RSPO3 is important for trabecular bone and fracture risk in mice and humans.

With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.

Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis.

Bone marrow ablation prompts transient bone formation in nearly the entire medullary cavity before marrow regeneration occurs. Here, we establish a procedure to direct bone formation in a desired particular site within the medullary cavity for support of biomedical devices. Local intramedullary injury was performed in the tibiae of rats and parathyroid hormone (PTH), alendronate, or saline was administered. Newly generated bone in the medulla was assessed by micro-CT and histology. To evaluate the function of newly generated bone, animals received intramedullary injury in tibiae followed by daily PTH. At day-14, implants were placed in the endocortical bone and the bone response to the implants was assessed. The fate of newly generated bone was compared with and without implants. We found that neither intramedullary injury nor medication alone resulted in bone formation. However, when combined, substantial bone was generated locally inside the diaphyseal medulla. Newly formed bone disappeared without implant placement but was retained with implants. Bone was especially retained around and between the implants. This study found that local bone marrow disruption followed by PTH or alendronate generated substantial cancellous bone locally in the diaphyseal medulla. This approach offers promise as a tissue engineering tool in medicine and dentistry.

A histological comparison of non-human rib models suited for sharp force trauma analysis.

Cut marks provide essential knowledge to interpret which and how tools were used, both in archaeological and forensic context. Lots of studies focused on experimentally produced cut marks on animal models to develop methods for stabbing incidents. However, animal models are criticized to be morphologically different in comparison to human bones. This study analyzed the bone composition and experimentally obtained cut marks done on ribs from humans, pigs and goats. Methods included a qualitative description of differences between the species and a quantitative analysis of the cut mark proportions in histological thin sections and micro CT scans. The results indicated that especially the cortical bone of non-human ribs was different in comparison to human bone tissue as they were more robust and usually juvenile. Plexiform bone dominates and remodeled lamellar bone is rarely visible. The knife impact tends to create debris inside the cut mark and stress fractures along lamellae and cement lines perpendicular to the cut mark. Moreover, entheses of the intercostal muscles are always affected by the incision. Pig ribs were shown to be better suited as a model for sharp force trauma than goat ribs in comparison to humans. Though, plexiform bone and non-remodeled bone made it not quite ideal. We suggested to use bone material from animals used for breeding instead of meat production as they are slaughtered at higher ages.

Bone ingrowth comparison of irregular titanium and cobalt-chromium coatings in a translational cancellous bone model.

The use of cobalt-chromium (CoCr)-bearing surfaces in total joint replacement (TJR) remains the predominate bearing surface. The conundrum with using this biomaterial has been selecting an ideal porous coating to assure reproducible skeletal attachment. There has been evidence that smooth CoCr beads may be inferior for skeletal attachment compared to identically shaped titanium (Ti) beads. Recent in vitro studies have demonstrated that an increased surface area and roughness favors osteoblast adhesion to metallic biomaterials. Therefore, we hypothesized that an irregular shape CoCr bead with an increased surface texture would help correct the negative bone responses that have been reported with smooth beaded CoCr coatings and thus allowing for bone ingrowth equivalently as an irregular commercially pure Ti porous coating with similar porosity. This investigation employed a weight-bearing translational sheep cancellous bone model to accurately simulate a cancellous bone response as it would be clinically in a human TJR. The data analyses obtained from this investigation revealed similar bone responses between the porous coatings. By 12 weeks the irregular shape CoCr coating was able to achieve similar bone ingrowth with skeletal interlock when compared to a clinically proven Ti porous coating.

Titania nanotube morphologies for osseointegration via models of in vitro osseointegrative potential and in vivo intramedullary fixation.

As total joint replacements increase annually, new strategies to attain solid bone-implant fixation are needed to increase implant survivorship. This study evaluated two morphologies of titania nanotubes (TiNT) in in vitro experiments and an in vivo rodent model of intramedullary fixation, to simulate joint arthroplasty conditions. TiNT surfaces were prepared via an electrochemical etching process, resulting in two different TiNT morphologies, an aligned structure with nanotubes in parallel and a trabecular bone-like structure. in vitro data showed bone marrow cell differentiation into osteoblasts as well as osteoblastic phenotypic behavior through 21 days. In vivo, both TiNT morphologies generated greater bone formation and bone-implant contact than control at 12 weeks, as indicated by µCT analyses and histology, respectively. TiNT groups also exhibited greater strength of fixation compared to controls, when subjected to wire pull-out testing. TiNT may be a promising surface modification for promoting osseointegration.

