Biomechanical Behavior of Injected Cement Spacers versus Traditional Cages in Low-Density Lumbar Spine under Compression Loading.

Background and Objectives: Osteoporosis renders the use of traditional interbody cages potentially dangerous given the high risk of damage in the bone-implant interface. Instead, injected cement spacers can be applied as interbody devices; however, this technique has been mainly used in cervical spine surgery. This study aimed at investigating the biomechanical behavior of cement spacers versus traditional cages in lumbar spine surgery. Materials and Methods: Destructive monotonic axial compression testing was performed on 20 human cadaveric low-density lumbar segments from elderly donors (14 f/6 m, 70.3 ± 12.0 y) treated with either injected cement spacers (n = 10) or traditional cages (n = 10) without posterior instrumentation. Stiffness, failure load and displacement were compared. The effects of bone density, vertebral geometry and spacer contact area were evaluated. Results: Cement spacers demonstrated higher stiffness, significantly smaller displacement (p < 0.001) and a similar failure load compared to traditional cages. In the cage group, stiffness and failure load depended strongly on bone density and vertebral height, whereas failure displacement depended on vertebral anterior height. No such correlations were identified with cement spacers. Conclusions: Cement spacers used in lumbar interbody stabilization provided similar compression strength, significantly smaller failure displacement and a stiffer construct than traditional cages that provided benefits mainly for large and strong vertebrae. Cement stabilization was less sensitive to density and could be more beneficial also for segments with smaller and less dense vertebrae. In contrast to the injection of cement spacers, the optimal insertion of cages into the irregular intervertebral space is challenging and risks damaging bone. Further studies are required to corroborate these findings and the treatment selection thresholds.

A Novel Technique for Treatment of Metaphyseal Voids in Proximal Humerus Fractures in Elderly Patients.

Background and Objectives: The treatment of proximal humerus fractures in elderly patients is challenging, with reported high complication rates mostly related to implant failure involving screw cut-out and penetration. Metaphyseal defects are common in osteoporotic bone and weaken the osteosynthesis construct. A novel technique for augmentation with polymethylmethacrylate (PMMA) bone cement was developed for the treatment of patients in advanced age with complex proximal humerus fractures and metaphyseal voids, whereby the cement was allowed to partially cure for 5-7 min after mixing to achieve medium viscosity, and then it was manually placed into the defect through the traumatic lateral window with a volume of 4-6 mL per patient. The aim of this retrospective clinical study was to assess this technique versus autologous bone graft augmentation and no augmentation. Materials and Methods: The outcomes of 120 patients with plated Neer three- and four-part fractures, assigned to groups of 63 cases with no augmentation, 28 with bone graft augmentation and 29 with cement augmentation, were assessed in this study. DASH, CS, pain scores and range of motion were analyzed at 3, 6 and 12 months. Statistical analysis was performed with factors for treatment and age groups, Neer fracture types and follow-up periods, and with the consideration of age as a covariate. Results: DASH and CS improved following cement augmentation at three and six months compared to bone grafting, being significant when correcting for age as a covariate (p ≤ 0.007). While the age group had a significant effect on both these scores with worsened values at a higher age for non-augmented and grafted patients (p ≤ 0.044), this was not the case for cement augmented patients (p ≥ 0.128). Cement augmentation demonstrated good clinical results at 12 months with a mean DASH of 10.21 and mean CS percentage of 84.83% versus the contralateral side, not being significantly different among the techniques (p ≥ 0.372), despite the cement augmented group representing the older population with more four-part fractures. There were no concerning adverse events specifically related to the novel technique. Conclusions: This study has detailed a novel technique for the treatment of metaphyseal defects with PMMA cement augmentation in elderly patients with complex proximal humerus fractures and follow-up to one year, whereby the cement was allowed to partially cure to achieve medium viscosity, and then it was manually placed into the defect through the traumatic lateral window. The results demonstrate clinically equivalent short-term results to 6 months compared to augmentation with bone graft or no augmentation-despite the patient group being older and with a higher rate of more severe fracture patterns. The technique appears to be safe with no specifically related adverse events and can be added in the surgeon's armamentarium for the treatment of these difficult to manage fractures.

