A number of techniques have been developed to improve the immediate mechanical anchorage of implants for enhancing implant longevity. This issue becomes even more relevant in patients with osteoporosis who have fragile bone. We have previously shown that a dynamic hip screw (DHS) can be augmented with a calcium sulphate/hydroxyapatite (CaS/HA) based injectable biomaterial to increase the immediate mechanical anchorage of the DHS system to saw bones with a 400% increase in peak extraction force compared to un-augmented DHS. The results were also at par with bone cement (PMMA). The aim of this study was to investigate the effect of CaS/HA augmentation on the integration of a different fracture fixation device (gamma nail lag-screw) with osteoporotic saw bones. Osteoporotic saw bones (bone volume fraction = 15%) were instrumented with a gamma nail without augmentation (n=8) or augmented (n=8) with a CaS/HA biomaterial (Cerament BVF, Bonesupport AB, Sweden) using a newly developed augmentation method described earlier. The lag-screws from both groups were then pulled out at a displacement rate of 0.5 mm/s until failure. Peak extraction force was recorded for each specimen along with photographs of the screws post-extraction. A non-parametric t-test was used to compare the two groups. CaS/HA augmentation of the lag-screw led to a 650% increase in the peak extraction force compared with the controls (p<0.01). Photographs of the augmented samples shows failure of the saw-bones further away from the implant-bone interface indicating a protective effect of the CaS/HA material. We present a novel method to enhance the immediate mechanical anchorage of a lag-screw to osteoporotic bone and it is also envisaged that CaS/HA augmentation combined with systemic bisphosphonate treatment can lead to new bone formation and aid in the reduction of implant failures and re-operations

Summary Statement. This work features a new approach to overcome drawbacks of commercial calcium phosphate cements in terms of application by on-site preparation and bone ingrowth by introduction of macropores in the material using a hydrofluoroalkane based aerosol foam. Introduction. The application of calcium phosphate bone cements (CPCs) into a void for example of an osteoporotic bone is very difficult as the cement paste is made outside the application site and subsequently applied into the damaged bone. A common drawback of especially apatitic cements is a very low resorption rate due to small pore size Therefore different approaches have been described to add macropores into the cement. 2. , leading to bone ingrowth and tissue penetration. The aim of this project is the use of two separate formulations in pressurised systems – a suspension and an emulsion – which can be mixed in a specially developed device and can be applied easily and efficiently into a bone directly during surgery leading to a self-hardening macro porous CPC foam. The intention is to fill voids in osteoporotic bones to ensure stability for implants like e.g. screws for femur neck fractures. An increased stability for implants can allow the possibility of a less invasive femur neck preserving therapy in contrast to a femur neck replacement. Other indications for such foam (i.e. kyphoplasty) are under evaluation. Methods. As suggested above two separate formulations for the components are developed to prevent premature hardening. Hydrofluoroalkanes were preferred as propellants to propane, butane or isobutane, due to their superior safety profile. The hardener component was formulated as propellant-in-water emulsion. Several parentally approved emulsifiers (e.g. Poloxamer 188) were tested in view of solubility at the given salt and binder concentration. The stability of resulting emulsions in pressurised containers, the corresponding foams as well as the foam expansion volume was analyzed. Porous hydroxyapatite is formed after addition of tetra-calciumphosphate, di-calciumphosphate dihydrate and tri-sodiumcitrat dehydrate incorporated in the suspension component. To overcome quick sedimentation of these solids, particle size was reduced by dry or non-aqueous wet milling, respectively. Changes in particle size distribution and enthalpy changes during processes were analyzed. Hardening properties of both components were tested particularly with regard to compressive strength. In order to apply the components, a suitable application system was developed and the hardened product analyzed using x-ray diffraction. Results. The optimised Ca. 2+. /(PO. 4. ). 3−. component is a submicron-sized suspension in a mixture of ethanol and HFA 134a. The development of the suspension led to new knowledge with regard to milling effects on the Ca. 2+. /(PO. 4. ). 3−. components. The optimised hardener component contains an aqueous solution of sodium phosphates, Povidone 90 and Poloxamer 188 emulsified in HFA 227. Both components are formulated in pressurised cans. Discussion/Conclusion. A two component bone foam for stabilisation in osteoporotic bones including a new mixing / application system, which allows actuation of the components and leads to a hardening process that results in hydroxyapatite in a suitable test setup, was developed. The new application system. Further steps i.e. proof of concept (in-vitro and in-vivo) are being taken

