Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice. Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1. +. ) and stem cell factor receptor, CD117 (c-kit. +. ) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1. +. mononuclear cell (MNC. sca-1+. ) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC. sca-1+,c-kit+. counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours. Sca-1. +. mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium. Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures

In 79 consecutive patients with unicameral bone cysts we compared the results of aspiration and injection of bone marrow with those of aspiration and injection of steroid. All were treated by the same protocol. The only difference was the substance injected into the cysts. The mean radiological follow-up to detect activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a total of 27 injections of bone marrow and 65 a total of 99 injections of steroid. Repeated injections were required in 57% of patients after bone marrow had been used and in 49% after steroid. No complications were noted in either group. In this series no advantage could be shown for the use of autogenous injection of bone marrow compared with injection of steroid in the management of unicameral bone cysts

Aims. Despite recent advances in arthroscopic rotator cuff repair, re-tear rates remain high. New methods to improve healing rates following rotator cuff repair must be sought. Our primary objective was to determine if adjunctive bone marrow stimulation with channelling five to seven days prior to arthroscopic cuff repair would lead to higher Western Ontario Rotator Cuff (WORC) scores at 24 months postoperatively compared with no channelling. Methods. A prospective, randomized controlled trial was conducted in patients undergoing arthroscopic rotator cuff repair. Patients were randomized to receive either a percutaneous bone channelling of the rotator cuff footprint or a sham procedure under ultrasound guidance five to seven days prior to index surgery. Outcome measures included the WORC, American Shoulder and Elbow Surgeons (ASES), and Constant scores, strength, ultrasound-determined healing rates, and adverse events. Results. Overall, 94 patients were randomized to either bone channelling or a sham procedure. Statistically significant improvements in all clinical outcome scores occurred in both groups from preoperative to all timepoints (p < 0.001). Intention-to-treat analysis revealed no statistical differences in WORC scores between the two interventions at 24 months postoperatively (p = 0.690). No differences were observed in secondary outcomes at any timepoint and healing rates did not differ between groups (p = 0.186). Conclusion. Preoperative bone channelling one week prior to arthroscopic rotator cuff repair was not associated with significant improvements in WORC, ASES, Constant scores, strength, or ultrasound-determined healing rates. Cite this article: Bone Joint J 2021;103-B(1):123–130

Limited success in regenerating large bone defects has been achieved by bridging them with osteoconductive materials. These substitutes lack the osteogenic and osteoinductive properties of bone autograft. A direct approach would be to stimulate osteogenesis in these biomaterials by the addition of fresh bone-marrow cells (BMC). We therefore created osteoperiosteal gaps 2 cm wide in the ulna of adult rabbits and either bridged them with coral alone (CC), coral supplemented with BMC, or left them empty. Coral was chosen as a scaffold because of its good biocompatibility and resorbability. In osteoperiosteal gaps bridged with coral only, the coral was invaded chiefly by fibrous tissue. It was insufficient to produce union after two months. In defects filled with coral and BMC an increase in osteogenesis was observed and the bone surface area was significantly higher compared with defects filled with coral alone. Bony union occurred in six out of six defects filled with coral and BMC after two months. An increase in the resorption of coral was also observed, suggesting that resorbing cells or their progenitors were present in bone marrow and survived the grafting procedure. Our findings have shown that supplementation of coral with BMC increased both the resorption of material and osteogenesis in defects of a clinical significance

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model

In 16 mature New Zealand white rabbits mesenchymal stem cells were aspirated from the bone marrow, cultured in monolayer and implanted on to a full-thickness osteochondral defect artificially made on the patellar groove of the same rabbit. A further 13 rabbits served as a control group. The rabbits were killed after 14 weeks. Healing of the defect was investigated histologically using haematoxylin and eosin and Safranin-O staining and with immunohistochemical staining for type-II collagen. We also used a reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA of type-I and type-II collagen. The semiquantitative histological scores were significantly higher in the experimental group than in the control group (p < 0.05). In the experimental group immunohistochemical staining on newly formed cartilage was more intense for type-II collagen in the matrix and RT-PCR from regenerated cartilage detected mRNA for type-II collagen in mature chondrocytes. These findings suggest that repair of cartilage defects can be enhanced by the implantation of cultured mesenchymal stem cells

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.