Cortical and Trabecular Bone Fracture Characterisation in the Vertebral Body Using Acoustic Emission.

The ability to rapidly detect localised fractures of cortical and/or trabecular bone sustained by the vertebral body would enhance the analysis of vertebral fracture initiation and propagation during dynamic loading. In this study, high rate axial compression tests were performed on twenty sets of three-vertebra lumbar spine specimens. Acoustic Emission (AE) sensor measurements of sound wave pressure were used to classify isolated trabecular fractures and severe compressive fractures of vertebral body cortical and trabecular bone. Fracture detection using standard AE parameters was compared to that of traditional mechanical parameters obtained from load cell and displacement readings. Results indicated that the AE parameters achieved slightly enhanced classification of isolated trabecular fractures, whereas the mechanical parameters better identified combined fractures of cortical and trabecular bone. These findings demonstrate that AE may be used to promptly and accurately identify localised fractures of trabecular bone, whereas more extensive fractures of the vertebral body are best identified by load cell readings due to the considerable loss in compressive resistance. The discrimination thresholds corresponding to the AE parameters were based on calibrated measurements of AE wave pressure and may ultimately be used to examine the onset and progression of vertebral fracture in other loading scenarios.

Application of multiple wrapped cancellous bone graft methods for treatment of segmental bone defects.

BACKGROUND: The aims of this study were to discuss the principle, therapeutic effect and influencing factors of multiple wrapped cancellous bone graft methods for treatment of segmental bone defects. METHODS: This study retrospectively analyzed the therapeutic effect of different wrapped autologous cancellous bone graft techniques on 51 patients aged (34.5 ± 11.5) years with segmental bone defects. Cancellous bones were wrapped with titanium mesh (n = 9), line mesh (n = 10), line suturing or line binding cortical block, (n = 13), or induced membrane (n = 19). The bone defeats were as follows: tibia (n = 23), radial bone (n = 10), humerus (n = 8), ulnar bone (n = 7), and femur (n = 3). The defect lengths were (5.9 ± 1.1) cm. The functionary recovery of adjacent joint was evaluated by the Paley's method and DASH, respectively. RESULTS: The incision healed by first intention in 48 cases and secondary healing in 3 cases. All patients were followed up for 19.1 ± 7.1 (12-48) months. Other than one patient with nonunion who received a secondary bone graft, all the patients were first intention of bone healing (the healing rate was 98.0%). The healing time was 6.1 ± 2.1 (3-15) months. There were no significant differences in the healing time among the 4 groups (χ2 = 1.864, P = 0.601). The incidence of complications in the grafted site was 11.8%, whereas it was 21.6% in the harvest site. At the last follow-up, all the patients had recovered and were able to engage in weight-bearing activities. The functional recovery was good to excellent in 78.4% of cases, there were no significant difference among the 4 groups (χ2 = 5.429, P = 0.143). CONCLUSIONS: Wrapped cancellous bone grafting is a modified free bone graft method that can be used in the treatment of small and large segmental bone defects as it prevents loosening and bone absorption after bone grafting. The effect of bone healing is related with the quality and quantity of grafted bone, stability of bone defects, property of wrapping material and peripheral blood supply.

High-speed X-ray visualization of dynamic crack initiation and propagation in bone.