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

Fatty marrow and bone loss are prominent pathologic features of osteoporosis. DNA hypermethylation shifts mesenchymal stem cells towards adipocytes impairing bone formation. Brown adipocytes produce growth factors advantageous to osteogenesis, whereas white adipocytes secrete pro-inflammatory cytokines deleterious to bone homeostasis. We assess DNA methylation inhibitor action to brown and white adipocyte formation in marrow fat of osteoporotic skeletons. Osteoporotic skeletons in mice were induced by glucocorticoid, ovariectomy or ageing. Marrow adipose volume and bone structure were quantified using OsO4 contrast-μCT imaging. Brown and white adipocytes were probed using immunostaining, RT-PCR and primary bone-marrow mesenchymal stem cell cultures. Abundant marrow fat and spare trabecular bone existed in osteoporotic skeletons. Osteoporosis increased expressions of general adipogenic markers PPARγ2 and FABP4 and white adipocyte markers TCF21 and HOXc9, whereas expressions of brown adipocyte markers PGC-1α and UCP-1 and osteogenic markers Runx2 and osteocalcin were significantly decreased. Number of UCP-1 immunostaining-positive brown adipocytes also reduced in osteoporotic bone. In vitro, DNA methylation inhibitor 5'-aza-deoxycystidine significantly increased brown adipocyte formation and osteogenic differentiation and mitigated dexamethasone-induced white adipocyte formation in mesenchymal stem cells. 5'-aza-deoxycystidine control of brown adipogenesis and white fat formation appeared to be regulated by increasing Wnt3a/β-catenin and reducing Dkk1. Disintegrated brown adipocyte and white fat cell differentiation contribute to osteoporosis pathogenesis. Maintaining DNA hypomethylation promotes Wnt signalling and brown adipocyte differentiation facilitating osteogenic differentiation. This study shed a new light to the contribution of brown adipocytic cells to bone metabolism during osteoporosis

The goal was to analyze the cellular response, specifically the osteogenic capacity, of titanium (Ti) implants harbouring a novel laserbased-surface-structure with the overall aim: augmented osteointegration. Surface micro-/nanoproperties greatly influence cell behaviour at the tissue-implant-interface and subsequent osteointegration. We investigated Ti-materials subjected to a specially developed shifted-Laser-Surface-Texturing (sLST) technology and compared them to a standard roughening-technique (sand-blasting-acid-etching, SLA). The biological response was evaluated with hMSCs, which are naturally available at the bone-implant-interface. We hypothesized: the novel surface is beneficial for our three different (young/healthy-YH; aged/healthy-AH;aged/osteoporotic-OP) cohorts.

The sLST was performed using a SPI-G3-series laser (beam-wavelength=1064nm, pulse-duration=200ns). For the SLA surface, Ti was sandblasted, afterwards acid-etched (HCl/H2SO4). Three different hMSC cohorts were studied: YH: n=6,29±6; AH: n=5,79±5; OP: n=5,76±5 years (osteoporosis confirmed via DEXA-scan). OP hMSCs show e.g. ColI-deficient-matrix and decreased mineralization. Cells were examined for survival, cell proliferation and cytoskeleton arrangement. Osteogenic differentiation was carried out over 21 days, matrix mineralization was validated with Alizarin-Red-S-staining and quantification.

