Cortical Bone Area Research Articles

Comparative Study of 3D Contact Area Percentage Between Zygomatic Implant and Bone in Different Surgical Approaches: Clinical and Biomechanical Perspectives.

Zygomatic implants, either alone or in combination with dental implant placement, have emerged as a viable surgical option for elderly patients with severe bone atrophy for occlusal restoration. This study aims to examine the biomechanical impact of the three-dimensional contact area between zygomatic implants and bone on biomechanics under different surgical methods. Using Cone Beam Computed Tomography (CBCT) images from 10 patients with severe bone atrophy, we reconstructed 3D maxillary bone models and created corresponding 3D zygomatic implant models. Two distinct surgical methods (extramaxillary or intrasinus approaches) were employed based on the position and angle of the zygomatic implant for each patient. The 3D bone-to-implant contact percentage (BIC%) was calculated, and finite element analysis with nonlinear contact was conducted to assess the relationship between 3D BIC% and surrounding bone stress for both surgical methods. The 3D BIC% of extramaxillary approach (57.63%) and intrasinus approach (56.49%) for total bone (including cortical and cancellous bone) was similar (P=0.425) in zygomatic implant surgery. In contrast, the intrasinus method exhibited higher 3D BIC% in cortical bone contact (28.08%) compared to the extramaxillary approach (21.92%) (P=0.011). The correlation between 3D BIC% and high bone stress was stronger in the intrasinus approach, likely due to increased contact area in cortical bone. The intrasinus approach led to lower bone stress and a more robust correlation between bone stress and 3D BIC%, particularly in cortical bone contact. Importantly, the coverage area of cortical bone surrounding the zygomatic implant significantly influenced biomechanical performance of the zygomatic implants.

Effect of different running protocols on bone morphology and microarchitecture of the forelimbs in a male Wistar rat model.

It is accepted that the metabolic response of bone tissue depends on the intensity of the mechanical loads, but also on the type and frequency of stress applied to it. Physical exercise such as running involves stresses which, under certain conditions, have been shown to have the best osteogenic effects. However, at high intensity, it can be deleterious for bone tissue. Consequently, there is no clear consensus as to which running modality would have the best osteogenic effects. Our objective was to compare the effects of three running modalities on morphological and micro-architectural parameters on forelimb bones. Forty male Wistar rats were randomly divided into four groups: high intensity interval training (HIIT), continuous running, combined running ((alternating HIIT and continuous modalities) and sedentary (control). The morphometry, trabecular microarchitecture and cortical porosity of the ulna, radius and humerus were analyzed using micro-tomography. All three running modalities resulted in bone adaptation, with an increase in the diaphyseal diameter of all three bones. The combined running protocol had positive effects on the trabecular thickness in the distal ulna. The HIIT protocol resulted in an increase in both medio-lateral diameter and cortical bone area over total area (Ct.Ar/Tt.Ar) at the ulnar shaft compared with sedentary condition. Moreover, the HIIT protocol decreased the mean surface area of the medulla (Ma.Ar) according to sedentary condition at the ulnar shaft. This study has shown that HIIT resulted in a decrease in trabecular bone fraction in favor of cortical bone area at the ulna.

Calorie restriction in mice impairs cortical but not trabecular peak bone mass by suppressing bone remodeling.

Calorie restriction (CR) can lead to weight loss and decreased substrate availability for bone cells. Ultimately, this can lead to impaired peak bone acquisition in children and adolescence and bone loss in adults. But the mechanisms that drive diet-induced bone loss in humans are not well characterized. To explore those in greater detail, we examined the impact of 30% CR for 4 and 8wk in both male and female 8-wk-old C57BL/6J mice. Body composition, areal bone mineral density (aBMD), skeletal microarchitecture by micro-CT, histomorphometric parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. After 8wk, CR mice lost weight and exhibited lower femoral and whole-body aBMD vs ad libitum (AL) mice. By micro-CT, CR mice had lower cortical bone area fraction vs AL mice, but males had preserved trabecular bone parameters and females showed increased bone volume fraction compared to AL mice. Histomorphometric analysis revealed that CR mice had a profound suppression in trabecular as well as endocortical and periosteal bone formation in addition to reduced bone resorption compared to AL mice. Bone marrow adipose tissue was significantly increased in CR mice. In vitro, the pace of adipogenesis in bone marrow stem cells was greatly accelerated with higher markers of adipocyte differentiation and more oil red O staining, whereas osteogenic differentiation was reduced. qRT-PCR and western blotting suggested that the expression of Wnt16 and the canonical β-catenin pathway was compromised during CR. In sum, CR causes impaired peak cortical bone mass due to a profound suppression in bone remodeling. The increase in marrow adipocytes in vitro and in vivo is related to both progenitor recruitment and adipogenesis in the face of nutrient insufficiency. Long-term CR may lead to lower bone mass principally in the cortical envelope, possibly due to impaired Wnt signaling.