This paper examines the fate of decalcified allografts (homografts) of iliac cancellous bone impregnated with autologous red marrow and implanted intermuscularly into the anterior abdominal wall of rabbits. In contrast to the findings of Urist and other workers that cortical bone decalcified with hydrochloric acid (HCl) and then freeze-dried is inductive to new bone formation in various heterotopic sites, evidence is presented that iliac bone decalcified by HCl and grafted alone to a muscular site is itself very weakly inductive to bone formation. However, when combined with autologous bone marrow the HCl-decalcified bone provides a better substrate for bone formation by marrow cells than does either undecalcified iliac bone, or iliac bone decalcified with ethylene-diamine-tetra-acetic acid. The freezing or freeze-drying of decalcified bone does not affect new bone formation when implanted alone or with autologous marrow. The differences between the cortical and cancellous bone as inductive substrates for osteogenesis are discussed and the interrelationship of bone and marrow in combined bone grafts are re-evaluated

1. This paper reports a histological study of the fate of sheep and calf cancellous bone grafts impregnated with autologous red marrow of Wistar rats and implanted intramuscularly as composite xenograft-autografts for two to twelve weeks. It also includes some biochemical estimations of certain types of sheep and calf bone used to prepare these composite grafts.

2. Only one of 223 devitalised bone xenografts implanted without autologous marrow formed new bone; in contrast 216 of 223 transplanted with marrow formed new bone.

3. The new bone formed by the composite grafts is derived from the autologous marrow. There was no evidence for an inductive effect upon the marrow of the various types of xenograft bone studied as described previously for allograft bone (Burwell 1966).

4. The highest score of new bone formation was found in composite grafts based on fully deproteinised sheep iliac bone prepared at Oswestry. Statistically this score was significantly higher than those registered by composite grafts prepared from intact (frozen and freeze-dried), decalcified (frozen and freeze-dried) and Kiel sheep bone, and by Kiel and Oswestry calf bone (Table II).

5. The histological evidence reported suggests that the high score with the sheep Oswestry composite grafts is because Oswestry bone is feebly immunogenic, if at all; and that such feeble or absent immunogenicity permits more marrow cells to differentiate into osteoblasts and lay down new bone without impediment.

6. The lower scores of new bone formation in most of the undeproteinised composite grafts of sheep origin–intact frozen, intact freeze-dried and Kiel–are attributed to residual immunogenicity within the organic material of the donor bone, because each type evoked the formation of mature plasma cells.

7. The Kiel bone grafts appeared to evoke less of a plasma cell reaction and may be less immunogenic than the intact and decalcified bone xenografts.

8. The sheep Oswestry CXA's formed significantly more new bone than did the calf Oswestry CXA's. This difference may be due to the different physical properties of the bone obtained from old sheep compared with the bone obtained from a young calf.

Aims. Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. Methods. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm. 2. ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. Results. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). Conclusion. This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells. Cite this article: Bone Joint J 2023;105-B(8):880–887

Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article: Bone Joint J 2019;101-B:361–364

The management of symptomatic osteochondral lesions of the talus (OLTs) can be challenging. The number of ways of treating these lesions has increased considerably during the last decade, with published studies often providing conflicting, low-level evidence. This paper aims to present an up-to-date concise overview of the best evidence for the surgical treatment of OLTs. Management options are reviewed based on the size of the lesion and include bone marrow stimulation, bone grafting options, drilling techniques, biological preparations, and resurfacing. Although many of these techniques have shown promising results, there remains little high level evidence, and further large scale prospective studies and systematic reviews will be required to identify the optimal form of treatment for these lesions. Cite this article: Bone Joint J 2021;103-B(2):207–212

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined. The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p > 0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p < 0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p > 0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p < 0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p > 0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p < 0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing

