Hip joint motion does not change one year after arthroscopic osteochondroplasty in patients with femoroacetabular impingement evaluated with dynamic radiostereometry

Purpose Dynamic radiostereometric analysis (dRSA) enables precise non-invasive three-dimensional motion-tracking of bones for assessment of joint kinematics. Hereby, the biomechanical effects of arthroscopic osteochondroplasty of the hip (ACH) can be evaluated in patients with femoroacetabular impingement (FAI). The aim was to investigate the pre- and postoperative range of motion (ROM) and the CT bone volume removed (BV) after ACH. We hypothesize increase in ROM 1 year after surgery. Methods Thirteen patients (6 female) with symptomatic FAI were included prospectively. The patient’s hips were CT-scanned and CT-bone models were created. Preoperative dRSA recordings were acquired during passive flexion to 90°, adduction, and internal rotation (FADIR). ACH was performed, CT and dRSA were repeated 3 months and 1 year postoperatively. Hip joint kinematics before, and 3 months and 1 year after ACH were compared pairwise. The bone volume removal was quantified and compared to change in ROM. Results Mean hip internal rotation, adduction and flexion were all unchanged after ACH at 1-year follow-up (p > 0.84). HAGOS scores revealed improvement of quality of life (QOL) from 32 to 60 (p = 0.02). The BV was between 406 and 1783 mm3 and did not correlate to post-operative ROM. Conclusions ACH surgery in FAI patients had no impact of ROM at 1-year follow-up. QOL improved significantly. This indicates that the positive clinical effects reported after ACH might be a result of reduced labral stress and cartilage pressure during end-range motion rather than increased ROM. Level of evidence Therapeutic prospective cohort study, level II.

Effect of Topical PTH 1-34 Functionalized to Biogran® in the Process of Alveolar Repair in Rats Submitted to Orchiectomy

(1) Background: There are many therapies for osteoporosis control and bone maintenance; anabolic drugs such as teriparatide and bone grafts help in the repair process and stimulate bone formation. Thus, the aim of the present study was to evaluate the behavior of repaired bone in the presence of PTH (teriparatide) associated with Biogran® (biomaterial) through a sonochemical procedure after extraction in rats. (2) Methods: The insertion of Biogran® with PTH in the alveolus was performed 30 days after incisor extraction. Euthanasia occurred after 60 days. (3) Results: The use of local treatment of PTH loaded with Biogran® in healthy rats promoted good results for micro-CT, with an increase in percentage and bone volume, number and trabecular separation and less total porosity. Greater immunostaining for Wnt, β-Catenin and osteocalcin proteins and lower expression for Thrombospondin-Related Adhesive Protein (TRAP), which shows an increase in the number of osteoblasts and inhibition of osteoclast action. However, the treated orchiectomized groups did not obtain such expressive results. (4) Conclusion: The use of Biogran® with PTH improved alveolar repair in rats. However, new researches with more efficient doses must be studied to collaborate effectively with the formation of a quality bone after the orchiectomy.

Physiological Reloading Recovers Histologically Disuse Atrophy of the Articular Cartilage and Bone by Hindlimb Suspension in Rat Knee Joint

Objective This study aimed to clarify physiological reloading on disuse atrophy of the articular cartilage and bone in the rat knee using the hindlimb suspension model. Design Thirty male rats were divided into 3 experimental groups: control group, hindlimb suspension group, and reloading after hindlimb suspension group. Histological changes in the articular cartilage and bone of the tibia were evaluated by histomorphometrical and immunohistochemical analyses at 2 and 4 weeks after reloading. Results The thinning and loss of matrix staining in the articular cartilage and the decrease in bone volume induced by hindlimb suspension recovered to the same level as the control group after 2 weeks of reloading. The proportion of the noncalcified and calcified layers of the articular cartilage and the thinning of subchondral bone recovered to the same level as the control group after 4 weeks of reloading. Conclusions Disuse atrophy of the articular cartilage and bone induced by hindlimb suspension in the tibia of rats was improved by physiological reloading.

