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

1 . Fresh bone autografts to a muscle bed in the rat gave rise to vigorous new bone formation from about the fourth day. The graft took the form of a hollow ossicle with central bone marrow at eighteen days: it became progressively more regular in outline and was still present at six months. 2. Fresh bone homografts produced two separate phases of new bone formation–early and late. In the early phase non-lamellar woven bone appeared at about the fourth day, continued to grow until eight days, and subsequently died. It arose from osteogenic cells of the homograft. In the late phase, which developed in relation to a few grafts after four weeks, the new bone was lamellar in character, and remained closely applied to the graft surface. Evidence is presented that this bone arose by metaplasia of the host connective tissues at the graft site. There was a local inflammatory response to the bone homograft. 3. Both phases of homograft new bone formation were abolished if the animal was prepared by a skin homograft from the same donor four weeks before, but not if four months elapsed between the two grafting procedures. 4. Freeze-dried bone homografts did not give rise to the early phase of homograft new bone but produced a few examples of the late phase after five months. The inflammatory response was less intense with freeze-dried homografts than with fresh homografts. 5. Skin homografts three weeks after fresh bone homografts from the same donor underwent an early rejection at five to six days. 6. Skin homografts three weeks after freeze-dried bone homografts from the same donor had a mean survival time of twelve days, which was significantly longer than the mean survival time of l0·9 days in normal rats

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft. A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r. 2. = 0.867, p < 0.01) and also between its thickness (r. 2. = 0.826, p < 0.01) and bone mineral density (r. 2. = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378). We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone

1. The widespread deformities commonly associated with diaphysial aclasis have been studied in seventy-six patients. Apart from the adaptations of growth due to pressure by neighbouring exostoses, all the deformities of the tubular bones can be explained in terms of the same underlying factor–diminished length of the bones affected by the disease. 2. When the condition first manifests itself the future pattern of bone growth is completely unpredictable except in so far as it is known that the more actively growing ends of the long bones are the more severely affected in each case. It has also been shown in this series that, in general, the bones with the smallest cross-sectional area at the epiphysial plates (such as the ulna and the fibula) are the most severely shortened of all. 3. The cause of this disturbance of growth is still unknown, but there is an undoubted relationship between the presence of exostoses or thickening of the metaphysial region and shortening of the bone involved. 4. The phenomena of migrating exostoses and disappearing exostoses are also described and are shown to be examples of the normal process of bone modelling applied in special circumstances. 5. Although the importance of the cartilage-capped exostoses is not underestimated, it is hoped that this study will stimulate further work on what is probably the basic defect in this disease–namely, the disturbance of bone growth

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

Florid reactive periostitis is a pronounced periosteal reaction, usually affecting the hands and feet, for which there is no obvious cause. It is rare in children and in long bones. We report an unusual case of florid reactive periostitis in a ten-year-old girl that involved both bones of the forearm. The lesion resolved over a period of one year, leaving a residual exostosis. She developed a physeal bar in the distal ulna in the region of the lesion at one-year follow-up. This was thought to be a complication of the biopsy procedure and was treated by resection and proximal ulnar lengthening

We matched 78 patients with a loose cemented Charnley Elite Plus total hip replacement (THR) by age, gender, race, prosthesis and time from surgery with 49 patients with a well-fixed stable hip replacement, to determine if poor bone quality predisposes to loosening. Clinical, radiological, biomechanical and bone mineral density indicators of bone quality were assessed. Patients with loose replacements had more pain, were more likely to have presented with atrophic arthritis and to have a history of fragility fracture, narrower femoral cortices and lower peri-prosthetic or lumbar spine bone mineral density (all t-test, p < 0.01). They also tended to be smokers (chi-squared test, p = 0.08). Vitamin-D deficiency was common, but not significantly different between the two groups (t-test, p = 0.31). In this series of cemented hip replacements performed between 1994 and 1998, aseptic loosening was associated with poor bone quality. Patients with a THR should be screened for osteoporosis and have regular radiological surveillance