Laser-texturing generated precisely the desired microgeometry. On nanostructural level, differently-sized Ti-droplets were formed stochastically by laser-induced-Ti-plasma. Live/dead-/Actin-stainings showed comparable results for all cohorts and surfaces in terms of survival and cell shape. On Ti-materials, cell growth showed no significant difference between the 3 cohorts. Alizarin quantification revealed the highest levels on laser-textured-surfaces; highest value for YH, followed by AH, lastly OP; no significance between AH/YH, but between OP/YH (p<0.0001). However, mineralization of all cohorts cultured on laser-textured-surfaces increased significantly (p<0.0001) compared to respective SLA-group, with >20fold higher value in the OP-cohort (AH:11fold, YH:6fold).

The data proves the biocompatibility of the laser-structured-Ti for young+aged cohorts. Osteogenic differentiation was significantly augmented on laser-treated-Ti. Most intriguingly, OP-donors could reach manifold increased mineralization, suggesting the novel laser texturing can counteract the osteoporotic phenotype. As osteogenesis-enhancing capacities may be related to mechanisms controlling cellular shape/fate, further investigations referring to this are currently ongoing. In conclusion, our laser-textured-Ti-materials are safe, can have a demand-oriented designer-surface-topography and represent a great potential for development into next-generation-implants suitable for different patient-cohorts, especially osteoporosis patients.

We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic material (RKKP and AP40) into healthy and osteopenic rats. After two months, a histomorphometric analysis was performed and the affinity index calculated. In addition, osteoblasts from normal and osteopenic bone were cultured and the biomaterials were evaluated in vitro.

In normal bone the rate of osseointegration was similar for all materials tested (p > 0.5) while in osteopenic bone AP40 did not osseointegrate (p > 0.0005).

In vitro, no differences were observed for all biomaterials when cultured in normal bone-derived cells whereas in osteopenic-bone-derived cells there was a significant difference in some of the tested parameters when using AP40.

Our findings suggest that osteopenic models may be used in vivo in the preclinical evaluation of orthopaedic biomaterials. We suggest that primary cell cultures from pathological models could be used as an experimental model in vitro.

Type-2 Diabetic (T2D) patients experience up to a 3-fold increase in bone fracture risk[1]. Paradoxically, T2D-patients have a normal or increased bone mineral density when compared to non-diabetic patients. This implies that T2D has a deleterious effect on bone quality, whereby the intrinsic material properties of the bone matrix are altered. Creating clinical challenges as current diagnostic techniques are unable to accurately predict the fracture probability in T2D-patients. To date, the relationship between cyclic fatigue loading, mechanical properties and microdamage accumulation of T2D-bone tissue has not yet been examined and thus our objective is to investigate this relationship.

Ethically approved femoral heads were obtained from patients, with (n=8) and without (n=8) T2D. To obtain the mechanical properties of the sample, one core underwent a monotonic compression test to 10% strain, the other core underwent a cyclic compression test at a normalized stress ratio between 0.0035mm/mm and 0.016mm/mm to a maximum strain of 3%. Microdamage was evaluated by staining the tissue with barium sulfate precipitate [2] and conducting microcomputed tomography scanning with a voxel size of 10μm.

The monotonically tested T2D-group showed no statistical difference in mechanical properties to the non-T2D-group, even when normalised against BV/TV. There was also no difference in BV/TV. For the cyclic test, the T2D-group had a significantly higher initial modulus (p<0.01) and final modulus (p<0.05). There was no difference in microdamage accumulation.

Previous population-level studies have found that T2D-patients have been shown to have an increased fracture risk when compared to non-T2D-patients. This research indicates that T2D does not impair the mechanical properties of trabecular bone from the femoral heads of T2D-patients, suggesting that other mechanisms may be responsible for the increased fracture risk seen in T2D-patients.

