Aims. With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). Methods. A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 10. 4. colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed. Results. Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf. Conclusion. In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022;11(2):49–60

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

Predictable fracture healing fails to occur in 5–10% of cases. This is particularly concerning among individuals with osteoporosis. With an increasing aging population, one in three women and one in five men above the age of 50 experience fragility fractures. As such, there is a critical need for an effective treatment option that could enhance fracture healing in osteoporotic bone. Lithium, the standard treatment for bipolar disorder, has been previously shown to improve fracture healing through modulation of the Wnt/beta-catenin pathway. We optimised the precise oral lithium administration parameters to improve mechanical strength and enhance healing of femoral fractures in healthy rats. A low dose of Lithium (20 mg/kg) administered seven days post fracture for a two week duration improved torsional strength by 46% at four weeks post fracture compared to non-treated animals. Application of lithium to enhance fracture healing in osteoporotic bone would have a significant healthcare impact and requires further study. Aim: To evaluate the efficacy of optimal lithium administration post fracture on quality of fracture healing in a rat osteoporotic model. Hypothesis: Lithium treatment in osteoporotic rats will improve the structural and mechanical properties of the healing bone despite the impaired nature of bone tissue. Sprague Dawley female rats (∼350 g, age ∼3 months) were bilaterally ovariectomised and maintained for 3 months to establish the osteoporotic phenotype. A unilateral, closed mid-shaft femoral fracture was created using a weight-drop apparatus. At seven days post fracture, the treatment group received 20 mg/kg-wt lithium chloride via oral gavage daily for 14 days. The control group received an equivalent dose of saline. All animals were sacrificed at day 28 and the femurs harvested bilaterally. Treatment efficacy was evaluated based on torsional loading and stereologic analysis. Lithium treatment positively impacted the healing femurs, with an average yield torque ∼1.25-fold higher than in the saline group (200±36 vs. 163±31 N-mm, p=0.15). Radiographically, the lithium-treated rats had a high level of restored periosteal continuity, larger bridging and intercortical callus at the fracture site. These hallmarks of healing were generally absent in the saline group. The Lithium group had significantly higher total volume (624±32 vs. 568±95 mm3), lower bone volume fraction (41±4 vs. 50±5%) and higher theoretical torsional rigidity (477±50 vs. 357±93 kN-mm2) compared to the saline group. Torsional strength and stereology values were similar for the contralateral femurs of the two groups. Lithium was found to enhance fracture healing in osteoporotic bone under the dosing regimen optimised in healthy femora. This is promising data as treatment represents an easily translatable pharmacological intervention for fracture healing that may ultimately reduce the healthcare burden of osteoporotic fractures

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

1. The appearance of decalcified bone matrix in the electron microscope is described. 2. In the matrix two types of collagen fibril have been distinguished. Differences observed are in solubility, x-ray diffraction pattern and appearance. In infant bone the form which appears as fine fibrils predominates. In adult bone the form which appears as tubular fibrils of larger diameter predominates. 3. In bones from elderly subjects the chemical reaction employed to convert collagen into eucollagen sometimes hydrolyses fatty acid esters, and lines due to the free fatty acid are found on the x-ray diffraction patterns of the insoluble residue after citrate extraction. 4. In ancient bones and fossils the stable tubular form of collagen survives, but not the fine fibrils. 5. When decalcified, the matrix in osteoporotic bones loses its architecture and fibrillar form. Under conditions in which only a small fraction is dissolved from normal bone most of the collagen in osteoporotic bone disperses in citric acid. The insoluble residue then gives a modified x-ray diffraction pattern. 6. Evidence has been produced to suggest that the immediate cause of many forms of osteoporosis is some local factor affecting the osteocytes, rather than a general chemical effect

Intramedullary rods manufactured from polyacetal were used to fix diaphyseal fractures in osteoporotic bone. They are pliable and can be introduced without further damage to such bone. Their low elastic modulus induces abundant callus. They can be locked with cortical bone screws without the need of jigs or radiographic control. Nine femoral and five tibial fractures were fixed in 10 patients, all with osteoporosis; 13 united primarily; one required bone grafting. No implant broke; however, no ambulant patient weighed more than 75 kg. The rods offer a promising treatment for diaphyseal fractures in osteoporotic bone