Bone Incorporation of a Poly (L-Lactide-Co-D, L-Lactide) Internal Fixation Device in a Rat's Tibia: Microtomographic, Confocal LASER, and Histomorphometric Analysis.

This study evaluated the bone incorporation process of a screw-shaped internal fixation device made of poly (L-lactide-co-D, L-lactide) (PLDLLA). Thirty-two male Wistar rats received 32 fixation devices (2 mm × 6 mm) randomly assigned to either the right or left tibia and one implant in each animal. After 7, 14, 28, and 42 days, the rats were euthanized and the specimens were subjected to microtomographic computed tomography (microCT) and histomorphometric analyses to evaluate bone interface contact (BIC%) and new bone formation (NBF%) in cortical and cancellous bone areas. The animals euthanized on days 28 and 42 were treated with calcein and alizarin red, and confocal LASER microscopy was performed to determine the mineral apposition rate (MAR). Micro-CT revealed a higher percentage of bone volume (p < 0.006), trabecular separation (p < 0.001), and BIC in the cortical (p < 0.001) and cancellous (p = 0.003) areas at 28 and 42 days than at 7 and 14 days. The cortical NBF at 42 days was greater than that at 7 and 14 days (p = 0.022). No statistically significant differences were observed in cancellous NBF or MAR at 28 and 42 days. Based on these results, it can be seen that the PLDLLA internal fixation device is biocompatible and allows new bone formation around the screw thread.

High circulating concentrations of estradiol are anabolic for bone mass and strength in an adult male to female transgender mouse model

The effects of gender affirming hormone therapy (GAHT) on bone microarchitecture and fracture risk in adult transgender women is unclear. To investigate the concept that skeletal integrity and strength in trans women may be improved by treatment with a higher dose of GAHT than commonly prescribed, we treated adult male mice with a sustained, high dose of estradiol. Adult male mice at 16 weeks of age were administered ~1.3 mg estradiol by silastic implant, implanted intraperitoneally, for 12 weeks. Controls included vehicle treated intact females and males. High-dose estradiol treatment in males stimulated the endocortical deposition of bone at the femoral mid-diaphysis, increasing cortical thickness and bone area. This led to higher stiffness, maximum force, and the work required to fracture the bone compared to male controls, while post-yield displacement was unaffected. Assessment of the material properties of the bone showed an increase in both elastic modulus and ultimate stress in the estradiol treated males. Treatment of male mice with high dose estradiol was also anabolic for trabecular bone, markedly increasing trabecular bone volume, number and thickness in the distal metaphysis which was accompanied by an increase in the histomorphometric markers of bone remodelling, mineralizing surface/bone surface, bone formation rate and osteoclast number. In conclusion, a high dose of estradiol is anabolic for cortical and trabecular bone in a male to female transgender mouse model, increasing both stiffness and strength. These findings suggest that increasing the current dose of GAHT administered to trans women, while considering other potential adverse effects, may be beneficial to preserving their bone microstructure and strength.

High muscular fitness level may positively affect bone strength and body composition in children with overweight and obesity

SummaryMuscular fitness plays a major role in bone health and body composition in overweight and obese children. It is key that the development of this muscle fitness is affected by absolute isometric strength and dynamic strength.PurposeTo compare bone health and body composition between overweight/obese children considering muscular fitness (MF) levels, and to investigate whether weight-bearing dynamic or absolute isometric strength, both involved in the development of this muscular fitness, are more related with bone health.MethodsMF of 59 overweight or obese children (10.1 ± 0.9 years, 27 females) was measured by a countermovement jump (CMJ), handgrip, and maximal isometric strength of knee extension. Participants were divided into four groups depending on their MF level performing a cluster analysis: 16 children with high MF (HMF) in all tests, 18 with high performance in isometric strength (HIS), 15 with high performance in CMJ (HCMJ) and 10 low isometric and low dynamic force values (LMF). Body composition values were measured by dual energy X-ray absorptiometry, and bone strength values were assessed by peripheral quantitative computed tomography. Motor skills were evaluated using TGMD-3. Multivariate analysis of covariance test was applied to analyse bone strength differences between children in the different MF groups, using maturity offset, height and weight as covariates, and correlations were investigated.ResultsHMF excelled in bone health. HIS had higher cortical bone area, periosteal circumference, bone mass, polar strength strain index and fracture load than LMF, while HCMJ only showed better results in trabecular bone area than LMF. HMF had significantly better values of fracture load and periosteal and endosteal circumferences than HCMJ, but not than HIS.ConclusionsHigh MF level shows positive effects on bone health in overweight/obese children. Those with highest isometric strength had better bone health compared to those with higher dynamic strength.Trial registrationThe research project was registered in a public database Clinicaltrials.gov in June 2020 with the identification number NCT04418713.