The initiation and propagation of physiological cracks in porcine cortical and cancellous bone under high rate loading were visualized using high-speed synchrotron X-ray phase-contrast imaging (PCI) to characterize their fracture behaviors under dynamic loading conditions. A modified Kolsky compression bar was used to apply dynamic three-point flexural loadings on notched specimens and images of the fracture processes were recorded using a synchronized high-speed synchrotron X-ray imaging set-up. Three-dimensional synchrotron X-ray tomography was conducted to examine the initial microstructure of the bone before high-rate experiments. The experimental results showed that the locations of fracture initiations were not significantly different between the two types of bone. However, the crack velocities in cortical bone were higher than in cancellous bone. Crack deflections at osteonal cement lines, a prime toughening mechanism in bone at low rates, were observed in the cortical bone under dynamic loading in this study. Fracture toughening mechanisms, such as uncracked ligament bridging and bridging in crack wake were also observed for the two types of bone. The results also revealed that the fracture toughness of cortical bone was higher than cancellous bone. The crack was deflected to some extent at osteon cement line in cortical bone instead of comparatively penetrating straight through the microstructures in cancellous bone. STATEMENT OF SIGNIFICANCE: Fracture toughness is with great importance to study for crack risk prediction in bone. For those cracks in bone, most of them are associated with impact events, such as sport accidents. Consequently, we visualized, in real-time, the entire processes of dynamic fractures in notched cortical bone and cancellous bone specimens using synchrotron X-ray phase contrast imaging. The onset location of crack initiation was found independent on the bone type. We also found that, although the extent was diminished, crack deflections at osteon cement lines, a major toughening mechanism in transversely orientated cortical bone at quasi-static rate, were still played a role in resisting cracking in dynamically loaded specimen. These finding help researchers to understand the dynamic fracture behaviors in bone.

Osteoblast precursors and inflammatory cells arrive simultaneously to sites of a trabecular-bone injury.

Background and purpose - Fracture healing in the shaft is usually described as a sequence of events, starting with inflammation, which triggers mesenchymal tissue formation in successive steps. Most clinical fractures engage cancellous bone. We here describe fracture healing in cancellous bone, focusing on the timing of inflammatory and mesenchymal cell type appearance at the site of injury Material and methods - Rats received a proximal tibial drill hole. A subgroup received clodronate-containing liposomes before or after surgery. The tibiae were analyzed with micro-CT and immunohistochemistry 1 to 7 days after injury. Results - Granulocytes (myeloperoxidase) appeared in moderate numbers within the hole at day 1 and then gradually disappeared. Macrophage expression (CD68) was seen on day 1, increased until day 3, and then decreased. Mesenchymal cells (vimentin) had already accumulated in the periphery of the hole on day 1. Mesenchymal cells dominated in the entire lesion on day 3, now producing extracellular matrix. A modest number of preosteoblasts (RUNX2) were seen on day 1 and peaked on day 4. Osteoid was seen on day 4 in the traumatized region, with a distinct border to the uninjured surrounding marrow. Clodronate liposomes given before the injury reduced the volume of bone formation at day 7, but no reduction in macrophage numbers could be detected. Interpretation - The typical sequence of events in shaft fractures was not seen. Mesenchymal cells appeared simultaneously with granulocyte and macrophage arrival. Clodronate liposomes, known to reduce macrophage numbers, seemed to be associated with the delineation of the volume of tissue to be replaced by bone. Most fracture healing studies in animal models concern cortical bone in shafts. However, most fractures in patients occur in cancellous bone in the metaphysis, such as the distal radius or in the vertebrae. A growing body of evidence suggests that there are important differences between the healing processes in cortical and cancellous bone.

Age-related mechanical strength evolution of trabecular bone under fatigue damage for both genders: Fracture risk evaluation.

Bone tissue is a living composite material, providing mechanical and homeostatic functions, and able to constantly adapt its microstructure to changes in long term loading. This adaptation is conducted by a physiological process, known as "bone remodeling". This latter is manifested by interactions between osteoclasts and osteoblasts, and can be influenced by many local factors, via effects on bone cell differentiation and proliferation. In the current work, age and gender effects on damage rate evolution, throughout life, have been investigated using a mechanobiological finite element modeling. To achieve the aim, a mathematical model has been developed, coupling both cell activities and mechanical behavior of trabecular bone, under cyclic loadings. A series of computational simulations (ABAQUS/UMAT) has been performed on a 3D human proximal femur, allowing to investigate the effects of mechanical and biological parameters on mechanical strength of trabecular bone, in order to evaluate the fracture risk resulting from fatigue damage. The obtained results revealed that mechanical stimulus amplitude affects bone resorption and formation rates, and indicated that age and gender are major factors in bone response to the applied loadings.

