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

Aims

The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.

1. In tuberculous disease of the hip, premature epiphysial fusion at the knee joint is due to rupture of the epiphysial cartilaginous plates consequent upon resorption of cancellous support and suppression of osteogenesis. 2. In the tibia, premature fusion is usually preceded by near-central "bulging" of the metaphysial and tibial marrow through the epiphysial plate. In the femur, epiphysial changes preceding fusion are of a fragmentary type. 3. Injury, in quiescent disease, plays little or no part in the causation of premature epiphysial fusion. 4. The factors which are responsible for these changes—local toxaemia and prolonged immobilisation—must exist for not less than two years. 5. In cases which are treated conservatively for long periods the incidence of premature fusion, with serious shortening of the limb, is so high that the wisdom of such treatment must be reconsidered

Aims

To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes.

Miller-Galante II total knee arthroplasty (MG II TKA) was performed on 32 knees in 30 patients. On both the femoral and tibial components, the fibre-metal area was plasma-sprayed with hydroxyapatite-tricalcium phosphate (HA-TCP). The clinical and radiographic outcome was evaluated. A mean pre-operative knee score of 26.0 ± 18.6 (SD) increased to 97.5 ± 3.5 and a mean pre-operative functional score of 21.7 ± 15.0 (SD) increased to 83.4 ± 12.4 at follow-up of seven years. Clear zones were common around the components at one month post-operatively but had completely disappeared after six months. An autopsy of a patient who underwent MG II TKA with HA-TCP two years previously, showed osteogenesis in all parts of the fibre-metal, and bone tissue comprised 77.7% of the interface. This coated prosthesis has good early fixation which is maintained at seven years with good clinical and radiographic outcomes

Using bone decalcilied with 0.6 N hydrochloric acid as an inducing agent, the inductive capacity of different soft tissue sites was investigated. Muscle and fascia regularly permitted the induction of bone, while spleen, liver and kidney suppressed bone induction. Bone formation could be induced in these organs if living autologous fascia was implanted together with the inducing agent; while bone formation was inhibited when living autologous spleen tissue was implanted with the inducing agent to normally favourable sites. The administration of systemic heparin and the diphosphonate ethane-1-hydroxyl, 1-diphosphonic acid (EHDP) suppressed bone induction. It is suggested that for bone induction to occur in soft tissues, three conditions must be present: 1) an inducing agent; 2) an osteogenic precursor cell; and 3) an environment which is permissive to osteogenesis. The presence of osteogenic inhibitors in spleen, liver and kidney is postulated

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

1. Experimental defects in the cranial vaults of young adult rabbits were implanted with decalcified, deproteinised and deep frozen homogenous whole bone. The experiments were similar to those of Ray and Holloway (1957) except that these workers used rats as the experimental animals. In addition, six control defects were made and not implanted. 2. All animals were killed six weeks after operation and thirty-four defects were studied by radiology and by histology. 3. All implants became surrounded by connective tissue and in all cases some new bone formed in apposition to implanted fragments. The degree of incorporation of the implants in new bone varied widely, not only between the three implanted groups, but also within each group. In general, new bone formation was greatest in defects implanted with deproteinised and whole bone, least in defects implanted with decalcified bone. 4. The fate of bone implants and the extent to which they can be said to induce osteogenesis are discussed

Three elderly sibling dwarfs are reported from a large and otherwise normal family. Their condition is an unusual and irregular form of cartilaginous defect, combined with club-feet, and bearing some resemblance to the Morquio type. A brief consideration of the literature of the generahised developmental bony syndromes shows confusion of thought and nomenclature. A plea is therefore made for simplification and a rational and simple grouping of these conditions is attempted. It seems particularly desirable that many confusing names for particular syndromes should be scrapped (for example, dyschondroplasia, chondro-osteodystrophy), although quite evidently the terms achondroplasia and osteogenesis imperfecta must remain because of their long-standing and general usage. Incidentally I have suggested elsewhere (Jackson 1951) that the name cleido-cranial dysostosis should be dropped, because it tends to lead the investigator away from the clinically more important lesions in the teeth and the cartilage bones of the pelvis and legs. It seems reasonable to confine the nomenclature of these various syndromes to the names used in the above classification, or something on those lines

We performed posterior fixation with a Hartshill-Ransford contoured loop in 43 patients with instability at the craniocervical junction. No external bracing was used. Fifteen patients had congenital malformations, ten had tumours, seven had 'bone-softening' conditions (such as osteogenesis imperfecta), five had suffered complicated fractures, three had occipito-C1-C2 hypermobility due to lax ligaments and three had severe degenerative spondylosis with pseudotumours of the transverse ligament. Twenty-nine patients had transoral decompression of the cord before fixation. In most cases, cancellous bone grafts taken from the iliac crest were used to induce fusion; in nine very ill patients, no bone graft was used. In the whole series there was no instance of construct failure, broken wire or laminar fracture. The best results were achieved in patients with tumours or bone-softening conditions. No patient with normal neurology deteriorated after surgery but seven had worse neurological deficits after operation than before. Neck stiffness caused half the patients to change their lifestyle

