This study aims to assess the fracture mechanics of type-2 diabetic (T2D) femoral bone using innovative site-specific tests, whilst also examining the cortical and trabecular bone microarchitecture from various regions using micro-computed tomography (CT) of the femur as the disease progresses. Male [Zucker Diabetic Fatty (ZDF: fa/fa) (T2D) and Zucker Lean (ZL: fa/+) (Control)] rats were euthanized at 12-weeks of age, thereafter, right and left femora were dissected (Right femora: n = 6, per age, per condition; Left femora: n=8-9, per age, per condition). Right femurs were notched in the posterior of the midshaft. Micro-CT was used to scan the proximal femur, notched and unnotched femoral midshaft (cortical) of the right femur and the distal metaphysis (trabecular) of the left femur to investigate microarchitecture and composition. Right femurs were fracture toughness tested to measure the stress intensity factor (Kic) followed by a sideways fall test using a custom-made rig to investigate femoral neck mechanical properties. There was no difference in trabecular and cortical tissue material density (TMD) between T2D and control rats. Cortical thickness was unchanged, but trabeculae were thinner (p<0.01) in T2D rats versus controls. However, T2D rats had a greater number of trabeculae (p<0.05) although trabecular spacing was not different to controls. T2D rats had a higher connectivity distribution (p<0.05) and degree of anisotropy (p<0.05) in comparison to controls. There was no difference in the mechanical properties between strains. At 12-weeks of age, rats are experiencing early-stage T2Ds and the disease impact is currently not very clear. Structural and material properties are unchanged between strains, but the trabecular morphology shows that T2D rats have more trabecular struts present in order to account for the thinner trabeculae

The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting, but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient friendly option, especially in case of a concomitant infection. Multiple types of scaffolds for the Masquelet procedure (MP) are available, however these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remains high. This paper describes three infected tibial defect nonunions with a segmental defect over ten centimeters long treated with a customized 3D printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts. Three male patients, between the age of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than ten centimeters (range 11–15cm). First stage MPs consisted of extensive debridement, external fixation and placement of anterior lateral thigh flaps (ALT). Positive cultures were obtained from all patients during this first stage, that were treated with specific systemic antibiotics during 12 weeks. The second stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure a custom 3D printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA derived autograft, iFactor and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT-scans 6 months post-operatively demonstrated active bone regeneration, also involving the central part of the scaffold. All three patients regained function and reported less pain with full weight-bearing. This case report shows that 3D printed PCL-TCP cages in combination with biological adjuncts is a novel addition to the surgical treatment of very large bone defects in (infected) posttraumatic nonunion of the tibia. This combination could overcome some of the current drawbacks in this challenging indication