Bone regeneration capacity of magnesium phosphate cements in a large animal model.

Magnesium phosphate minerals have captured increasing attention during the past years as suitable alternatives for calcium phosphate bone replacement materials. Here, we investigated the degradation and bone regeneration capacity of experimental struvite (MgNH4PO4·6H2O) forming magnesium phosphate cements in two different orthotopic ovine implantation models. Cements formed at powder to liquid ratios (PLR) of 2.0 and 3.0 g ml-1 were implanted into trabecular bone using a non-load-bearing femoral drill-hole model and a load-bearing tibial defect model. After 4, 7 and 10 months the implants were retrieved and cement degradation and new bone formation was analyzed by micro-computed tomography (µCT) and histomorphometry. The results showed cement degradation in concert with new bone formation at both defect locations. Both cements were almost completely degraded after 10 months. The struvite cement formed with a PLR of 2.0 g ml-1 exhibited a slightly accelerated degradation kinetics compared to the cement with a PLR of 3.0 g ml-1. Tartrat-resistant acid phosphatase (TRAP) staining indicated osteoclastic resorption at the cement surface. Energy dispersive X-ray analysis (EDX) revealed that small residual cement particles were mostly accumulated in the bone marrow in between newly formed bone trabeculae. Mechanical loading did not significantly increase bone formation associated with cement degradation. Concluding, struvite-forming cements might be promising bone replacement materials due to their good degradation which is coupled with new bone formation. STATEMENT OF SIGNIFICANCE: Recently, the interest in magnesium phosphate cements (MPC) for bone substitution increased, as they exhibit high initial strength, comparably elevated degradation potential and the release of valuable magnesium ions. However, only few in vivo studies, mostly including non-load-bearing defects in small animals, have been performed to analyze the degradation and regeneration capability of MPC derived compounds. The present study examined the in vivo behavior of magnesiumammoniumphosphate hexahydrate (struvite) implants with different porosity in both mechanically loaded and non-loaded defects of merino sheep. For the first time, the effect of mechanical stimuli on the biological outcome of this clinically relevant replacement material is shown and directly compared to the conventional unloaded defect situation in a large animal model.

A New Ensemble Classification System For Fracture Zone Prediction Using Imbalanced Micro-CT Bone Morphometrical Data.

Trabecular bone fractures constitute a major health issue for the modern societies, with the currently established prediction methods of fracture risk, such as bone mineral density (BMD), resulting in errors up to 40%. Fracture-zone prediction based on bone's microstructure has been recently proposed as an alternative prediction method of fracture risk. In this paper, a classification system (CS) for the automatic fracture-zone prediction based on an Ensemble of Imbalanced Learning methods is proposed, following the observation that the percentage of the actual fractured bone area is significantly smaller than the intact bone in the case of a fracture event. The sample is divided into Volumes of Interest (VOIs) of specific size and 29 morphometrical parameters are calculated from each VOI, which serve as input features for the CS in order for it to separate the input patterns in to two classes: fractured and nonfractured. To this end, two well-established Imbalanced Learning methods, namely Random Undersampling and Synthetic Minority Oversampling, and two popular classification algorithms, namely Multilayer Perceptrons and Support Vector Machines, are tested and combined accordingly, to provide the best possible performance on a dataset that contains 45 specimens' pre- and postfailure scans. The best combination is then compared with three well-established Ensembles of Imbalanced Learning methods, namely RUSBoost, UnderBagging and SMOTEBagging. The experimental results clearly show that the proposed CS outperforms the competition, scoring in some occasions more than 90% in G-Mean and Area under Curve metrics. Finally, an investigation on the significance of the various trabecular bone's biomechanical parameters is made using the sequential forward floating selection technique, in order to identify possible biomarkers for fracture-zone prediction.

Hemostasis and Safety of a Novel Fibrin Dressing Versus Standard Gauze in Bleeding Cancellous Bone in a Caprine Spine Surgery Model.

