We have reviewed retrospectively 80 patients who were treated for traumatic fractures of the femur with a Grosse-Kempf nail to assess the incidence and causes of persisting pain in the proximal thigh. At a mean of 21 months after operation 33 patients had residual pain severe enough to interfere with their lifestyle or mobility. This was in the region of the scar on the greater trochanter in three-quarters of the patients. Only four showed no radiological abnormality. There was nonunion of the fracture in two, Paget’s disease in one, breakage of the nail in two and prominence of the proximal locking screw in five, although we found no correlation between prominence of the nail and pain. There was a strong relationship between pain and heterotopic ossification at the proximal end of the implant; this was present in 64% of the patients with pain as compared with those without pain (p < 0.001, Mann-Whitney U test). Of the 80 patients, 27 had the implant removed after 18 months, 17 of them because of pain. In six of these 17, the pain was not relieved. Prominence of the nail proximally was not associated with pain, but protuberance of laterally-based proximal locking screws caused problems. We found a strong association between heterotopic bone formation and pain, but it is uncertain whether this is the true cause or merely an indication of some other factor such as traumatic damage to the glutei during insertion of the nail. Removal of the implant does not always cure such pain

Objectives

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1).

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-β1 (rhTGF-β1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-β1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 μg rhTGF-β1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 ± 5.6% bone-implant contact in the control group to 36 ± 2.9% in the rhTGF-β stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-β1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-β1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth

Objectives

Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline.

Skeletal scintigraphy, which has now been established as a useful and accurate method of detecting early skeletal metastases and assessing their response to treatment, has been investigated for its pathological basis. Histological examination of several hundred necropsy specimens, from sixty-eight patients who died from malignant disease, showed a significant increase of osteoid and immature woven bone in the presence of metastatic cancer. Tumour-cell suspensions of the VX2 carcinoma were injected into the medullary cavity or on to the periosteal surface of the ilia or tibiae of New Zealand white rabbits. A combination of bone destruction and new bone formation, similar to the autopsy material, was seen. There were at least two mechanisms for the new bone production. Initially, intramembranous ossification was seen in the fibrous stroma surrounding the tumour. Once the cortex was involved and cortical bone destruction had occurred, large amounts of woven bone resembling fracture callus were laid down. The new bone had a markedly increased avidity for boneseeking isotopes, indicating why skeletal scintigraphy was useful. A further twenty rabbits, in whose ilia the VX2 carcinoma was growing, were treated by local irradiation. When treatment was successful the tumour was destroyed, the production of new bone ceased, and the lesion lost its increased avidity for bone-seeking isotopes, indicating that skeletal scintigraphy could be used to assess the response of skeletal metastases to therapy

In osteogenesis imperfecta the formation of callus is usually plentiful and sometimes rather excessive but the excess is absorbed in the normal way as consolidation occurs. In hyperplastic callus formation the amount of callus formed is large, or even enormous; and, once its limits are defined and ossification has occurred, some part of the original swelling remains as a thickening of the bone. "Callus" may form with or without injury and with or without fracture. The interest of the present case lies partly in the fact that there is no history of multiple fractures to indicate classical osteogenesis imperfecta, and partly in the familial incidence which has also been noted in other records. It is important to recognise the true nature of the condition in order to avoid the tragedy of unnecessary amputation. In one of Brailsford's cases the lesion is said to have become malignant but there is no other evidence in the literature that the condition has any relationship to malignancy. The clinical appearance can easily give rise to the suspicion of malignancy, and on histological examination the highly cellular and rapidly growing callus can be confused with a malignant condition. In fact, for the short time in which the bone formation runs riot the behaviour of a malignant neoplasm is closely simulated. It is thought that the present account may be of interest because of the invariable relief of pain after x-ray treatment of each new lesion, the length of time over which the case has been followed and the resemblance between the radiographic appearances in the patient now and those of her aunt taken twenty years ago

Bone morphogenetic protein (BMP) has a crucial role in osteochondrogenesis of bone formation as well as in the repair of fractures. The interaction between hedgehog protein and BMPs is inferred from recent molecular studies. Hedgehog genes encode secreted proteins which mediate patterning and growth during skeletal development. We have shown that Indian hedgehog gene (Ihh) is expressed in cartilage anlage and later in mature and hypertrophic chondrocytes. This finding suggests that Ihh may regulate the development of chondrocytes. Our results in this study have shown that Ihh transcripts were expressed in hypertrophic chondrocytes in mice at three days but not at three weeks, although a similar expression pattern of α1 (X) collagen could be observed in both types of cartilage. To investigate the possibility that there are direct and age-dependent functions of Ihh in chondrocytes, cultured chondrocytes were treated with the amino-terminal fragment of Sonic hedgehog protein (Shh-N) which can functionally substitute for Ihh protein. Shh-N did not affect the proliferation and differentiation of chondrocytes from three-week-old mice but had a significant effect on three-day-old mice. It enhanced proliferation up to 128% of the control culture in a dose-dependent manner. Although there was no effect in Shh-N-treated cultures, Shh-N enhanced the stimulatory effect of parathyroid hormone (PTH) on the synthesis of proteoglycans. Because the effects of Shh-N on chondrocyte differentiation in this culture system differed from those of bone morphogenetic protein-2 (BMP2) and PTH, in terms of proteoglycan synthesis and ALPase activity, it is unlikely that BMP2 or PTH/PTH-related protein mediates the direct effects of Ihh in chondrocytes. Our study shows that Ihh can function in chondrocytes in a direct and age-dependent fashion

Objectives

Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model.

Objectives

Many in vitro studies have investigated the mechanism by which mechanical signals are transduced into biological signals that regulate bone homeostasis via periodontal ligament fibroblasts during orthodontic treatment, but the results have not been systematically reviewed. This review aims to do this, considering the parameters of various in vitro mechanical loading approaches and their effects on osteogenic and osteoclastogenic properties of periodontal ligament fibroblasts.

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

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

Aims

The purpose of this study was to evaluate the biological fixation of a 3D printed porous implant, with and without different hydroxyapatite (HA) coatings, in a canine model.

Aims

To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA.

Aims

This single-centre observational study aimed to describe the results of extensive bone impaction grafting of the whole acetabular cavity in combination with an uncemented component in acetabular revisions performed in a standardized manner since 1993.

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

Aims

To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs).

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