Changes In Trabecular Bone Research Articles

Relationship between altered knee kinematics and subchondral bone remodeling in a clinically translational model of ACL injury.

Abnormal joint kinematics are commonly reported in the acute and chronic stages of recovery after anterior cruciate ligament (ACL) injury and have long been mechanistically implicated as a primary driver in the development of posttraumatic osteoarthritis (PTOA). Though strongly theorized, it is unclear to what extent biomechanical adaptations after ACL injury culminate in the development of PTOA, as data that directly connects these factors does not exist. Using a preclinical, noninvasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on joint kinematics and the pathogenetic mechanisms involved in the development of PTOA. A total of 32, 16-week-old Long-Evans rats were exposed to a noninvasive ACL injury. Marker-less deep learning software (DeepLabCut) was used to track animal movement for sagittal-plane kinematic analyses and micro computed tomography was used to evaluate subchondral bone architecture at days 7, 14, 28, and 56 following injury. There was a significant decrease in peak knee flexion during walking (p < .05), which had a moderate-to-strong negative correlation (r = -.59 to -.71; p < .001) with subchondral bone plate porosity in all load bearing regions of the femur and tibia. Additional comprehensive analyses of knee flexion profiles revealed dramatic alterations throughout the step cycle. This occurred alongside considerable loss of epiphyseal trabecular bone and substantial changes in anatomical orientation. Knee flexion angle and subchondral bone microarchitecture are severely impacted after ACL injury. Reductions in peak knee flexion angle after ACL injury are directly associated with subchondral bone plate remodeling.

Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats.

BackgroundMetformin (MF) is a widely used biguanide oral hypoglycemic agent, which has obvious anti-inflammatory and immunomodulatory effects. However, the mechanism of MF on rheumatoid arthritis (RA) remains uncertain. In this study, we investigated the therapeutic effects of MF on collagen-induced arthritis (CIA).MethodsCIA was induced in rats by intradermal injection of a mixture of bovine type II collagen and incomplete Freund’s adjuvant (IFA) on day 0 and day 7 through the base of the tail. Intraperitoneal injection of MF (100 mg/kg) was given every 3 days, from day 14 for 3 weeks. The effects of MF on arthritis-induced systemic inflammation and synovitis were studied by pathological analysis of the knee joint and serological examination of peripheral blood in CIA rats. The bone protection effect of MF was studied by microscopic computed tomography (micro-CT) and histological analysis of the knee joint. The effects of MF on chondrocytes in CIA rats were studied by detecting the relevant pro-apoptotic mediators in the chondrocytes.ResultsAfter administration of MF in CIA rats, systemic inflammation and synovitis caused by arthritis were significantly suppressed. Histomorphometry and micro-CT analysis of the knee joint revealed that MF can protect bone by inhibiting the changes of trabecular bone in CIA rats. Histological analysis of the knee joint found that MF can inhibit osteoclast formation and degradation of the cartilage layer matrix. Detection of the relevant pro-apoptotic mediators in chondrocytes revealed that MF can significantly inhibit the apoptosis of chondrocytes in CIA rats.ConclusionsOur study showed that MF can inhibit systemic inflammation and synovitis and plays a role in bone protection by inhibiting cartilage layer matrix degradation, osteoclast formation, and chondrocyte apoptosis.

No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups (n = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA.

Hypophosphatemic Hypovitaminosis D Induces Osteomalacia in the Adult Female Rat.

Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D-depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D-depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.

Deterioration of bone microstructure by aging and menopause in Japanese healthy women: analysis by HR-pQCT.

Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT. Study participants were 61 healthy Japanese women (31-70years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed. Trabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength. Trabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

Evaluating the Therapeutic Potential of Bone-Marrow Mesenchymal Stromal Cells and Exercise in a Post-Traumatic Osteoarthritis Model: Functional and Radiographic Analysis

Background & Aim The management and optimal treatment of post-traumatic osteoarthritis (PTOA) in the young active patient remains a challenge. Rehabilitation has long been used as a treatment modality for patients with OA in order to improve knee function by decreasing joint pain and stiffness. This study aims to analyze the interaction between bone-marrow mesenchymal stromal cells (BM-MSCs) and exercise as a therapeutic strategy to halt or ameliorate the progression of PTOA in a meniscus destabilization model. Methods, Results & Conclusion 12 week old wild-type C57BL/6 male mice (n=185) underwent destabilization of medial meniscus (DMM) surgery in the right knee. At 3 weeks after surgery, the animals received an intra-articular injection (vehicle or BM-MSCs) and were randomly assigned to their respective activity group (free cage,FC; or treadmill,T). OA development was evaluated using micro-CT, X-Ray and routine histology (OARSI and osteophyte scoring system). Gait analysis was performed and several kinematic parameters were quantified. BM-MSCs adhere to the synovial membrane 24h after injection (Fig1).Histopathologic scores demonstrated cartilage degradation and osteophyte formation beginning at 8w post-DMM predominantly in the treadmill groups. Ectopic bone formation was significantly more prominent in the T+BM-MSCs group at 12w (Fig2). Micro-CT analysis revealed marked anatomical changes in femoral and tibial trabecular and subchondral bone on the medial side, ectopic ossification and osteophyte formation, strongly correlated with the T+BM-MSCs group over time. Gait analysis revealed an antalgic pattern in all groups starting at 4w. Only treadmill injection groups were not significantly different by 12w, suggesting that the combination of injection and exercise ameliorated motion/function. Pain behavior at 12w was lowest in the treadmill groups, with no significant differences between groups or across timepoints. Footprint area and intensity imbalance were significant increased starting at 8w. Significance differences were observed only between the T+BM-MSCs group and FC no injection at 12w (Fig 3). The fate of BM-MSCs injected into an OA joint environment is affected by mechanical loading. Further studies are necessary to understand how the interaction between mechanical and biologic factors influences the biologic responses to implanted cells. Such information will help to identify rehabilitation techniques to aid development of innovative therapies to mitigate or ameliorate the development of PTOA.

Raman microspectroscopy demonstrates reduced mineralization of subchondral bone marrow lesions in knee osteoarthritis patients

IntroductionBone marrow lesions (BMLs) are frequently identified by MRI in the subchondral bone in knee osteoarthritis (KOA). BMLs are known to be closely associated with joint pain, loss of the cartilage and structural changes in the subchondral trabecular bone (SCTB). Despite this, understanding of the nature of BMLs at the trabecular tissue level is incomplete. Thus, we used Raman microspectroscopy to examine the biochemical properties of SCTB from KOA patients with presence or absence of BMLs (OA-BML, OA No-BML; respectively), in comparison with age-matched cadaveric non-symptomatic controls (Non-OA CTL). MethodsTibial plateau (TP) specimens were collected from 19 KOA arthroplasty patients (6-Male, 13-Female; aged 56–74 years). BMLs were identified ex-vivo by MRI, using PDFS- and T1-weighted sequences. The KOA specimens were then categorized into an OA-BML group (n = 12; containing a BML within the medial condyle only) and an OA No-BML group (n = 7; with no BMLs identified in the TP). The control (CTL) group consisted of Non-OA cadaveric TP samples with no BMLs and no macroscopic or microscopic evidence of OA-related changes (n = 8; 5-Male, 3-Female; aged 44–80 years). Confocal Raman microspectroscopy, with high spatial resolution, was used to quantify the biochemical properties of SCTB tissue of both the medial and the lateral condyle in each group. ResultsThe ratios of peak intensity and integrated area of bone matrix mineral (Phosphate (v1), Phosphate (v2) and Phosphate (v4)), to surrogates of the organic phase of bone matrix (Amide I, Proline and Amide III), were calculated. Within the medial compartment, the mineral:organic matrix ratios were significantly lower for OA-BML, compared to Non-OA CTL. These ratios were also significantly lower for the OA-BML medial compartment, compared to the OA-BML lateral compartment. There were no group or compartmental differences for Carbonate:Phosphate (v1, v2 and v4), Amide III (α-helix):Amide III (random-coil), Hydroxyproline:Proline, or Crystallinity. ConclusionAs measured by Raman microspectroscopy, SCTB tissue in BML zones in KOA is significantly less mineralized than the corresponding zones in individuals without OA. These data are consistent with those obtained using other methods (e.g. Fourier transform infrared spectroscopy; FTIR) and with the increased rate of bone remodeling observed in BML zones. Reduced mineralization may change the biomechanical properties of the trabecular bone in BMLs and the mechanical interaction between subchondral bone and its overlying cartilage, with potential implications for the development and progression of OA.