The clinical use of hydroxyapatite (HA) coating is controversial especially in regard to the long-term performance of the coating and the effects of resorption. In each of 15 consenting patients we inserted two implants, coated with either HA or fluorapatite (FA) into the iliac crest. They were harvested at a mean of 13.6 ± 0.6 months after surgery. Histological examination showed that bone ongrowth on the HA-coated implants was significantly greater (29%) than that on the FA-coated implants. When bone was present on the coating surface the HA coating was significantly thicker than the FA coating. When bone marrow was present, the HA coating was significantly thinner than the FA coating. The reduction in coating thickness when covered by bone or bone marrow was 23.1 ± 9.7 μm for HA and 5.1 ± 1.7 μm for FA (p < 0.01) suggesting that FA is more stable than HA against resorption by bone marrow. The findings suggest that in man the osteoconductive properties of HA coating are superior to those of FA. Resorption rates for both coatings were approximately 20% of the coating thickness per year. Bone ongrowth appears to protect against resorption whereas bone marrow seems to accelerate resorption. No adverse reaction was seen in the surrounding bone

We have studied core biopsy specimens from 16 femoral heads affected by idiopathic avascular necrosis at the silent stage, when there were no clinical or radiographic manifestations but scintigraphy was positive. All the specimens showed necrosis of trabeculae and of bone marrow, but the most common and characteristic feature was evidence of old and new haemorrhage in the marrow. In the areas of intramedullary haemorrhages, trabeculae and bone marrow were completely necrotic, with a transitional area of incomplete necrosis between these areas and those without haemorrhagic lesions, where the trabeculae and bone marrow were normal. There was good correlation between necrosis and haemorrhagic episodes, and it was concluded that repeated intramedullary haemorrhage at the silent stage is probably related to the pathogenesis of idiopathic avascular necrosis of the femoral head

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.

Aims

The aim of this study is to evaluate the surgical treatment with the best healing rate for patients with proximal femoral unicameral bone cysts (UBCs) after initial surgery, and to determine which procedure has the lowest adverse event burden during follow-up.

Aims

Arthroscopic microfracture is a conventional form of treatment for patients with osteochondritis of the talus, involving an area of < 1.5 cm². However, some patients have persistent pain and limitation of movement in the early postoperative period. No studies have investigated the combined treatment of microfracture and shortwave treatment in these patients. The aim of this prospective single-centre, randomized, double-blind, placebo-controlled trial was to compare the outcome in patients treated with arthroscopic microfracture combined with radial extracorporeal shockwave therapy (rESWT) and arthroscopic microfracture alone, in patients with ostechondritis of the talus.

Aims

The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

We describe two patients with a diffuse haemangioma of the lower limb complicated by pathological fracture of the femoral shaft, one of whom was treated by a bone graft and immobilisation in a cast, and the other by external fixation and injection of bone marrow. A review of the literature identified difficulty in control of bleeding and obtaining bony union

Acute bone and joint infections in children are serious, and misdiagnosis can threaten limb and life. Most young children who present acutely with pain, limping, and/or loss of function have transient synovitis, which will resolve spontaneously within a few days. A minority will have a bone or joint infection. Clinicians are faced with a diagnostic challenge: children with transient synovitis can safely be sent home, but children with bone and joint infection require urgent treatment to avoid complications. Clinicians often respond to this challenge by using a series of rudimentary decision support tools, based on clinical, haematological, and biochemical parameters, to differentiate childhood osteoarticular infection from other diagnoses. However, these tools were developed without methodological expertise in diagnostic accuracy and do not consider the importance of imaging (ultrasound scan and MRI). There is wide variation in clinical practice with regard to the indications, choice, sequence, and timing of imaging. This variation is most likely due to the lack of evidence concerning the role of imaging in acute bone and joint infection in children. We describe the first steps of a large UK multicentre study, funded by the National Institute for Health Research, which seeks to integrate definitively the role of imaging into a decision support tool, developed with the assistance of individuals with expertise in the development of clinical prediction tools.

Cite this article: Bone Joint J 2023;105-B(3):227–229.

