We performed a biomechanical study to compare the augmentation of isolated fractured vertebral bodies using two different bone tamps. Compression fractures were created in 21 vertebral bodies harvested from red deer after determining their initial strength and stiffness, which was then assessed after standardised bipedicular vertebral augmentation using a balloon or an expandable polymer bone tamp. The median strength and stiffness of the balloon bone tamp group was 6.71 kN (. sd. 2.71) and 1.885 kN/mm (. sd. 0.340), respectively, versus 7.36 kN (. sd. 3.43) and 1.882 kN/mm (. sd. 0.868) in the polymer bone tamp group. The strength and stiffness tended to be greater in the polymer bone tamp group than in the balloon bone tamp group, but this difference was not statistically significant (strength p > 0.8, and stiffness p = 0.4)

1. Experiments to examine the antigenicity of homologous bone tissues in rats are reported. The tissues studied included fresh marrow-free cortical bone blocks and chips, fresh, boiled, frozen and freeze-dried marrow-containing iliac bone, fresh iliac bone devoid of marrow, and fresh red marrow. 2. The various tissues were transplanted from hooded to Wistar rats. Three weeks later a skin graft from each donor was transplanted to its respective host to detect the presence of transplantation immunity, which was indicated by the early rejection of the skin graft. 3. Homografts of fresh cortical bone evoked transplantation immunity indicating that it contained transplantation antigens which were also in the skin. 4. Homografts of fresh marrow-containing iliac bone also evoked transplantation immunity, which was shown to be caused by the red marrow. 5. Fresh iliac homografts devoid of marrow did not elicit transplantation immunity. This suggests that iliac bone tissue may not contain transplantation antigens or that the small amount of iliac bone inserted was insufficient. 6. Microscopy of the grafts, removed after three weeks, showed that the inflammatory infiltrations around the bone homografts and autografts were not very different, but that the amount of new bone formed was different. The autografts produced a lot of new bone, the homografts only a little. 7. It is suggested that the immune response evoked in the host by the foreign graft impairs the formation of new bone by fresh homografts of cortical blocks, cortical chips and marrow-containing iliac bone. 8. The impairment of new bone formation by homografts of marrow-free iliac bone is discussed. Such bone grafts fail to evoke detectable transplantation immunity. Why these grafts do not form more new homologous bone than the other homografts studied, is not clear. 9. Homografts of boiled and frozen iliac bone do not evoke any detectable change in the sensitivity of the host to donor tissue. 10. Homografts of freeze-dried marrow-containing iliac bone elicit a slight but significant prolongation of the survival of skin homografts. The implication, in terms of modern immunological theory, is that in such grafts certain tissue antigens still persist

1. The antigenicity of homologous cortical and cancellous bone has been investigated in eighty-four rabbits. 2. The primary immune responses which occur in lymph nodes draining homografts of fresh tissues (Burwell and Gowland 1961, 1962) have been used as a histological indicator of the antigenicity of fresh homologous cortical bone freed from soft tissues. 3. The secondary immune responses which occur in lymph nodes draining homografts of fresh marrow-containing iliac bone (Burwell 1962a, b) have been used also as a histological indicator of the antigenicity of homografts of 1) fresh cortical bone freed from soft tissues, 2) fresh marrow-free iliac bone, and 3) mairow-containing iliac bone treated by boiling, freezi ng, freeze-drying and merthiolate solution. 4. It is found that whereas fresh homologous cortical bone fails usually to produce cytological evidence of a primary response in the regional lymph nodes, fresh homologous cortical bone chips inserted into the drainage areas of lymph nodes sensitised previously to donor ..tissue evoke constantly cytological evidence of a secondary response. 5. Fresh homologous marrow-free iliac bone inserted into the drainage areas of lymph nodes sensitised previously to donor tissue does not produce detectable evidence of a secondary response. 6. Homografts of boiled marrow-containing iliac bone do not elicit a secondary response in lymph nodes previously sensitised to donor tissue. 7. Previous work has shown that homografts of frozen (–20 degrees Centigrade) marrow-containing iliac bone do not evoke a primary response in lymph nodes draining such grafts. In the present work it is shown that similar frozen homografts inserted into the drainage areas of lymph nodes previously sensitised to donor tissue evoked a secondary response in three of six lymph nodes. 8. Homografts offreeze-dried marrow-containing iliac bone fail usually to evoke a secondary response in lymph nodes sensitised to donor tissue. 9. Homografts of marrow-containing iliac bone treated by immersion in merthiolate solution before being inserted into the drainage areas of lymph nodes previously sensitised to tissue from the donor elicited a secondary response in three of five lymph nodes. 10. Knowledge concerning the antigenicity offresh and treated homologous bone is discussed in the light of recent work

