Advertisement for orthosearch.org.uk
Results 1 - 20 of 206
Results per page:
The Journal of Bone & Joint Surgery British Volume
Vol. 68-B, Issue 2 | Pages 268 - 274
1 Mar 1986
Alderson M Speers D Emslie K Nade S

The acute childhood diseases haematogenous staphylococcal osteomyelitis and septic arthritis were studied concurrently using avian models which closely resemble the human diseases. Ultrastructural studies during the initial stages of bone and joint infection showed that adherence of bacteria to cartilage, bacterial proliferation, cartilage destruction and subsequent bacterial spread along the vascular channels within cartilage were common to both disease processes. Histological studies revealed that transphyseal blood vessels were present in the growing chickens and were a likely explanation for the frequency of the concurrence of acute osteomyelitis and adjacent joint infection following intravenous injection of bacteria. Transphyseal vessels provide a direct connection between the growth plate (physis) and epiphyseal cartilage supplying a route for bacteria to spread from an osteomyelitic focus in the metaphysis to the epiphysis and subsequently to the joint lumen


Bone & Joint Research
Vol. 11, Issue 4 | Pages 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims. Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model. Methods. A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes. Results. Gross and histological examinations showed that TTT technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In the TTT group, haematoxylin and eosin (H&E) staining demonstrated a better epidermis and dermis recovery, while immunohistochemical staining showed that TTT technique promoted local collagen deposition. The TTT technique also benefited to angiogenesis and immunomodulation. In the TTT group, blood flow in the wound area was higher than that of other groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the TTT group with double immune-labelling of CD31 and α-Smooth Muscle Actin (α-SMA). The number of M2 macrophages at the wound site in the TTT group was also increased. Conclusion. The TTT technique accelerated wound healing through enhanced angiogenesis and immunomodulation. Cite this article: Bone Joint Res 2022;11(4):189–199


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 865 - 870
1 Aug 2024
Broida SE Sullivan MH Rose PS Wenger DE Houdek MT

Aims. Venous tumour thrombus (VTT) is a rare finding in osteosarcoma. Despite the high rate of VTT in osteosarcoma of the pelvis, there are very few descriptions of VTT associated with extrapelvic primary osteosarcoma. We therefore sought to describe the prevalence and presenting features of VTT in osteosarcoma of both the pelvis and the limbs. Methods. Records from a single institution were retrospectively reviewed for 308 patients with osteosarcoma of the pelvis or limb treated between January 2000 and December 2022. Primary lesions were located in an upper limb (n = 40), lower limb (n = 198), or pelvis (n = 70). Preoperative imaging and operative reports were reviewed to identify patients with thrombi in proximity to their primary lesion. Imaging and histopathology were used to determine presence of tumour within the thrombus. Results. Tumours abutted the blood vessels in 131 patients (43%) and encased the vessels in 30 (10%). Any form of venous thrombus was identified in 31 patients (10%). Overall, 21 of these thrombi were determined to be involved with the tumour based on imaging (n = 9) or histopathology (n = 12). The rate of VTT was 25% for pelvic osteosarcoma and 1.7% for limb osteosarcoma. The most common imaging features associated with histopathologically proven VTT were enhancement with contrast (n = 12; 100%), venous enlargement (n = 10; 83%), vessel encasement (n = 8; 66%), and visible intraluminal osteoid matrix (n = 6; 50%). Disease-specific survival (DSS) for patients with VTT was 95% at 12 months (95% CI 0.87 to 1.00), 50% at three years (95% CI 0.31 to 0.80), and 31% at five years (95% CI 0.14 to 0.71). VTT was associated with worse DSS (hazard ratio 2.3 (95% CI 1.11 to 4.84). Conclusion. VTT is rare with osteosarcoma and occurs more commonly in the pelvis than the limbs. Imaging features suggestive of VTT include enhancement with contrast, venous dilation, and vessel encasement. VTT portends a worse prognosis for patients with osteosarcoma, with a similar survivability to metastatic disease. Cite this article: Bone Joint J 2024;106-B(8):865–870


Bone & Joint Research
Vol. 10, Issue 8 | Pages 474 - 487
2 Aug 2021
Duan M Wang Q Liu Y Xie J

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases


The Bone & Joint Journal
Vol. 101-B, Issue 8 | Pages 1024 - 1031
1 Aug 2019
Fujiwara T Medellin MR Sambri A Tsuda Y Balko J Sumathi V Gregory J Jeys L Abudu A

Aims. The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods. A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results. Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. Conclusion. The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024–1031


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

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. Methods. We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests. Results. In the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing. Conclusion. Cigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing. Cite this article:Bone Joint Res. 2020;9(3):99–107


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 4 | Pages 732 - 738
1 Jul 1999
Meek RMD McLellan S Crossan JF

