Objectives. Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature. Methods. In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1

Objectives. Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors. Methods. We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used. Results. As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions. Conclusions. It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury. Cite this article: Bone Joint Res 2015;4:170–175

1. The present study is an attempt to analyse and apportion significance to the role of inductive mechanisms in bone transplantation. 2. The experimental model used in the present work is that of the composite homograftautograft of cancellous bone previously described (Burwell 1964a). 3. Iliac bone was removed from hooded rats and washed free from its marrow. The bone was then treated by various physical and chemical methods (some of which have been used by other workers to prepare bank bone), namely freezing (-20 degrees Centigrade, -79 degrees Centigrade, -196 degrees Centigrade); freeze-drying (without sterilisation, sterilisation with high energy radiation, sterilisation with ß-propiolactone); decalcification (with E.D.T.A.); irradiation (in the frozen state at a dose of 4 million rads); boiling in water; immersion in merthiolate solution; extraction of organic components with ethylenediamine: and calcining at 660 degrees Centigrade. The treated bone was then impregnated with fresh autologous marrow procured from the femoral shaft of the Wistar rat into which the treated composite graft was to be implanted. The grafts were inserted intramuscularly and removed for study after two, six and twelve weeks. 4. After fixation, serial sectioning and staining, each graft was examined microscopically, and the proportion of new bone/grafted bone scored using an arbitrary scale (0-4). The mean score (and the standard error of the mean score) was then plotted for each treated composite graft and also for several types of fresh cancellous bone grafts. 5. It was found (Fig. 2) that the various treated composite grafts formed a spectrum of bone-forming capacities–the maximum scores being attained by the frozen and freeze-dried composite grafts, the lowest scores by the "deproteinised" composite grafts. 6. The reasons for these differences are discussed. It is concluded that cancellous bone, after transplantation, has the property to induce and promote osteogenesis in marrow; moreover, that this property is contained in the organic components of bone. 7. From the standpoint of inductive mechanisms, cancellous bone treated by freezing or freeze-drying seems to be the most suitable devitalised bone for grafting purposes; bone which has been boiled or merthiolated less suitable; and "deproteinised" bone the least suitable. 8. Freeze-dried bone sterilised physically (by high energy radiation) or chemically (by ß-propiolactone) did not form significantly less new bone than did freeze-dried bone which had not been sterilised. 9. Remodelling mechanisms in bone transplantation are briefly discussed and attention drawn to the deficiencies of present knowledge. The quantitative studies of other workers have indicated that freeze-dried bone may be more rapidly remodelled than is frozen bone. 10. The importance of fresh red marrow in promoting osteogenesis in bone transplantation and in the healing of certain fractures, is emphasised. It seems likely that the interrelationship of bone and marrow revealed by experiment has wider significance not only in health and in response to injury but also in causation of certain idiopathic bone disorders

Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis

A total of 20 patients with a depressed fracture of the lateral tibial plateau (Schatzker II or III) who would undergo open reduction and internal fixation were randomised to have the metaphyseal void in the bone filled with either porous titanium granules or autograft bone. Radiographs were undertaken within one week, after six weeks, three months, six months, and after 12 months. The primary outcome measure was recurrent depression of the joint surface: a secondary outcome was the duration of surgery. The risk of recurrent depression of the joint surface was lower (p < 0.001) and the operating time less (p < 0.002) when titanium granules were used. The indication is that it is therefore beneficial to use porous titanium granules than autograft bone to fill the void created by reducing a depressed fracture of the lateral tibial plateau. There is no donor site morbidity, the operating time is shorter and the risk of recurrent depression of the articular surface is less. . Cite this article: Bone Joint J 2015; 97-B:836–41

