Trabecular Density Research Articles

Farklı maloklüzyon gruplarında ortodontik tedavinin mandibular kondil kemik kalitesine etkisi

Purpose: The aim of this study was to investigate the effects of orthodontic treatment on the mandibular condyle head bone formation according to different orthodontic malocclusion groups.
 Materials and Methods: In the study, forty-eight patients were examined. Individuals included in the study were grouped according to malocclusion groups. Our study was carried out retrospectively. The quality of mandibular condyle bone in panoramic images of patients before and after orthodontic treatment were compared retrospectively. This examination was carried out by a fractal analysis method.
 Results: According to the findings we obtained from our study; the change in mandibular condyle bone quality before and after orthodontic treatment by age and gender was not found to be statistically different. After orthodontic treatment in individuals with Class I and III malocclusions, the trabecular density structure of the mandibular condyle bone increased and decreased in individuals with Class II malocclusion. The change in mandibular condyle bone quality before and after orthodontic treatment by malocclusion groups was found to be statistically different. 
 Conclusion: The fractal analysis method is a technique that facilitates the diagnosis of minimal changes occurring on the radiographs of orthodontic treatment patients and to evaluate the prognosis of the disease. A relationship was found between orthodontic treatment applied to different malocclusion groups and mandibular condyle head bone formation. When evaluating orthodontic treatments, mandibular condyle head bone formation should be taken into consideration.

Sesamoid bones also show functional adaptation in their microanatomy-The example of the patella in Perissodactyla.

The patella is the largest sesamoid bone of the skeleton. It is strongly involved in the knee, improving output force and velocity of the knee extensors, and thus plays a major role in locomotion and limb stability. However, the relationships between its structure and functional constraints, that would enable a better understanding of limb bone functional adaptations, are poorly known. This contribution proposes a comparative analysis, both qualitative and quantitative, of the microanatomy of the whole patella in perissodactyls, which show a wide range of morphologies, masses, and locomotor abilities, in order to investigate how the microanatomy of the patella adapts to evolutionary constraints. The inner structure of the patella consists of a spongiosa surrounded by a compact cortex. Contrary to our expectations, there is no increase in compactness with bone size, and thus body size and weight, but only an increase in the tightness of the spongiosa. No particular thickening of the cortex associated with muscle insertions is noticed but a strong thickening is observed anteriorly at about mid-length, where the strong intermediate patellar ligament inserts. The trabeculae are mainly oriented perpendicularly to the posterior articular surface, which highlights that the main stress is anteroposteriorly directed, maintaining the patella against the femoral trochlea. Conversely, anteriorly, trabeculae are rather circumferentially oriented, following the insertion of the patellar ligament and, possibly also, of the quadriceps tendon. A strong variation is observed among perissodactyl families but also intraspecifically, which is in accordance with previous studies suggesting a higher variability in sesamoid bones. Clear trends are nevertheless observed between the three families. Equids have a much thinner cortex than ceratomorphs. Rhinos and equids, both characterized by a development of the medial border, show an increase in trabecular density laterally suggesting stronger stresses laterally. The inner structure in tapirs is more homogeneous despite the absence of medial development of the medial border with no "compensation" of the inner structure, which suggests different stresses on their knees associated with a different morphology of their patellofemoral joint.

Comparison of Trabecular Bone Score-Adjusted FRAX™ and FRAX™-Bone Mineral Density in Postmenopausal Women with Clinical Vertebral Fractures: A Cross-Sectional, Analytic Study