Dupuytren’s disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren’s tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-ß) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren’s disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-ß was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren’s tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren’s nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-ß stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-ß. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-ß was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 489 - 495
1 Apr 2006
Matthews TJW Hand GC Rees JL Athanasou NA Carr AJ

We have studied cellular and vascular changes in different stages of full thickness tears of the rotator cuff. We examined biopsies from the supraspinatus tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery and compared them with biopsies from four uninjured subscapularis tendons. Morphological and immunocytochemical methods using monoclonal antibodies directed against leucocytes, macrophages, mast cells, proliferative and vascular markers were used. Histological changes indicative of repair and inflammation were most evident in small sized rotator cuff tears with increased fibroblast cellularity and intimal hyperplasia, together with increased expression of leucocyte and vascular markers. These reparative and inflammatory changes diminished as the size of the rotator cuff tear increased. Marked oedema and degeneration was seen in large and massive tears, which more often showed chondroid metaplasia and amyloid deposition. There was no association between the age of the patient and the duration of symptoms. In contrast, large and massive tears showed no increase in the number of inflammatory cells and blood vessels. Small sized rotator cuff tears retained the greatest potential to heal, showing increased fibroblast cellularity, blood vessel proliferation and the presence of a significant inflammatory component. Tissue from large and massive tears is of such a degenerative nature that it may be a significant cause of re-rupture after surgical repair and could make healing improbable in this group


Bone & Joint Research
Vol. 7, Issue 2 | Pages 148 - 156
1 Feb 2018
Pinheiro M Dobson CA Perry D Fagan MJ

Objectives. Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. Methods. Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. Results. The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. Conclusion. The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease. Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes’ disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148–156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 1 | Pages 147 - 153
1 Jan 1997
Brown MF Hukkanen MVJ McCarthy ID Redfern DRM Batten JJ Crock HV Hughes SPF Polak JM

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 4 | Pages 604 - 610
1 May 2003
Reed AAC Joyner CJ Isefuku S Brownlow HC Simpson AHRW

Our aim was to develop a clinically relevant model of atrophic nonunion in the rat to test the hypothesis that the vessel density of atrophic nonunion reaches that of normal healing bone, but at a later time-point. Atrophic nonunion is usually attributed to impaired blood supply and is poorly understood. We determined the number of blood vessels at the site of an osteotomy using immunolocalisation techniques in both normally healing bones and in atrophic nonunion. At one week after operation there were significantly fewer blood vessels in the nonunion group than in the healing group. By eight weeks, the number in the atrophic nonunion group had reached the same level as that in the healing group. Our findings suggest that the number of blood vessels in atrophic nonunion reaches the same level as that in healing bone, but at a later time-point. Diminished vascularity within the first three weeks, but not at a later time-point, may prevent fractures from uniting


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 141 - 144
1 Jan 2002
Petersen W Hohmann G Stein V Tillmann B

We studied the vascular pattern of human posterior tibial tendons by injection techniques and immunohistochemically using antibodies against laminin. The intravascular volume of the posterior tibial tendon was determined using a new method of injection of a solution of . 99m. Tc and gelatin ink into the lower legs of cadavers. Three segments of 1 cm length from different regions of the human posterior tibial tendon were measured using a gamma well counter. The main blood supply arises from the posterior tibial artery. Blood vessels enter the paratenon of the posterior tibial tendon via a mesotenon from the posterior aspect. From the paratenon, the blood vessels penetrate the posterior tibial tendon and anastomose with a longitudinally orientated intratendinous network. The number of vessels in the substance of the tendon is consistently less than that in the surrounding paratenon. The distribution of blood vessels within the posterior tibial tendon is not homogeneous. In the retromalleolar region the intravascular volume was significantly reduced with a mean value of 15 μl/g of tendon tissue. There was no significant difference between the mean intravascular volumes of the proximal and distal areas (distal, 27.7 μl/g tendon tissue; proximal, 30 μl/g tendon tissue). The immunohistochemical investigation showed that there was no immunostaining for laminin in the anterior part of the tendon in the region where it passes behind the medial malleolus. This region is avascular. The most frequent site of rupture of the posterior tibial tendon is in the region behind the medial malleolus. A potential endogenous risk factor may be the limited healing potential of avascular tissue


The Bone & Joint Journal
Vol. 98-B, Issue 9 | Pages 1155 - 1159
1 Sep 2016
Trieb K