We compared peri-prosthetic bone mineral density between identical cemented and cementless LCS rotating platform total knee arthroplasties. Two matched cohorts had dual energy x-ray absorptiometry scans two years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic bone mineral density. The knee that was not operated on was also scanned to enable the calculation of a relative bone mineral density difference. Oxford Knee and American Knee Society scores were comparable in the two cohorts. Statistical analysis revealed no significant difference in absolute, or relative peri-prosthetic bone mineral density with respect to the method of fixation. However, the femoral peri-prosthetic bone mineral density and relative bone mineral density difference were significantly decreased, irrespective of the method of fixation, particularly in the anterior distal portion of the femur, with a mean reduction in relative bone mineral density difference of 27%. There was no difference in clinical outcome between the cemented and cementless LCS total knee arthroplasty. However, both produce stress-shielding around the femoral implants. This leads us to question the use of more expensive cementless total knee components

1. An immunological examination of the sera of thirty rabbits which had received primary and secondary homografts of cancellous bone into a subcutaneous site did not reveal the presence of circulating precipitins, haemagglutinins or passive haemagglutinins. These findings are consistent with the observations of Bonfiglio and his colleagues (1955). 2. Electrophoretic examination of the serum of four rabbits receiving primary and secondary homografts of bone into an intramuscular site did not reveal any change in the serum protein fractions. 3. A search for auto-antibodies produced by primary and secondary autografts of cancellous bone was unsuccessful in fifteen rabbits. 4. The multiple injections of saline extracts of bone into four rabbits did not evoke the production of demonstrable circulating antibodies, results which are in accord with the findings of Bonfiglio and colleagues (1955) and Curtiss and colleagues (1959). 5. For the first time the production of classical antibodies in response to injections of extracts of heterologous bone has been recorded. The repeated injections of a saline extract of rabbit bone intraperitoneally into ten mice produced demonstrable precipitins and passive haemagglutinins both to protein and polysaccharide fractions present in the bone extracts. 6. Knowledge concerning the production of humoral antibodies to transplants and extracts of bone has been reviewed

We investigated whether the presence of a pathological fracture increased the risk of local recurrence in patients with a giant cell tumour (GCT) of bone. We also assessed if curettage is still an appropriate form of treatment in the presence of a pathological fracture. We conducted a comprehensive review and meta-analysis of papers which reported outcomes in patients with a GCT with and without a pathological fracture at presentation. We computed the odds ratio (OR) of local recurrence in those with and without a pathological fracture. . We selected 19 eligible papers for final analysis. This included 3215 patients, of whom 580 (18.0%) had a pathological fracture. The pooled OR for local recurrence between patients with and without a pathological fracture was 1.05 (95% confidence interval (CI) 0.66 to 1.67, p = 0.854). Amongst the subgroup of patients who were treated with curettage, the pooled OR for local recurrence was 1.23 (95% CI 0.75 to 2.01, p = 0.417). . A post hoc sample size calculation showed adequate power for both comparisons. . There is no difference in local recurrence rates between patients who have a GCT of bone with and without a pathological fracture at the time of presentation. The presence of a pathological fracture should not preclude the decision to perform curettage as carefully selected patients who undergo curettage can have similar outcomes in terms of local recurrence to those without such a fracture. Cite this article: Bone Joint J 2015;97-B:1566–71

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (. sd. 15.7) to 124.6 (. sd. 46.2) in periosteal bone for gentamicin and 31.9 (. sd. 8.9) in endosteal and 2.9 (. sd. 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds

Objectives. To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches. Methods. In our previous work, we reported changes to intra-operative blood flow during hip resurfacing arthroplasty comparing two surgical approaches. In this study, we report the vascularity and the metabolic bone function in the proximal femur in these same patients at one year after the surgery. Vascularity and bone function was assessed using scintigraphic techniques. Of the 13 patients who agreed to take part, eight had their arthroplasty through a posterior approach and five through a trochanteric-flip approach. Results. One year after surgery, we found no difference in the vascularity (vascular phase) and metabolic bone function (delayed phase) at the junction of the femoral head/neck between the two groups of patients. Higher radiopharmaceutical uptake was found in the region of the greater trochanter in the trochanteric-flip group, related to the healing osteotomy. Conclusions. Our findings using scintigraphic techniques suggest that the greater intra-operative reduction in blood flow to the junction of the femoral head/neck, which is seen with the posterior approach compared with trochanteric flip, does not result in any difference in vascularity or metabolic bone function one year after surgery