We prospectively evaluated the percutaneous injection of autogenous bone marrow for the treatment of active simple bone cysts in ten consecutive children with cysts in the proximal humerus, proximal femur or tibia. The treatment included percutaneous biopsy, aspiration of fluid and the injection of autogenous bone marrow aspirated from the iliac crest. All the patients became painfree after a mean of two weeks and resumed full activities within six weeks. All ten cysts consolidated radiologically and showed remarkable remodelling within four months. Review at 12 to 48 months showed satisfactory healing without complications. Percutaneous injection of autologous bone marrow appears to be an effective treatment for active simple bone cysts

We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect. The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow. In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks. Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation. The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis

In a post-mortem study, we compared subjects with metal implants with and without visible wear with an age-matched control group to determine the extent and effects of dissemination of wear debris. In subjects with stainless-steel and cobalt-chrome prostheses metal was found in local and distant lymph nodes, bone marrow, liver and spleen. The levels were highest in subjects with loose, worn joint prostheses and the main source of the debris was the matt coating. Metal levels were also raised in subjects with implants without visible wear and, to a less extent, in those with dynamic hip screws. Necrosis of lymph nodes was seen in those cases with the most wear, and potential damage to more distant organs such as the bone marrow, liver and spleen in the long term cannot be discounted. The consequences for the immune system and the role of metal dissemination in the possible induction of neoplasia are discussed

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

Aims

Hip arthroscopy (HA) has become the treatment of choice for femoroacetabular impingement (FAI). However, less favourable outcomes following arthroscopic surgery are expected in patients with severe chondral lesions. The aim of this study was to assess the outcomes of HA in patients with FAI and associated chondral lesions, classified according to the Outerbridge system.

We describe the treatment by subperiosteal resection of an aneurysmal bone cyst in the distal fibula in eight patients and highlight the role of the periosteum in the regeneration of bone defects. The mean age of the patients was 13.5 years (12 to 17). Seven had an open growth plate. The mean size of the resected specimen was 5.12 cm (3.5 to 8.0). None of the patients received instillation of bone marrow, autogenous bone graft, allograft or any synthetic bone substitutes. All had complete regeneration of the bone defect within three to nine months, with no joint instability or recurrence. The mean length of follow-up was 11.5 years (2 to 18). At the final follow-up there was no difference in the range of movement, alignment or stability of the ankle when compared with the opposite side. The periosteum played a major role in the complete filling of the bone defects and avoided the morbidity of other techniques

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility

Metal meshes are used in revision surgery of the hip to contain impacted bone grafts in cases with cortical or calcar defects in order to provide rotational stability to the stem. However, the viability of bone allografts under these metal meshes has been uncertain. We describe the histological appearances of biopsies obtained from impacted bone allografts to the calcar contained by a metal mesh in two femoral reconstructions which needed further surgery at 24 and 33 months after the revision procedure. A line of osteoid and viable new bone was observed on the surface of necrotic trabeculae. Active bone marrow between these trabeculae showed necrotic areas in some medullary spaces with reparative fibrous tissue and isolated reactive lymphocytes. This is interpreted as reparative changes after revascularisation of the cancellous allografts. These pathological findings are similar to those reported in allografts contained by cortical host bone and support the hypothesis that incorporation of morcellised bone under metal meshes is not affected by these devices

Aternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced mount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells

Systemic mastocytosis is a rare condition that often involves the bone marrow. We report the case of a patient with systemic mastocytosis who underwent total hip replacement. Technical difficulties encountered during the procedure included a narrow medullary canal and abnormally hard bone, later confirmed by laboratory measurements. Follow-up at five years showed a good clinical and radiological outcome