Indirect foraminal decompression and improvement in the lumbar alignment after percutaneous cement discoplasty.

PURPOSE: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical procedure, that can provide a segmental stabilizing and indirect decompression effect in case of severely degenerated discs characterized by vacuum phenomenon. The objective of this study was to evaluate the effects of PCD on spinopelvic radiological parameters and their associations with the clinical outcome. METHODS: Retrospective analysis of prospectively collected dataset of 28 patients (112 lumbar segments) who underwent single- or multilevel PCD was performed. Spinopelvic, intrasegmental and intersegmental parameters were measured on lumbar X-rays pre-, postoperatively and 6 months after the surgery. Correlations between radiological parameters and clinical outcome data were determined. RESULTS: Sacral slope significantly increased (p < .001), and pelvic tilt (p < .05) was decreased after the PCD procedure. Segmental and total lordosis (p < .05, p < .05) disc and foraminal height showed significantly increase (p < .001, p < .001) after procedure. Pain and disability (ODI) significantly decreased due to PCD. An association was found between postoperative increase in SS and improvement in ODI (r = 0.39, p < .05). The change in low back pain was correlated with segmental scoliosis correction (p < .001). Moderate correlation was detected between the increase in disc height and ODI (p < .05) as well as leg pain (p < .01). CONCLUSION: PCD is an effective minimally invasive technique to treat axial pain and disability related to severe lumbar disc degeneration. Our study shows that an improvement in lumbar alignment and a significant indirect foraminal decompression could be achieved with the procedure. These changes can significantly contribute to the pain relief and increase in the patients' functional capacity. These slides can be retrieved under Electronic Supplementary Material.

Autopsy Features of Fatal Donkey Attack.

Lethal donkey attacks have very rarely been described. The case of a 65-year-old man who was found deceased on a country road with 2 domestic donkeys nearby is, therefore, reported. Examination of the body revealed contusions and lacerations of the face and scalp, a comminuted fracture of the left maxilla, comminuted fracturing of the right radius and ulna and of the left anterior superior iliac spine, a flail chest, and pulmonary contusions. In addition, there were bite marks on the left thigh, right buttock, right axilla/upper arm, and left cheek which corresponded to the dental arcades of the donkeys. Death had resulted from blunt chest trauma due to an attack by 1 or 2 donkeys. Deaths and serious injuries are much more commonly caused by horses; however, this case shows that even domesticated donkeys may also rarely be capable of inflicting significant trauma and so should be approached with circumspection.

Full-Field Calcium K-Edge X-ray Absorption Near-Edge Structure Spectroscopy on Cortical Bone at the Micron-Scale: Polarization Effects Reveal Mineral Orientation.

Here, we show results on X-ray absorption near edge structure spectroscopy in both transmission and X-ray fluorescence full-field mode (FF-XANES) at the calcium K-edge on human bone tissue in healthy and diseased conditions and for different tissue maturation stages. We observe that the dominating spectral differences originating from different tissue regions, which are well pronounced in the white line and postedge structures are associated with polarization effects. These polarization effects dominate the spectral variance and must be well understood and modeled before analyzing the very subtle spectral variations related to the bone tissue variations itself. However, these modulations in the fine structure of the spectra can potentially be of high interest to quantify orientations of the apatite crystals in highly structured tissue matrices such as bone. Due to the extremely short wavelengths of X-rays, FF-XANES overcomes the limited spatial resolution of other optical and spectroscopic techniques exploiting visible light. Since the field of view in FF-XANES is rather large the acquisition times for analyzing the same region are short compared to, for example, X-ray diffraction techniques. Our results on the angular absorption dependence were verified by both site-matched polarized Raman spectroscopy, which has been shown to be sensitive to the orientation of bone building blocks and by mathematical simulations of the angular absorbance dependence. As an outlook we further demonstrate the polarization based assessment of calcium-containing crystal orientation and specification of calcium in a beta-tricalcium phosphate (ß-Ca3(PO4)2 scaffold implanted into ovine bone. Regarding the use of XANES to assess chemical properties of Ca in human bone tissue our data suggest that neither the anatomical site (tibia vs jaw) nor pathology (healthy vs necrotic jaw bone tissue) affected the averaged spectral shape of the XANES spectra.