Environmental and Genetic Factors Affecting Bone Diseases and Phenotypes in Mouse Models

Bone diseases and phenotypes are affected in multiple ways. We focused on studying the effects of genetic and environmental factors, especially their impact on bone properties. Firstly, we investigated the effects of β-caryophyllene (BCP), a naturally occurring dietary cannabinoid, on protecting bone from vitamin D deficiency in mice fed on a diet lacking or supplemented with vitamin D (VD). We found that the VD-deficient diet enhanced the length of femur and tibia bones (P<0.05), and increased bone volume (BV; P<0.01) and the trabecular bone volume fraction (BV/TV; P <0.01) compared to the D+ diet. When given BCP-containing diet, mice exhibited higher BV and bone mineral density (BMD; P<0.05) than the control group. The trabecular and cortical bone were also affected by VD and BCP. In addition, the inclusion of dietary BCP improved the serum concentrations of klotho (P < 0.05). In summary, these data indicate that BCP enhances the level of klotho in the serum, leading to improved bone properties and mineralization in an experimental mouse model. Under conditions lacking UV light, the D-deficient diet could affect multiple properties of bone, including trabecular and cortical bone, in mice. The D-deficient diet can also result in weight loss in mice. My second project is to evaluate the bone properties in a mouse model with Il-1rn mutation. When knockout for IL-1rn, mice of Balb/c genomic background exhibited susceptibility to spontaneous arthritis disease (SAD), while those of a DBA/1 background were resistant to developing SAD. Our progress on the study of SAD suggested that some of the bone phenotypes, BMD, BV, tibia length, and cortical thickness, were different between wildtype and IL-1rn knockout mice both in Balb/c and DBA/1 strains. The two congenic mouse strains were also evaluated for bone properties. The results revealed that IL-1rn affected BMD differently between Balb/c and DBA/1 mouse strains. The absence of IL-1rn decreased BMD in Balb/c mice and increased BMD in DBA/1 -/- mice compared with wildtype animals. QTL in DBA.B -/- which affect arthritis in congenic strains also regulated BMD, with interferon activated gene 202b (Ifi202b) being the most favored candidate gene for BMD. Our data suggest some of the bone phenotypes are affected by the regulation of gene expression in the context of IL-1ra loss. To our knowledge, this is the first study to investigate the relationship of gene interaction in bone phenotypes with the loss of IL-1ra in an animal model. In my third study, we studied the different effects between endogenously produced and diet-supplied vitamin C on spontaneous arthritis disease susceptibility. In this study, we sought to investigate whether the source of vitamin C (endogenously produced or exogenously supplied) influences the development of inflammatory arthritis using a mouse model of SAD. SAD-susceptible Balb/c IL-1rn-/- mice were bred with vitamin C-deficient Sfx mice to produce a double mutant (SAD-susceptible, vitamin C-deficient) mouse strain. The three strains were raised, with the double mutant and Sfx mice supplied with vitamin C in drinking water, and mice’s arthritis severity scores were measured biweekly. Incidence and average severity for each strain were calculated. At four months of age, the mice were sacrificed, and body measurements and leg samples were collected. X-ray microcomputed tomography was used to scan the legs to characterize the bone profile. Femur length, tibia length, and bone volume were found to be significantly lower in double mutant mice than in Balb/c IL-1rn-/- mice. There was no significant difference in bone mineral density and femur thickness between the two arthritis-susceptible strains. The double mutant mice had an earlier onset of arthritis as well as a more severe disease than that of the Balb/c knockout (KO) strain. Our findings suggest that the source of vitamin C could affect both the susceptibility of mice to SAD and the severity of disease. In addition, we examined the sex differences in several mouse models of inflammatory arthritis. To understand the basis for these differences we conducted analysis of several mouse models of inflammatory arthritis. The study of whether there are gender and symmetry differences in experimental arthritis expression in the mouse models may be of significance to the study of human rheumatoid arthritis. Our observations and statistical analyses on the incidence of arthritis in four different animal models incorporated relatively large numbers of mice allowing for robust conclusions. Our research showed that there is a sexual dimorphism for arthritis incidence and severity of arthritis in mice harboring specific genetic modifications. For F2 population the incidence of arthritis was 57.1% in female mice and 75.6% in male mice. There was a difference in severity related to sex in two populations: B6.DR1/ B6.DR4 (P < 0.001) and F2 (P = 0.023). Among these populations, scores for the right hindlimbs were significantly higher than those for the left hindlimbs in males (P<0.05). When examining disease manifestation using the collagen induced arthritis model with DBA/1 mice, sex-dimorphism did not reach statistical significance. However, left hindlimbs showed a tendency toward greater disease expression over the right. Our results suggest that sex difference of arthritis exists in animal models not only in terms of gender, but also of left and right limbs. Using animal models, this work has laid the foundation for future research on gender differences in rheumatoid arthritis. In conclusion, our studies on genetic and environmental factors regulating bone phenotypes and diseases have significant implications. Not only have they raised the concept of sexual dimorphism in disease, but they have highlighted the influence of genetic background on bone disease. The link between different sources of vitamins and immune-mediated disease is intriguing and warrants further research, as is the bone protective effect of BCP.