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment

1. Previous immunological studies have shown that homografts of fresh marrow-free iliac bone are only weakly, if at all, antigenic. 2. In view of this finding an attempt was made to produce a foreign bone graft capable of forming new bone as readily as an iliac autograft by the following method. Living cells of high osteogenic potential and of autologous type were introduced into the graft by combining homologous fresh marrow-free iliac bone with the animal's own red marrow to form a fresh composite homograft-autograft of cancellous bone. 3. Such fresh composite homograft-autografts were inserted into a muscular site in Wistar rats and removed for microscopical examination at intervals of one to seven days and at two, six and twelve weeks after transplantation. 4. It is found that bone and marrow together as a fresh composite homograft-autograft form considerably more new bone than do either of the components of the graft transplanted separately. Homografts of fresh marrow-free iliac bone form, in general, a small amount of early phase and late phase new bone. Autografts of red marrow transplanted alone to a muscular site formed new bone in thirteen to thirty experiments (43 per cent). 5. The stimulus to osteogenesis, and the cellular source of osteoblasts, in marrow autografts is discussed in the light of present knowledge. The concept is suggested that after its transplantation there develops in marrow an inductive system leading to osteoblastic differentiation and bone formation. It is proposed that the necrosis of a portion of a marrow graft liberates osteogenic substances which are taken up by primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of the marrow which are induced, thereby, to differentiate as osteoblasts. 6. The cellular source of osteoblasts in a fresh composite homograft-autograft of cancellous bone is discussed. It is deduced that the new bone is derived mainly from the contained marrow of the graft, by mechanisms similar to those leading to osteoblastic differentiation in transplanted autografts of marrow. 7. The stimulus to the greater formation of new bone by fresh composite autograft-homografts than by autografts of marrow transplanted alone is discussed. Two explanations are suggested: 1) a more extensive necrosis of marrow in a composite homograft-autograft than in marrow transplanted alone; and 2) an inductive effect of bone upon marrow. 8. The new bone formed by autografts of fresh marrow-containing iliac bone, it is concluded, is derived not only from osteoblasts on the surfaces of the grafted bone but also from primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of its marrow. 9. Mechanisms which may play a role in the histogenesis of woven bone are discussed. 10. The significance of the relation of bone and marrow is considered briefly in the light of knowledge concerning the venous patterns of bone and marrow

Aims

The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI.

Aims

Osteonecrosis (ON) can cause considerable morbidity in young people who undergo treatment for acute lymphoblastic leukaemia (ALL). The aims of this study were to determine the operations undertaken for ON in this population in the UK, along with the timing of these operations and any sequential procedures that are used in different joints. We also explored the outcomes of those patients treated by core decompression (CD), and compared this with conservative management, in both the pre- or post-collapse stages of ON.

Magnetic resonance images (MRI) were obtained of 10 healthy volunteers and 70 patients suffering from various orthopaedic disorders. Selected images of soft tissue, joint, bone and spinal abnormalities are presented and their interpretation is described. Although we have been using MRI for only a very short time, it is already possible to see its advantages: it provides good images of soft-tissues, detailed pictures of bone marrow, and excellent visualisation of the spine and spinal cord. The decision-making process in surgical procedures will in the future be influenced by this technique

The effects on articular cartilage of continuous and intermittent excessive pressures have been studied in the knees of rabbits. Severe degenerative changes in the cartilage were observed; these resembled the typical lesions seen in osteoarthritis in man. They included fibrillation of cartilage, death of chondrocytes, eburnation of joint surfaces, sclerosis of bone and the production of "bone cysts." Regeneration of cartilage was common and it was brought about either by the deeply situated chondrocytes which had escaped death or by metaplasia of young connective tissue cells of the bone marrow

We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential

We have evaluated bone-marrow activity in the proximal femur of patients with corticosteroid-induced osteonecrosis and compared it with that of patients with osteonecrosis related to sickle-cell disease and with a control group without osteonecrosis. Bone marrow was obtained by puncture of the femoral head outside the area of necrosis and in the intertrochanteric region. The activity of stromal cells was assessed by culturing fibroblast colony-forming units (FCFUs). We found a decrease in the number of FCFUs outside the area of osteonecrosis in the upper end of the femur of patients with corticosteroid-induced osteonecrosis compared with the other groups. We suggest that glucocorticosteroids may also have an adverse effect on bone by decreasing the number of progenitors. The possible relevance of this finding to osteonecrosis is discussed

We examined specimens of hydroxyapatite-coated femoral prostheses from four patients who had died within nine months of implantation for fractured neck of femur. Histology showed newly formed immature bone overlying the hydroxyapatite coating with new trabeculae bridging to the endosteal bone layer. In the diaphysis, where there had been contact between the hydroxyapatite and the cortex, there was dense, firmly anchored bone with an haversian architecture. In other places the newly formed bone had a trabecular structure, containing bone marrow tissue with normal cellularity. It appeared that biological osseointegration had taken place