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 aim of our study was to evaluate if PTH is able to increase the trabecular density of osteoporotic bone at the site of an implant and whether the anabolic effect of PTH at this side is stronger then the effect of an osteoclast inhibitor like alendronate. 48 cement rod was inserted in the tibia of 48 female rats, of which 36 had been ovariectomized. The cement rods, which served as implants, were made of Palacos R bone cement. After implantation, the 36 ovariectomized rats were divided in 3 groups. One was injected subcutaneusly with PTH (1–34) at a dose of 60 g/kg BW. The second was injected with alendronate at a dose of 205 g/kg BW. The third with vehicle only. The remaining 12 sham operated rats were also injected with vehicle only. All injections were given three times a week and the rats were killed 2 weeks after implantation. The tibial segments around the hole of the rods were prepared histologically. Thus the surfaces which had been in contact with the rod appeared as straight lines and could be analyzed histomorphometricly. The trabecular density of the bone closest to the implant was measured. One femur of all animals was used for measurement by DEXA. There was a substantial increase in the trabecular density close to the rods with PTH treatment (Anova p=0.002). PTH lead to a trabecular density of 89%, where as the ovariectomized animals revealed a trabecular density of 58% and the sham operated control of 68%. No significant increase of implant related trabecular density could be found in the alendronate treated group. In this group a density of 72% was established. DEXA showed the expected differences in bone mineral content (Anova p=0.001). In this study, intermittent PTH treatment increased implant-related trabecular density in osteoporotic bone after 2 weeks. No such positive effect could be found with alendronate treatment at such a short period of time. We think the reason for this phenomenon could be the early onset of the anabolic PTH effect on regenerating bone, whereas alendronate is thought to only inhibit bone resorption, which might lead to a later effect. The early onset of PTH effects even in osteoporotic bone suggests that intermittent PTH treatment might lead to an increased micro-interlock between implant and bone and might therefore be considered as a possible drug to enhance incorporation of orthopedic implants

Because of the decreased holding power of the screws, fixation of osteoporotic fractures has a high failure rate (10%–25%). It should also be reported that even if fixation does not fail, several osteoporotic patients with fractures have unsatisfactory functional results due to bony malunion. Elderly patients with osteoporosis demand better fixation techniques. Treatment goals in this particular patient population include: proper fracture alignment, stable fixation and early rehabilitation. A surgeon should adopt a minimally-invasive technique in order to relieve the patient of physiological stress and allow for full-weight bearing of the fractured limb. Several fixation augmentation techniques have been proposed such as the use of PMMA, calcium phosphate cement, oblique screw insertion and cannulated ported screws. Our studies indicated that osteoporotic bone fixation can be greatly improved by using implants coated with calcium phosphates such as hydroxyapatite. Hip fractures are the most severe form of fracture in patients with osteoporosis. Cut-out of the load-bearing implant is seen more frequently compared to patients with good bone quality often leading to revision surgery. We compared dynamic hip screw (DHS) fixation with hydroxyapatite(HA)-coated AO/ASIF screws to DHS fixation with standard AO/ASIF screws in osteoporotic trochanteric fractures. One-hundred-andtwenty patients were divided into two groups and randomized to receive 135° 4-hole DHS with either standard lag and cortical AO/ASIF screws (Group A) or HA-coated lag and cortical AO/ASIF screws (Group B). Inclusion criteria were: female, age > 65 years, AO/OTA fracture type A1 or A2 and a bone mass density (BMD) T-score lower than −2.5. Exclusion criteria included lag screw extension into the proximal third of the femoral head. Between the two groups, there were no differences in patient age, BMD, screw position in the femoral head, tip apex distance, quality of reduction and fracture impaction at the 6-month follow-up. In Group A, femoral neck shaft angle (FNSA) reduced over time (134 ± 5° postoperative vs. 126 ± 12° at 6 months, p = 0.003), whereas in Group B, no reduction occurred over time, as indicated by the lack of difference between the FNSA post-operative (134 ± 7°) and at 6 months (133 ± 7°). Lag screw cut-out occurred in four Group A cases but not in Group B (p < 0.05, = 0.8). Three patients with cases of cut-out underwent revision with bipolar prostheses. At 6 months, the Harris hip score was 60 ± 25 (Group A) and 71 ± 18 (Group B) (p= 0.007). External fixation could be a viable treatment option in elderly trochanteric fracture patients since it typically involves a low energy trauma. However post-operative complications associated with inadequate pin fixation have limited its use. Because of the development of HA-coated screws, we compared external fixation with HA-coated screws (H-CP) to DHS with AO/ASIF stainless-steel screws in osteoporotic trochanteric fractures. Forty patients were divided into two groups and randomized for treatment with either 135° 4-hole DHS (Group A) or external fixation with 4 H-CP (Group B). Inclusion criteria were: female, age > 65 years, AO/OTA fracture type A1–2 and a BMD T-score lower than −2.5. All fixators were removed at 3 months. There were no differences in patient age, fracture type, BMD, ASA, hospital stay and quality of reduction. Average number of blood transfusions was 2 ± 0.1 in Group A, whereas no blood transfusions were required in Group B (p < 0.005). Post-operative FNSA was 134 ± 6 ° in Group A and 132 ± 4° in Group B (ns). In Group A, the varus collapse of the fracture at 6 months was 6 ± 8° and in Group B 2 ± 1° (p = 0.002). The Harris hip score was 62 ± 20 in Group A and 63 ± 17 in Group B (ns). In Group B, no screw infection occurred. Conclusion: A valuable strategy that will benefit the elderly osteoporotic patient and provide for early mobilization is the use of a minimally-invasive technique, a well-restored anatomy of the fractured limb, no blood transfusion requirements and early rehabilitation. These should also be beneficial for maintaining the overall well-being of the patient. Our results demonstrate that enhanced screw osteointegration and fracture fixation will have a positive impact on the quality of life in the elderly osteoporotic patient