Background: Ethnicity differentially modulate fracture risk prediction using FRAX™-bone mineral density (BMD). Objective: To compare FRAX™-BMD and trabecular bone score (TBS)-adjusted FRAX™ in the 10-year probability of fracture among Thai postmenopausal woman (PMW) with vertebral fracture (VF). Materials and Methods: The present study was a cross-sectional study conducted by retrospective review of medical records of PMW with VF older than 45 years undergoing lumbar and hip DXA scan. The authors excluded the PMW having been treated with metal implant at the spine, 3 or more lumbar VF, or cancer spreading to vertebral spine. The authors assessed the difference in means of normally distributed data by dependent sample t-test, the correlation between TBS and LS BMD by Pearson correlation, and the difference in proportions of PMW who met intervention threshold (IT) before and after TBS-adjusted FRAX™ by McNemar’s test. A p<0.05 was considered statistically significant. Results: Of the 119 patients, the mean age was 70.8±8.1 years. The mean 10-year probability of a hip fracture by TBS-adjusted FRAX™ was significantly higher than that by FRAX™-BMD with the mean difference of 0.44% (95% CI 0.13 to 0.76). The higher difference in means, using TBSadjusted FRAX™, was even significantly greater in the 10-year probability of major osteoporotic fractures. For either the IT of major osteoporotic fracture or hip fracture, TBS-adjusted FRAX™ resulted in four added PMWs who needed treatment, but without statistical significance. Conclusion: TBS-adjusted FRAX™ had a higher 10-year probability of fracture than FRAX™-BMD. Keywords: Trabecular bone score; FRAX™; Bone mineral density; Postmenopausal women; Osteoporosis

The effect of humeral implant thickness and canal fill on interface contact and bone stresses in the proximal humerus.

BackgroundStem size is an important element for successful time zero primary fixation of a press-fit humeral stem in shoulder arthroplasty. Little basic science research, however, has been conducted on the effects of implant thickness and canal fill on load transfer, contact, and stress shielding. The purpose of this finite element study was to determine the effects of varying stem thickness on bone contact, bone stresses, and bone resorption owing to stress shielding.MethodsThree generic short-stem implant models were developed and varied based on cross-sectional thickness (thinner – 8 mm, medium – 12 mm, thicker – 16 mm). Using a finite element model, three outcome measures were determined (1) the amount of bone-to-implant contact, (2) changes in cortical and trabecular bone stresses from the intact state, and (3) changes in cortical and trabecular strain energy densities which can predict bone remodeling or stress shielding.ResultsIncreasing the size of the humeral stem had no significant effects on bone-to-implant contact during loading (P > .07). The thinner implant with the lowest canal fill ratio produced significantly lower changes in stress from the intact state in both cortical and trabecular bone (P < .002). In addition, the thinner implant resulted in a substantially lower volume of bone predicted to stress shield and resorb when compared with the medium and thicker stems.DiscussionThe results demonstrate that thinner implants and lower canal fill may be beneficial over thicker sizes, provided equal initial fixation can be achieved. The thinner implant has a greater degree of load sharing and increases the mechanical load placed on surrounding bone, reducing the risk of stress shielding and bone resorption.

A simple technique of removal of a stripped and incarcerated cannulated screw adjacent to the calcar in the femoral neck in a resource-limited setting: A case report

Osteosynthesis of fracture neck of the femur with multiple cannulated screws is one of the standard techniques used, especially in non-elderly patients. Implant exit from the femoral neck is done in cases with hardware failure, infection, prominence, non-union, and pain among others. The femoral neck is unique due to its precarious blood supply, distribution of forces, and formation of dense trabeculae. The cannulated screw placed adjacent to the calcar region is known to get incarcerated due to increased osseointegration, bony ingrowth, and bending. These screws can present in various modes of fatigue for which different extraction techniques and sophisticated instruments have been employed, most of which are not readily available at every center. We present a case where a stripped and incarcerated screw was removed using a technique with simple instruments in a resource-limited setting which can be reproduced for any cannulated screw and in any center.

Erythropoietin Eliminates Increased Bone Marrow Adiposity and Alters Bone Features in Obese Mice