Cortical unlike trabecular bone loss is not associated with vascular calcification progression in CKD patients

BackgroundVascular calcification progression has been associated with the loss of trabecular bone in chronic kidney disease (CKD) patients. There are few data evaluating the relationship between cortical bone loss and vascular calcification in this population. The aim of this study was to prospectively evaluate the association between changes in cortical bone density and coronary artery calcification (CAC) progression in non-dialyzed CKD patients.MethodsChanges of cortical and trabecular bone, and changes of calcium score, were analyzed using vertebral tomographic images from a prospective study. Automatic delineation of the cortical bone layer was performed by Image J software, and trabecular bone was determined by selecting a region of interest using Vitrea 2® software. Cortical and trabecular bone density (BD) were expressed in Hounsfield Units (HU), and coronary artery calcium score in Agatston Units (AU).ResultsSeventy asymptomatic patients [57.8 ± 10.2 years, 63% males, 20% diabetic, estimated glomerular filtration rate (eGFR) = 37.3 (24.8–51.3) mL/min/1.73m2] were followed for 24 months. The mean cortical and trabecular BD did not change over time. While 49 patients lost either bone, 29 (41%) patients lost cortical [− 4.4%/year (ranging from − 7.15 to − 0.5)] and 39 (56%) lost trabecular bone [− 3.15%/year (− 13.7 to − 0.25)]. There was no association between cortical and trabecular BD changes (p = 0.12). CAC was observed in 33 (46%) patients at baseline, and 30 (91%) of them showed CAC progression. While an inverse correlation between trabecular bone and calcium score changes was observed (p = 0.001), there was no correlation between cortical bone and calcium score changes (p = 0.34).ConclusionCKD patients experience either cortical or trabecular bone loss over time, but these changes do not take place simultaneously in all patients. Cortical, unlike trabecular bone loss, is not associated with vascular calcification progression in these patients.

Applied mechanical loading to mouse hindlimb acutely increases skeletal perfusion and chronically enhanced vascular porosity.

Blood supply is essential for osteogenesis, yet its relationship to load-related increases in bone mass is poorly defined. Herein, we aim to investigate the link between load-induced osteogenesis and the blood supply (bone perfusion and vascular porosity) using an established osteogenic noninvasive model of axial loading. Accordingly, 12 N mechanical loads were applied to the right tibiae of six male C57BL6 mice at 10-12 wk of age, 3 times/wk for 2 wk. Skeletal perfusion was measured acutely (postloading) and chronically in loaded and contralateral, nonloaded hindlimbs by laser-Doppler imaging. Vascular and lacunar porosity of the cortical bone and tibia load-related changes in trabecular and cortical bone was measured by nanoCT and micro-CT, respectively. We found that the mean skeletal perfusion (loaded: nonloaded limb ratio) increased by 56% immediately following the first loading episode (vs. baseline, P < 0.01), and a similar increase was observed after all loading episodes, demonstrating that these acute responses were conserved for 2 wk of loading. Loading failed, however, to engender any significant chronic changes in mean perfusion between the beginning and the end of the experiment. In contrast, 2 wk of loading engendered an increased vascular canal number in the tibial cortical compartment (midshaft) and, as expected, also increased trabecular and cortical bone volumes and modified tibial architecture in the loaded limb. Our results indicate that each episode of loading both generates acute enhancement in skeletal blood perfusion and also stimulates chronic vascular architectural changes in the bone cortices, which coincide with load-induced increases in bone mass.NEW & NOTEWORTHY This study investigated modifications to the blood supply (bone perfusion and intracortical vascular canals) in mechanoadaptive responses in C57BL6 mice. Each episode of mechanical loading acutely increases skeletal perfusion. Two weeks of mechanical loading increased bone mass and cortical vascular canal number, while there was no chronic increase in hindlimb perfusion. Our findings suggest that the blood supply may participate in the processes that govern load-induced bone formation.