Objectives. To quantify and compare peri-acetabular bone mineral density (BMD) between a monoblock acetabular component using a metal-on-metal (MoM) bearing and a modular titanium shell with a polyethylene (PE) insert. The secondary outcome was to measure patient-reported clinical function. Methods. A total of 50 patients (25 per group) were randomised to MoM or metal-on-polyethlene (MoP). There were 27 women (11 MoM) and 23 men (14 MoM) with a mean age of 61.6 years (47.7 to 73.2). Measurements of peri-prosthetic acetabular and contralateral hip (covariate) BMD were performed at baseline and at one and two years’ follow-up. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC), University of California, Los Angeles (UCLA) activity score, Harris hip score, and RAND-36 were also completed at these intervals. Results. At two years, only zone 1 showed a loss in BMD (-2.5%) in MoM group compared with a gain in the MoP group (+2.2%). Zone 2 showed loss in both groups (-2.2% for MoM; -3.9% for MoP) and zones 3 and 4 a gain in both groups (+0.1% for MoM; +3.3% for MoP). No other between-group differences were detected. When adjusting for BMD of the contralateral hip, no differences in BMD were observed. The only significant differences in functional scores at two years were higher UCLA activity (7.3 (. sd. 1.2) vs 6.1 (. sd. 1.5); p = 0.01) and RAND-36 physical function (82.1 (. sd. 13.0) vs 64.5 (. sd. 26.4); p = 0.02) for MoM bearings versus MoP. One revision was performed in the MoM group, for aseptic acetabular loosening at 11 months. Conclusions. When controlling for systemic BMD, there were no significant differences between MoM and MoP groups in peri-acetabular BMD. However, increasing reports of adverse tissue reactions with large head MoM THR have restricted the use of the monoblock acetabular component to resurfacing only

We studied the bone mineral density (BMD) and the bone mineral content (BMC) of the proximal tibia in patients with a well-functioning uncemented Oxford medial compartment arthroplasty using the Lunar iDXA bone densitometer. Our hypothesis was that there would be decreased BMD and BMC adjacent to the tibial base plate and increased BMD and BMC at the tip of the keel. There were 79 consecutive patients (33 men, 46 women) with a mean age of 65 years (44 to 84) with a minimum two-year follow-up (mean 2.6 years (2.0 to 5.0)) after unilateral arthroplasty, who were scanned using a validated standard protocol where seven regions of interest (ROI) were examined and compared with the contralateral normal knee. All had well-functioning knees with a mean Oxford knee score of 43 (14 to 48) and mean Knee Society function score of 90 (20 to 100), showing a correlation with the increasing scores and higher BMC and BMD values in ROI 2 in the non-implanted knee relative to the implanted knee (p = 0.013 and p = 0.015, respectively). The absolute and percentage changes in BMD and BMC were decreased in all ROIs in the implanted knee compared with the non-implanted knee, but this did not reach statistical significance. Bone loss was markedly less than reported losses with total knee replacement. There was no significant association with side, although there was a tendency for the BMC to decrease with age in men. The BMC was less in the implanted side relative to the non-implanted side in men compared with women in ROI 2 (p = 0.027), ROI 3 (p = 0.049) and ROI 4 (p = 0.029). The uncemented Oxford medial compartment arthroplasty appears to allow relative preservation of the BMC and BMD of the proximal tibia, suggesting that the implant acts more physiologically than total knee replacement. Peri-prosthetic bone loss is an important factor in assessing long-term implant stability and survival, and the results of this study are encouraging for the long-term outcome of this arthroplasty. Cite this article: Bone Joint J 2013;95-B:1480–3

The major advantage of hip resurfacing is the decreased amount of bone resection compared with a standard total hip replacement. Fracture of the femoral neck is the most common early complication and poor bone quality is a major risk factor. We undertook a prospective consecutive case control study examining the effect of bone mineral density changes in patients undergoing hip resurfacing surgery. A total of 423 patients were recruited with a mean age of 54 years (24 to 87). Recruitment for this study was dependent on pre-operative bilateral femoral bone mineral density results not being osteoporotic. The operated and non-operated hips were assessed. Bone mineral density studies were repeated over a two-year period. The results showed no significant deterioration in the bone mineral density in the superolateral region in the femoral neck, during that period. These findings were in the presence of a markedly increased level of physical activity, as measured by the short-form 36 health survey physical function score