Accessing osteocyte lacunar geometrical properties in human jaw bone on the submicron length scale using synchrotron radiation µCT.

The architectural properties of the osteocyte cell network provide a valuable basis for understanding the mechanisms of bone remodelling, mineral homeostasis, ageing and pathologies. Recent advances in synchrotron microtomography enable unprecedented three-dimensional imaging of both the bone lacunar network and the extracellular matrix. Here, we investigate the three-dimensional morphological properties of osteocyte lacunae in human healthy and bisphosphonate-related osteonecrotic jaw bone based on synchrotron X-ray computed tomography images, with a spatial isotropic voxel size of 300 nm. Bisphosphonate-related osteonecrosis of the jaw is a relatively new disease with increasing incidence, which remains poorly understood. A step forward in elucidating this malady is to assess whether, and how, the morphology of the osteocyte lacunar network is modified in the affected jaw tissue. We evaluate thousands of cell lacunae from five specimens of which three originate from patients diagnosed with bisphosphonate-associated osteonecrosis. In this exploratory study, we report three-dimensional quantitative results on lacunar volumes (296-502 µm(3)), shape (approximated by an ellipsoidal shape with principal axes a > b > c, such that a = 2.2b and a = 4c) and spatial distribution (i.e., 50% of the mineralized matrix volume is located within 12 µm to the closest lacunar boundary) at submicron resolution on such specimens. We observe that the average lacunar volumes of the bisphosphonate-related osteonecrotic jaw specimens were within the range of volumes found in the two specimens originating from healthy donors and conclude that lacunar volumes are not the key element in the course of bisphosphonate-related osteonecrotic jaw. In three out of five specimens we observe lacunar volume sizes in segmented osteons to be significantly different compared to lacunar volumes in the adjacent tissue regions. Furthermore, we quantify the number of lacunae containing small dense objects (on average 9%). In contrast to lacunar morphology we report the lacunar density (16,000-50,000 per mm(3)) to be different in jaw bone tissue compared to what has been reported in femoral sites.

Homogenized finite element simulations can predict the primary stability of dental implants in human jawbone.

Adequate primary stability is a pre-requisite for the osseointegration and long-term success of dental implants. Primary stability depends essentially on the bone mechanical integrity at the implantation site. Clinically, a qualitative evaluation can be made on medical images, but finite element (FE) simulations can assess the primary stability of a bone-implant construct quantitatively based on high-resolution CT images. However, FE models lack experimental validation on clinically relevant bone anatomy. The aim of this study is to validate such an FE model on human jawbones. Forty-seven bone biopsies were extracted from human cadaveric jawbones. Dental implants of two sizes (Ø3.5 mm and Ø4.0 mm) were inserted and the constructs were subjected to a quasi-static bending-compression loading protocol. Those mechanical tests were replicated with sample-specific non-linear homogenized FE models. Bone was modeled with an elastoplastic constitutive law that included damage. Density-based material properties were mapped based on µCT images of the bone samples. The experimental ultimate load was better predicted by FE (R2 = 0.83) than by peri-implant bone density (R2 = 0.54). Unlike bone density, the simulations were also able to capture the effect of implant diameter. The primary stability of a dental implant in human jawbones can be predicted quantitatively with FE simulations. This method may be used for improving the design and insertion protocols of dental implants.

Development of an in vitro biofilm model of the human supra-gingival microbiome for Oral microbiome transplantation.