Abstract. Background. Schwannomas are slow-growing, benign tumours normally originating from the Schwann cells of the nerve sheath. Intraosseous schwannoma accounts for 0.175% of primary bone tumours and extremely rare especially outside the axial skeleton. Monoclonal gammopathy has been associated with soft tissue schwannomas but never with the intraosseous variety. Presenting problem. A 55-year-old woman with a background of monoclonal gammopathy of undetermined significance (MGUS) presented with a 2-year history of right thigh pain. CT scan showed a well defined, lytic lesion with a thin peripheral rim of sclerosis in the midshaft of the femur. MRI displayed a hyperintense, well marginated and homogenous lesion. Definitive diagnosis was made based on the classical histopathological appearance of schwannoma. Clinical management. We managed our patient with local curettage and prophylactic cephalomedullary nailing on the basis of a high mirel score. Discussion. Intraosseous schwannomas are poorly understood but most commonly reported in middle-aged women. Radiologically, their differential diagnosis includes malignant bone tumours, solitary bone cysts, aneurysmal bone cysts and giant cell tumours. As a result, they are usually diagnosed incidentally on histology. Although malignant transformation is possible in soft tissue schwannomas, all intraosseous schwannomas reported to date have been benign. This case demonstrates the importance of suspecting intraosseous schwannoma as a differential diagnosis for lytic bone lesions to avoid the overtreatment of patients. We also highlight monoclonal gammopathy of undetermined significance as a potential risk factor for a poorly understood disease and make recommendations about the appropriate management of these lesions. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Objectives. We aimed to evaluate if union of clavicle fractures can be predicted at six weeks post-injury by the presence of bridging callus detected by ultrasound. Methods. Adult patients who sustained a displaced midshaft clavicle were recruited prospectively. We assessed patient demographics, functional scores and radiographic predictors with a standardized protocol at six weeks. Ultrasound evaluation of the fracture site was undertaken to determine if sonographic bridging callus was present. Nonunion was determined by CT scanning at six months post-injury. Clinical features at six weeks were used to stratify patients at high risk of nonunion and a QuickDASH ≥40, fracture movement on examination or absence of callus on radiograph. Results. 112 patients completed follow-up at six months with a nonunion incidence of 17% (n=18/112). Sonographic bridging callus was detected in 62.5% (n=70/112) of the cohort at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n=69/70). If absent, nonunion developed in 40.5% of cases (n=17/42). The sensitivity to predict union with sonographic bridging callus at six weeks was 73.4% and the specificity was 94.4%. Regression analysis found failure to detect sonographic bridging callus at six weeks was associated with nonunion, older age, female sex, and greater overall fracture displacement (Nagelkerke R2=0.60). Of the cohort, 30.4% (n=34/112) had absent sonographic bridging callus at six weeks in combination with one or more of the ‘high risk’ clinical features. If one was present the nonunion rate was 47.1%, increasing to 60% with two risk factors and 100% when combined with all three. Conclusions. Ultrasound can accurately predict fracture healing at six weeks following a displaced midshaft clavicle fracture. When combined with poor clinical recovery this could be used to target patients for early operative intervention. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Mice are increasingly used for fracture healing research because of the possibility to use transgenic animals to conduct research on the molecular level. Mice from both sexes can be used, however, there is no consensus in the literature if fracture healing differs between female and male mice. Therefore, the aim of the present study was to analyze the similarities and differences in endochondral fracture healing between female and male C57BL/6J mice, since this mouse strain is mainly used in bone research. For that purpose, 12-weeks-old female and male mice received a standardized femur midshaft osteotomy stabilized by an external fixator. Mice were euthanized 10 and 21 days after fracture and bone regeneration was analyzed by biomechanical testing, µCT analysis, histology, immunohistochemistry and gene expression analysis. At day 21, male mice displayed a significantly larger fracture callus than female mice accompanied by higher number of osteoclasts, higher tissue mineral density and absolute values of bone volume, whereas relative bone volume to tissue volume ratio did not differ between the groups. Biomechanical testing revealed significantly increased bending stiffness in both fractured and intact femurs from male vs. female mice, whereas relative bending stiffness of fractured femurs related to the intact femurs did not differ. 10 days after fracture, male mice display significantly more cartilage and less fibrous tissue area in the fracture callus than female mice, whereas bone area did not differ. On the molecular level, male mice displayed increased active β-catenin expression in the fracture callus, whereas estrogen receptor α (ERα) expression was reduced. In conclusion, male mice showed more prominent cartilaginous callus formation, increased mineralization and whole callus tissue formation, whereas functional outcome after fracture did not differ from female mice. This might be due either to the heavier weight of male mice or because of differences in molecular signaling pathways