Introduction. A long nail is often recommended for treatment of complex trochanteric fractures but requires longer surgical and fluoroscopy times. A possible solution could be a nail with an appropriate length which can be locked in a minimally invasive manner by the main aiming device. We aimed to determine if such a nail model* offers similar structural stability on biomechanical testing on artificial bone as a standard long nail when used to treat complex trochanteric fractures. Method. An artificial osteoporotic bone model was chosen. As osteosynthesis material two cephalomedullary nails (CMN) were chosen: a superior locking nail (SL-Nail) which can be implanted with a singular targeting device, and a long nail (long-nail) with distal locking using free-hand technique. AO31-A2.2 fractures were simulated in a standardized manner. The insertion of the nail was strictly in accordance with the IFU and surgical manual of the manufacturer. The nail was locked dynamically proximally and statically distally. Axial height of the construct, varus collapse, and rotational deformity directly after nail insertion were simulated. A Universal Testing Machine was used. Measurements were made with a stereo-optic tracking system. Reactive movements were recorded and evaluated in all six degrees of freedom. A comparative analysis provided information about the stability and deformation of the assemblies to be compared. Result. There was a detectable difference in the axial fracture movement resulting in narrowing of the fracture gap. The load displacement was 1.7mm higher for the SL-Nail. There was no difference in varus collapse or rotational deformity between the nail variants. Conclusion. We conclude that there are small differences which are clinically insignificant and that a superior locking nail can safely be used to manage complex trochanteric fractures. *DCN SL nail, SWEMAC, Linköping, Sweden. Funding: no funding

Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation. Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation. We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically

Introduction. Osteoporosis accounts for a major risk factor of fracture-associated disability or premature death in the elderly. Enhancement of bone anabolism for slowing osteoporosis is highly demanding. Exerkine fibronectin type III domain containing 5 (FNDC5) regulates energy metabolism, inflammation, and aging. This study was aimed to investigate whether Fndc5 signaling in osteoblasts changed estrogen deficiency-mediated bone loss or microarchitecture deterioration. Method. Female osteoblast-specific Fndc5 transgenic mice (Fndc5Tg), which overexpressed Fndc5 under the control of key osteoblast marker osteocalcin promoter, were given bilateral ovariectomy to induce estrogen deficiency-mediated osteoporosis. Bone mass, microstructures, and biomechanical properties were quantified using μCT imaging and material testing. Dynamic bone formation was traced using fluorescence calcein. Osteogenic differentiation and adipocyte formation of bone-marrow mesenchymal cells were investigated using von Kossa staining and Nile red staining, respectively. Serum osteocalcin, CTX-1 and TRAP5b levels were quantified using designated ELISA kits. Mitochondrial respiration was investigated using Seahorse Extracellular Flux Analyzer. Result. Fndc5Tg mice developed relatively higher bone mass and microarchitecture than wild-type mice. Fndc5 overexpression attenuated the losses of bone mineral density and trabecular network, including trabecular volume, thickness, and trabecular number, and improved cortical thickness and porosity in ovariectomized mice. Gain of Fndc5 function preserved biomechanical characteristics (maximum load, breaking force, and energy), serum bone formation marker osteocalcin levels, and bone formation rate, whereas it reduced serum bone resorption makers CTX-1 and TRAP5b levels, osteoclast overburden, and marrow adiposis. In vitro, Fndc5 reversed the estrogen deficiency-mediated mineralized matrix underproduction and adipocyte formation of bone-marrow mesenchymal cells, and inhibited osteoclast formation in osteoporotic bone. Mechanistically, Fndc5 activated AMPK signaling, promoting mitochondrial respiration and ATP production to enhance osteoblastic activity. Conclusion. Fndc5 signaling exerted bone-protective actions delaying estrogen deficiency-mediated osteoporosis. This study highlighted a new molecular remedial option for osteoporosis development by manipulating Fndc5 functions

