1. The intraosseous and extraosseous circulation of the talus was examined in thirty necropsy specimens.

2. The blood supply to the talus is quite diffuse and arises from the three major arteries of the lower leg.

3. The common patterns of circulation, as well as the variations, have been documented.

1. A method is described for the in vivo and in vitro study of osteogenesis by implanting a modified transparent chamber in half lop-eared rabbits (as originated by Sandison 1928). This method allows the daily observation and photography of the developing bone and the study of its intimate connection with the vascularity of the area.

2. The osteogenetic potential of a variety of substances can also be investigated by this method. The tissue in the chamber can easily be prepared for its final examination by optical and electron microscopy and by other laboratory techniques.

In this study the direct relationship between the type of bone implant used, the vascular reaction caused to the host and the revascularisation of the implant has been studied. It was found that the best graft was that which was the most rapidly and permanently vascularised. Not only was the biological affinity between the graft and the bed important, but the structural facilities offered by the implant for the "penetration" by the host vessels were also of paramount importance. Thus small, fresh, cancellous bone grafts offered the best chance of rapid incorporation provided they were not crushed to the point of making vascular progress difficult. The findings from this investigation so strongly suggest that the rapid revascularisation of the bone grafts was because of an end-to-end anastomosis of the vessels of the host with those in the implant that it seems justified to consider that the best bone graft is that which is richest in vessels. Apart from a recent short paper by Graf (1960), we have not found this assertion before. It is this which seems to make the fresh, autogenous, cancellous implant so superior to all others.

We believe that any new material for bone grafts should be tested by the technique described here. The material which one day may replace fresh, autogenous, cancellous implants will have to show the same readiness to vascular penetration, vascular osteogenesis and vascular permanency that at present is exhibited only by the cancellous autograft.

1. It has been shown that in experimental rickets the well known changes in the epiphysial cartilage which so seriously affect growth are accompanied by severe interference with the progress of the metaphysial vessels into the growth cartilage.

2. Further evidence has been found that, by the repeated increase in their number, the cartilage cells occupying the more distal part of the proliferative segment become more and more affected by their remoteness from the epiphysial vessels, which supply the transudates to these cells. At a given distance these cells are affected and change, becoming hypertrophic, with increasingly large vacuolae, and are rich in glycogen and alkaline phosphatase.

3. The hypertrophic cells alter the nature of the intercellular substance they deposit and this becomes calcifiable. Provided that the metaphysial vessels are situated at an appropriate distance–about three cell capsules away–and that the blood has its necessary components, calcification occurs.

4. Calcification produces the advancing, rigid multitubular structure within which the progressing metaphysial vessels are protected.

5. The interruption of calcification by the withdrawal of fat-soluble vitamins breaks down the whole mechanism of growth and stops the vessels growing into their proper position. The administration of the required vitamins re-establishes the normal sequence of events and allows the vessels to play their decisive role in osteogenesis.

6. Any mechanism which causes the interruption of the vascular progression, whether from metaphysial ischaemia (Trueta and Amato 1960), from severe pressure (Trueta and Trias 1961) or from lack of calcification by withdrawing the fat-soluble vitamins, equally interrupts growth.

We have attempted to summarise in a short space investigations that have occupied several years, and we realise that whatever the merits of such an effort the results can only be modest. Many important aspects of the osteogenetic process still remain a mystery and thus are subjected to theory and controversy. Such is the case with this constant attendant at osteogenesis which is alkaline phosphatase. But of one thing we are certain, namely that bone is an organised "soft" tissue of which only part has been made rigid by the deposit of calcium salts. The organiser is the osteogenetic vessel from which springs the syncytial frame of cells and their connections on which the bone architecture is established. Endothelial cell, intermediate cell, osteoblast, osteocyte, osteoclast; these constitute the normal sequence of cellular phylogeny in the constant elaboration and removal of the bone substance. The initial cells on which the whole process rests are those of the capillary-sinusoid vessel which is responsible for providing the transudates on which the life and health of the whole syncytium depends.

If our findings were confirmed, a better understanding of the nature and characteristics of primitive malignant bone tumours would be possible. Each type of tumour from endothelioma to malignant osteoclastoma, including reticulum-cell sarcoma and osteogenic sarcoma, would be initiated by a different cell of the syncytium, but in its monstrous deviation from the normal would still preserve most of the characteristics of its healthy ancestor. Thus the endothelioma causes bone expansion, bone reaction and even bone necrosis, but not proper bone formation, whereas the osteogenic sarcoma or osteoblastoma forms bone; and with the same fidelity to their origin osteoclasts are seen in the malignant osteolytic tumour.