Evaluation of trabecular bone changes in patients with periodontitis using fractal analysis: A periapical radiography study.

The present study was aimed to evaluate the trabecular bone changes between healthy individuals and periodontitis patients with fractal dimension analysis on digital periapical radiographs. Data from 35 healthy and 35 individuals with periodontitis were confirmed from the database of our faculty and included in the study. Two regions of interest (ROI) were selected belonging to mesial and distal region of mandibular first molar on periapical radiographs. The mean fractal dimension (FD) values of two regions were calculated with using box-counting method. Student t test was used for the comparison of the FDs. The mean FD of individuals with periodontitis was 0.97, whereas it was 1.04 for the healthy group. The mean FD values were significantly higher in the healthy group (P<0.05). In the periodontitis group, as the FD of mesial interdental bone increased, the FD of distal interdental bone increased significantly (P<0.05). Because of FD numerically showing changes in bone trabeculation, changes in the alveolar bone can be detected quantitatively.

Megakaryocyte-Driven Myelofibrosis Leads to Progressive Osteosclerosis in G6b-B Knockout Mice

Bone and bone marrow are not only anatomically, but also functionally interdependent. In a systematic review, we examined bone health in patients with hematopoietic disorders and demonstrated that an increased hematopoietic cell proliferation, such as in patients with hemolytic anemias, was associated with bone loss, while bone marrow hypocellularity, such as in patients with chronic myelofibrosis (CMF), was associated with bone gain [Steer K et al. J Bone Miner Res 2017]. Since bone mass in CMF increases at the expense of bone marrow, it contributes to patients' morbidity as it is associated with bone pain, and mortality as it may lead to bone marrow failure. A mouse model with a global knockout of the megakaryocyte (MK) lineage specific inhibitory receptor G6b-B was shown to develop myelofibrosis secondary to aberrant platelet production and function [Mazharian A et al Sci Signal 2012]. Moreover, a group of patients with primary myelofibrosis was identified to have loss-of-function mutations in the G6b-B gene [Hofmann I et al Blood 2018]. The objective of this study was to characterize temporal changes in the skeleton of the G6b-B knockout mice. We examined age- and sex-related changes in 4, 8, 16, and 32 week-old G6b-B+/+, G6b-B-/- female and male mice. Starting from 8 weeks-of-age, spleen progressively increased in female G6b-B-/- mice compared to corresponding G6b-B+/+ mice, reaching 2.9-fold increase at 32 weeks (p &lt; 0.001) (Fig.1A). Micro-computed tomography analysis of femur demonstrated that starting at 8 weeks of age female G6b-B-/- mice had a significantly higher proportion of cortical bone and a respectively lower proportion of marrow (Fig.1B). Starting at 16 weeks of age, female G6b-B-/- mice developed trabecula in the medullary cavity normally occupied by the bone marrow, which by 32 weeks led to a 38-fold increase (p &lt; 0.001) in the proportion of bone to tissue volume compared to G6b-B+/+ (Fig.1C,D). At 32-weeks of age, female G6b-B-/- mice also demonstrated a 7-fold increase in BV/TV (p &lt; 0.001) in the region of metaphysis. While some abnormalities were found in male G6b-B-/- mice, they were considerably less severe compared to females. To establish whether the observed bone phenotype is due to MK and platelet functional defects, we performed microcomputed tomography analysis on femurs of 22 week-old G6b-Bfl/fl;Gp1ba-Cre-/- mice with a MK/platelet-specific knockout of G6b-B. Changes in trabecular bone of G6b-Bfl/fl;Gp1ba-Cre-/- mice recapitulated changes of G6b-B-/- mice. However, periosteal perimeter in male G6b-Bfl/fl;Gp1ba-Cre-/- mice was significantly larger, and in female G6b-Bfl/fl;Gp1ba-Cre-/- mice - significantly smaller than in corresponding control mice, while in global G6b-B-/- mice periosteal perimeter was not affected. Female G6b-B-/- mice demonstrated severe splenomegaly as well as progressive osteosclerosis, which was confirmed in G6b-Bfl/fl;Gp1ba-Cre-/- mice, indicating that trabecular bone gain in G6b-B-/- mice is consequent to a MK disfunction. Dramatic sexual dimorphism suggests that sex-related factors play an important role in the development of osteosclerosis. The differences in cortical bone phenotype between the global and conditional knockout of G6b-B suggest the potential role of G6b-B signaling in osteoclasts or osteoblasts. This study demonstrates that MK-associated myelofibrosis is sufficient to induce osteosclerosis of bone marrow, and that sex hormones play an important role either in protecting male mice from osteosclerosis or in exacerbating osteosclerosis in female mice. Disclosures No relevant conflicts of interest to declare.