Neuropathic changes in the foot are common with a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy is often delayed in diabetic patients with harmful consequences including amputation. The appropriate diagnosis and treatment can avoid an extensive programme of treatment with significant morbidity for the patient, high costs and delayed surgery. The pathogenesis of a Charcot foot involves repetitive micro-trauma in a foot with impaired sensation and neurovascular changes caused by pathological innervation of the blood vessels. In most cases, changes are due to a combination of both pathophysiological factors. The Charcot foot is triggered by a combination of mechanical, vascular and biological factors which can lead to late diagnosis and incorrect treatment and eventually to destruction of the foot. This review aims to raise awareness of the diagnosis of the Charcot foot (diabetic neuropathic osteoarthropathy and the differential diagnosis, erysipelas, peripheral arterial occlusive disease) and describe the ways in which the diagnosis may be made. The clinical diagnostic pathways based on different classifications are presented. Cite this article: Bone Joint J 2016;98-B:1155–9


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1127 - 1133
1 Aug 2013
Lama P Le Maitre CL Dolan P Tarlton JF Harding IJ Adams MA

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes always precede disc herniation. Cite this article: Bone Joint J 2013;95-B:1127–33


The Journal of Bone & Joint Surgery British Volume
Vol. 41-B, Issue 3 | Pages 600 - 610
1 Aug 1959
Amato VP Bombelli R

The main findings in this experimental work on rats fed on lathyrus odoratus (sweet-pea) meal are as follows:. 1. Growth is retarded. 2. The growth plate is disorganised and normal ossification at the metaphysis is interfered with. 3. The small blood vessels are seriously affected and probably contribute quite largely to the disorganisation and lack of calcification. 4. Alkaline phosphatase activity is increased. 5. Raising of the periosteum and laying down of new bone result in exostoses. The possible underlying etiology and the role of cement substance, endocrine factors and the blood vessels are discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 38-B, Issue 4 | Pages 928 - 933
1 Nov 1956
Lewis OJ

1. Periosteal bone is supplied by periosteal vessels and endochondral bone by the nutrient artery. 2. In the earliest stages of development the metaphysis is supplied by vessels derived only from the nutrient artery. Later, metaphysial arteries derived from the periosteum take over the supply of its peripheral part, the extent of their area of supply progressively increasing. 3. In injected specimens the blood vessels approaching the epiphysial cartilaginous plate end in saccular dilations. Histological sections show these dilations to be blood-filled cartilage lacunae, with no endothelial lining and into which open the blood vessels approaching the epiphysial plate


The Journal of Bone & Joint Surgery British Volume
Vol. 39-B, Issue 2 | Pages 346 - 357
1 May 1957
Sladden RA

1. In five out of eleven cases of osteoclastoma it was found that osteoclasts were present inside clearly defined blood vessels either within the tumours or in the tissues immediately surrounding the tumours. In two further cases it was found that osteoclasts protruded into the vessels although they were not lying free within the vessels. 2. The possible modes of entry of these cells into the blood stream are discussed. Although accidental dissemination of osteoclasts into damaged blood vessels could not be excluded, it was felt that the process was equally likely to be related to some inherent property of the osteoclasts. From further observations it is suggested that osteoclasts are capable of local destruction of the connective tissues of the vessel walls, probably by enzyme action. Such an action might be analogous to the processes by which, in the opinion of many, osteoclasts bring about the resorption of bone. 3. There did not seem to be any relationship between the finding of intravascular osteoclasts and the malignancy of the tumour, assessing the latter either on histological or clinical grounds. The finding of intravascular osteoclasts does not therefore appear to be of any prognostic significance


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 3 | Pages 531 - 537
1 May 1999
Corbett SA Hukkanen M Batten J McCarthy ID Polak JM Hughes SPF

Our aim was to investigate whether nitric oxide synthase (NOS) isoforms, responsible for the generation of NO, are expressed during the healing of fractures. To localise the sites of expression compared with those in normal bone we made standardised, stabilised, unilateral tibial fractures in male Wistar rats. Immunostaining was used to determine the precise tissue localisation of the different NOS isoforms. Western blotting was used to assess expression of NOS isoform protein and L-citrulline assays for studies on NOS activity. Control tissue was obtained from both the contralateral uninjured limb and limbs of normal rats. Immunohistochemistry showed increased expression of endothelial NOS (eNOS) to be strongest in the cortical blood vessels and in osteocytes in the early phase of fracture repair. Western blot and image analysis confirmed this initial increase. Significantly elevated calcium-dependent NOS activity was observed at day 1 after fracture. Inducible NOS (iNOS) was localised principally in endosteal osteoblasts and was also seen in chondroblasts especially in the second week of fracture healing. Western blotting showed a reduction in iNOS during the early healing period. Significantly reduced calcium-independent NOS activity was also seen. No neuronal NOS was seen in either fracture or normal tissue. Increased eNOS in bone blood vessels is likely to mediate the increased blood flow recognised during fracture healing. eNOS expression in osteocytes may occur in response to changes in either mechanical or local fluid shear stress. The finding that eNOS is increased and iNOS reduced in early healing of fractures may be important in their successful repair