Over thirty years ago the late Sir Arthur Keith (1927) expressed his suspicion that the cells which assume a bone-forming role are derived from the endothelium of the capillary system. We hope we have contributed to show that his suspicion was right.

From this work it may be concluded that persistent compression affects the growth plate by interference with the blood flow on one or both sides of the growth cartilage.

Despite exertion of the same pressure upon both sides of the growth plate, only the metaphysial side was readily affected in the early stages, for, as long as no damage was caused to the epiphysial side of the growth cartilage, the lesions were fully reversible.

Interference with growth was directly proportionate to the damage caused by compression to the epiphysial side of the growth plate and, in general, to the duration of compression.

The first signs of interference with the metaphysial side of the plate were the lack of vascular progression and concomitant retardation of calcification.

When severe degeneration was not present the growth cartilage recovered within four days.

The matrix was ready for calcification all the time, as shown by the extremely rapid calcification occurring soon after the compression had ceased and the vessels were able to reach their proper place.

It seems justified to believe that the first hypertrophic cell not to be calcified after removal of the clamp is the one around which the matrix has not yet changed sufficiently to have an affinity for the apatite crystals. As in moderate compression, the division of the proliferative cells continues and it seems it must be the age, or even more likely the distance from the transudate coming from the epiphysial side of the growth cartilage that conditions the maturity of the cell, which prepares the field for calcification and thus initiates the osteogenic process.

Views similar to this have been advanced by Ham (1957) and his school.

In this work the role of the blood vessels surrounding the epiphysial growth plate has been studied. The nutritional dependence of the proliferative cells on the epiphysial vessels has been established whereas the metaphysial vessels were seen to take part in calcification and ossification at the metaphysis.

As it does not seem likely that the blood circulating in the two systems of vessels had a different constitution, particularly in hormones and vitamins, it seems permissible to assume that it is the characteristics, particularly in shape and number, of such vessels that make growth the orderly process it is, with the repeated birth of a cell at the top of a column and burial at the bottom end. But, despite this undeniable role of the vessels, growth depends on the ability of the cartilage cell to form a matrix which, in due course, will be avid for apatite crystals.

Throughout this work data have been gathered favouring the concept that the metaphysial vascular arrangement is primarily related to the process of enchondral ossification, and has very limited, if any, responsibility for the nourishment of the growth cartilage.

The present evidence favours the suggestion that when the chondrocytes of the column have become too far separated from their source of nourishment (the epiphysial vessels) they and their surrounding matrix suffer changes which prepare them for the process of calcification. At least calcium and phosphate ions will be required for this to take place. The proximity of the vessel and also the fact that it is not isolated by a membrane at its very end suggests a profuse interchange of fluids with the surrounding area.

1. The three age types of acute haematogenous osteomyelitis are conditioned in their respective clinical features by the differing nature of their vascular bone pattern.

2. In the infant the condition causes severe and often permanent epiphysial damage and joint infection, a large involucrum but only transient damage to the shaft and metaphysis.

3. In the child the condition is responsible for extensive cortical damage with involucrum formation, but, except for some stimulation of growth, permanent damage to the growth cartilage and to joints is exceptional. Chronicity of the disease is rare if treatment has been effective.

4. In the adult acute osteomyelitis of the long bones is rare. It causes very frequent joint infection; the cortex is absorbed instead of sequestrating. The whole of the bone is invaded and frequently leaves chronic infection in the bone marrow.

5. The vascular characteristics of the bones in each age group and their relation to the onset of infection are described.

6. Some general directives for management based on these facts are suggested.

1. Vascular anatomical studies of the spine are described and the possibility of spread of infection from pelvis to spine through the paravertebral venous plexus is discussed.

2. Though a venous route does exist, our studies do not support the supposition that infection is likely to spread by this route; nor is there any clear clinical, pathological or anatomical evidence that such spread occurs.

3. Nineteen cases of pyogenic osteomyelitis of the spine are recorded, six of which followed urinary infections. The condition is compared with osteomyelitis as it occurs in the other bones of adults.

1. In five series of experiments in eighty-two rabbits we succeeded in causing rarefaction of the calcaneum of all the animals soon after it was relieved from muscular compressing forces; new bone was generated when the calcaneum was subjected again to the stresses and strains of muscle contraction.