Bone marrow (BM) adipose tissue (BMAT) and BM adipocytes are developmentally distinct from other fat depots and differ from white and brown adipose tissue adipocytes in their lipid composition. BMAT also negatively regulates hematopoiesis. Obesity results in BMAT expansion, which increases bone resorbing osteoclasts and is associated with reduced osteoblast bone forming potential leading to increased risk of fractures. Factors that could limit the expansion of BMAT and decrease the negative effects on bones and hematopoiesis could be useful in restoring bone and BM homeostasis.Erythropoietin (EPO) is essential for erythroid differentiation. In animal models of diet induced obesity, EPO lowers inflammation, reduces white fat mass and promotes glucose tolerance. Here, we investigated the EPO effect on BMAT, bones and distinct BM cell populations under obesogenic conditions. Young C57BL6/J female mice (6 weeks) were placed on normal chow diet (ND) or on 60% kcal high fat diet (HFD) for 4 weeks and were treated with EPO 1200 IU/kg or saline daily for 10 more days on HFD. This course of EPO treatment increased hematocrit without affecting whole body fat mass. For bone analysis, femurs were harvested and analyzed using micro-computed tomography (micro-Ct), and hematoxylin and eosin staining to identify bone and marrow features. HFD decreased trabecular number and increased trabecular spacing, but increased the cortical bone volume, suggesting the adaptation of the bones to withstand the increased body mass in HFD fed mice. EPO treatment reduced trabecular mineral density, trabecular number and spacing, and bone volume/tissue volume under both ND and HFD conditions. However, with EPO treatment, cortical bone volume decreased only in ND fed mice but not in HFD fed mice and cortical bone mineral density increased in HFD fed mice. Consistent with these selective EPO associated changes in bone loss were decreased trabecular osteocytes and decreased trabecular lining osteoblasts in ND fed mice and analogous trends in HFD fed mice, while EPO treatment reduced osteocytes in the cortical bones and osteoblasts in the periosteal region of cortical bones in ND fed mice but not in HFD fed mice. Histology sections showed that EPO treatment markedly reduced BMAT in ND and HFD fed mice, and inhibited the increase in BMAT with HFD feeding. External fat depots did not exhibit any decrease in fat mass following the ten day EPO treatment, suggesting that BMAT is more sensitive and has a quicker response to EPO treatment in both ND and HFD fed mice.Contrary to published reports that link EPO stimulated bone loss to increased osteoclast number and activity, we did not find that EPO increased osteoclasts detected by tartarate resistant acid phosphatase (TRAP) staining. Although femur sections showed an increase in osteoclasts with HFD feeding, EPO treatment reduced osteoclasts in HFD fed mice and had no significant effect in ND fed mice. These data suggest that bone loss, especially trabecular bone, accompanying EPO stimulated increase in hematocrit is not due to increase osteoclast activity but rather is due in part to decreased osteoblasts and osteocytes. Flow cytometry analysis of BM cell populations demonstrated that EPO treatment in ND fed mice decreased hematopoietic cells by 40% and increased erythroid precursor cells by 70%. Although EPO stimulated increase in hematocrit was comparable in ND and HFD fed mice, corresponding changes in % hematopoietic cells and % erythroid precursor cells in BM cell populations were not evident in HFD fed mice. This suggests that in obese mice, EPO treatment abrogates the suppression of hematopoiesis exerted by the expanding BMAT and results in the increased hematopoietic cell proliferation concomitant with EPO stimulated erythropoiesis.In summary, EPO treatment decreases trabecular bone in ND and HFD fed mice, decreases cortical bone volume in ND fed mice, but increases cortical bone mineral density in HFD fed mice. Concomitant with EPO stimulated increased hematocrit is a decrease in BMAT and abrogation of BMAT expansion in diet-induced obese mice. Changes in BMAT are prior to detectable changes in fat mass in external fat depots, suggesting increased sensitivity of BMAT to EPO treatment compared with white adipose tissue. These changes exemplify EPO response in non-hematopoietic tissue of bone and BMAT that accompany bone marrow stimulated erythropoiesis. DisclosuresNo relevant conflicts of interest to declare.

Higher Serum 25-Hydroxy Vitamin D Is Associated With Better Measures of Bone Microarchitecture and Strength