The Journal of Bone & Joint Surgery British Volume
Vol. 47-B, Issue 4 | Pages 612 - 633
1 Nov 1965
d'Aubigné RM Postel M Mazabraud A Massias P Gueguen J

1. Idiopathic necrosis of the femoral head is generally considered to be a rare disease but it appears to be rather frequent in France in view of the fact that 139 cases were recorded in the orthopaedic clinic of Hôpital Cochin between 1959 and 1963. Ninety cases treated by operation have been analysed in this paper. Men are nearly exclusively affected between the ages of eighteen and seventy, with the highest incidence between thirty and fifty years of age. Both hips are affected in 52 per cent of cases. 2. The etiology is unknown, but steroid therapy was noted in 36 per cent of the cases and some history of slight injury in 30 per cent. The sudden onset of pain in half the cases suggests the obliteration of one of the blood vessels supplying the femoral head. 3. Radiographs are often normal at the time of onset of the symptoms but later they show increased density of the head localised to the antero-superior aspect, and later still collapse of this weight-bearing region. The extent of the lesion appears to be determined from the very beginning rather than to be progressive. The superior joint space is never reduced and may in fact be widened. 4. Pathological examination of the head and neck confirms necrosis of the cancellous bone and the integrity of the overlying cartilage, but shows deep to the necrotic region a highly reactive zone characterised by hypervascularity and raised metabolism. These features have been demonstrated by injection of the blood vessels and also by the uptake of phosphorus 32 and by the succino-deshydrogenase test. 5. In six cases microscopic vascular lesions were found in the antero-lateral pedicle of the femoral head. 6. The high degree of activity of the tissue deep to the necrotic zone gives some hope for revascularisation of the necrotic segment. For this reason protection from pressure may be the way to prevent dramatic collapse of the head. Rest, medical treatment and freedom from weight bearing, however, do not achieve adequate protection. Varus or rotation osteotomy of the femoral neck not only gives relief from pain but appears to prevent collapse of the femoral head. 7. When destruction of the head has already taken place good results may be expected from the insertion of a metallic prosthesis, provided the acetabulum is sound. The results are less favourable when the acetabulum has been altered by secondary arthritic change, and arthrodesis may have to be considered if the disease is unilateral or when a prosthesis has been successfully inserted on the other side


The Journal of Bone & Joint Surgery British Volume
Vol. 47-B, Issue 2 | Pages 304 - 318
1 May 1965
Urist MR Wallace TH Adams T

1. Autografts, isografts and homografts of fibrocartilaginous callus were observed in the anterior chamber of the eye in rats. Proliferation of cartilage ceased, endochondral ossification followed, and the end-product was a new and complete ossicle with a cortex and a marrow cavity. The size and shape of the ossicle was determined by the size and shape of the sample of callus. Thus the callus in the eye performed the function of a cartilage model like that of the developing epiphysis or a healing fracture of a long bone. 2. Fibrocartilaginous callus, heavily labelled with . 3. H-thymidine, was transplanted to the eye twenty-four hours after the last injection, when there was little if any radioactive thymidine circulating in the blood. A few small chondrocytes with labelled nuclei persisted in the cores of new bone trabeculae, but the largest part of the labelled callus was resorbed and replaced by unlabelled new bone. 3. Homografts of labelled callus produced the same results as autografts at twenty-five days, but between twenty-five and forty-five days the donor cells were destroyed by the immune response of the host. 4. Isogenous transplants in host rats treated with . 3. H-thymidine between nine and thirteen days, when the callus was invaded by new blood vessels, produced many osteogenetic cells with labelled nuclei and made it possible to trace the origin of the new bone. The label appeared in the progenitor cells within twenty-four hours. While remaining thereafter in progenitor cells, it appeared also in osteoclasts (or chondroclasts) and osteoblasts in forty-eight to seventy-two hours, and in osteocytes in ninety-six to 120 hours. Chondrocytes did not proliferate and were not labelled in the eye. 5. Homogenous transplants in host rats treated with . 3. H-thymidine between five and one days before the operation also produced new bone, but contained no labelled osteoprogenitor or bone cells after twenty-five days in the eye. At forty-five days the donor tissue had been destroyed by the immune response of the host. 6. Devitalised callus was encapsulated in inflammatory connective tissue and scar. When the dead callus was absorbed by the capillaries of the host new bone formation by induction produced a scanty deposit as a delayed event in a few instances. 7. Irrespective of whether it originated in the donor or the host, a connective-tissue cell type that proliferated rapidly and became labelled with . 3. H-thymidine was identified as a progenitor cell. Differentiation and specialisation as osteoprogenitor cells occurred after the growth of blood vessels into the interior of the callus, and developed inside of excavation chambers in cartilage. Except that the interaction of the donor tissue and host cells leading to new bone formation by induction takes place in the interior of the excavation chamber, the biophysico-chemical mechanism is unknown