In Vivo Efficacy of Neutrophil-Mediated Bone Regeneration Using a Rabbit Calvarial Defect Model

Reconstruction of bone due to surgical removal or disease-related bony defects is a clinical challenge. It is known that the immune system exerts positive immunomodulatory effects on tissue repair and regeneration. In this study, we evaluated the in vivo efficacy of autologous neutrophils on bone regeneration using a rabbit calvarial defect model. Methods: Twelve rabbits, each with two surgically created calvarial bone defects (10 mm diameter), were randomly divided into two groups; (i) single application of neutrophils (SA-NP) vs. SA-NP control, and (ii) repetitive application of neutrophils (RA-NP) vs. RA-NP control. The animals were euthanized at 4 and 8 weeks post-operatively and the treatment outcomes were evaluated by micro-computed tomography, histology, and histomorphometric analyses. Results: The micro-CT analysis showed a significantly higher bone volume fraction (bone volume/total volume) in the neutrophil-treated groups, i.e., median interquartile range (IQR) SA-NP (18) and RA-NP (24), compared with the untreated controls, i.e., SA-NP (7) and RA-NP (14) at 4 weeks (p < 0.05). Similarly, new bone area fraction (bone area/total area) was significantly higher in neutrophil-treated groups at 4 weeks (p < 0.05). Both SA-NP and RA-NP had a considerably higher bone volume and bone area at 8 weeks, although the difference was not statistically significant. In addition, immunohistochemical analysis at 8 weeks revealed a higher expression of osteocalcin in both SA-NP and RA-NP groups. Conclusions: The present study provides first hand evidence that autologous neutrophils may have a positive effect on promoting new bone formation. Future studies should be performed with a larger sample size in non-human primate models. If proven feasible, this new promising strategy could bring clinical benefits for bone defects to the field of oral and maxillofacial surgery.

EVALUATION OF MINERALIZED PLASMATIC MATRIX DURING SINUS LIFT WITH THE SIMULTANEOUS PLACEMENT OF DENTAL IMPLANTS

Objectives:Mineralized plasmatic matrix is reported to improve the quality of the bone/fibrin mixture, creating a stable and easy to handle homogeneous material. However, few studies evaluate the use of the mineralized plasmatic matrix during sinus lift with the simultaneous placement of dental implants. Purpose: This study evaluated the efficiency or not of MPM compared to the xenograft bone grafting in the maxillary sinus lift. Patients and methods:This study was conducted randomly on patients selected for treatment with a total of sixteen lateral windows sinus lift with simultaneous implant placement. Their ages ranged between 20 and 60 years old. Participating patients were divided into two groups equally and randomly The control group: eightsinus floor elevation was performed using simultaneous implant placement. As a grafting material, Xenograft was used. The study group: eight Sinus floor elevation was achieved with simultaneous implant placement. Xenograft has been used in the form of MPM as a grafting material. CBCT taken before and after sinus augmentation to measure bone volume and height after 1 week of baseline (T0), after 6 months (T1), and after 12 months of baseline (T0) (T2). The Osstell(PT) was used for assessment implant stability at implant insertion (PT0) as well as for loading visit (PT1). Result:A significant difference was observed between the two groups in bone volume (p=0.049). No significant difference was observed between the two groups (p=0.129) in height of graft. Conclusion:MPM eliminated the need for barrier membranes when a guided bone regeneration procedure is considered.The useofMPM as a grafting bone offered greater graft stability and handling.

Determination of anisotropic elastic parameters from morphological parameters of cancellous bone for osteoporotic lumbar spine

In biomechanics, large finite element models with macroscopic representation of several bones or joints are necessary to analyze implant failure mechanisms. In order to handle large simulation models of human bone, it is crucial to homogenize the trabecular structure regarding the mechanical behavior without losing information about the realistic material properties. Accordingly, morphology and fabric measurements of 60 vertebral cancellous bone samples from three osteoporotic lumbar spines were performed on the basis of X-ray microtomography (μCT) images to determine anisotropic elastic parameters as a function of bone density in the area of pedicle screw anchorage. The fabric tensor was mapped in cubic bone volumes by a 3D mean-intercept-length method. Fabric measurements resulted in a high degree of anisotropy (DA = 0.554). For the Young’s and shear moduli as a function of bone volume fraction (BV/TV, bone volume/total volume), an individually fit function was determined and high correlations were found (97.3 ≤ R2 ≤ 99.1,p < 0.005). The results suggest that the mathematical formulation for the relationship between anisotropic elastic constants and BV/TV is applicable to current μCT data of cancellous bone in the osteoporotic lumbar spine. In combination with the obtained results and findings, the developed routine allows determination of elastic constants of osteoporotic lumbar spine. Based on this, the elastic constants determined using homogenization theory can enable efficient investigation of human bone using finite element analysis (FEA).