Summary Statement. Tibia plateau split fracture fixation with two cancellous screws is particularly suitable for non-osteoporotic bone, whereas four cortical lag screws provide a comparable compression in both non-osteoporotic and osteoporotic bone. Angle-stable locking plates maintain the preliminary compression applied by a reduction clamp. Introduction. Interfragmentary compression in tibia plateau split fracture fixation is necessary to maintain anatomical reduction and avoid post-traumatic widening of the plateau. However, its amount depends on the applied fixation technique. The aim of the current study was to quantify the interfragmentary compression generated by a reduction clamp with subsequent angle-stable locking plate fixation in an osteoporotic and non-osteoporotic synthetic human bone model in comparison to cancellous or cortical lag screw fixation. Methods. Adult synthetic human tibiae with hard or soft cancellous bone were osteotomised at the lateral tibia plateau creating a split fracture (AO type 41-B1) and fixed with either two 6.5 mm cancellous, four 3.5 mm cortical lag screws or 3.5 mm LCP proximal lateral tibia plate, preliminary compressed by a reduction clamp (n = 5 per group). Interfragmentary compression was measured by a pressure sensor film after instrumentation. One-way analysis of variance (ANOVA) with Bonferroni post hoc correction was performed for statistical analysis (p < 0.05). Results. Applying a reduction clamp, interfragmentary compression was 0.6 MPa ± 0.1 in non-osteoporotic and osteoporotic bone. The locking plate was able to maintain the compression (0.5 MPa ± 0.1) in non-osteoporotic and osteoporotic bone, but it was significantly lower compared to four cortical lag screws (non-osteoporotic p = 0.01; osteoporotic p = 0.03). Comparing four 3.5 mm cortical lag screws, compression was not significantly different between the non-osteoporotic (1.7 MPa ± 0.7) and osteoporotic bone (1.4 MPa ± 0.5). Two 6.5 mm cancellous lag screws achieved significantly higher compression in non-osteoporotic (2.1 MPa ± 0.6) compared to osteoporotic (0.8 MPa ± 0.2, p = 0.01) bone. Conclusion. Preliminary compression applied by a reduction clamp was maintained by angle-stable locking plates. The two 6.5 mm cancellous screw technique would especially be appropriate for young human non-osteoporotic bone, whereas the four 3.5 mm cortical screw configuration could also be applied in osteoporotic bone

Glucocorticoid excess is shown to deteriorate bone tissue integrity, increasing the risk of osteoporosis. Marrow adipogenesis at cost of osteogenesis is a prominent feature of this osteoporosis condition. Epigenetic pathway histone deacetylase (HDAC)-mediated histone acetylation regulates osteogenic activity and bone mass. This study is aimed to figure out what role of acetylated histone reader bromodomain-containing protein 4 (BRD4) did play in glucocorticoid-induced osteoporosis. Bone-marrow mesenchymal stem cells were incubated in osteogenic medium with or without 1 μM dexamethasone. Mineralized matrix and adipocyte formation were probed using von Kossa and Nile Red O staining, respectively. Osteogenic and adipogenic marker expression were quantified using RT-PCR. The binding of acetylated histone to promoter of transcription factors were detected using chromatin immunoprecipitation-PCR. Bone mineral density and microstructure in osteoporotic bone were quantified with microCT system. Glucocorticoid repressed osteogenic transcription factor Runx2 expression and mineralized matrix formation along with a low level of acetylated lysine 9 at histone 3 (H3K9ac), whereas BRD4 signaling and adipocytic formation were increased in cell cultures. BRD4 knockdown reversed the H3K9ac enrichment in Runx2 promoter and osteogenesis, but downregulated adipogenic differentiation. Silencing BRD4 attenuated H3K9ac occupancy in forkhead box P1 (Foxp1) relevant to lipid metabolism upon glucocorticoid stress. Foxp1 interference downregulated adipogenic activities of glucocorticoid-treated cells. In vivo, treatment with BRD4 inhibitor JQ-1 compromised the glucocorticoid-induced bone mineral density loss, spare trabecular structure, and fatty marrow, as well as improved biomechanical properties of bone tissue. Taken together, BRD4-mediated Foxp1 pathways drive mesenchymal stem cells shifting toward adipocytic cells rather than osteogenic cells to aggravates excessive marrow adipogenesis in the process of glucocorticoid-induced osteoporosis. Pharmacological inhibition of BRD4 signaling protects bone tissue from bone loss and fatty marrow in glucocorticoid-treated mice. This study conveys a new molecular insight into epigenetic regulation of osteogenesis and adipogenesis in osteoporotic skeleton and highlight the remedial effect of BRD4 inhibitor on glucocorticoid-induced bone loss