L-Glutamine Increases IGF-1 Liver Expression to Prevent Bone Loss in Sickle Mice

BACKGROUND: Chronic red blood cell (RBC) hemolysis that accompanies sickle cell disease (SCD) is associated with elevated iron storage in tissues, in particular the liver (Nguyen et al. 2014). Iron storage within the liver leads to oxidative stress and fibrosis, reducing circulating antioxidants (vitamin D &amp; hemopexin) and essential hormones, namely insulin-like growth factor-1 (IGF-1). We have previously shown that SCD mice progressively develop a pronounced osteopenia, although the particular drivers of this are unknown (Green et al. 2015). Outside studies suggest this is largely due to the significant decrease of IGF-1 expression, which is vital for bone growth and development (Xiao et al. 2016). FDA approval of L-glutamine (GLN) is said to reduce the acute complications of SCD by increasing antioxidant capacity of RBCs, however opposing research has led to uncertainty about the proposed therapeutic mechanism (Quinn 2018). GLN is utilized ubiquitously as a precursor for antioxidant synthesis to combat oxidative stress; therefore, the benefit experienced by sickle patients may be explained by means outside of RBC usage. Under normal conditions the liver is one of the primary sources of GLN for the body. However, the liver becomes a major site of GLN consumption during disease states to maintain homeostatic activity and reduce hepatic damage from oxidative stress (Cruzat et al. 2018). We hypothesize that GLN therapy prevents sickle bone loss by increasing liver expression of IGF-1. METHODS: Male Townes sickle mice (SS, Jackson) and littermate controls (AA) were evaluated at 4, 8, 12 and 16 wks old. (n=10/group, IACUC approved). Half the animals received GLN in drinking water (0.7% w/v) from weaning at 4 wks old until sacrifice. Changes in femoral cortical and trabecular bone were assessed by µCT. Livers were weighed, as hepatomegaly provides a clinical index for iron storage and cirrhosis in SCD. In addition, plasma concentrations of liver derived IGF-1, the antioxidant hemopexin (HPX), and gamma-glutamyl transferase (GGT) activity were measured to determine therapeutic efficacy. RESULTS: At 4wks there was no difference in bone, but SS livers were 20% larger than AA although liver plasma markers did not significantly differ. GLN therapy was effective at 8 wks, preventing cortical bone thinning in SS mice and reducing hepatomegaly by 12%; which remained consistent at all ages. IGF-1 plasma concentrations reflected this reduction in liver size with ~2 fold increase. HPX and GGT levels were similar to controls within treatment group, but were significantly reduced in untreated SS mice. At 12 wks, GLN effects split into two groups: (i) elevated IGF-1 (GLN+, like AA) or (ii) reduced IGF-1 (GLN-) consistent with loss of GLN effect in these mice. At 12 wks, cortical and trabecular bone in GLN+ mice group were similar to AA, while bone of GLN- mice were comparable to untreated SS mice. Protective effect of GLN on cortical bone remained by 16 wks, but was lost in trabecular bone, even in GLN+ mice. HPX concentrations followed a similar pattern, however GGT activity of GLN+ group reduced to GLN- rates. DISCUSSION: Our studies reveal that GLN therapy increases the expression of IGF-1 and prevents the osteopenia that develops in adolescence in SCD. However, the protective effects of GLN on trabecular bone in SS mice appears to be lost with skeletal maturity. GLN therapy increases the amount of HPX available to prevent iron absorption into the tissue; however sickle RBC hemolysis still occurs during GLN therapy, thereby delaying oxidative stress derived hepatic damage as suggested by GGT at 16 wks. Why cortical and trabecular bone respond differently to GLN in SCD at maturity is not yet clear. Previous studies have shown that systemic liver derived IGF-1 preferentially affects cortical bone growth in normal mice, while locally produced IGF-1 is responsible for trabecular. In a similar manner to the liver, we speculate that iron accumulate within sickle bone may alter local bone cell expression of IGF-1. Disclosures No relevant conflicts of interest to declare.