ObjectivesTo determine whether serum 25-hydroxy vitamin D (25-OH D) levels are associated with bone microarchitecture and strength in a multi-racial cohort of young adults. We also determined if race and calcium intake modified these associations. MethodsThis cross-sectional study included 176 young adults who identified as Asian, Black, or White (50% women). High-resolution peripheral quantitative computed tomography (HR-pQCT, 2nd generation) scans of the distal radius and tibia were used to assess bone microarchitecture and strength by micro-finite element analysis. We measured 25-OH D levels (ng/mL, immunoassay), dietary intake (Block’s Food Frequency Questionnaire), and physical activity (questionnaire). We used linear regression to estimate the association between 25-OH D and standardized bone measures, adjusting for race, sex, age, weight, height, calcium intake, and physical activity. The interactions of 25-OH D with race and calcium intake (mg/d) were tested and models were stratified for significant interactions (P < 0.05). ResultsMean age and BMI were 23.7 ± 3.1 years and 24.1 ± 3.1 kg/m2, respectively. 43.9% of the subjects were vitamin D deficient (<20 ng/ml) with greater prevalence in Asian (38.9%) and Black (43.1%) compared to White (18.1%) subjects (P < 0.001 for group differences). At the distal radius, higher 25-OH D was related with higher cortical area (β ± SE = 0.018 ± 0.006, P = 0.005), cortical porosity (β ± SE = 0.023 ± 0.008, P = 0.006) and failure load (β ± SE = 0.023 ± 0.007, P = 0.001). At the distal tibia, higher 25-OH D was related with higher trabecular density (β ± SE = 0.020 ± 0.008, P = 0.015), trabecular thickness (β = 0.016 ± 0.008 P = 0.044) and lower trabecular separation (β ± SE = –0.017 ± 0.008 P = 0.046). There were no significant interactions for 25-OH D and calcium intake. Significant interactions were seen for 25-OH D and race, with stronger associations observed in White compared to Asian or Black subjects. ConclusionsThis study suggests that higher 25-OH D is associated with better bone microarchitecture and strength at the distal radius and tibia in young adults. As poor bone microarchitecture is associated with increased fracture risk, these findings may have implications for fracture risk later in life. Funding SourcesU.S. Army Medical Research Acquisition Activity.

Anatomical basis of the support of fibula to tibial plateau and its clinical significance

BackgroundThe fibula is only indirectly involved in the composition of the human knee joint and has therefore been neglected in the research on knee osteoarthritis. Nonuniform settlement of the proximal tibia plateau is clinically defined as when the height of the medial tibial plateau is lower than that of the lateral side in medial compartment knee osteoarthritis (KOA). The non-uniform settlement of the proximal tibia plateau may be caused by fibular support on the lateral side. Orthopedic surgeons practice partial fibulectomy based on the clinical manifestation of nonuniform settlement, and this technique has been shown to reduce pain and improve function in patients with medial compartment KOA. However, this hypothesis of the mechanism of nonuniform settlement lacks an anatomical basis.MethodsThe P45 polyester plastination technique was used to prepare sections of the proximal tibiofibular joint to investigate the distribution of the bone trabeculae in the region of the lateral tibial plateau.ResultsThere was uneven distribution of trabeculae in the lateral condyle of the tibia and the head and neck of the fibula. The fibula and the posterolateral cortex of the shaft of the tibia united to form an arch beam via the tibiofibular joint. Many thick, dense trabeculae were present in a longitudinal direction above the tibiofibular arch.ConclusionsThe fibula supports the lateral tibial plateau, and the trabeculae were concentrated above the tibiofibular arch.

Quantitative CT-Based Methods for Bone Microstructural Measures and Their Relationships With Vertebral Fractures in a Pilot Study on Smokers.

ABSTRACTOsteoporosis causes fragile bone, and bone microstructural quality is a critical determinant of bone strength and fracture risk. This study pursues technical validation of novel CT‐based methods for assessment of peripheral bone microstructure together with a human pilot study examining relationships between bone microstructure and vertebral fractures in smokers. To examine the accuracy and reproducibility of the methods, repeat ultra‐high‐resolution (UHR) CT and micro‐CT scans of cadaveric ankle specimens were acquired. Thirty smokers from the University of Iowa COPDGene cohort were recruited at their 5‐year follow‐up visits. Chest CT scans, collected under the parent study, were used to assess vertebral fractures. UHR CT scans of distal tibia were acquired for this pilot study to obtain peripheral cortical and trabecular bone (Cb and Tb) measures. UHR CT‐derived Tb measures, including volumetric bone mineral density (BMD), network area, transverse trabecular density, and mean plate width, showed high correlation (r > 0.901) with their micro‐CT‐derived values over small regions of interest (ROIs). Both Cb and Tb measures showed high reproducibility—intra‐class correlation (ICC) was greater than 0.99 for all Tb measures except erosion index and greater than 0.97 for all Cb measures. Female sex was associated with lower transverse Tb density (p < 0.1), higher Tb spacing (p < 0.05), and lower cortical thickness (p < 0.001). Participants with vertebral fractures had significantly degenerated values (p < 0.05) for all Tb measures except thickness. There were no statistically significant differences for Cb measures between non‐fracture and fracture groups. Vertebral fracture‐group differences of Tb measures remained significant after adjustment with chronic obstructive pulmonary disease (COPD) status. Although current smokers at baseline had more fractures—81.8% versus 63.2% for former smokers—the difference was not statistically significant. This pilot cross‐sectional human study demonstrates CT‐based peripheral bone microstructural differences among smokers with and without vertebral fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dominant and nondominant distal radius microstructure: Predictors of asymmetry and effects of a unilateral mechanical loading intervention

Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral high resolution peripheral quantitative computed tomography (HRpQCT) data collected over a 12-month period as part of a clinical trial that prescribed a well-controlled, compressive loading task to the nondominant forearm. Baseline data from 102 women age 21–40, and longitudinal data from 66 women who completed the 12-month trial, were examined to determine factors responsible for side-to-side asymmetries in bone structure and change in structure over time. Cross-sectionally, the dominant radius had 2.4%–2.7% larger cross-sectional area, trabecular area, and bone mineral content than the nondominant radius, but no other differences were noted. Those who more strongly favored their dominant arm had significantly more, thinner, closely spaced trabecular struts in their dominant versus nondominant radius. Individuals assigned to a loading intervention had significant bilateral gains in total bone mineral density (2.0% and 1.2% in the nondominant versus dominant sides), and unilateral gains in the nondominant (loaded) cortical area (3.1%), thickness (3.0%), bone mineral density (1.7%) and inner trabecular density (1.3%). Each of these gains were significantly predicted by loading dose, a metric that included bone strain, number of cycles, and strain rate. Within individuals, change was negatively associated with age, meaning that women closer to age 40 experienced less of a gain in bone versus those closer to age 21. We believe that dominant/nondominant asymmetries in bone structure reflect differences in habitual loads during growth and past ability to adapt, while response to loading reflects current individual physiologic capacity to adapt.

High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures.

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

Severe Bone Microarchitecture Impairment in Women With Pregnancy and Lactation-Associated Osteoporosis.

ContextPregnancy- and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures, mostly vertebral, during the third trimester of pregnancy or the early postpartum period.ObjectiveThe aim of this study was to evaluate bone microarchitecture in women with PLO to better understand the pathophysiology of this disease.Methods In this retrospective study, we included women with PLO referred to our bone center between November 2007 and July 2012. We assessed bone mineral density (BMD) by dual-energy x-ray absorptiometry, bone turnover markers, and bone microarchitecture by high-resolution peripheral quantitative computed tomography. Results were compared with a control group of healthy lactating women.ResultsOf the 7 primiparous patients with PLO, 6 suffered vertebral fractures and 1 developed a hip fracture during the seventh month of gestation. Fractures occurred within the eighth month of pregnancy and the fourth month post partum; vertebral fractures were multiple in 85.7%. Major or minor risk factors for osteoporosis were present in 86% of our patients. Trabecular density, number, and thickness were 34%, 20% and 22% lower than controls (P < .01, P = .01, and P = .01, respectively). Cortical parameters were also deteriorated but to a lesser extent.ConclusionIn comparison with healthy lactating women, patients with PLO presented severe deterioration of bone trabecular and cortical microarchitecture. This significant compromise may explain the occurrence of multiple fractures in these otherwise healthy young women. Further prospective studies are needed to determine whether bone microarchitecture might be able to be restored in the future.

The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice.

Glucocorticoid-induced osteoporosis (dexamethasone) is a primary cause of secondary osteoporosis by the decreasing formation and increasing resorption activities. Previously, the in vitro study showed that 70% ethanol and aqueous extract of deer antler have increased alkaline phosphatase in osteoblast cell that known as marker of bone formation. The mind of this study is to analyze the effect of deer antlers in increasing the bone trabecular density of osteoporosis-induced male mice. This study used a post-test control group design. A total of 54 healthy male mice were randomly divided to nine groups, i.e.,healthy control, osteoporotic, positive control, 70% ethanol (4, 8, and 12mg/kg BW), and aqueous extracts (4, 8, and 12mg/kg BW) of deer antler groups. All of the interventions were given 1mL of test sample for 4weeks orally. The bone densities were determined using histomorphometry by Image J and Adobe Photoshop. The statistical data were performed using SPSS 23 and statistical significance was set at p<0.05. The results showed that alendronate group, 70% ethanol, and aqueous extract groups increased bone density and calcium levels in serum (p<0.05) compared to osteoporotic group in dose dependent manner. It indicated that 70% ethanol and aqueous extract of deer antler stimulating bone turnover and aqueous extract showed the highest. Dexamethasone induction for 4weeks caused osteoporotic mice and the administration of 70% ethanol and aqueous extracts of deer antler from East Kalimantan increased trabecular bone density and calcium levels in dose dependent manner.