Permanent growth arrest of the longer bone is an option in the treatment of minor leg-length discrepancies. The use of a tension band plating technique to produce a temporary epiphysiodesis is appealing as it avoids the need for accurate timing of the procedure in relation to remaining growth. We performed an animal study to establish if control of growth in a long bone is possible with tension band plating. Animals (pigs) were randomised to temporary epiphysiodesis on either the right or left tibia. Implants were removed after ten weeks. Both tibiae were examined using MRI at baseline, and after ten and 15 weeks. The median interphyseal distance was significantly shorter on the treated tibiae after both ten weeks (p = 0.04) and 15 weeks (p = 0.04). On T. 1. -weighted images the metaphyseal water content was significantly reduced after ten weeks on the treated side (p = 0.04) but returned to values comparable with the untreated side at 15 weeks (p = 0.14). Return of growth was observed in all animals after removal of implants. Temporary epiphysiodesis can be obtained using tension band plating. The technique is not yet in common clinical practice but might avoid the need for the accurate timing of epiphysiodesis. Cite this article: Bone Joint J 2013;95-B:855–60

We retrospectively reviewed 40 hips in 36 patients who had undergone acetabular reconstruction using a titanium Kerboull-type acetabular reinforcement device with bone allografts between May 2001 and April 2006. Impacted bone allografts were used for the management of American Academy of Orthopaedic Surgeons Type II defects in 17 hips, and bulk bone allografts together with impacted allografts were used for the management of Type III defects in 23 hips. A total of five hips showed radiological failure at a mean follow-up of 6.7 years (4.5 to 9.3), two of which were infected. The mean pre-operative Merle d’Aubigné score was 10 (5 to 15) vs 13.6 (9 to 18) at the latest follow-up. The Kaplan-Meier survival rate at ten years, calculated using radiological failure or revision of the acetabular component for any reason as the endpoint, was 87% (95% confidence interval 76.3 to 97.7). A separate experimental analysis of the mechanical properties of the device and the load-displacement properties of bone grafts showed that a structurally hard allograft resected from femoral heads of patients with osteoarthritis should be preferentially used in any type of defect. If impacted bone allografts were used, a bone graft thickness of < 25 mm was acceptable in Type II defects. This clinical study indicates that revision total hip replacement using the Kerboull-type acetabular reinforcement device with bone allografts yielded satisfactory mid-term results

1. The bone cysts of osteoarthritis are found in relation to defects in the watertight layer between the joint space and the cancellous bone; these defects are sometimes obvious openings, but more often they are openings closed by fibrous tissue, fibrocartilage or new bone. The small cysts lie close to the surface. Their rounded outlines suggest the agency of fluid pressure in their formation, and the fluid and cells found in the cysts are compatible with origin in the joint space and articular cartilage. 2. The hypothesis is advanced that the cysts are formed by the intrusion of synovial fluid under pressure into the substance of the bone, and the sclerosis around by displacement of the trabeculae and their reinforcement by new bone. 3. The objections to the hypothesis that the cysts represent a primary degeneration in the bone are discussed