BACKGROUND: Decorticated bone is a significant source of blood loss in scoliosis surgery. Current hemostatic methods include packed gauze (GS), physical barriers such as bone wax, and xenograft collagen-based materials. We assessed the safety and efficacy of a novel fibrin dressing (dextran-thrombin-fibrinogen [DTF]) compared to GS. This dressing comprises lyophilized thrombin and fibrinogen embedded in an elastic electrospun nanofiber dextran matrix. PURPOSE: The study tests the hypothesis that DTF is more efficacious than GS in control of bleeding from cancellous bone. STUDY DESIGN: A preclinical Good Laboratory Practices (GLP) study. METHODS: We enrolled 10 goats that were followed for 28 ± 1 days. Each animal was randomly assigned to the test or control group. Both test and control animals had 4 cancellous bone injuries. Test animal injuries were treated with DTF, whereas standard GS was used to control bleeding in the control animals. Bleeding at the bone injury site was characterized as either none, oozing, flowing, or pulsatile and was assessed at 4 and 8 minutes after dressing application. Goats were survived 28 ± 1 days and then necropsied. RESULTS: Application of the fibrin dressing to bleeding cancellous bone, both posterior spinal lamina, and iliac crest graft sites, resulted in control of bleeding within 4 minutes at all injury sites. Eighty percent of control injury sites continued to bleed after 8 minutes and required application of bone wax to control bleeding. There were no differences in prothrombin time, partial thromboplastin time, or fibrinogen levels between test and control animals at 1 or 28 days. We observed no adverse histologic reactions at 28 days. CONCLUSION: The fibrin dressing is an efficacious and safe method of controlling blood loss from cancellous bone in a spine surgery model.

Isolated metaphyseal injury influences unrelated bones.

Background and purpose - Fracture healing involves different inflammatory cells, some of which are not part of the traditional bone field, such as B-cells and cytotoxic T-cells. We wanted to characterize bone healing by flow cytometry using 15 different inflammatory cell markers in a mouse model of metaphyseal injury, and incidentally discovered a previously unknown general skeletal reaction to trauma. Material and methods - A bent needle was inserted and twisted to traumatize the cancellous bone in the proximal tibia of C57/Bl6 female mice. This is known to induce vivid bone formation locally in the marrow compartment. Cells were harvested from the injured region, the uninjured contralateral tibia, and the humerus. The compositions of the immune cell populations were compared to those in untraumatized control animals. Results - Tibial metaphyseal injury led to substantial changes in the cell populations over time. Unexpectedly, similar changes were also seen in the contralateral tibia and in the humerus, despite the lack of local trauma. Most leukocyte subsets were affected by this generalized reaction. Interpretation - A relatively small degree of injury to the proximal tibia led to systemic changes in the immune cell populations in the marrow of unrelated bones, and probably in the entire skeleton. The few changes that were specific for the injury site appeared to relate to modulatory functions.

Trabecular Microstructure and Damage Affect Cement Leakage From the Basivertebral Foramen During Vertebral Augmentation.

STUDY DESIGN: A prospective study on cadaver specimens. OBJECTIVE: To explore why cement leakage from basivertebral foramen (BF) easily occurs during vertebral augmentation procedures. SUMMARY OF BACKGROUND DATA: Type B (through BF, basivertebral foramen) cement leakage is the most common type after vertebral augmentation, but the mechanism of this is still controversial. The contribution of vertebral trabecular bone orientation and trabecular damage during compression fracture to cement leakage is still unknown. METHODS: In this study, 12 fresh-frozen human lumbar spines (T12-L5) were collected and divided into 24 three-segment units. Mechanical testing was performed to simulate a compression fracture. MicroCT were performed on all segments before and after mechanical testing, and trabecular microstructure of the superior, middle (containing BF), and inferior 1/3 of each vertebral body was analyzed. The diameter variation of intertrabecular space before and after compression fracture was used to quantify trabecular injury. After mechanical testing, vertebral augmentation, and imaging-based diagnosis were used to evaluate cement leakage. RESULTS: Trabecular bone microstructural parameters in middle region (containing BF) were lower than those of the superior or inferior regions (P < 0.01). After compressive failure, 3D-reconstruction of the vertebral body by MicroCT demonstrated that intertrabecular distance in the middle region was markedly increased. Type B cement leakage was the most common type after vertebral augmentation, as found previously in Wang et al. (Spine J 2014;14: 1551-1558). CONCLUSION: The presence of the BF and the relative sparsity of trabecular bone make the middle region of the vertebral body the mechanically weakest region. Trabecular bone in middle region suffered the most severe damage during compressive failure of the vertebral body, which resulted in the greatest intervertebral spacing, and subsequently the highest percentage of type B cement leakage. These data suggest specific mechanisms by which cement may leak from the BF, and the contribution of trabecular microstructure and trabecular injury. LEVEL OF EVIDENCE: 4.