Bone and muscle development in three inbred female mouse strains

ABSTRACTMuscle force is thought to be one of the main determinants of bone development. Hence, peak muscle growth is expected to precede peak bone growth. In this study, we investigated muscle and bone development in female C57BL/6 J, DBA/2JRj, and C3H/HeOuJ mice. Femoral cortical and trabecular bone structure and the weights of selected muscles were assessed at the ages of 8, 16, and 24 weeks. Muscle mass increased from 8 to 24 weeks in all 3 strains, suggesting peak muscle development at 24 weeks or later. Bone volume fraction, trabecular number, and connectivity density of the femur decreased or remained unchanged, whereas trabecular density and trabecular thickness largely increased. These results suggest a peak in trabecular bone accrual at 8 weeks or earlier followed by further increases in density and structural reorganization of trabeculae. Cortical density, cortical thickness, and cortical cross sectional area increased over time, suggesting a peak in cortical bone accrual at 24 weeks or later. In conclusion, our data provide evidence that growth of muscle lags behind trabecular bone accrual.

Spatio-Temporal Bone Remodeling after Hematopoietic Stem Cell Transplantation

The interaction of hematopoietic cells and the bone microenvironment to maintain bone homeostasis is increasingly appreciated. We hypothesized that the transfer of allogeneic T lymphocytes has extensive effects on bone biology and investigated trabecular and cortical bone structures, the osteoblast reconstitution, and the bone vasculature in experimental hematopoietic stem cell transplantations (HSCT). Allogeneic or syngeneic hematopoietic stem cells (HSC) and allogeneic T lymphocytes were isolated and transferred in a murine model. After 20, 40, and 60 days, bone structures were visualized using microCT and histology. Immune cells were monitored using flow cytometry and bone vessels, bone cells and immune cells were fluorescently stained and visualized. Remodeling of the bone substance, the bone vasculature and bone cell subsets were found to occur as early as day +20 after allogeneic HSCT (including allogeneic T lymphocytes) but not after syngeneic HSCT. We discovered that allogeneic HSCT (including allogeneic T lymphocytes) results in a transient increase of trabecular bone number and bone vessel density. This was paralleled by a cortical thinning as well as disruptive osteoblast lining and loss of B lymphocytes. In summary, our data demonstrate that the adoptive transfer of allogeneic HSCs and allogeneic T lymphocytes can induce profound structural and spatial changes of bone tissue homeostasis as well as bone marrow cell composition, underlining the importance of the adaptive immune system for maintaining a balanced bone biology.

Exposure to acrylamide induces skeletal developmental toxicity in zebrafish and rat embryos.

Acrylamide is a well-known carcinogen and neurotoxic substance that has been discovered in frying or baking carbohydrate-rich foods and is widely found in soils and groundwater. The purpose of this study was to investigate the adverse effects of exposure to acrylamide on skeletal development. After treatment with acrylamide in zebrafish embryos, the survival and hatching rates decreased, and the body length shortened, with cartilage malformation and a decrease in skeletal area. Exposure to acrylamide in maternal rats during the lactation period disturbed bone mineral density, serum levels of parathyroid hormone, and the expression of skeletal development-related genes in neonates. Exposure to acrylamide in pregnant rats during the pregnancy period decreased the trabecular density and inhibited cartilage formation by delaying the differentiation of osteoblasts and promoting the maturation of osteoclasts in rat embryos. Furthermore, acrylamide intervention downregulated the expression of chondrocyte and osteoblast differentiation-related genes (sox9a, bmp2, col2a1, and runx2), and upregulated the expression of osteoclast marker genes (rankl and mcsf) in zebrafish and rat embryos at different gestational stages. Our results indicated that exposure to acrylamide dysregulated signature gene and protein expression profiles of skeletal development by suppressing the differentiation and maturation of osteoblasts and cartilage matrix and promoting the formation of osteoclasts, and ultimately induced skeletal abnormality in morphology, which brings increasing attention to the intergenerational toxicity of acrylamide via mother-to-child transmission.