#2717 Fermentable and viscous dietary fiber types improve cortical bone in a rat model of chronic kidney disease-mineral and bone disorder

Abstract Background and Aims Renal osteodystrophy is highly prevalent among people with chronic kidney disease (CKD). We recently showed that inulin, a prebiotic fermentable dietary fiber, improved cortical bone parameters in rats with moderate-to-severe CKD. Our objective was to evaluate if this effect was unique to the prebiotic fibers or if other fiber properties, such as viscosity, could be beneficial to bone in a rat model of CKD-mineral and bone disorder (CKD-MBD). Method 22-week-old Cy/+ male rats (50% kidney function compared to normal; CKD hereafter) were randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (−fermentability, −viscosity), 2) Inulin (+fermentability, −viscosity), 3) Psyllium husk (−fermentability, +viscosity), or 4) Pectin (+ fermentability, +viscosity). These diets were formulated with a semi-purified, casein-based background diet with 0.7% calcium and 0.7% phosphorus. Treatments lasted 10 weeks, and rats were euthanized at 32 weeks of age (kidney failure; ∼15% of normal). Micro-computed tomography (μCT) at 12-μm resolution was performed on the proximal tibia. Serum creatinine, plasma phosphorus, and plasma calcium were analyzed using colorimetric assays. One-way ANOVA was used to test the effect of dietary fiber types on outcome measures. Results At 32 weeks of age, serum creatinine was lower in the inulin, psyllium, and pectin-treated CKD rats (&amp;lt;0.04). Plasma calcium concentrations were similar between treatments, but phosphorus was lower in the psyllium and pectin-treated CKD rats (p &amp;lt; 0.02). Bone cortical area was higher in the inulin and psyllium-treated CKD rats compared to cellulose-treated rats (p &amp;lt; 0.007). Cortical thickness was higher in the inulin, psyllium, and pectin-treated CKD rats compared to cellulose-treated rats (p &amp;lt; 0.02). There was less cortical porosity in the inulin, psyllium, and pectin-treated rats (p &amp;lt; 0.02). Fermentable or viscous fibers did not impact trabecular bone volume, thickness, spacing, and number (p &amp;lt; 0.05). Plasma phosphorus was negatively associated with cortical area (r = −0.56; p &amp;lt; 0.0001) and cortical thickness (r = −0.75; p &amp;lt; 0.0001), and positively associated with cortical porosity (r = 0.74; p &amp;lt; 0.0001). Conclusion Fermentable and viscous fibers improved cortical bone but had no effect on trabecular bone. This effect may be, at least in part, due to the fiber's ability to lower plasma phosphorus and likely parathyroid hormone.

Comparative Effects of Including Inorganic, Organic, and Hydroxy Zinc Sources on Growth Development, Egg Quality, Mineral Excretion, and Bone Health of Laying Quails.

The purpose of this study was to determine the effects of the dietary addition of zinc (Zn) in the form of sulphate (Zn-S), glycine (Zn-G), and hydroxychloride (Zn-H) on quail performance, eggshell quality, antioxidant status, mineral excretion, biomechanical properties and mineralization of bone. A total of 75 female quails (10-weeks-old) were randomly distributed into 3 groups with 5 replications, each with 5 female quails. Treatment groups were set up by adding Zn-S and Zn-H as the inorganic form and Zn-G as the organic form of zinc to the corn-soybean basal diet (34.14mg/kg Zn) to obtain 50mg/kg Zn and the feeding experiment lasted for 12 weeks. Performance parameters and egg production were not impaired by the Zn source (P > 0.05). The inclusion of Zn-S in the diet produced a reduction in eggshell thickness, while an improvement in yolk antioxidant capacity (measured as MDA concentration) was detected compared to the other Zn sources (P < 0.05). Shear strength and cortical bone area increased (P < 0.05) with Zn-G supplementation, however, the mineral concentration of the tibia was higher (P < 0.01) in those quails who had received Zn-H. Lower levels of mineral excretion were observed in both types of supplementations compared to Zn-S. Therefore, it can be stated that Zn-G or Zn-H supplementation in the diet of laying quails could be an interesting strategy to reduce mineral excretion and improve bone mineralization without affecting performance compared to Zn-S. However, further studies are needed to determine the differences between Zn-G and Zn-H.