The roles of architecture and estrogen depletion in microdamage risk in trabecular bone.

Bone quantity, or density, has insufficient power to discriminate fracture risk in individuals. Additional measures of bone quality, such as microarchitectural characteristics and bone tissue properties, including the presence of damage, may improve the diagnosis of fracture risk. Microdamage and microarchitecture are two aspects of trabecular bone quality that are interdependent, with several microarchitectural changes strongly correlated to damage risk after compensating for bone density. This study aimed to delineate the effects of microarchitecture and estrogen depletion on microdamage susceptibility in trabecular bone using an ovariectomized sheep model to mimic post-menopausal osteoporosis. The propensity for microdamage formation in trabecular bone of the distal femur was studied using a sequence of compressive and torsional overloads. Ovariectomy had only minor effects on the microarchitecture at this anatomic site. Microdamage was correlated to bone volume fraction and structure model index (SMI), and ovariectomy increased the sensitivity to these parameters. The latter may be due to either increased resorption cavities acting as stress concentrations or to altered bone tissue properties. Pre-existing damage was also correlated to new damage formation. However, sequential loading primarily generated new cracks as opposed to propagating existing cracks, suggesting that pre-existing microdamage contributes to further damage of bone by shifting load bearing to previously undamaged trabeculae, which are subsequently damaged. The transition from plate-like to rod-like trabeculae, indicated by SMI, dictates this shift, and may be a hallmark of bone that is already predisposed to accruing greater levels of damage through compromised microarchitecture.

Insufficient Penetration of Bone Cement Into the Trabecular Bone: A Potential Risk for Delayed Bone Cement Displacement After Kyphoplasty?

OBJECTIVE: Balloon kyphoplasty is a minimally invasive procedure used in the treatment of vertebral compression fractures. Although cement leakage is a well-known complication of the procedure, delayed displacement of the injected bone cement material, occurring several weeks after kyphoplasty, is a rare occurrence. In this report, we describe a case of delayed dislodgement of the bone cement occurring 4 weeks after successful kyphoplasty for an osteoporotic compression fracture of L4. CASE REPORT: A balloon kyphoplasty was successfully performed for the clinical management of an osteoporotic compression fracture of the L4 vertebral body in a 74-year-old patient with Kummel disease. However, further progression of the collapse of L4 vertebra was identified on radiographic imaging obtained 4 weeks after the kyphoplasty. A cystic filling pattern of the bone cement was observed, rather than the expected matrix-like pattern, which contributed to the continued progression of the collapse of the vertebral body. CONCLUSIONS: As delayed displacement of bone cement can result in progression of an osteoporotic compression fracture of the vertebrae, we propose that sufficient penetration of bone cement into the microstructure of the trabecular bone of the vertebral body during kyphoplasty could reduce the risk of this phenomenon.

Inter-trabecular bone formation: a specific mechanism for healing of cancellous bone.