Effect of Methotrexate Injection on Orthodontic Tooth Movement: An Experimental Study on Rats

Introduction. Knowledge about the effects of medications, vitamins, and various supplements on orthodontic tooth movement (OTM) is imperative for orthodontists. This study aimed to assess the effect of methotrexate (MTX) injection on OTM in rats. Materials and Methods. Twenty-eight male Wistar rats were randomized into four groups (n = 7). The first molar and central incisor were connected using a nickel-titanium (NiTi) coil spring with a 50 g load in each rat. The two experimental groups received 0.75 mg/kg and 1.5 mg/kg MTX, respectively, intraperitoneally for 21 days. The negative control group did not receive any injection and did not undergo orthodontic treatment. The positive control group underwent orthodontic treatment and received 0.9% saline (NaCl) injections for 21 days. All rats were sacrificed with chloroform inhalation after 21 days; their maxilla was resected, and the mean number of Howship’s lacunae, blood vessels, osteoclasts, and resorption lacunae was counted. The reduction in bone volume (bone volume to total volume ratio (BV/TV)) at the site of the maxillary molar was quantified by microcomputed tomography (micro-CT). Results. OTM, the number of osteoclasts, and the number of blood vessels significantly increased in rats treated with MTX ( P < 0.05 ). However, the increase in the number of Howship’s lacunae and resorption lacunae was not significant ( P > 0.05 ). Lower BV/TV in the MTX groups was in agreement with the increased number of osteoclasts. Conclusion. Injection of MTX can significantly increase OTM and decrease root resorption in rats.

Multi-Targeting DKK1 and LRP6 Prevents Myeloma-Induced Bone Disease

Multiple myeloma (MM) is characterised by an expansion of malignant plasma cells in the bone marrow, systemic bone loss and destructive osteolytic bone lesions. These are mediated by an imbalance in bone remodeling, in which bone resorption is exacerbated and bone formation is suppressed. More than 90% of MM patients present with osteolytic lesions that can lead to pain and increased risk of fracture, significantly impacting their quality of life. Bone-targeted treatments currently used in the clinic can suppress lesion progression and reduce fracture risk, however these agents cannot replace lost bone and patients continue to fracture. Therapeutic strategies aimed at promoting bone formation are therefore required to overcome the loss of skeletal integrity and subsequent fractures in MM patients. Therapeutic agents that target the canonical Wnt signaling pathway, a potent regulator of bone formation, have the potential to address these skeletal complications, where they could rebuild lost bone and improve bone strength in affected individuals. We have demonstrated a novel anti-LRP6 agent, which potentiates Wnt signaling through binding the Wnt receptor LRP6, prevented the development of myeloma-induced bone loss primarily through preventing bone resorption. However, since MM patients present with both increased bone resorption and decreased bone formation, we hypothesised that combining anti-LRP6 with the bone anabolic anti-DKK1 (100mg/kg twice weekly intravenously) would lead to more robust improvements in bone structure than single treatment approaches. MicroCT analysis demonstrated a 74% increase in femoral trabecular bone volume per tissue volume (BV/TV) in naïve, non-tumour bearing mice given the combination treatment compared to control agents (p&lt;0.0001). Mice injected with 5TGM1eGFP murine myeloma cells had a 34% reduction in femoral BV/TV compared to naïve controls (p&lt;0.0001). Combination treatment drastically improved BV/TV in 5TGM1-bearing mice by 111% (p&lt;0.0001), compared to control, and this improvement with the combination treatment strategy was 25% greater than anti-LRP6 single treatment approaches (p&lt;0.001). MicroCT analysis in L4 lumbar vertebrae demonstrated similar bone structural changes in 5TGM1-bearing mice treated with the combination strategy. Consequently, this combination significantly improved resistance to fracture in L4 vertebrae in 5TGM1eGFP-bearing mice compared to their controls (p&lt;0.001), and it provided greater protection against fracture compared to anti-LRP6 single agent treatment. Interestingly, these improvements in bone volume were primarily due to reduced bone resorption, with significant reductions in osteoclast numbers and osteoclast surface per bone surface demonstrated in 5TGM1eGFP-bearing mice treated with the combination strategy (p&lt;0.001) compared to control. Importantly, tumour activity was not altered with either single or combination Wnt-promoting treatment strategies. This study defines a novel therapeutic strategy, which will reduce fractures and improve quality of life in patients with MM when used in combination with tumour-targeted treatments. Figure 1 Figure 1. Disclosures Cong: Novartis Institutes for Biomedical Research: Current Employment. Daley: Novartis Institutes of Biomedical Research: Current Employment.