Intermittent treatment with parathyroid hormone (PTH) has an anabolic effect on both intact cancellous and cortical bone. Very little is known about the effect of the administration of PTH on the healing of fractures or the incorporation of orthopaedic implants. We have investigated the spontaneous ingrowth of callus and the formation of bone in a titanium chamber implanted at the medioproximal aspect of the tibial metaphysis of the rat. Four groups of ten male rats weighing approximately 350 g were injected with human PTH (1-34) in a dosage of 0, 15, 60 or 240 μg/kg/day, respectively, for 42 days from the day of implantation of the chamber. During the observation period the chamber became only partly filled with callus and bone and no difference in ingrowth distance into the chamber was found between the groups. The cancellous density was increased by 90%, 132% and 173% in the groups given PTH in a dosage of 15, 60 or 240 μg/kg/day, respectively. There was a linear correlation between bone density and the log PTH doses (r. 2. = 0.6). Our findings suggest that treatment with PTH may have a potential for enhancement of the incorporation of orthopaedic implants as well as a beneficial effect on the healing of fractures when it is given in low dosages

Objectives. Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Methods. Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Results. Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. Conclusion. These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures. Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620–628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2

We treated 26 patients with 27 aneurysmal bone cysts by curettage and cryotherapy and evaluated local tumour control, complications and functional outcome. The mean follow-up time was 47 months (19 to154). There was local recurrence in one patient. Two patients developed deep wound infections and one had a postoperative fracture. We compared our results with previous reports in which several different methods of treatment had been used and concluded that curettage with adjuvant cryotherapy had similar results to those of marginal resection, and that no major bony reconstruction was required. We recommend the use of cryotherapy as an adjuvant to the surgical treatment of aneurysmal bone cysts. It provides local tumour control. Combination with bone grafting achieved consolidation of the lesion in all our patients

Aims. Accurate estimations of the risk of fracture due to metastatic bone disease in the femur is essential in order to avoid both under-treatment and over-treatment of patients with an impending pathological fracture. The purpose of the current retrospective in vivo study was to use CT-based finite element analyses (CTFEA) to identify a clear quantitative differentiating factor between patients who are at imminent risk of fracturing their femur and those who are not, and to identify the exact location of maximal weakness where the fracture is most likely to occur. Methods. Data were collected on 82 patients with femoral metastatic bone disease, 41 of whom did not undergo prophylactic fixation. A total of 15 had a pathological fracture within six months following the CT scan, and 26 were fracture-free during the five months following the scan. The Mirels score and strain fold ratio (SFR) based on CTFEA was computed for all patients. A SFR value of 1.48 was used as the threshold for a pathological fracture. The sensitivity, specificity, positive, and negative predicted values for Mirels score and SFR predictions were computed for nine patients who fractured and 24 who did not, as well as a comparison of areas under the receiver operating characteristic curves (AUC of the ROC curves). Results. The sensitivity of SFR was 100% compared with 88% for the Mirels score, and the specificity of SFR was 67% compared with 38% for the Mirels score. The AUC was 0.905 for SFR compared with 0.578 for the Mirels score (p = 0.008). Conclusion. All the patients who sustained a pathological fracture of the femur had an SFR of > 1.48. CTFEA was far better at predicting the risk of fracture and its location accurately compared with the Mirels score. CTFEA is quick and automated and can be incorporated into the protocol of CT scanners. Cite this article: Bone Joint J 2020;102-B(5):638–645

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2

Aims. To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods. Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results. Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion. In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. Cite this article:Bone Joint Res. 2020;9(3):139–145