We undertook this retrospective study to determine the rate of recurrence and functional outcome after intralesional curettage for chondroblastoma of bone. The factors associated with aggressive behaviour of the tumour were also analysed. We reviewed 53 patients with histologically-proven chondroblastoma who were treated by intralesional curettage in our unit between 1974 and 2000. They were followed up for at least two years to a maximum of 27 years. Seven (13.2%) had a histologically-proven local recurrence. Three underwent a second intralesional curettage and had no further recurrence. Two had endoprosthetic replacement of the proximal humerus and two underwent below-knee amputation after aggressive local recurrence. One patient had the rare malignant metastatic chondroblastoma and eventually died. The mean Musculoskeletal Tumour Society functional score of the survivors was 94.2%. We conclude that meticulous intralesional curettage alone can achieve low rates of local recurrence and excellent long-term function

1. Experimental avascular necrosis of the femoral head was produced in rabbits and the histological and radiographic changes were compared. 2. Avascular bone which was not re-ossified or altered in any way showed no change in density to x-rays. 3. Areas of avascular bone which were being repaired by the formation of appositional new bone showed an absolute increase in density in the radiographs. This is apparently due to simple increase in bulk of bone to be penetrated by the x-ray beam. On this basis, increasing density in radiographs of bone suspected of being dead is a sign of increasing re-ossification rather than of increasing necrosis. 4. Re-ossification of dead bone occurred rapidly in the absence of simultaneous resorption of necrotic trabeculae. It is thus suggested that the term "creeping substitution" is misleading and does not reflect accurately the histological findings, at least as they occur in rabbits

Atypical cartilaginous tumours are usually treated by curettage. The purpose of this study was to show that radiofrequency ablation was an effective alternative treatment. . We enrolled 20 patients (two male, 18 female, mean age 56 years (36 to 72) in a proof-of-principle study. After inclusion, biopsy and radiofrequency ablation were performed, followed three months later by curettage and adjuvant phenolisation. The primary endpoint was the proportional necrosis in the retrieved material. Secondary endpoints were correlation with the findings on gadolinium enhanced MRI, functional outcome and complications. Our results show that 95% to 100% necrosis was obtained in 14 of the 20 patients. MRI had a 91% sensitivity and 67% specificity for detecting residual tumour after curettage. The mean functional outcome (MSTS) score six weeks after radiofrequency ablation was 27.1 (23 to 30) compared with 18.1 (12 to 25) after curettage (p < 0.001). No complications occurred after ablation, while two patients developed a pathological fracture after curettage. We have shown that radiofrequency ablation is capable of completely eradicating cartilaginous tumour cells in selective cases. MRI has a 91% sensitivity for detecting any residual tumour. Radiofrequency ablation can be performed on an outpatient basis allowing a rapid return to normal activities. If it can be made more effective, it has the potential to provide better local control, while improving functional outcome. Cite this article: Bone Joint J 2014;96-B:1540–5

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats. Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group. Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function

1. Cancellous bone cubes from calf and man were deproteinised with hydrogen peroxide and with ethylenediamine. 2. Long bones were removed aseptically from sheep, stored in the bone bank and used for cancellous homografts. 3. Holes were drilled in the upper part of the tibia or ulna or in the lower part of the femur of sheep. Some were left empty; others were filled with plugs of the deproteinised heterogenous bone, with autografts, or with homografts. 4. Histological appearances were studied after seventeen and thirty-six days. 5. At seventeen days repair was more advanced in the plugged holes; the biological result was better with the ethylenediamine-treated than with the peroxide-treated material. After thirty-six days repair was at an advanced stage. As much new bone had been deposited on the trabeculae of the deproteinised heterografts as on those of the homografts. 6. There was no evidence of metaplastic bone formation; new bone seemed to form from endosteal osteoblasts. 7. Certain clinical implications are briefly discussed