Different subchondral trabecular bone microstructure and biomechanical properties between developmental dysplasia of the hip and primary osteoarthritis

ObjectiveDevelopmental dysplasia of the hip (DDH) is recognized as a frequent cause of secondary osteoarthritis (OA). The purpose in this study was to compare structural and biomechanical properties of subchondral trabecular bone ​and its relationship with cartilage damage between patients with DDH and patients with primary hip OA. MethodsForty-three femoral head specimens obtained from patients who underwent total hip arthroplasty [DDH, n ​= ​17; primary OA, n ​= ​16; and normal control (NC), n ​= ​10] were scanned by microcomputed tomography and analyzed by individual trabecula segmentation to obtain the microstructural types of subchondral trabecular bone. The biomechanical properties were analyzed by micro–finite element analysis, and cartilage damage was evaluated by histology. The linear regression analysis was used to indicate the association between microstructures, biomechanical property, and articular cartilage. ResultsThe DDH group showed the lowest total bone volume fractions (BV/TV) and plate BV/TV in the three groups (p ​< ​0.05). There were also different discrepancies between the three groups in plate/rod trabecular number, plate/rod trabecular thickness, trabecular plate surface area/trabecular rod length, and junction density with different modes (plate–plate, rod–rod, and plate–rod junction density). The micro–finite element analysis, histology, and linear regression revealed that the subchondral trabecular bone in the DDH group had inferior biomechanical properties ​and cartilage damage of patients with DDH was more serious with different subchondral trabecular bone microstructures. ConclusionOur findings detected deteriorating subchondral trabecular bone microstructures in patients with DDH. The mass and type of subchondral trabecular bone play a key role in mechanical properties in DDH, which might be related to cartilage damage. The translational potential of this articleOur findings suggested that changes of subchondral trabecular bone play a critical role ​in DDH progression and that the improvement on subchondral trabecular bone may be a sensitive and promising way in treatment of DDH.

Radiographic changes in trabecular bone around implant‐supported fixed complete dentures

Radiographic changes in trabecular bone around implant‐supported fixed complete dentures

Radiographic changes of trabecular bone density after loading of implant-supported complete dentures: A 3-year prospective study.

Bone tissues may undergo remodeling under functional mechanical stimuli. This prospective study on implant-supported fixed complete dentures (IFCDs) evaluated the radiographic trabecular bone changes in density by means of gray levels and texture analysis variables after up to 3-year loading. The sample consisted of digital periapical radiographs of 63 distal implants of hybrid IFCDs installed in 30 patients (22 women, mean age of 62 ± 7.8 years). Digital periapical radiographs were taken after prosthesis installation, and 1 and 3 years after IFCD loading. Longitudinal images of each implant were superimposed, and the same regions of interest were selected for measurement of gray levels statistics (mean gray levels, SD, and coefficient of variation [CV]) and texture parameters (correlation, contrast, entropy, and angular second moment). Data were analyzed by mixed regression models. Mean gray levels increased for 1 year (P < .05), for 3 years (P < .01) and for maximum bite force (P < .01). The interaction between bruxism and time in 1 year was significant (P < .01) for a decrease in CV. No significant effect of texture analysis variables was found (P > .05). The results suggest an increase of radiographic bone density as measured by an increase in mean gray levels and a decrease in CV in IFCD distal implants up to 3 years of loading.