Aims: Does PHILOS (Proximal Humeral Internal Locking system) construct provides better þxation than Clover leaf plate and T-plate in a simulated 2-part fracture of proximal humerus, in an osteoporotic bone model?Materials and Methods: Biomechanical laboratory study. Third generation composite Humerus model was used, with short e-glass epoxy þbres forming cortex and polyurethane cancellous core. Low density polyure-thane core (1.2gm/cc) was used to simulate an osteoporotic model. Osteotomy at surgical neck of humerus was carried out to create 2-part fracture of proximal humerus. Samples were randomised to receive one of the implants. Following þxation samples were placed in a custom made jig to þx proximal and distal ends without interfering with implants and osteotomy site. All samples were subjected to cyclical torque, Torque to failure, Cyclical compression and Compression loading to failure. Results were entered in a database. Results: PHILOS provided signiþcantly better þxation in ÔTorque to failureñ experiment. PHILOS construct shows less plastic deformation in cyclical torque and cyclical compression. Locking screws did not Ôback offñ in any of the experiments involving PHILOS construct, however ordinary screws did back off both in Ôtoque and compressionñ testing. Conclusions: PHILOS construct provides better stability in Torque and compression as compared to conventional plating devices, in an osteoporotic bone model

Introduction: Screw loosening is a common complication of osteoporotic fracture fixation leading to implant loosening, fracture malunion and non-union. Because recent animal studies have shown that bisphosphonates improve implant fixation we wanted to assess whether alendronate (ALN) improves screw fixation in a clinical setting of osteoporotic fractures. Methods: Sixteen consecutive patients with AO/OTA A1 pertrochanteric fractures were selected. Inclusion criteria were: female over the age of 65, BMD T-score less than −2.5 SD. Fractures were fixed with a pertrochanteric fixator and 4 hydroxyapatite (HA)-coated screws. Two screws were implanted in the femoral head (screw positions 1 and 2) and two in the femoral diaphysis (screw positions 3 and 4). Patients were randomized to either postoperative systemic administration of ALN, 70 mg per week for 3 months (Group A) or no ALN. Fixators were removed at 3 months post-op in all patients. Results: All the fractures healed. No differences in screw insertion torque between the two groups were found. No pin loosening or infection occurred. The combined mean extraction torque of the screws implanted at positions 1 and 2 (cancellous bone) was 3181 ± 1385 N/mm in Group A and 1890 ± 813 N/mm in Group B (p < 0.001). The combined mean extraction torque of the screws implanted at positions 3 and 4 (cortical bone) was 4327 ± 1720 N/mm in Group A and 3785 ± 1181 N/mm in Group B (ns). Discussion and Conclusion: This is the first study to demonstrate in a clinical setting improved screw fixation following post-operative ALN treatment. We observed a two-fold fixation increase in the screws implanted in cancellous bone. With cortical bone, the difference in screw fixation was less marked. Besides its bone preserving ALN should be recommended as an effective solution to improve fixation in osteoporotic bone