There have been conflicting reports on the effects of gamma irradiation on the material properties of cortical allograft bone. To investigate changes which result from the method of preparation, test samples must be produced with similar mechanical properties to minimise variations other than those resulting from treatment. We describe a new method for the comparative measurement of bone strength using standard bone samples. We used 233 samples from six cadavers to study the effects of irradiation at a standard dose (28 kGy) alone and combined with deep freezing. We also investigated the effects of varying the dose from 6.8 to 60 kGy (n = 132). None of the treatments had any effect on the elastic behaviour of the samples, but there was a reduction in strength to 64% of control values (p < 0.01) after irradiation with 28 kGy. There was also a dose-dependent reduction in strength and in the ability of the samples to absorb work before failure. We suggest that irradiation may cause an alteration in the bone matrix of allograft bone, but provided it is used in situations in which loading is within its elastic region, then failure should not occur

Aims. To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. Methods. Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. Results. MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. Conclusion. The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. Cite this article:Bone Joint Res. 2020;9(2):49–59

1. A series of experiments on adult rabbits was carried out in which a tendon was transplanted and embedded in a bony tunnel and traversed a joint after the manner of a tenodesis. 2. Histological observations were made on the reaction of surrounding bone and tendon at intervals over a period of 307 days. 3. The findings suggest that the buried tendon undergoes a process of progressive degeneration, and that host cells issuing from the adjacent bone marrow infiltrate and ultimately replace it by new tendon tissue. 4. The invading cells are believed to be derived, as a result of the provocative stimuli provided by the experiment, from primitive reticular cells of the haemopoietic tissue. 5. The tunnelled bone undergoes considerable remodelling and associated with this is the presence of a considerable number of osteoblasts and osteoclasts

Aims. The management of acetabular defects at the time of revision hip arthroplasty surgery is a challenge. This study presents the results of a long-term follow-up study of the use of irradiated allograft bone in acetabular reconstruction. Patients and Methods. Between 1990 and 2000, 123 hips in 110 patients underwent acetabular reconstruction for aseptic loosening, using impaction bone grafting with frozen, irradiated, and morsellized femoral heads and a cemented acetabular component. A total of 55 men and 55 women with a mean age of 64.3 years (26 to 97) at the time of revision surgery are included in this study. Results. At a mean follow-up of 16.9 years, there had been 23 revisions (18.7%), including ten for infection, eight for aseptic loosening, and three for dislocation. Of the 66 surviving hips (58 patients) that could be reassessed, 50 hips (42 patients; 75.6%) were still functioning satisfactorily. Union of the graft had occurred in all hips with a surviving implant. Survival analysis for all indications was 80.6% at 15 years (55 patients at risk, 95% confidence interval (CI) 71.1 to 87.2) and 73.7% at 20 years (eight patients at risk, 95% CI 61.6 to 82.5). Conclusion. Acetabular reconstruction using frozen, irradiated, and morsellized allograft bone and a cemented acetabular component is an effective method of treatment. It gives satisfactory long-term results and is comparable to other types of reconstruction. Cite this article: Bone Joint J 2018;100-B:1449–54

Objectives. MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results. MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion. In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562

Objectives. Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods. We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results. Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion. The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023

We describe a patient with insufficient bone regeneration of the tibia after bone transport over an intramedullary nail, in whom union was ultimately achieved after exchange nailing and intramedullary application of rh-bone morphogenetic protein-7 at the site of distraction

Aims. Loosening is a well-known complication in the fixation of fractures using devices such as locking plates or unilateral fixators. It is believed that high strains in the bone at the bone-screw interface can initiate loosening, which can result in infection, and further loosening. Here, we present a new theory of loosening of implants. The time-dependent response of bone subjected to loads results in interfacial deformations in the bone which accumulate with cyclical loading and thus accentuates loosening. Methods. We used an ‘ideal’ bone-screw system, in which the screw is subjected to cyclical lateral loads and trabecular bone is modelled as non-linear viscoelastic and non-linear viscoelastic-viscoplastic material, based on recent experiments, which we conducted. Results. We found that the interfacial deformation in the bone increases with the number of cycles, and the use of a non-linear viscoelastic-viscoplastic model results in larger deformations, some of which are irrecoverable. There is an apparent trend in which interfacial deformations increase with increasing porosity of bone. Conclusion. The developed time-dependent model of the mechanical behaviour of bone permits prediction of loosening due to cyclical loads, which has not been possible previously. Application of this model shows that implant loosening will be accentuated by cyclical loading due to physiological activities, and the risks of loosening are greater in osteoporotic patients. Cite this article: S. Xie, K. Manda, P. Pankaj. Time-dependent behaviour of bone accentuates loosening in the fixation of fractures using bone-screw systems. Bone Joint Res 2018;7:580–586. DOI: 10.1302/2046-3758.710.BJR-2018-0085.R1