Background and purpose - Studies of fracture healing have mainly dealt with shaft fractures, both experimentally and clinically. In contrast, most patients have metaphyseal fractures. There is an increasing awareness that metaphyseal fractures heal partly through mechanisms specific to cancellous bone. Several new models for the study of cancellous bone healing have recently been presented. This review summarizes our current knowledge of cancellous fracture healing. Methods - We performed a review of the literature after doing a systematic literature search. Results - Cancellous bone appears to heal mainly via direct, membranous bone formation that occurs freely in the marrow, probably mostly arising from local stem cells. This mechanism appears to be specific for cancellous bone, and could be named inter-trabecular bone formation. This kind of bone formation is spatially restricted and does not extend more than a few mm outside the injured region. Usually no cartilage is seen, although external callus and cartilage formation can be induced in meta-physeal fractures by mechanical instability. Inter-trabecular bone formation seems to be less sensitive to anti-inflammatory treatment than shaft fractures. Interpretation - The unique characteristics of inter-trabecular bone formation in metaphyseal fractures can lead to differences from shaft healing regarding the effects of age, loading, or drug treatment. This casts doubt on generalizations about fracture healing based solely on shaft fracture models.

Gamma correction 99mTc-hydroxymethylene diphosphonate pinhole bone scan diagnosis and histopathological verification of trabecular contusion in young rats.

The aim of this rat experiment using gamma correction pinhole bone scan (GCPBS) was two-fold: first, to confirm whether specific unwashed micro Tc-hydroxymethylene diphosphonate (Tc-HDP) uptake occurs in trabecular contusion (TC) and washed out uptake occurs in edema and/or hemorrhage-irritated trabeculae, and, second, to histopathologically identify the tissue in which the Tc-HDP uptake is unwashed. Five young Sprague-Dawley rats were used for the contusion model and one rat was used as a control. Trauma was inflicted on the femoral shaft with a free-falling iron ball. The presence of injury was confirmed by means of Tc-HDP pinhole bone scan and radiography with built-in scales. All rats were carefully killed for histopathologic verification. The size and shape of the unwashed high Tc-HDP uptake in TC were assessed on a 50-fold magnified GCPBS (mGCPBS), and the findings were compared with those of hematoxylin eosin (H&E) stain findings. mGCPBS showed TC with osteoblastic rimming and high unwashed Tc-HDP uptake. H&E stain findings showed osteoblastic rimming. The smallest TC was 0.03 mm in transaxial diameter on both mGCPBS and H&E stain findings. The four shapes of TC were bar-like, round, ovoid, and pinpointed in the longitudinal, oblique, and transaxial sections. The size and shape shown on mGCPBS and H&E stain findings were in good accord, demonstrating that TC was coated with osteoblastic rimming, which is pathognomonic of contusion. This sign was not seen for the control rat. mGCPBS is useful in the diagnosis of TC because osteoblastic rimming, typically stained in the base, is marked with unwashed high Tc-HDP uptake.

Screw insertion in trabecular bone causes peri-implant bone damage.

Secure fracture fixation is still a major challenge in orthopedic surgery, especially in osteoporotic bone. While numerous studies have investigated the effect of implant loading on the peri-implant bone after screw insertion, less focus has been put on bone damage that may occur due to the screw insertion process itself. Therefore, the aim of this study was to localize and quantify peri-implant bone damage caused by screw insertion. We used non-invasive three-dimensional micro-computed tomography to scan twenty human femoral bone cores before and after screw insertion. After image registration of the pre- and post-insertion scans, changes in the bone micro-architecture were identified and quantified. This procedure was performed for screws with a small thread size of 0.3mm (STS, N=10) and large thread size of 0.6mm (LTS, N=10). Most bone damage occurred within a 0.3mm radial distance of the screws. Further bone damage was observed up to 0.6mm and 0.9 mm radial distance from the screw, for the STS and LTS groups, respectively. While a similar amount of bone damage was found within a 0.3mm radial distance for the two screw groups, there was significantly more bone damage for the LTS group than the STS group in volumes of interest between 0.3-0.6mm and 0.6-0.9 mm. In conclusion, this is the first study to localize and quantify peri-implant bone damage caused by screw insertion based on a non-invasive, three-dimensional, micro-CT imaging technique. We demonstrated that peri-implant bone damage already occurs during screw insertion. This should be taken into consideration to further improve primary implant stability, especially in low quality osteoporotic bone. We believe that this technique could be a promising method to assess more systematically the effect of peri-implant bone damage on primary implant stability. Furthermore, including peri-implant bone damage due to screw insertion into patient-specific in silico models of implant-bone systems could improve the accuracy of these models.