1. The effects of the insertion of pieces of fresh cancellous bone into the subcutaneous tissues of the ear upon lymph nodes and spleens have been investigated in seventy rabbits. 2. The main immunological response is found to occur in the first regional nodes draining the sites of insertion of homografts of bone, which show a considerable increase in weight compared with nodes draining autografts of bone. 3. An increased number of large and medium lymphoid cells occurs principally in the first regional node of the homografted animals, as Scothorne and McGregor (1955) observed using skin as the homografted tissue. 4. The large and medium lymphoid cell response is found in both the cortex and the medulla of the lymph nodes. In the cortex a sectoral distribution of the cellular response is observed and the name reactive cortex is given to these sectors. Evidence is presented to show that the sectoral pattern of reactivity is probably determined by the localised entry into the node of iso-antigens through lymphatic vessels draining the bed of the graft. 5. We have made a quantitative analysis of the large and medium lymphoid cell response in the reactive parts of the diffuse lymphoid tissue of the cortex. The mean maximal large and medium lymphoid cell response occurs five days after the insertion of bone homografts. 6. The origin and fate of the large and medium lymphoid cells and their role in the production of antibodies is reviewed in the light of recent work. 7. A correlation is made between the maximal production of large and medium lymphoid cells in the first regional lymph node, the invasion of the graft bed with small lymphocytes and the inhibition of new bone formation in the homografts

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

Resection of a primary sarcoma of the diaphysis of a long bone creates a large defect. The biological options for reconstruction include the use of a vascularised and non-vascularised fibular autograft. The purpose of the present study was to compare these methods of reconstruction. Between 1985 and 2007, 53 patients (26 male and 27 female) underwent biological reconstruction of a diaphyseal defect after resection of a primary sarcoma. Their mean age was 20.7 years (3.6 to 62.4). Of these, 26 (49 %) had a vascularised and 27 (51 %) a non-vascularised fibular autograft. Either method could have been used for any patient in the study. The mean follow-up was 52 months (12 to 259). Oncological, surgical and functional outcome were evaluated. Kaplan–Meier analysis was performed for graft survival with major complication as the end point. At final follow-up, eight patients had died of disease. Primary union was achieved in 40 patients (75%); 22 (42%) with a vascularised fibular autograft and 18 (34%) a non-vascularised (p = 0.167). A total of 32 patients (60%) required revision surgery. Kaplan–Meier analysis revealed a mean survival without complication of 36 months (0.06 to 107.3, . sd. 9) for the vascularised group and 88 months (0.33 to 163.9, . sd. 16) for the non-vascularised group (p = 0.035). . Both groups seem to be reliable biological methods of reconstructing a diaphyseal bone defect. Vascularised autografts require more revisions mainly due to problems with wound healing in distal sites of tumour, such as the foot. Cite this article: Bone Joint J 2014;96-B:1258–63

Intra-articular resection of bone with soft-tissue balancing and total knee replacement (TKR) has been described for the treatment of patients with severe osteoarthritis of the knee associated with an ipsilateral malunited femoral fracture. However, the extent to which deformity in the sagittal plane can be corrected has not been addressed. We treated 12 patients with severe arthritis of the knee and an extra-articular malunion of the femur by TKR with intra-articular resection of bone and soft-tissue balancing. The femora had a mean varus deformity of 16° (8° to 23°) in the coronal plane. There were seven recurvatum deformities with a mean angulation of 11° (6° to 15°) and five antecurvatum deformities with a mean angulation of 12° (6° to 15°). The mean follow-up was 93 months (30 to 155). The median Knee Society knee and function scores improved from 18.7 (0 to 49) and 24.5 (10 to 50) points pre-operatively to 93 (83 to 100) and 90 (70 to 100) points at the time of the last follow-up, respectively. The mean mechanical axis of the knee improved from 22.6° of varus (15° to 27° pre-operatively to 1.5° of varus (3° of varus to 2° of valgus) at the last follow-up. The recurvatum deformities improved from a mean of 11° (6° to 15°) pre-operatively to 3° (0° to 6°) at the last follow-up. The antecurvatum deformities in the sagittal plane improved from a mean of 12° (6° to 16°) pre-operatively to 4.4° (0° to 8°) at the last follow-up. Apart from varus deformities, TKR with intra-articular bone resection effectively corrected the extra-articular deformity of the femur in the presence of antecurvatum of up to 16° and recurvatum of up to 15°