The high prevalence of dental caries and periodontal disease place a significant burden on society, both socially and economically. Recent advances in genomic technologies have linked both diseases to shifts in the oral microbiota - a community of >700 bacterial species that live within the mouth. The development of oral microbiome transplantation draws on the success of fecal microbiome transplantation for the treatment of gut pathologies associated with disease. Many current in vitro oral biofilm models have been developed but do not fully capture the complexity of the oral microbiome which is required for successful OMT. To address this, we developed an in vitro biofilm system that maintained an oral microbiome with 252 species on average over 14 days. Six human plaque samples were grown in 3D printed flow cells on hydroxyapatite discs using artificial saliva medium (ASM). Biofilm composition and growth were monitored by high throughput sequencing and confocal microscopy/SEM, respectively. While a significant drop in bacterial diversity occurred, up to 291 species were maintained in some flow cells over 14 days with 70% viability grown with ASM. This novel in vitro biofilm model represents a marked improvement on existing oral biofilm systems and provides new opportunities to develop oral microbiome transplant therapies.

Fatigue life of 3D-printed porous titanium dental implants predicted by validated finite element simulations.

Introduction: Porous dental implants represent a promising strategy to reduce failure rate by favoring osseointegration or delivering drugs locally. Incorporating porous features weakens the mechanical capacity of an implant, but sufficient fatigue strength must be ensured as regulated in the ISO 14801 standard. Experimental fatigue testing is a costly and time-intensive part of the implant development process that could be accelerated with validated computer simulations. This study aimed at developing, calibrating, and validating a numerical workflow to predict fatigue strength on six porous configurations of a simplified implant geometry. Methods: Mechanical testing was performed on 3D-printed titanium samples to establish a direct link between endurance limit (i.e., infinite fatigue life) and monotonic load to failure, and a finite element model was developed and calibrated to predict the latter. The tool was then validated by predicting the fatigue life of a given porous configuration. Results: The normalized endurance limit (10% of the ultimate load) was the same for all six porous designs, indicating that monotonic testing was a good surrogate for endurance limit. The geometry input of the simulations influenced greatly their accuracy. Utilizing the as-designed model resulted in the highest prediction error (23%) and low correlation between the estimated and experimental loads to failure (R2 = 0.65). The prediction error was smaller when utilizing specimen geometry based on micro computed tomography scans (14%) or design models adjusted to match the printed porosity (8%). Discussion: The validated numerical workflow presented in this study could therefore be used to quantitatively predict the fatigue life of a porous implant, provided that the effect of manufacturing on implant geometry is accounted for.

Complication Pattern After Percutaneous Cement Discoplasty: Identification of Factors Influencing Reoperation and Length of Hospital Stay.

OBJECTIVE: Percutaneous cement discoplasty (PCD) was introduced to treat symptomatic vertical instability of the lumbar spine in a minimally invasive way. The aim of the present study was to analyze the complication pattern after PCD and to identify factors that predict the chance of cement leakage, reoperation, and length of hospital stay (LOS). METHODS: patients were treated with PCD within the study period. Clinical features and complications were analyzed by applying descriptive statistics, whereas perioperative factors predictive of cement leakage, reoperation, and LOS were identified by regression models. RESULTS: Cement leakage rate was 30.4% in the total cohort; however, only fifth of them were symptomatic. Cement leakage itself did not have a significant influence on clinical outcome. Other complications and nonsurgical adverse events were registered only in 2.0% of cases. Age, subcutaneous fat tissue thickness, low viscosity cement, lower level of surgeon's experience and the number of operated levels were identified as risk factors of cement leakage (P < 0.01; c-index = 0.836). Type of procedure, Charlson comorbidity score, reoperation, and nonsurgical adverse events significantly increased the LOS (P < 0.01). Cement leakage, early surgical practice, and increased subcutaneous fat tissue thickness were risk factors for reoperation (P < 0.01; c-index = 0.72). CONCLUSIONS: PCD is a relatively safe and effective procedure for treating spinal instability caused by advanced-stage disc degeneration characterized by vacuum phenomenon. Cement leakage is not uncommon but is only a radiologic complication without clinical consequences in most cases. On the other hand, it can increase the LOS and is a significant risk factor for reoperation.