It is common belief that consolidated intramedullary nailed trochanteric femur fractures can result in secondary midshaft or supracondylar fractures, involving the distal screws, when short or long nails are used, respectively. In addition, limited data exists in the literature to indicate when short or long nails should be selected for treatment. The aim of this biomechanical cadaveric study was to investigate short versus long Trochanteric Femoral Nail Advanced (TFNA) fixation in terms of construct stability and generation of secondary fracture pattern following trochanteric fracture consolidation. Eight intact human cadaveric femur pairs were assigned to 2 groups of 8 specimens each for nailing using either short or long TFNA with blade as head element. Each specimen was first biomechanically preloaded at 1 Hz over 2000 cycles in superimposed synchronous axial compression to 1800 N and internal rotation to 11.5 Nm. Following, internal rotation to failure was applied over an arc of 90° within 1 second under 700 N axial load. Torsional stiffness, torque at failure, angle at failure and energy at failure were evaluated. Fracture patterns were analyzed. Outcomes in the groups with short and long nails were 9.7±2.4 Nm/° and 10.2±2.9 Nm/° for torsional stiffness, 119.8±37.2 Nm and 128.5±46.7 Nm for torque at failure, 13.5±3.5° and 13.4±2.6° for angle at failure, and 887.5±416.9 Nm° and 928.3±461.0 Nm° for energy at failure, respectively, with no significant differences between them, P≥0.167. Fractures through the distal locking screw occurred in 5 and 6 femora instrumented with short and long nails, respectively. Fractures through the lateral entry site of the head element were detected in 3 specimens within each group. For short nails, fractures through the distal shaft region, not interfacing with the implant, were detected in 3 specimens. From biomechanical perspective, the risk of secondary peri-implant fracture after intramedullary nailed trochanteric fracture consolidation is similar when using short or long TFNA. Moreover, for both nail versions the fracture pattern does not unexceptionally involve the distal locking screw

In vitro femoral studies have demonstrated the addition of hydroxyapatite (HA), to morcellised bone graft (MBG) decreases femoral prosthesis subsidence. However, with an increased risk of femoral fracture during the impaction of a MBG:HA mixture, possibly due to greater force transmission to the femoral cortex via the HA. The aim was to compare the hoop strains and subsidence of a 1:1 mixture of MBG:HA with pure bone allograft during impaction and subsequent endurance testing in a revision hip arthroplasty model. Materials and methods Large Sawbone femurs were prepared to represent a femur with bone loss (Sawbones, Sweden). 12 uniaxial strain gauges were attached to each femur at 0, 90, 180 and 270 degrees, at distal, midshaft, proximal points to measure hoop strain. Impaction grafting was performed using X-Change 2 instruments and an Instron servohydaulic machine for 2 distal impactions and 4 proximal impactions for 60 impactions each. Study groups. The study consisted of four experimental groups: 1)Pure MBG, force of 1.98 kN 2)Pure MBG, force 3.63kN. 3)1:1 mixture of MBG: porous HA (pHA), 4)1:1 mixture MBG: non porous HA (npHA). 6 samples of each group were performed. Endurance testing. The potted femur was loaded in a manner representing the walking cycle (1.98kN) at 1 Hz for 50 000 cycles. The displacement of the femoral head during loading was measured by two displacement transducers (LVDT) were mounted on aluminum brackets to measure vertical displacement and rotation. Statistical analysis. Statistical analysis was performed using a Mann – Whitney U test for total subsidence and prosthesis cyclical movement at 6 hours between the control MBG1.98 and the other experimental groups. Subsequent analysis compared pHA and npHA mixes with and HA to MBG3. 65kN. Level of significance was taken at p<0.05. Results. Distal strain gauges:. All experimental groups had a significantly greater distal hoop strain than MBG1.98 kN (p=0.004). Middle strain gauges:. No significant differences between the HA groups and MBG1.98. MBG3.65 was significantly greater (p=0.02). Top strain gauges:. No significant differences, p=0.9. Endurance testing There was a non significant trend towards decreased subsidence in the HA groups compared to the bone groups. (p=0.7) but significantly less cyclical subsidence between HA groups and MBG 1.98 (p=0.02). No difference between the MBG 3.65 kN and HA groups for the cyclical subsidence. Statistically significant difference in cyclical rotation between both the MBG1.98 and the pHA (p=0.02) and npHA(p=0.02) and the bone 3.65 and pHA and npHA groups(p=0.04). Conclusion. The addition of HA to MBG decreases total and cyclical subsidence. There were significantly greater hoop strains in the distal and midshaft strain gauges with greater impaction force and in the distal gauges with the use of HA. Endurance testing demonstrated a significant decrease in cyclical motion and cyclical rotational stability of the prosthesis with a trend to a decrease in total subsidence during endurance testing with HA groups. The addition of HA might have longer term benefits in terms of prosthesis stability and subsequent graft healing but caution is needed during impaction