The screw fastening torque applied during bone fracture fixation has a decisive influence on subsequent bone healing. Insufficient screw tightness can result in device/construct instability; conversely, excessive torques risk damaging the bone causing premature fixation failure. This effect is even more prominent in osteoporotic bone, a condition associated annually with almost 9 million fractures worldwide. During fracture fixation, screw tightening torque is applied using subjective feel. This approach may not be optimal for patient”s recovery, increasing risk of fixation failure, particularly in osteoporotic bone, and potentially require revision surgical interventions. Besides bone density, various factors influence the performance of screw fixation. These factors include bone geometry, cortical thickness and time-dependant relaxation behaviour of the bone. If the influence of screw fastening torque on the bone and relationships between these factors was better understood, the surgical technique could be optimised to reduce the risk of complications. Within this study, we developed an axisymmetric finite element (FE) model of bone screw tightening incorporating viscoelastic behaviour of the cortical bone such as creep and stress relaxation. The model anticipated time-dependent behaviour of the bone for different bone thickness and density after a typical bone fixation screw had been inserted. The idealised model has been developed based on CT scans of bones with varying densities and inserted screws. The model was validated through a series of experiments involving bovine tibiae (4–5 months) to evaluate the evolution of surface strains with time (Ncorr v1.2). Stress distribution was assessed in photoelastic experiments using acrylic analogues. Relaxation tests have been performed in aqueous environment for up to 48 hours to ensure the relaxation would be complete. The creep behaviour (maximum principal strain) was compared against computational predictions. Our early simulations predicted relaxation strains on the surface of the bone to be 1.1% within 24 hours comparing favourably to 1.3% measured experimentally. Stress distribution patterns were in agreement with photoelastic results. Using experimentally derived viscoelastic properties, the model has the potential to predict creep and stress relaxation patterns after screw insertion with different fastening torques for bones with varying density and geometry. We aim to develop this into a planning tool providing guidance to surgeons for optimal tightening when using screw fixation, particularly in reduced quality bone

Recent studies have shown that bone mineral distribution is more heterogeneous in bone tissue from an animal model of osteoporosis and osteoporotic human vertebral trabeculae. These tissue alterations may play a role in bone fragility seen in osteoporosis, albeit that they are not detectable by current diagnostic techniques (dual-energy X-ray absorptiometry, DXA). Type II Diabetes Mellitus (T2DM) also increases a patient's fracture risk beyond what can be explained or diagnosed by DXA, and is associated with impaired bone cell function, compromised collagen structure and reduced mechanical properties. However, it is not currently known whether osteoporosis or T2DM leads to an increased mineral heterogeneity in the femoral head of humans, a common osteoporotic fracture site. In this study, we examine bone microarchitecture, mineralisation and mechanical properties of trabecular bone from osteoarthritic, diabetic and osteoporotic patients. We report that while osteoporotic trabecular bone has significantly deteriorated mechanical properties and microarchitecture compared to the other groups, there is also a significant increase in mean mineral content. Moreover, the heterogeneity of the mineral content in osteoporotic bone is significantly higher than osteoarthritic (+35%) and diabetic (+13%) groups. We propose that the compromised architecture following bone loss at the onset of osteoporosis alters the mechanical environment, which initiates compensatory changes in mineral content. We show for the first time that trabecular bone mineralisation is significantly more heterogeneous (+20%) in T2DM compared to osteoarthritic controls. Interestingly, bone microarchitecture and mechanical properties are not significantly different between diabetic and osteoarthritic groups despite this increase in mineral heterogeneity

Osteoporosis is a worldwide spread, silent disease steadily increasing due to demographic shift; it results in bone loss and increased porosity that lead to an increase in bone fragility and to low-energy fractures. In such a contest, we worked on the development of 3D scaffolds engineered to mimic the features of human healthy bone. Healthy and osteoporotic bone microCT scans were obtained from tissues discarded during surgical interventions (Istituto Ortopedico Rizzoli-Italy). The obtained .STL file was used to 3D print a type I collagen solution to mimic bone matrix whereas mesoporous bioactive glass/nano-hydroxyapatite were embedded within the collagen fibers to mimic the inorganic phase of human bone. The rheological properties of the Type I collagen/mesoporous glass suspensions were investigated at different collagen concentration and temperatures. The possibility of incorporating growth factors (IGF and β-TGF) in the scaffold struts was investigated proposing several approaches and their retained activity was assessed. Different co-culture of osteoblasts and osteoclasts set-ups were explored in order to define the influence of both chemical and topographical stimuli on the osteoblast-osteoclast coupling