Relationships between obesity markers and bone parameters in community-dwelling older adults

BackgroundOsteoporosis is an age-related condition that can lead to fragility fractures and other serious consequences. The literature data on the impact of obesity on bone health are contradictory. The main reasons for this discrepancy could be the imperfect nature of the body mass index (BMI) as a marker of obesity, the metabolic status (inflammation and metabolically healthy obesity), and/or heterogeneity in bone variables and architecture or sex.AimsTo examine the relationship between bone variables and three validated obesity criteria.MethodsIn this cross-sectional study, participants were classified as obese according to their BMI, waist circumference (WC), and fat mass (FM). Bone variables and architecture were assessed using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively.ResultsOne hundred sixty-eight adults aged 55 or over (men: 68%) were included. 48 (28%) participants were obese according to the BMI, with 108 (64%) according to the FM, and 146 (87%) according to the WC. Bone variables were positively correlated with WC and BMI (Pearson’s r = 0.2–0.42). In men only, the obesity measures were negatively correlated with cortical bone density (Pearson’s r = − 0.32 to − 0.19) and positively correlated with cortical bone area (Pearson’s r = 0.22–0.39).ConclusionOur findings indicate that independent of sex and obesity criteria, when significant, being obese seems to lead to higher bone parameters than being non-obese, except for cortical bone density. Thus, in the obese population, assessing cortical density might help the physician to identify bone alteration. Further researches are needed to confirm our findings.

Morphologic and mechanical adaptive variations in Saiga tatarica calcaneus: A model for interpreting the bone functional adaptation of wild artiodactyl in captivity.

Captivity alters the locomotor behavior of wild artiodactyls and affects the mechanical loading of the calcaneus; however, the resulting adaptive changes in calcaneus morphology have not been sufficiently studied to date. This study aimed to investigate the morphological and mechanical adaptive variations in the calcaneus of Saiga tatarica to understand further the functional adaptation of the calcaneus in wild artiodactyl to captivity. Paired calcanei from autopsy samples of six captive wild artiodactyls (S. tatarica) and six domesticated artiodactyls (Ovis aries) were divided into skeletally immature and mature groups using X-ray evaluation of growth plate closure. High-resolution microcomputed tomography revealed a calcaneal diaphyseal cross-section. The mechanical and nanomorphological characteristics of the trabecular bone were determined by atomic force microscopy. The percent cortical bone area (%CA), cortical thickness ratio (CTR), and Young's modulus (E) differed between species in the immature groups but not in the mature groups. S. tatarica had significantly higher growth rates for %CA, CTR, and E in the mid-shaft than O. aries (p < 0.05). The calcaneus morphology of S. tatarica converges with that of domesticated O. aries during ontogeny. These results indicate that the calcaneus of wild artiodactyls can undergo potentially transitional changes during the short-term adaptation to captivity. The above parameters can be preliminarily identified as morphological signs of functional bone adaptation in artiodactyls.

Population trends in human rib cross-sectional shapes.

Rib fractures remain the most frequent thoracic injury in motor vehicle crashes. Computational human body models (HBMs) can be used to simulate these injuries and design mitigation strategies, but they require adequately detailed geometry to replicate such fractures. Due to a lack of rib cross-sectional shape data availability, most commercial HBMs use highly simplified rib sections extracted from a single individual during original HBM development. This study provides human rib shape data collected from chest CT scans of 240 females and males across the full adult age range. A cortical bone mapping algorithm extracted cross-sectional geometry from scans in terms of local periosteal position with respect to the central rib axis and local cortex thickness. Principal component analysis was used to reduce the dimensionality of these cross-sectional shape data. Linear regression found significant associations between principal component scores and subject demographics (sex, age, height, and weight) at all rib levels, and predicted scores were used to explore the expected rib cross-sectional shapes across a wide range of subject demographics. The resulting detailed rib cross-sectional shapes were quantified in terms of their total cross-sectional area and their cortical bone cross-sectional area. Average-sized female ribs were smaller in total cross-sectional area than average-sized male ribs by between 20% and 36% across the rib cage, with the greatest differences seen in the central portions of rib 6. This trend persisted although to smaller differences of 14%-29% when comparing females and males of equal intermediate weight and stature. Cortical bone cross-sectional areas were up to 18% smaller in females than males of equivalent height and weight but also reached parity in certain regions of the rib cage. Increased age from 25 to 80 years was associated with reductions in cortical bone cross-sectional area (up to 37% in females and 26% in males at mid-rib levels). Total cross-sectional area was also seen to reduce with age in females but to a lesser degree (of up to 17% in mid-rib regions). Similar regions saw marginal increases in total cross-sectional area for male ribs, indicating age affects rib cortex thickness moreso than overall rib cross-sectional size. Increased subject height was associated with increased rib total and cortical bone cross-sectional areas by approximately 25% and 15% increases, respectively, in mid-rib sections for a given 30 cm increase in height, although the magnitudes of these associations varied by sex and rib location. Increased weight was associated with approximately equal changes in both cortical bone and total cross-sectional areas in males. These effects were most prominent (around 25% increases for an addition of 50 kg) toward lower ribs in the rib cage and had only modest effects (less than 12% change) in ribs 2-4. Females saw greater increases with weight in total rib area compared to cortical bone area, of up to 21% at the eighth rib level. Results from this study show the expected shapes of rib cross-sections across the adult rib cage and across a broad range of demographics. This detailed geometry can be used to produce accurate rib models representing widely varying populations.