Aims: Loss of distal þxation occurs with this the blade plate, especially in the setting of a very distal femur fracture and/or in osteoporotic bone. The LISS (Less Invasive Stabilization System) provides a þxation construct for supracondylar/intracondylar distal femoral fractures, with features including submuscular þxation and percutaneous placement of self-drilling unicortical þxed angled screws. The purpose of this study was to evaluate the biomechanical characteristics of the LISS versus the angled blade plate in an osteoporotic human cadaveric femoral model. Methods: Twenty-four matched pairs of fresh frozen human femora were utilized. Three groups of eight pairs each were tested to failure in one-time axial loading, one-time torsional loading and cyclical axial loading. A fracture model was created to simulate an AO 33–A3 fracture. Results: The average axial load to failure was 34% higher for the LISS compared with the blade plate (p = 0.03). All 8 LISS constructs failed by plastic deformation of the implant only, while 3/8 blade plates failed by loss of distal þxation. The blade plate had a 47% higher torsional moment to failure (p= 0.05). Permanent deformation after cyclical axial loading was signiþcantly lower for the LISS (p = 0.01). Conclusions: Of signiþcant interest is potential loss of þxation in catastrophic loading of a supracondylar femoral fracture þxation construct. In conclusion, biomechanical testing of the LISS demonstrates in comparison to the blade plate: (1) superior þxation of the distal femoral Ç block È in axial loading, (2) lower torsional strength, and (3) less permanent deformation in cyclical axial loading. The results further indicate that one-time axial loading of the LISS þxation construct will ultimately result in þxator plastic deformation, rather than screw pullout

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.

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.

Although dynamic hip screw (DHS) is considered the treatment of choice for pertrochanteric fractures, we theorized that external fixation would produce clinical outcomes equal to, if not better than, outcomes obtained with conventional treatment. As external fixation is minimally-invasive, we expected a lower rate of morbidity and a reduced need for blood transfusions. We compared fixation with DHS vs. Orthofix pertrochanteric fixator (OPF) in elderly pertrochanteric fracture patients. Forty consecutive pertrochanteric fracture patients were randomized to receive either 135A1 4-hole DHS (Group A) or OPF with 4 HA-coated pins (Group B). Inclusion criteria were: female, age B3 65 years, AO type A1 or A2 and BMD less than −2.5 T score. There were no differences in patient age, fracture type, BMD, ASA, hospital stay or quality of reduction. Operative time was 64 B1 6 minutes in Group A and 34 B1 5 minutes in Group B (p < 0.005). Average number of post-operative blood transfusions was 2.0 B1 0.1 in Group A, and none in Group B (p < 0.0001). Pain was measured 5 days post-operatively and was lower in Group B (p < 0.005). Fracture varization at 6 months was 6 B1 8A1 in Group A and 2 B1 1A1 in Group B (p = 0.002). In Group B, no pin-tract infections occurred. Pin fixation improved over time, as shown by pin extraction torque (2770 B1 1710 N/mm) greater than insertion torque (1967 B1 1254 N/mm), (p= 0.001). Harris hip score at 2 years was 62 B1 20 in Group A and 63 B1 17 in Group B. This study shows that OPF with HA-coated pins is an effective treatment for this patient population. Operative time is brief, blood loss is minimal, fixation is adequate and the reduction is maintained over time.

Age-related fragility fractures are highly correlated with the loss of bone integrity and deteriorated morphology of the osteocytes. Previous studies have reported low-magnitude high-frequency vibration(LMHFV) promotes osteoporotic diaphyseal fracture healing to a greater extent than in age-matched normal fracture healing, yet how osteoporotic fractured bone responds to the mechanical signal has not been explored. As osteocytes are prominent for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance fracture healing in ovariectomized metaphyseal fracture through morphological changes and mineralisation in the osteocyte Lacuno-canalicular Network(LCN). As most osteoporotic fractures occur primarily at the metaphysis, an osteoporotic metaphyseal fracture model was established.