Biomechanical Assessment of Fracture Loads and Patterns of the Odontoid Process.

STUDY DESIGN: Laboratory study. OBJECTIVE: This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process. SUMMARY OF BACKGROUND DATA: Odontoid fractures of the second cervical vertebra (C2) represent the most common spine fracture type in the elderly. However, very little is known about the underlying biomechanical fracture mechanisms. MATERIALS AND METHODS: A total of 42 C2 human anatomic specimens were scanned via computed tomography, divided in six groups, and subjected to combined quasistatic loading at -15°, 0°, and 15° in sagittal plane and -50° and 0° in transverse plane until fracturing. Bone mineral density (BMD), height, fusion state of the ossification centers, stiffness, yield load, and ultimate load were assessed. RESULTS: While lowest values for stiffness, yield load, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences were observed between the study groups ( P ≥0.235). BMD correlated positively with yield load ( r2 =0.350, P <0.001) and ultimate load ( r2 =0.955, P <0.001) but not with stiffness ( r2 =0.082, P =0.07). The specimens with clearly distinguishable fusion of the ossification centers revealed less data scattering of the biomechanical outcomes. CONCLUSION: Load direction plays a subordinate role in traumatic fractures of the odontoid process. BMD was associated with significant correlation to the biomechanical outcomes. Thus, odontoid fractures appear to result from of an interaction between the load magnitude and bone quality.

[Orthopedic treatment of vertebral compression fractures in osteoporosis]. / A kompressziós csigolyatörések ortopédiai kezelése osteoporosisban.

Vertebral compression fracture is the most common type of fractures in osteoporosis increasing the mortality and morbidity of the systemic disease. Adequate treatment of the vertebral compression fractures is always in the focus of the national and international spine meetings and one of the most innovative fields in the spine care is the surgical therapy of the osteoporotic spine. Here, the authors summarize the orthopedic treatment options for vertebral compression fractures based on a literature review and their own institutional experience.

The Alveolar Ridge Splitting Technique on Maxillae: A Biomechanical Human Cadaveric Investigation.

The alveolar ridge splitting technique (ARST) offers an alternative to classic ridge augmentation techniques for successful insertion of dental implants. However, the buccal lamella is at risk of fracturing during ARST distraction. To better understand the fracture mechanisms and displacement limits of the split lamella, this study conducted biomechanical tests on human cadaveric maxilla specimens having extremely atrophied alveolar ridges treated with ARST. A total of 12 standardized alveolar splits were prepared on the maxillae of 3 elderly female donors using an oscillating piezoelectric saw. Mimicking the surgical distraction process of the lamella, each split was tested to failure using a dental osteotome attached to the crosshead of an electromechanical testing system. All specimens were scanned by means of high-resolution peripheral quantitative computed tomography prior to and post testing to evaluate split geometries and failure modes. Split stiffness, failure force, and displacement were 27.4 ± 18.7 N/mm, 12.0 ± 8.4 N, and 0.97 ± 0.31 mm, with no significant differences between anatomical sides and split locations (p ≥ 0.17). Stiffness correlated significantly with failure force (R 2 = 0.71, p < 0.01). None of the alveolar split widths correlated significantly with the outcomes from biomechanical testing (p ≥ 0.10). The results suggest that simple geometrical measures do not predict the allowed extent of lamella distraction prior to failure. More sophisticated methods are required for surgical planning to optimize the ARST outcomes. Still, the present study may advocate a clinical protocol for the maxilla where the implant site is prepared directly after osteotomy setting and immediately before full lamella dislocation, when the lamella is still stable, resistant to mechanical stress, and bone loss caused by the abrasion of the burr is minimized.

Finite Element Analysis and Biomechanical Testing to Analyze Fracture Displacement of Alveolar Ridge Splitting.

