). Conclusion. Split tendon transfers are an effective treatment for children and youth with CP and spastic equinovarus foot deformities. Clinical data presented can be used for future study designs; a more standardized functional and patient-focused approach to evaluating outcomes of surgical intervention of gait may be warranted. Cite this article: Bone Jt Open 2023;4(5):283–298

Aims. To determine whether obesity and malnutrition have a synergistic effect on outcomes from skeletal trauma or elective orthopaedic surgery. Methods. Electronic databases including MEDLINE, Global Health, Embase, Web of Science, ScienceDirect, and PEDRo were searched up to 14 April 2024, as well as conference proceedings and the reference lists of included studies. Studies were appraised using tools according to study design, including the Oxford Levels of Evidence, the Institute of Health Economics case series quality appraisal checklist, and the CLARITY checklist for cohort studies. Studies were eligible if they reported the effects of combined malnutrition and obesity on outcomes from skeletal trauma or elective orthopaedic surgery. Results. A total of eight studies (106,319 patients) were included. These carried moderate to high risk of bias. Combined obesity and malnutrition did not lead to worse outcomes in patients undergoing total shoulder arthroplasty or repair of proximal humeral fractures (two retrospective cohort studies). Three studies (two retrospective cohort studies, one case series) found that malnourishment and obesity had a synergistic effect and led to poor outcomes in total hip or knee arthroplasty, including longer length of stay and higher complication rates. One retrospective cohort study pertaining to posterior lumbar fusion found that malnourished obese patients had higher odds of developing surgical site infection and sepsis, as well as higher odds of requiring a revision procedure. Conclusion. Combined malnutrition and obesity have a synergistic effect and lead to poor outcomes in lower limb procedures. Appropriate preoperative optimization and postoperative care are required to improve outcomes in this group of patients. Cite this article: Bone Joint J 2024;106-B(10):1044–1049

Aims. This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis. Methods. A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included “adolescent idiopathic scoliosis”,“3D”, and “progression”. The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included. Results. Torsion index (TI) and apical vertebral rotation (AVR) were identified as accurate predictors of curve progression in early visits. Initial TI > 3.7° and AVR > 5.8° were predictive of curve progression. Thoracic hypokyphosis was inconsistently observed in progressive curves with weak evidence. While sagittal wedging was observed in mild curves, there is insufficient evidence for its correlation with curve progression. In curves with initial Cobb angle < 25°, Cobb angle was a poor predictor for future curve progression. Prediction accuracy was improved by incorporating serial reconstructions in stepwise layers. However, a lack of post-hoc analysis was identified in studies involving geometrical models. Conclusion. For patients with mild curves, TI and AVR were identified as predictors of curve progression, with TI > 3.7° and AVR > 5.8° found to be important thresholds. Cobb angle acts as a poor predictor in mild curves, and more investigations are required to assess thoracic kyphosis and wedging as predictors. Cumulative reconstruction of radiographs improves prediction accuracy. Comprehensive analysis between progressive and non-progressive curves is recommended to extract meaningful thresholds for clinical prognostication. Cite this article: Bone Jt Open 2024;5(3):243–251

Two hundred and eighty-three patients with tuberculosis of the thoracic and/or lumbar spine have been followed for 10 years from the start of treatment. All patients received PAS plus isoniazid daily for 18 months, either with streptomycin for the first three months (SPH) or no streptomycin (PH), by random allocation. There was also a second random allocation for all patients: in Masan to inpatient rest in bed (IP) for six months followed by outpatient treatment or to ambulatory outpatient treatment from the start (OP), and in Pusan to outpatient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). A favourable status was achieved on their allocated regimen by 88% of patients at 10 years. Some of the remaining patients also attained a favourable status after additional chemotherapy and/or operation, and if these are included the proportion achieving such a status increases to 96%. There were five patients whose deaths were attributed to their spinal disease. A sinus or clinically evident abscess was present on at least one occasion in the 10-year period in 42% of the patients. Residual sinuses persisted at 10 years in two patients, at death at seven years in a third and at default in the seventh year in a fourth. Thirty-five patients had paraparesis at some time during the 10-year period, including two who died with paraplegia before five years. Complete resolution occurred in 26 patients (in six after additional chemotherapy and/or surgery). At 10 years two patients had severe paraplegia and one a moderate paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