Time course of rapid bone loss and cortical porosity formation observed by longitudinal μCT in a rat model of CKD.

Rodent studies of bone in chronic kidney disease have primarily relied on end-point examinations of bone microarchitecture. This study used longitudinal in vivo microcomputed tomography (in vivo μCT) to characterize the onset and progression of bone loss, specifically cortical porosity, in the Cy/+ rat of model of CKD. Male CKD rats and normal littermates were studied. In vivo μCT scans of the right distal tibia repeated at 25, 30, and 35 weeks were analyzed for longitudinal changes in cortical and trabecular bone morphometry. In vitro μCT scans of the tibia and femur identified spatial patterns of bone loss across distal, midshaft and proximal sites. CKD animals had reduced BV/TV and cortical BV at all time points but developed cortical porosity and thinning between 30 and 35 weeks. Cortical pore formation was localized near the endosteal surface. The severity of bone loss was variable across bone sites, but the distal tibia was representative of both cortical and trabecular changes. The distal tibia was found to be a sensitive suitable site for longitudinal imaging of both cortical and trabecular bone changes in the CKD rat. CKD trabecular bone loss progressed through ~30 weeks followed by a sudden acceleration in cortical bone catabolism. These changes varied in timing and severity across individuals, and cortical bone loss and porosity progressed rapidly once initiated. The inclusion of longitudinal μCT in future studies will be important for both reducing the number of required animals and to track individual responses to treatment.

Micro-CT analysis of chronic apical periodontitis induced by several specific pathogens.

To conduct three-dimensional micro-CT analysis of bone destruction, periapical sclerotic changes and inflammatory root resorption (IRR) to compare the differences between Enterococcus faecalis (Ef)- and Porphyromonas gingivalis (Pg)-induced chronic apical periodontitis (CAP). Mono-species bacteria-induced CAP was established in the first and second molars of the right maxilla and mandible of male Sprague-Dawley rats. Fifteen animals were divided into three groups with five rats in each group: control group, Ef-CAP group and Pg-CAP group. The maxilla and mandible were harvested and then scanned by micro-CT. Alveolar bone destruction was evaluated by measuring the volume of alveolar bone resorption, bone volume fraction (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N) and trabecular spacing (Tb. Sp). The results were analysed using one-way analysis of variance and Fisher's least significant difference methods (LSD). The sclerotic changes in the periapical bone were graded and the IRR indexes were scored. The data were analysed using the chi-square test. The alveolar bone resorption volume of the Pg-CAP group was significantly larger than that of the Ef-CAP group (P<0.01). In the maxilla, both Pg-CAP and Ef-CAP groups had a significant decrease in BV/TV and increase in Tb. Sp (P<0.01) with the more significant changes of trabecular bone in the Pg-CAP group. A significant reduction of Tb. N was only found in the Pg-CAP group (P<0.05). There was no significant change in Tb. Th in either group (P>0.05). In the mandible, except for an increase in Tb. Sp in the Pg-CAP group (P<0.05), there was no significant change in BV/TV, Tb. Th or Tb. N (P>0.05). No obvious sclerotic change was observed. IRR was detected in significantly more root surfaces in the Pg-CAP group (240 surfaces, 60%) than those in the Ef-CAP group (178 surfaces, 44.5%) (P<0.001). The IRR extension was also significantly more advanced in the Pg-CAP group (P<0.05). Pg-CAP caused more substantial alveolar bone destruction and IRR than Ef-CAP. The maxilla was more susceptible to CAP in terms of microstructural changes of trabecular bone than the mandible. Tb. Sp was the most sensitive index for evaluating the residual alveolar bone of CAP.