Mitochondrial Calcium Uniporter Deficiency in Zebrafish Causes Cardiomyopathy With Arrhythmia

Mitochondrial Ca2 + uptake influences energy production, cell survival, and Ca2 + signaling. The mitochondrial calcium uniporter, MCU, is the primary route for uptake of Ca2 + into the mitochondrial matrix. We have generated a zebrafish MCU mutant that survives to adulthood and exhibits dramatic cardiac phenotypes resembling cardiomyopathy and sinus arrest. MCU hearts contract weakly and have a smaller ventricle with a thin compact layer and reduced trabecular density. Damaged myofibrils and swollen mitochondria were present in the ventricles of MCU mutants, along with gene expression changes indicative of cell stress and altered cardiac structure and function. Using electrocardiography, we found that MCU hearts display conduction system defects and abnormal rhythm, with extended pauses resembling episodes of sinus arrest. Together, our findings suggest that proper mitochondrial Ca2 + homeostasis is crucial for maintaining a healthy adult heart, and establish the MCU mutant as a useful model for understanding the role of mitochondrial Ca2 + handling in adult cardiac biology.

Soluble RANKL exaggerates hindlimb suspension-induced osteopenia but not muscle protein balance.

We examined the hypothesis that exaggerating unloading-induced bone loss using a combination of hindlimb suspension (HLS) and exogenous injections of receptor activator of nuclear factor-κB ligand (RANKL) also exaggerates gastrocnemius and quadriceps muscle loss. Forty, male C57Bl/6J mice (16 weeks) were subjected to HLS or normal ambulation (ground control, GC) for 14 days. Mice received three intraperitoneal injections of either human recombinant soluble RANKL or phosphate-buffered saline as control (n = 10/group) at 24 h intervals starting on Day 1 of HLS. GC + RANKL and HLS mice exhibited similar decreases in trabecular bone volume and density in both proximal tibias and distal femurs. However, RANKL affected trabecular number, separation, and connectivity density, while HLS decreased trabecular thickness. The combination of RANKL and HLS exacerbated these changes. Similarly, GC + RANKL and HLS mice saw comparable decreases in cortical bone volume, thickness, and strength in femur midshafts, and combination treatment exacerbated these changes. Plasma concentrations of P1NP were increased in both groups receiving RANKL, while CTX concentrations were unchanged. HLS decreased gastrocnemius weight and was associated with a reduction in global protein synthesis, and no change in proteasome activity. This change was correlated with a decrease in S6K1 and S6 phosphorylation, but no change in 4E-BP1 phosphorylation. Injection of RANKL did not alter gastrocnemius or quadriceps muscle protein metabolism in GC or HLS mice. Our results suggest that injection of soluble RANKL exacerbates unloading-induced bone loss, but not unloading-induced gastrocnemius or quadriceps muscle loss.

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT.

Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in skeletal microstructure. We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy X-ray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N= 24) or placebo (N= 10) for 6 months; all then received teriparatide for 24 months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60 mg q6M) for 24 months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p= 0.01), cortical area and thickness (both 2.7%, p< 0.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: -5.1%, all p< 0.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p< 0.001 and 3.3%, p= 0.02) and cortical vBMD (1.7% and 3.2%; both p< 0.01), and failure load (1.1% and 3.6%; both p< 0.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p< 0.001) and number (2.4%, p= 0.03) increased at the tibia, while thickness (3.0%, p= 0.02) increased at the radius. After 48 months of sequential treatment, significant increases in total vBMD (tibia: p< 0.001; radius: p= 0.01), trabecular microstructure (p< 0.05), cortical thickness (tibia: p< 0.001; radius: p= 0.02), and whole bone strength (p< 0.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP. © 2022 American Society for Bone and Mineral Research (ASBMR).

Chronic Kidney Disease-Induced Vascular Calcification Impairs Bone Metabolism.

ABSTRACTAn association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD‐induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age‐matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross‐talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).