We studied the effects of high-dose irradiation on the mechanical properties and morphology of cortical bone in rabbits for 52 weeks after a single dose of 50 Gy of electron-beam to the tibia. After four weeks, the bending strength of the irradiated bone was unchanged, but at 12 weeks, the strength had decreased significantly. At 24 weeks after irradiation mean strength was less than half of controls but by 52 weeks there was a tendency toward recovery. Similar, synchronous changes of damage and recovery were seen in cortical porosity, haematopoietic cells in the bone marrow and endosteal new bone formation

1. Primary reticulum-cell sarcoma of bone arises from the reticulo-histiocytic elements of bone marrow. 2. The authors have studied ten cases of primary reticulum-cell sarcoma of bone, and have compared the clinical, pathological and radiographic features with those of thirty-five cases of Ewing's sarcoma. 3. In their microscopic studies Hortega's staining techniques were used in addition to orthodox methods. 4. There are histological differences between a reticulum-cell sarcoma and Ewing's sarcoma. 5. Certain clinical and radiographic features help the differentiation between the two tumours. 6. The progress and treatment of the reticulum-cell sarcoma are reviewed in detail

The internal pressure of simple bone cysts was found to be slightly higher than the normal pressure of the bone marrow in the contralateral limb. The pressure within the cyst was measured during drilling with a Kirschner wire; it gradually decreased as the number of drill-holes increased. The PO2 of the cyst fluid was markedly lower than that of either venous or arterial blood measured synchronously. It is suggested that venous obstruction in the bone is the likely cause of these cysts. Seven patients with simple bone cysts were treated by the multiple drill-hole method, and the clinical outcome was excellent. Multiple drilling may prove to be the treatment of choice for simple bone cysts in the younger patient, as it presents fewer hazards than other procedures

We have reviewed 41 patients with pustulotic arthro-osteopathy (PAO), all having both the typical skin rash of pustulosis palmaris et plantaris and bone lesions. The most common bones affected were the clavicle, sternum and ribs. Changes in the clavicle started, not as an enthesopathy, but with periosteal bone formation, indicative of a bone marrow disorder. About 30% of the patients also had lesions in the spine, sacroiliac region or the peripheral joints. Bone and joint lesions followed a variable and intermittent clinical course over a long period of time. Biopsies in eight cases showed similar inflammatory changes in skin, bone and synovium, with infiltration of lymphocytes and polymorphonuclear leucocytes. This suggests that there is a common pathogenesis in the three tissues

The passage of technetium-labelled methylene diphosphonate (99mTc-MDP) across rat bone was examined by autoradiography. The autoradiographs showed that shortly after an injection of the bone-seeking agent there was activity outside the bone, within the bone marrow and also adjacent to the highly vascular epiphysial plate; the distribution of the isotope in the incubated bone appeared to be non-uniform, a high concentration being seen adjacent to the epiphysial plate and also on the surfaces of the bone. The evidence suggested that a two-fold mechanism resulted in the uneven distribution of 99mTc-MDP. The first factor probably represented the regional distribution of blood flow with a transcapillary movement of the tracer from the capillary bed to the extravascular space; the subsequent incorporation of the tracer into bone appeared to depend on the nature of the bone matrix

We studied nine patients who had had a transtrochanteric anterior rotational osteotomy, as developed by Sugioka, for osteonecrosis of the femoral head. At a mean of 2.5 years after the initial operation we carried out a histological study of the previously necrotic femoral head which had not shown collapse of the new primary weight-bearing site. In seven joints, there was proliferation of fibrous tissue in the dead trabeculae with vascular ingrowth. New bone covering dead trabeculae created the characteristic appearance of ‘creeping substitution’. However, these changes were limited and did not extend over the entire necrotic area. Dead bone remained in all the cases. In the other two heads we did not observe proliferation of fibrous tissue or vascular ingrowth, only dead trabeculae and dead bone marrow