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures

We developed a rat model of limb lengthening to study the basic mechanism of distraction osteogenesis, using a small monolateral external fixator. In 11-week-old male rats we performed a subperiosteal osteotomy in the midshaft of the femur with distraction at 0.25 mm every 12 hours from seven days after operation. Radiological and histological examinations showed a growth zone of constant thickness in the middle of the lengthened segment, with formation of new bone at its proximal and distal ends. Osteogenic cells were arranged longitudinally along the tension vector showing the origin and the fate of individual cells in a single section. Typical endochondral bone formation was prominent in the early stage of distraction, but intramembraneous bone formation became the predominant mechanism of ossification at later stages. We also showed a third mechanism of ossification, ‘transchondroid bone formation’. Chondroid bone, a tissue intermediate between bone and cartilage, was formed directly by chondrocyte-like cells, with transition from fibrous tissue to bone occurring gradually and consecutively without capillary invasion. In situ hybridisation using digoxigenin-11-UTP-labelled complementary RNAs showed that the chondroid bone cells temporarily expressed type-II collagen mRNA. They did not show the classical morphological characteristics of chondrocytes, but were assumed to be young chondrocytes undergoing further differentiation into bone-forming cells. We found at least three different modes of ossification during bone lengthening by distraction osteogenesis. We believe that this is the first report of such a rat model, and have shown the validity of in situ hybridisation techniques for the study of the cellular and molecular mechanisms involved in distraction osteogenesis

A significant source of failure for external fixation devices is loosening of the fixation implant. As bone competence drops with ageing or disease such as osteoporosis, the risk of loosening is likely to increase. However it is not clear how fixator configuration should be adapted to minimise loosening in weaker bone. The aim of this study was to assess the effect of bone competence on the yielding of bone tissue surrounding fixation implants, and thereby inform the selection of fixator configuration to minimise loosening. External fixation of the tibial midshaft using half-pins and Illizarov wires was modelled using finite-element analysis. Half-pin configurations of two and three stainless steel and titanium pins pins were assessed. Illizarov wire configurations of two and four wires were studied, over a range of wire tensions. Bone competence was varied by changing the cortical thickness and elastic properties of the bone fragments to approximate: a) young, high-density bone, b) middle-aged, mid-porosity bone and c) old-aged, severely porous bone. Bone elastic properties were taken from a recent study of cortical bone conducted by the authors. The interaction between implants and bone was modelled with contact analysis, enabling realistic separation. Implant loosening was included using a bone-specific, strain-based yield criterion. Regions where bone tissue yielded were identified as likely sites of loosening. In all cases loading was applied to simulate a one-legged stance. Half-pin fixation. Increasing the number of half-pins from two to three produced an approximate 80% reduction of yielded bone volume in all age groups. The volume of yielded bone increased with ageing, approximately three times greater in old-aged bone than in young bone. In the young and middle-aged cases yielded bone never penetrated the full cortex. Contrastingly, the full cortex was yielded in the old-aged bone fragments for both two- and three-pin fixation. In all cases the volume of yielded bone was greater at the pin(s) nearest to the fracture gap. The use of titanium pins increased the volume of yielded bone around half-pins by approximately 1.7 times. These results suggest bone competence, number of half-pins, location of half-pins and half-pin material all significantly influence implant loosening. Illizarov wire fixation. Increasing the number of Illizarov wires reduced the volume of yielded bone by approximately 60% in all age groups. The volume of yielded bone increased with ageing by a factor of approximately 2.0 times from young to old bone. Bone yielding never progressed through the entire cortex; it reached a maximum of 70% of the cortical thickness in two-wire fixation of the old-aged bone fragment. This is a possible reason for the lower rate of loosening in Illizarov wire fixation as compared to half-pin fixation. Increasing wire tension reduced the volume of yielded bone. These results suggest that bone competence, number of wires, wire tension and wire arrangement significantly influence loosening

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Objectives

Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness.

Objectives

Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown.

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology.

Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing.

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.