In a clinical, radiological and biochemical study of forty-two patients from Oxford with osteogenesis imperfecta, it was found that patients could be divided simply into mild, moderate and severe groups according to deformity of long bones. In the severe group (seventeen patients) a family history of affected members was uncommon and fractures began earlier and were more frequent than in the mild group (twenty-two patients); sixteen patients in the severe group had scoliosis and eleven had white sclerae; no patients in the mild group had white sclerae or scoliosis. Radiological examination of the femur showed only minor modelling defects in patients in the mild group, whereas in the severe group five distinct appearances of bone (thin, thick, cystic and buttressed bones, and those with hyperplastic callus) were seen. The polymeric (structural) collagen from skin was unstable to depolymerisation in patients in the severe group, but normal in amount, whereas the reverse was found in the mild group. This division according to long bone deformity may provide a basis for future research more useful than previous classifications

We used an experimental rabbit model of leg lengthening to study the morphology and function of muscle after different distraction rates. Lengthening was in twice-daily increments from 0.4 to 4 mm per day. New contractile tissue formed during lengthening, but some damage to the muscle fibres was seen even at rates of less than 1 mm per day; abnormalities increased with larger rates of lengthening. There was proliferation of fibrous tissue between the muscle fibres at distraction rates of over 1 mm per day. Active muscle function showed adaptation when the rate was 1.0 mm per day or less, but muscle compliance was normal only after rates of 0.4 mm per day. Muscle responded more favourably at rates of distraction slower than those shown to lead to the most prolific bone formation. At present the rate of distraction in clinical practice is determined mainly by factors which enhance osteogenesis. Our study suggests that it may be advisable to use a slower rate of elongation in patients with poor muscle compliance associated with the underlying pathology; this will allow better accommodation by the contractile and connective tissues of the muscles

We have examined the process of fusion of the intertransverse processes and bone graft in the rabbit by in situ hybridisation and evaluated the spatial and temporal expression of genes encoding pro-α1 (I) collagen (COL1A1), pro-α1 (II) collagen (COL2A1) and pro-α1 (X) collagen (COL10A1). Beginning at two weeks after operation, osteogenesis and chondrogenesis occurred around the transverse process and the grafted bone at the central portion of the area of the fusion mass. Osteoblasts and osteocytes at the newly-formed woven bone expressed COL1A1. At the cartilage, most chondrocytes expressed COL2A1 and some hypertrophic chondrocytes COL10A1. In some regions, co-expression of COL1A1 and COL2A1 was observed. At four weeks, such expressions for COL1A1, COL2A1 and COL10A1 became prominent at the area of the fusion mass. From four to six weeks, bone remodelling progressed from the area of the transverse processes towards the central zone. Osteoblasts lining the trabeculae expressed a strong signal for COL1A1. At the central portion of the area of the fusion mass, endochondral ossification progressed and chondrocytes expressed COL2A1 and COL10A1. Our findings show that the fusion process begins with the synthesis of collagens around the transverse processes and around the grafted bone independently. Various spatial and temporal osteogenic and chondrogenic responses, including intramembranous, endochondral and transchondroid bone formation, progress after bone grafting at the intertransverse processes. Bone formation through cartilage may play an important role in posterolateral spinal fusion

Experiments on white mice were undertaken to determine the reaction of bone to the intramedullary introduction of the virus of tick-borne encephalitis. The following conclusions were drawn. 1. The tick-borne encephalitis virus S47, when introduced intraosteally in white mice, provokes osteitis. 2. Inflammation may lead to acute necrosis of bone, preceded by marked medullary oedema and subsequent proliferation, or it may take a milder form with haemorrhagic effusion into the marrow tissue and subsequent hyperplasia of connective tissue. 3. Damage to the epiphysial and articular cartilage may ensue in the course of acute necrotic osteitis. 4. Skeletal and extra-skeletal osteogenesis is a characteristic feature of viral osteitis. 5. In radiographs in acute viral osteitis with extensive necrosis the expanded bone appears to be thickened. 6. Viruses of the S47 strain introduced intraosteally preserve their affinity for brain tissue after three passages through bone. 7. Viruses introduced into the bony tissue preserve their toxicity and are found in the bony tissue after ten days in quantities lethal for young mice when inoculated intracerebrally. 8. The tick-borne encephalitis virus S47 is pathogenic when inoculated into the marrow in white mice. 9. In osteitis of non-bacterial origin in man the possibility of viral infection should be considered

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

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. 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

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

Objectives

MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.

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