Currently available fracture fixation devices that were originally developed for healthy bone are often not effective for patients with osteoporosis. Resulting outcomes are unsatisfactory, with longer recovery times, often requiring re-surgery for failed cases. One major issue is the design of bone screws, which can loosen or pull-out from osteoporotic bone. Design improvements are possible, but the development of new screws is a lengthy and expensive process due to the manufacture of the complex geometry involved. The aim of this research was to validate our currently available 3D printing technology in the design, manufacture and testing of screws. Three standard wood screw designs were reverse-engineered using computational modelling and then fabricated in polymeric resin using 3D rapid prototyping on a Stereolithography (SLA) machine. The original metal screws and the 3D screws (n=5 of each) were then inserted into a synthetic bone block (Sawbones, PCF5) representing the mechanical properties of severely osteoporotic cancellous bone. Pull-out tests were conducted in accordance with ASTM 543-13. The three metal screws exhibited pull-out strengths of 125, 74 and 118 N respectively. The 3D printed screws by comparison showed pull-out strengths approximately 15–20 % lower than their metal counterparts. However, when the results were normalised to the material tested, showing the relative changes to the first design, the pattern of results in the metal and 3D printed groups were almost identical (within 3 % of each other), showing excellent correlation. This study is the first to show that 3D Rapid Prototyping can be used in the pre-clinical testing of orthopaedic screws. The methodology provides a cheaper, faster development process for screws, allowing huge scope for development and improvement. Future work will include expanding the study to include more screw configurations as well as testing in higher density foams to compare performance in healthier bone

Suture anchor have been used in surgical procedure of tendon or ligament repair. Recently, there has been developed an all suture anchor (soft anchor) which can be used even when the insertion area is narrow. But, the stability of soft anchors due to narrow zone has not been elucidated. This purpose of this study was to investigate stability of soft anchors with respect to their fixation intervals. Polyurethane foams with two different bone densities (10 pcf; 0.16g / cm³, 20 pcf; 0.32g / cm³) were used. All suture anchors and conventional suture anchors were fixed at 10mm, 5mm, and 2.5mm intervals. The failure load was measured using a mechanical testing machine. The average load to failure of conventional suture anchor were 200.4N, 200.2N, 184.7N in the 10mm, 5mm and 2.5mm interval with 10pcf foam bones and 200.4 N, 200.2 N and 184.7 N with the 20 pcf foam bone respectively. Average load to failure load of soft anchor was 97.3N, 93.9N and 76.9N with 10pcf foam bones and 200.4 N, 200.2 N and 184.7 N with 20 pcf foam bone. Suture screw spacing and bone density are important factors in anchor pullout strength. In osteoporotic bone density, insertion of the suture screw interval of 5 mm might be necessary

The aim of management of an adult distal humeral fracture is to restore mobility, stability and pain-free elbow function. Good results are usually achieved in the majority of fractures treated with ORIF, but the management of comminuted fractures in elderly, frail patients with osteoporotic bone remains controversial. The literature focuses on elbow replacement if stable internal fixation cannot be achieved, with “bag-of-bones” management now rarely discussed eg. key-note paper - 10 successful cases reported by Brown RF & Morgan RG in 1971 (JBJS 53-B(3):425-428). We present the experience in two units in which conservative management has been actively adopted in selected cases by consultants with a subspecialty interest in the elbow. All patients over the age of 60 with distal humeral fractures (2007 – 2009) who had been treated conservatively were reviewed clinically and radiologically. Duration of follow-up and outcome, including the Oxford and quick DASH scores, were recorded, with the fractures classified using the AO system. There were 25 patients, 19 female and 6 male. 19/25 patients have been successfully treated conservatively with a mean Range Of Movement: Extension/Flexion: 45/125, Pronation/Supination 74/70. Only 5 underwent subsequent total elbow replacement and one delayed ORIF. There is a significant complication rate following surgical treatment with ORIF or elbow replacement in elderly, frail patients, including infection, painful non-union and/or stiffness. We believe that there is a role for initial conservative treatment in selected patients with low, displaced, comminuted humeral fractures in osteoporotic bone. Initial early mobilisation as pain allows can give good functional results without the risks of operation. It does not preclude future surgery if conservative treatment fails, but this is not required in the majority of cases