In two centres in Korea 350 patients with a diagnosis of tuberculosis of the thoracic and/or lumbar spine were allocated at random: in Masan to in-patient rest in bed (IP) for six months followed by out-patient treatment or to ambulatory out-patient treatment (OP) from the start; in Pusan to out-patient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). All patients recieved chemotherapy with PAS with isoniazid for eighteen months, either supplemented with streptomycin for the first three months (SPH) or without this supplement (PH), by random allocation. The main analysis of this report concerns 299 patients (eighty-three IP, eighty-three OP, sixty-three J, seventy No J; 143 SPH, 156 PH). Pre-treatment factors were similar in both centres except that the patients in Pusan had, on average, less extensive lesions although in a greater proportion the disease was radiographically active. One patient (J/SPH) died with active spinal disease and three (all No J/SPH) with paraplegia. A fifth patient (IP/PH) who died from cardio respiratory failure also had pulmonary tuberculosis. Twenty-three patients required operation and/or additional chemotherapy for the spinal lesion. A sinus or clinically evident abscess was either present initially or developed during treatment in 41 per cent of patients. Residual lesions persisted in ten patients (four IP, two OP, one J, three No J; six SPH, four PH) at five years. Thirty-two patients had paraparesis on admission or developing later. Complete resolution occurred in twenty on the allocated regimen and in eight after operation or additional chemotherapy or both. Of the remaining four atients, all of whom had operation and additional chemotherapy, three died and one still had paraparesis at five years. Of 295 patients assessed at five years 89 per cent had a favourable status. The proportions of the patients responding favourably were similar in the IP (91 per cent) and OP (89 per cent) series, in the J (90 per cent) and No J (84 per cent) series and in the SPH (86 per cent) and PH (92 per cent) series.

Aims. To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration. Methods. We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map. Results. After screening of 5,660 articles, we included 166 studies reporting prognostic factors for outcomes after rTKA, with a median sample size of 319 patients (30 to 303,867). Overall, 50% of the studies reported prospectively collected data, and 61% of the studies were performed in a single centre. In some studies, multiple associations were reported; 180 different prognostic factors were reported in these studies. The three most frequently studied prognostic factors were reason for revision (213 times), sex (125 times), and BMI (117 times). Studies focusing on functional scores and patient-reported outcome measures as prognostic factor for the outcome after surgery were limited (n = 42). The studies reported 154 different outcomes. The most commonly reported outcomes after rTKA were: re-revision (155 times), readmission (88 times), and reinfection (85 times). Only five studies included costs as outcome. Conclusion. Outcomes and prognostic factors that are routinely registered as part of clinical practice (e.g. BMI, sex, complications) or in (inter)national registries are studied frequently. Studies on prognostic factors, such as functional and sociodemographic status, and outcomes as healthcare costs, cognitive and mental function, and psychosocial impact are scarce, while they have been shown to be important for patients with osteoarthritis. Cite this article: Bone Jt Open 2023;4(5):338–356

Aims. Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results. A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion. Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614

Aims. Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation. Methods. This systematic review protocol describes a broad search of multiple databases to identify eligible papers. Studies must be published after 2000, include at least five patients, patients must be aged > 16 years or treated as skeletally mature, and the paper must describe a fracture of interest and at least one of our primary outcomes of interest. We did not place restrictions on language or journal. All abstracts and full texts will be screened and extracted by two independent reviewers. Risk of bias and quality of evidence will be analyzed using standardized appraisal tools. A random-effects meta-analysis followed by a subgroup analysis will be performed, given the anticipated heterogeneity among studies, if sufficient data are available. Conclusion. The lack of easily accessible LMIC outcome data, combined with international clinical guidelines that are often developed by HIC surgeons for use in HIC environments, makes the clinical decision-making process infinitely more difficult for surgeons in LMICs. This protocol will guide research on surgical management, outcomes, and complications of lower limb shaft fractures in LMICs, and can help guide policy development for better surgical intervention delivery and improve global surgical care. Cite this article: Bone Jt Open 2024;5(11):1020–1026

Aims. The aims of this study were to identify and evaluate the current literature examining the prognostic factors which are associated with failure of total elbow arthroplasty (TEA). Methods. Electronic literature searches were conducted using MEDLINE, Embase, PubMed, and Cochrane. All studies reporting prognostic estimates for factors associated with the revision of a primary TEA were included. The risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and the quality of evidence was assessed using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Due to low quality of the evidence and the heterogeneous nature of the studies, a narrative synthesis was used. Results. A total of 19 studies met the inclusion criteria, investigating 28 possible prognostic factors. Most QUIPS domains (84%) were rated as moderate to high risk of bias. The quality of the evidence was low or very low for all prognostic factors. In low-quality evidence, prognostic factors with consistent associations with failure of TEA in more than one study were: the sequelae of trauma leading to TEA, either independently or combined with acute trauma, and male sex. Several other studies investigating sex reported no association. The evidence for other factors was of very low quality and mostly involved exploratory studies. Conclusion. The current evidence investigating the prognostic factors associated with failure of TEA is of low or very low quality, and studies generally have a moderate to high risk of bias. Prognostic factors are subject to uncertainty, should be interpreted with caution, and are of little clinical value. Higher-quality evidence is required to determine robust prognostic factors for failure of TEA. Cite this article: Bone Joint Res 2024;13(5):201–213

Aims. With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting. Methods. MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used. Results. A total of nine studies were included, made up of four randomized controlled trials (domain 1) and five cohort studies (domain 2). PROMs and knee function specific scores developed for reporting TKA were unable to detect any difference between PFA and TKA. There was no significant difference in complications between PFA and TKA. PFAs were found to have a better postoperative range of motion. Conclusion. TKA and PFA are both viable options for patients with primary PFJ OA. Over time, we have seen an emphasis on patient satisfaction and better quality of life. Recommending sacrificing healthy medial and lateral compartments to treat patellofemoral joint arthritis should be given further thought. Cite this article: Bone Jt Open 2023;4(12):948–956