A cross-sectional study on the age-related cortical and trabecular bone changes at the femoral head in elderly female hip fracture patients

Bone is in a continuous state of remodeling whereby old bone is absorbed and new bone is formed in its place. During this process, new formations reinforce the bone in the direction of the dominant stress trajectories through a functional adaptation. In normal aging, the balance between bone resorption and formation can be shifted. How this affects the functional adaptation remains to be investigated. Furthermore, how or whether the bone continues to change beyond the age of 85 is not yet studied in detail. In this study we examined the age-related changes in the cortical and trabecular bone in old age, and assessed whether we can find evidence of the presence of functional adaptation. We measured cortical and trabecular parameters from micro-computed tomography scans of the femoral head extracted from hip fracture patients between the age of 70 and 93 years. A significant decrease in global trabecular bone mineral density (38.1%) and cortical thickness (13.0%) was seen from the 9th to the 10th decade of life. The degree of anisotropy was maintained globally as well as locally in both high and low stress regions. The local trabecular bone mineral density decreased in both high stress and low stress regions between the 9th and 10th decade of life with similar trends. This suggests that the role of functional adaptation in maintaining the bone structural integrity in old age may be limited. This study highlights the need for a controlled clinical trial examining the cause of the continued bone degradation throughout old age.

Skeletal Anomalies in Senegalese Sole (Solea senegalensis), an Anosteocytic Boned Flatfish Species

Skeletal anomalies affect animal welfare and cause important economic problems in aquaculture. Despite the high frequency of skeletal problems in reared Solea senegalensis, there is lack of information regarding the histological features of normal and deformed vertebrae in this flatfish. The aim of this study was to describe the histopathological and radiographical appearance of vertebral body anomalies. Sixty-seven juvenile fish were radiographically examined 104 or 105 days after hatching. Through radiographic images, vertebral segments were selected and processed for histopathological examination from 7 normal and 7 affected fish. Alterations in bone shape and vertebral fusion were the most significant anomalies in the vertebral bodies. These alterations occurred most frequently between the last 3 abdominal vertebrae and the first 10 caudal centra. Radiographically, deformed vertebrae showed flattening of the endplates and narrowing of the intervertebral spaces. The radiographic findings concurred with the histological lesions where affected vertebrae exhibited irregular endplates and changes in trabecular bone. Radiolucent cartilaginous tissue was evident in the endplates of the deformed vertebra and, in some cases, the cartilaginous material extended from the growth zone into the intervertebral space. These changes were likely the primary alterations that led to vertebral fusion. Fused vertebrae were often reshaped and showed a reorganization of the trabeculae. The formation of metaplastic cartilage is frequent in a variety of anomalies affecting teleost species.

Mandibular indexes and fractal properties on the panoramic radiographs of the patients using aromatase inhibitors.

This study was conducted to evaluate fractal dimension (FD), mandibular cortical width (MCW), panoramic mandibular index (PMI), and mandibular cortical index (MCI) on panoramic radiographs to determine the mandibular cortical and trabecular bone changes in females with breast cancer undergoing aromatase inhibitors (AIs) treatment. In this retrospective study, FD analysis, PMI, MCI, and MCW were assessed over panoramic radiographs of 34 females under AI therapy as a patient group and 34 healthy age-gender matched individuals as a control group. Mean FD values and MCW were slightly but not significantly lower in the patient group (1.47 ± 0.06 and4.1 ± 1.2 respectively). FDs measured onthe supracortical area above the angulus mandibula (FD2) and anterior to the mental foramen (FD4) were significantly lower in patients (p = 0.037 andp = 0.046 respectively). Among the measured regions in patients, FD2 was significantly lower (p = 0.001). PMI was also significantly lower in patients (p = 0.001) and MCI were similar in both groups (p = 0.604). AI use affects bone quality and evaluating FD, PMI, and MCW in panoramic radiography can be used to determine the effect of this drug on the jaw bones in the early period. Aromatase inhibitors are the most commonly used drugs in breast cancer patients. This drug is thought to have osteoporotic effects on the jawbone. This study is the first study to evaluate osteoporotic changes with measurements made on panoramic radiographs and the results of the study are significant. We think this study will shed light on the studies that will investigate the effects of the drug on the jaw bones.