Femoral shaft fractures are potentially devastating injuries. Despite this, clinical studies of the biomechanics of this injury are lacking. We aimed to clinically evaluate bone behaviour under high and low energy trauma in paediatric, adult and older patients. Single-centre retrospective study identifying all diaphyseal femoral fractures between Feb 2015-Feb 2017. Peri-prosthetic and pathological fractures were excluded. Patients were subdivided into groups 1 (paediatric, <16yo), 2 (adult, 17–55yo) and 3 (older, >55yo) to reflect immature, peak bone age and osteoporotic bone respectively. Chi-Squared analysis assessed significance of bone age to degree of comminution and fracture pattern. A p-value <0.05 was significant. A total 4130 radiographs were analysed with 206 femoral shaft fractures identified. Forty-three patients were excluded with 163 remaining. Group 1, 2 and 3 included 38, 37 and 88 patients respectively. Mean age 50.8 (SD 32.8) with male-to-female ratio of 1:1.2. Groups 1 and 3 included majority simple fractures (35/38 and 62/88 respectively). Group 2 included more comminuted injuries (33/37). Bone age to degree of comminution proved significant (p<0.05) with a bimodal distribution of simple fractures noted in groups 1 and 3. Energy to fracture was significant in group 2, where a high energy injury was associated with comminution (p<0.05). This study is the first to demonstrate an association between fracture comminution and age. Simple femoral shaft fractures showed a bimodal age distribution in paediatric and older patients regardless of mechanism energy. High energy mechanism trauma was directly related to fracture comminution at peak bone age

The expression of the mechanosensor, integrin αvβ3, is reduced in osteoporotic bone cells compared to controls. MLO-Y4 osteocytes experience altered mechanotransduction under estrogen deficiency and it is unknown whether this is associated with defective αvβ3 expression or signalling. The objectives of this study are to (1) investigate αvβ3 expression and spatial organisation in osteocytes during estrogen deficiency, and (2) establish whether altered responses of osteocytes under estrogen deficiency correlate to defective αvβ3 expression and functionality. MLO-Y4 cells were cultured as follows: Ctrl (no added estradiol), E+ (10nM 17β-estradiol for 5 days), and Ew (10nM 17β-estradiol for 3 days and withdrawal for 2 days). Cells were cultured with/without 0.5µM IntegriSense750 (αvβ3 antagonist). Laminar oscillatory fluid flow of 1Pa at 0.5Hz was applied for 1hr. αvβ3 content was quantified using an ELISA. The location and quantity of αvβ3 and focal-adhesions was determined by immunocytochemistry. Estrogen withdrawal under static conditions led to lower cell and focal-adhesion area (p<0.05), compared to E+ cells. Fluid flow led to higher αvβ3 content (p<0.05) in all groups, compared to static counterparts, with αvβ3 blocking altering this response. Fluid flow on Ew cells had the highest αvβ3 levels (p<0.05), but αvβ3 did not localise at focal-adhesions sites. Cell morphologies were similar after treatment with the αvβ3 antagonist to the Ew group. These results suggest there are fewer functional focal-adhesion sites at which αvβ3 integrins localise to facilitate mechanotransduction. To further understand these results, we are analysing osteocyte mechanotransduction by quantifying PGE2 and gene expression (COX-2, RANKL, OPG, SOST)