1. The response of the first regional lymph node to a homograft of fresh iliac cancellous bone inserted subcutaneously into the rabbit's ear three weeks after the introduction of a similar graft from the same donor into the same ear has been investigated in thirty rabbits. Fifteen rabbits which received second-set autografts of cancellous bone have also been studied. 2. The insertion of second-set homografts of fresh marrow-containing cancellous bone evokes an immune secondary response in the lymph nodes draining the grafts. 3. The increase in weight of the first regional lymph nodes on the side receiving second-set homografts is more rapid and of greater magnitude than that of nodes draining first-set homografts of cancellous bone. Second-set autografts evoke weight changes in the draining nodes similar to those in nodes draining first-set autografts of cancellous bone. 4. The histological changes which occur in the lymph nodes draining the second-set homografts (secondary response) are described and compared with those occurring in lymph nodes draining first-set homografts of cancellous bone (primary response). 5. In the primary response the distribution of large and medium lymphoid cells is throughout an activated sector of the cortex of the lymph node (Burwell and Gowland 1961), but in the secondary response these cells are found peripherally within the activated sector of the node. In both the primary and the secondary responses large and medium lymphoid cells are found in the medullary trabeculae of the lymph nodes. 6. The differences between the primary response of lymph nodes draining a tissue homograft (cancellous bone) and the primary response of lymph nodes draining classical antigens, and reported by other workers, are described. 7. Knowledge concerning the inflammatory response in the tissues of the host surrounding homografts of fresh cortical and cancellous bone implanted into animals previously sensitised to tissue from the respective donor is reviewed. 8. The late phase of new bone formation by homografts of fresh cancellous bone is discussed in the light of immunological studies

Aims. Antibiotic-loaded bone cements (ALBCs) may offer early protection against the formation of bacterial biofilm after joint arthroplasty. Use in hip arthroplasty is widely accepted, but there is a lack of evidence in total knee arthroplasty (TKA). The objective of this study was to evaluate the use of ALBC in a large population of TKA patients. Materials and Methods. Data from the National Joint Registry (NJR) of England and Wales were obtained for all primary cemented TKAs between March 2003 and July 2016. Patient, implant, and surgical variables were analyzed. Cox proportional hazards models were used to assess the influence of ALBC on risk of revision. Body mass index (BMI) data were available in a subset of patients. Results. Of 731 214 TKAs, 15 295 (2.1%) were implanted with plain cement and 715 919 (97.9%) with ALBC. There were 13 391 revisions; 2391 were performed for infection. After adjusting for other variables, ALBC had a significantly lower risk of revision for any cause (hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; p < 0.001). ALBC was associated with a lower risk of revision for all aseptic causes (HR 0.85, 95% CI 0.77 to 0.95; p < 0.001) and revisions for infection (HR 0.84, 95% CI 0.67 to 1.01; p = 0.06). The results were similar when BMI was added into the model, and in a subanalysis where surgeons using only ALBC over the entire study period were excluded. Prosthesis survival at ten years for TKAs implanted with ALBC was 96.3% (95% CI 96.3 to 96.4) compared with 95.5% (95% CI 95.0 to 95.9) in those implanted with plain cement. On a population level, where 100 000 TKAs are performed annually, this difference represents 870 fewer revisions at ten years in the ALBC group. Conclusion. After adjusting for a range of variables, ALBC was associated with a significantly lower risk of revision in this registry-based study of an entire nation of primary cemented knee arthroplasties. Using ALBC does not appear to increase midterm implant failure rates. Cite this article: Bone Joint J 2019;101-B:1331–1347