2. We found evidence that during muscle action pressure forces are transmitted through the bone, and that the presence or absence of these pressure forces conditions the balance between bone formation and bone removal.

3. In the calcaneum of the rabbit lack of muscular action seems to be the most important factor inducing osteoporosis. It is possible that the origin of post-traumatic osteoporosis has the same basis.

4. In our experiments bone rarefaction was characterised by a great increase in the vascularity of the bone; this increase ceased when the bone reached its final precarious bone density. Thus, vascular over-activity accompanied the removal of bone; but bone reconstruction was also seen to be accompanied by a more localised increase in vascularity.

5. From our experiments we cannot suggest that the inhibition of muscle contraction accompanying Sudeck's syndrome is responsible for this disorder, because we were unable in our animals to cause any of the other signs characteristic of Sudeck's bone atrophy. But the constancy with which we caused bone atrophy by the removal of muscle action may possibly help to explain the mechanism of bone absorption accompanying Sudeck's disease.

1. A study of normal and osteoarthritic hyaline cartilage has been made with the electron microscope and x-ray diffraction.

2. Normal cartilage consists of a three-dimensional network of collagen fibrils with no preferred orientation, surrounded by a matrix containing polysaccharide.

3. In the osteoarthritic joint the collagen fibrils show definite orientation and a decreased proportion of ground substance. X-ray diffraction confirms this and shows the orientation to be at right angles to the surface of the femoral head.

4. Tensional forces across the joint may explain why osteoarthritic changes first appear in the non-weight-bearing area of the joint.

1. The results of a study of the characteristics of the vessels found in forty-six human femoral heads during the growth period are described.

2. Of the three different sources of blood entering the human adult femoral head it was found that from birth to about three to four years the vessels of the ligamentum teres do not contribute to the nourishment of the head.

3. After the fourth year the metaphysial vessels decrease in importance until they finally disappear, leaving the head with only one source of blood through the lateral epiphysial vessels; the ligamentum teres is not yet contributing to the circulation of the head.

4. After about eight or nine years it was found that the vessels of the ligamentum teres contribute to the blood supply of the head while the metaphysial blood flow is still arrested.

5. Finally, at puberty, after a period of activity of the metaphysial vessels, epiphysial fusion takes place, bringing together the three sources of blood characteristic of the adult.

Osteoarthritis, as seen in the hip, is a disease which eventually embraces all the tissues of the joint but begins as a reaction of the juxta-chondral blood vessels to a degeneration of the articular cartilage; this reaction results in a hyperaemia of the bone. To our surprise we found that daily use preserves rather than "wears out" articular cartilage; indeed inadequate use is the commonest cause of cartilage degeneration and ensuing vascular invasion. To this factor are added the effects of excessive pressure in the many patients who require surgical treatment for advanced osteoarthritis of a hip the seat of some anatomical incongruity. This etiology based on cartilage suffering does not exclude, but indeed explains, the osteoarthritis implanted on joints of a normal shape which have been previously affected by acute or chronic inflammation or by hormonal dysfunction, such as acromegalic osteoarthritis. The stimulus to vessel growth and invasion is the same in all these cases—namely cartilage damage. Once the vessels have entered the cartilage the bone and marrow of the osteophyte are inevitably laid down. What is so damaging in osteoarthritis seems to be not the degeneration of the cartilage but the vigorous and persistent attempt at repair, an attempt which aggravates the already disordered function of the joint not only by osteophyte formation but by the hypervascularity which weakens the structure of the bone beyond the point where it can carry its increased load. The collapse that follows provokes further reparative efforts with the same deplorable results. The osteoarthritic process thus appears to be an attempt to transform a decaying joint into a youthful one and for this, as in the miraculous rejuvenation depicted in Goethe's Faust, a high price must ultimately be paid.

1. The form and distribution of the blood vessels within the adult human femoral head are described.

2. It has been found possible to delimit the proximal femoral epiphysis in mature years by reference to arterial form alone.

3. Two morphologically different sets of vessels are described interposed between the arterioles and venules of the bone marrow. One, a true capillary bed, lies mainly within the fat marrow; the other, constituted by sinusoids, lies within the red marrow. The departure of these findings from current views is noted.

4. A capillary system is described in relationship to the calcified zone of the articular cartilage.

5. No evidence has been found in support of the common belief that the circulation within the femoral head decreases quantitatively with advancing age.