The alveolar ridge splitting technique enables reconstruction of atrophied alveolar ridges prior implantation. However, in cases of severe atrophy, there is an unpredictable risk of fracturing the buccal lamella during the expansion. Currently, there is no preoperative assessment to predict the maximum distraction of the lamella. The aim of this study was to develop a biomechanical model to mimic the alveolar ridge splitting and a finite element (FE) model to predict the experimental results. The biomechanical testing was conducted on porcine mandibles. To build the FE model high resolution peripheral quantitative computer tomography scans of one specimen was performed after the osteotomy outline, but before the lamella displacement. A servo-electric testing machine was used for the axial tension test to split the lamellae. Results showed, in line with clinical observations, that the lamellae broke primarily at the base of the splits with a median displacement of 1.27 mm. The FE model could predict fracture force and fracture displacement. Fracture force showed a nonlinear correlation with the height of the bone lamella. In conclusion, good correspondence between mechanical testing and virtual FE analysis showed a clinically relevant approach that may help to predict maximum lamella displacement to prevent fractures in the future.

Effect of gypsum on proliferation and differentiation of MC3T3-E1 mouse osteoblastic cells.

Recently, calcium sulfate dihydrate has been demonstrated as safe biodegradable osteoconductive bone void filler. However, its exact mechanism of action on bone cells is yet unknown. In this study, the influence of gypsum on gene expression and proliferation of MC3T3-E1 mouse pre-osteoblastic cells was investigated. Cells were cultured on gypsum disc, slice, polymethylmethacrylate (PMMA), or plastic culture plate for 15 days. Cell viability, alkaline phosphatase (ALP) activity and expression profile of 15 genes involved in bone metabolism were measured in cultures. Cell proliferation on gypsum was increased by almost 2-fold, while an inhibitory effect of PMMA on proliferation rate of osteoblasts was noted. Cells cultured on gypsum disc surface exhibited an increased ALP activity and markedly different gene expression profile. Quantitative real-time PCR data indicated the expression of genes that might provide a basis for an osteoinductive potential. MC3T3-E1 cells expressed genes typical of bone fracture healing like type II collagen and fibronectin 1. These effects might be related to the calcium content of gypsum and mediated likely via SMAD3. Our results suggest that gypsum can support new bone formation by its calcium content and modulatory effect on gene expression profile of bone cells.

[Review of the application of synthetic bone grafts. The role of the gypsum in bone substitution: molecular biological approach, based on own research results]. / A szintetikus csontpótló graftok alkalmazásának összefoglalása. A gipsz szerepe a csontpótlásban: molekuláris biológiai megközelítéssel, saját eredményeink alapján.

Properties of bone graft can determine the effectiveness, short and long term success of bone substitution procedure. In this paper, a brief report about advantages and disadvantages of modern bone substitution processes is presented and authors have explicated the opportunity of the usage of gypsum as bone graft. Recently, calcium sulfate dihydrate has been demonstrated as safe biodegradable osteoconductive bone void filler. However, its exact mechanism of action on bone cells and the molecular process of bone substitution is yet unknown. Authors have investigated the effect of gypsum on bone cells using molecular biology methods. Gypsum proved to be an ideal culture surface for proliferation of mice preosteoblastic cells, while polymethilmetacrylate bone cement - generally used in clinical practice as bone substitution material - inhibited cell growth. Gene expression profile of cells has significantly changed on gypsum surface - genes involved in new bone formation have expressed with an increased ratio - and an increased alkaline phosphatase activity has been measured from these cultures. Our results support the use of gypsum as synthetic bone graft and new properties of calcium sulfate dihydrate have been demonstrated due to molecular biological approach.

New approaches for cement-based prophylactic augmentation of the osteoporotic proximal femur provide enhanced reinforcement as predicted by non-linear finite element simulations.