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

We report the results of the treatment of nine children with an aneurysmal bone cyst of the distal fibula (seven cysts were juxtaphyseal, and two metaphyseal). The mean age of the children was 10 years and 3 months (7 years and 4 months to 12 years and 9 months). All had open physes. All cysts were active and in seven cases substituted and expanded the entire width of the bone (type-2 lesions). The mean longitudinal extension was 5.7 cm (3 to 10). The presenting symptoms were pain, swelling and pathological fracture. Moderate fibular shortening was evident in one patient. In six patients curettage was performed, using phenol as adjuvant in three. Three with juxtaphyseal lesions underwent resection. A graft from the contralateral fibula (one case) and allografts (two cases) were positioned at the edge of the physis for reconstruction. The mean follow-up was 11.6 years (3.1 to 27.5). There was no recurrence. At the final follow-up there was no significant difference in the American Orthopaedic Foot and Ankle Society scores (excellent/good in all cases) and in growth disturbance, alignment, stability and bone reconstitution, but in the resection group the number of operations, including removal of hardware, complications (two minor) and time of immobilisation/orthosis, were increased. Movement of the ankle was restricted in one patient. The potential risks in the management of these lesions include recurrence, physeal injury, instability of the ankle and hardware and graft complications. Although resection is effective it should be reserved for aggressive or recurrent juxtaphyseal lesions

We present the long-term outcome, at a median of 18 years (12.8 to 23.5) of open posterior bone block stabilisation for recurrent posterior instability of the shoulder in a heterogenous group of 11 patients previously reported on in 2001 at a median follow-up of six years. We found that five (45%) would not have chosen the operation again, and that four (36%) had further posterior dislocation. Clinical outcome was significantly worse after 18 years than after six years of follow-up (median Rowe score of 60 versus 90 (p = 0.027)). The median Western Ontario Shoulder Index was 60% (37% to 100%) at 18 years’ follow-up, which is a moderate score. At the time of surgery four (36%) had glenohumeral radiological osteoarthritis, which was present in all after 18 years. This study showed poor long-term results of the posterior bone block procedure for posterior instability and a high rate of glenohumeral osteoarthritis although three patients with post-traumatic instability were pleased with the result of their operations

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

Introduction. The objective of this study was to determine if a synthetic bone substitute would provide results similar to bone from osteoporotic femoral heads during in vitro testing with orthopaedic implants. If the synthetic material could produce results similar to those of the osteoporotic bone, it could reduce or eliminate the need for testing of implants on bone. Methods. Pushout studies were performed with the dynamic hip screw (DHS) and the DHS Blade in both cadaveric femoral heads and artificial bone substitutes in the form of polyurethane foam blocks of different density. The pushout studies were performed as a means of comparing the force displacement curves produced by each implant within each material. Results. The results demonstrated that test material with a density of 0.16 g/cm. 3. (block A) produced qualitatively similar force displacement curves for the DHS and qualitatively and quantitatively similar force displacement curves for the DHS Blade, whereas the test material with a density of 0.08 g/cm. 3. (block B) did not produce results that were predictive of those recorded within the osteoporotic cadaveric femoral heads. Conclusion. This study demonstrates that synthetic material with a density of 0.16 g/cm. 3. can provide a good substitute for cadaveric osteoporotic femoral heads in the testing of implants. However we do recognise that no synthetic material can be considered as a definitive substitute for bone, therefore studies performed with artificial bone substrates may need to be validated by further testing with a small bone sample in order to produce conclusive results

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105–116

Objectives. We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis. Methods. The MEDLINE, EMBASE and Cochrane Library databases were searched using defined search terms. The primary outcome measure was spinal fusion, assessed as success or failure in accordance with radiograph, MRI or CT scan review at 24-month follow-up. The secondary outcome measure was time to fusion. Results. A total of six studies (three prospective and three retrospective) reporting on the use of BMP2 met the inclusion criteria (203 patients). Of these, four provided a comparison of BMP2 and bone graft whereas the other two solely investigated the use of BMP2. The primary outcome was seen in 92.3% (108/117) of patients following surgery with BMP2. Although none of the studies showed superiority of BMP2 to bone graft for fusion, its use was associated with a statistically quicker time to achieving fusion. BMP2 did not appear to increase the risk of complication. Conclusion. The use of BMP2 is both safe and effective within the revision setting, ideally in cases where bone graft is unavailable or undesirable. Further research is required to define its optimum role. Cite this article: Mr P. Bodalia. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Joint Res 2016;5:145–152. DOI: 10.1302/2046-3758.54.2000418