A total of 72 six-month old female Sprague-Dawley rats (n=72) were obtained(animal ethical approval ref: 16–037-MIS). Half of the rats underwent bilateral ovariectomy(OVX) and kept for 3 months for osteoporosis induction. Metaphyseal fracture on left distal femur was created by osteotomy and fixed by a plate. Rats were then randomized to (1) OVX+LMHFV(20 mins/day and 5 days/week, 35Hz, 0.3g), (2) OVX control, (3) SHAM+LMHFV, (4) SHAM control. Assessments of morphological structural changes, functional markers of the LCN(Scanning Electron Microscopy, FITC-Imaris, immunohistochemistry), mineralization status(EDX, dynamic histomorphometry) and healing outcomes(X-ray, microCT, mechanical testing) were performed at week 1, 2 and 6 post-fracture. One‐way ANOVA with post-hoc test was performed. Statistical significance was set at p < 0.05.

Our results showed LMHFV could significantly enhance the morphology of the LCN. There was a 65.3% increase in dendritic branch points(p=0.03) and 93% increase in canalicular length(p=0.019) in the OVX-LMHFV group at week 2 post-fracture. Besides, a similar trend was also observed in the SHAM+LMHFV group, with a 43.4% increase in branch points and 53% increase in canaliculi length at week 2. A significant increase of E11 and DMP1 was observed in the LMHFV groups, indicating the reconstruction of the LCN. The decreasing sclerostin and increasing FGF23 at week 1 represented the active bone formation phase while the gradual increase at week 6 signified the remodelling phase. Furthermore, Ca/P ratio, mineral apposition rate and bone formation rate were all significantly enhanced in the OVX+LMHFV group. The overall bone mineral density in BV was significantly raised in the OVX+LMHFV group at week 2(p=0.043) and SHAM+LMHFV at week 6(p=0.04). Quantitative analysis of microCT showed BV/TV was significantly increased at week 2 in OVX+LMHFV group(p=0.008) and week 6(p=0.001) in both vibration groups. In addition, biomechanical testing revealed that the OVX+LMHFV group had a significantly higher ultimate load(p=0.03) and stiffness(p=0.02) at week 2.

To our best knowledge, this is the first report to illustrate LMHFV could enhance osteocytes' morphology, mineralisation status and healing outcome in a new osteoporotic metaphyseal fracture animal model. Our cumulative data supports that the mechanosensitivity of bone would not impair due to osteoporosis. The revitalized osteocyte LCN and upregulated osteocytic protein markers implied a better connectivity and transduction of signals between osteocytes, which may foster the osteoporotic fracture healing process through an enhanced mineralisation process. This could stimulate further mechanistic investigations with potential translation of LMHFV to our fragility fracture patients.

Aims: Fixation failure due to osteoporosis is a major complication of osteosynthesis using compression hip screws (CHS). Biocompatible materials have been developed to improve CHS purchase and to limit fixation failure. Cortoss™ is a novel, injectable composite that interdigitates with bone, mimicking native cortical bone. This pilot study tested the immediate anchoring strength and safety of Cortoss in patients with peritrochanteric fracture. Methods: Ethical Committee approval and patient informed consent were obtained. Screws were advanced under fluoroscopy to their final position, and torque was measured electronically. Screws were backed out approximately 1 cm, 2.5 mL Cortoss was injected under fluoroscopy, and the screw was reinserted. An increase in rotational torque of at least 30% was achieved after allowing time for the bone filler to set. Results: The study population consisted of 20 patients (18 females, 2 males), 70 years or older (range 70 to 96 years) with osteoporosis. The mean preaugmentation torque was 1.23 Nm (range 0 to 4.8 Nm) and the mean postaugmentation torque was 1.81 Nm (range 0.7 to 4.8 Nm). All 20 screws were judged clinically tight after fixation. X-ray images showed that Cortoss contacted the screw threads and interdigitated with surrounding bone. No adverse events were reported. Conclusions: Cortoss provided safe and effective anchorage of CHS. By preventing screw cutout, Cortoss may provide long-term benefit to osteoporotic hip fracture patients by limiting fixation failure.