BACKGROUND: High incidence and increased mortality related to secondary, contralateral proximal femoral fractures may justify invasive prophylactic augmentation that reinforces the osteoporotic proximal femur to reduce fracture risk. Bone cement-based approaches (femoroplasty) may deliver the required strengthening effect; however, the significant variation in the results of previous studies calls for a systematic analysis and optimization of this method. Our hypothesis was that efficient generalized augmentation strategies can be identified via computational optimization. METHODS: This study investigated, by means of finite element analysis, the effect of cement location and volume on the biomechanical properties of fifteen proximal femora in sideways fall. Novel cement cloud locations were developed using the principles of bone remodeling and compared to the "single central" location that was previously reported to be optimal. FINDINGS: The new augmentation strategies provided significantly greater biomechanical benefits compared to the "single central" cement location. Augmenting with approximately 12ml of cement in the newly identified location achieved increases of 11% in stiffness, 64% in yield force, 156% in yield energy and 59% in maximum force, on average, compared to the non-augmented state. The weaker bones experienced a greater biomechanical benefit from augmentation than stronger bones. The effect of cement volume on the biomechanical properties was approximately linear. Results of the "single central" model showed good agreement with previous experimental studies. INTERPRETATION: These findings indicate enhanced potential of cement-based prophylactic augmentation using the newly developed cementing strategy. Future studies should determine the required level of strengthening and confirm these numerical results experimentally.

Alterations of mass density and 3D osteocyte lacunar properties in bisphosphonate-related osteonecrotic human jaw bone, a synchrotron µCT study.

Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for treating osteoporosis or cancer, is a severe and most often irreversible side effect whose underlying pathophysiological mechanisms remain largely unknown. Osteocytes are involved in bone remodeling and mineralization where they orchestrate the delicate equilibrium between osteoclast and osteoblast activity and through the active process called osteocytic osteolysis. Here, we hypothesized that (i) changes of the mineralized tissue matrix play a substantial role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is altered in BRONJ. Synchrotron µCT with phase contrast is an appropriate tool for assessing both the 3D morphology of the osteocyte lacunae and the bone matrix mass density. Here, we used this technique to investigate the mass density distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in human bone samples from the jaw, femur and tibia. First, we compared healthy human jaw bone to human tibia and femur in order to assess the specific differences and address potential explanations of why the jaw bone is exclusively targeted by the necrosis as a side effect of BP treatment. Second, we investigated the differences between BRONJ and control jaw bone samples to detect potential differences which could aid an improved understanding of the course of BRONJ. We found that the apparent mass density of jaw bone was significantly smaller compared to that of tibia, consistent with a higher bone turnover in the jaw bone. The variance of the lacunar volume distribution was significantly different depending on the anatomical site. The comparison between BRONJ and control jaw specimens revealed no significant increase in mineralization after BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ group compared to the control jaw. Interestingly, the osteocyte-lacunar volume distribution was not altered after BP treatment.

Effect of vertebroplasty filler materials on viability and gene expression of human nucleus pulposus cells.

Consequences of intradiscal cement leakage--often occurring after vertebral cement augmentation for the treatment of vertebral compression fractures--are still unknown. In this study, we have investigated the influences of vertebroplasty filler materials (polymethylmethacrylate-, calcium phosphate- and calcium sulfate-based bone cement) on isolated nucleus pulposus cells. Cell viability of cultured human nucleus pulposus cells were measured after treatment with vertebroplasty filler materials. Gene expression profile of selected genes was determined with quantitative real-time PCR. The widely used polymethylmethacrylate and calcium phosphate cement significantly decreased cell number in a dose- and time-dependent manner while calcium sulfate cement affected cell viability less. Expression of genes involved in matrix metabolism of nucleus pulposus--aggrecan, collagens, small proteoglycans--as well as important transcription factors have also significantly changed due to treatment (e.g., 2.5-fold decrease in aggrecan expression was determined in cultures due to polymethylmethacrylate treatment). Our results suggest that vertebroplasty filler materials--depending on the type of applied material--can accelerate the degeneration of nucleus pulposus cells resulting in a less flexible disc in case of intradiscal cement leakage. This process may increase the risk of a subsequent new vertebral fracture, the main complication of vertebral augmentation.