The Impact of Systemic Simvastatin on Bone Remodeling Following Rapid Maxillary Expansion: An In Vivo Study

A midpalatal suture contention after rapid maxillary expansion (RME) is a major orthodontic challenge. The objective of this study is to evaluate the effect of systemic simvastatin on suture bone remodeling after disjunction. For that, 15 Wistar rats were used. In 10, orthodontic appliances were installed and activated for 5 days for RME. These animals were randomly divided into two groups: control (CT, n = 5) and simvastatin (SVT, n = 5). Also, animals without intervention (HG, n = 5) were used. In the SVT and CT groups, 5 mg/kg of simvastatin and distilled water were administered by gavage, respectively, for 20 consecutive days. Then, the animals were euthanized and scanned in micro-computed tomography (µCT). The images were analyzed through pixel linear measurement at four different points (P1, P2, P3 and P4), in the intra-incisor distance (DI) and in the suture distance (SD). Microtomographic parameters, such as cortical bone area (Ct.Ar), cortical area fraction (Ct.Ar/Tt.Ar), and cortical thickness (Ct.Th), were obtained. Also, bone volume fraction (BV/TV) and empty space (EV) were extracted. Then, histological slides were prepared for descriptive and histomorphometric analysis. There was a statistically significant difference in the linear measurements, microtomographic parameters, and histomorphometric results between the experimental groups. In conclusion, simvastatin demonstrated an osteoinductive and antiresorptive effect in the palatine suture region after RME.

Atomic Layer Deposition of Zirconia on Titanium Implants Improves Osseointegration in Rabbit Bones.

Atomic layer deposition (ALD) is a method that can deposit zirconia uniformly on an atomic basis. The effect of deposited zirconia on titanium implants using ALD was evaluated in vivo. Machined titanium implants (MTIs) were used as the Control. MTIs treated by sandblasting with large grit and acid etching (SA) and MTIs deposited with zirconia using ALD are referred to as Groups S and Z, respectively. Twelve implants were prepared for each group. Six rabbits were used as experimental animals. To evaluate the osteogenesis and osteocyte aspects around the implants, radiological and histological analyses were performed. The bone-to-implant contact (BIC) ratio was measured and statistically analyzed to evaluate the osseointegration capabilities. In the micro-CT analysis, more radiopaque bone tissues were observed around the implants in Groups S and Z. Histological observation found that Groups S and Z had more and denser mature bone tissues around the implants in the cortical bone area. Many new and mature bone tissues were also observed in the medullary cavity area. For the BIC ratio, Groups S and Z were significantly higher than the Control in the cortical bone area (P < 0.017), but there was no significant difference between Groups S and Z. MTIs deposited with zirconia using ALD (Group Z) radiologically and histologically showed more mature bone formation and activated osteocytes compared with MTIs (Control). Group Z also had a significantly higher BIC ratio than the Control. Within the limitations of this study, depositing zirconia on the surface of MTIs using ALD can improve osseointegration in vivo.

Zoledronate reduces loading-induced microdamage in cortical ulna of ovariectomized rats

As a daily physiological mechanism in bone, microdamage accumulation dissipates energy and helps to prevent fractures. However, excessive damage accumulation might bring adverse effects to bone mechanical properties, which is especially problematic among the osteoporotic and osteopenic patients treated by bisphosphonates. Some pre-clinical studies in the literature applied forelimb loading models to produce well-controlled microdamage in cortical bone. Ovariectomized animals were also extensively studied to assimilate human conditions of estrogen-related bone loss. In the present study, we combined both experimental models to investigate microdamage accumulation in the context of osteopenia and zoledronate treatment. Three-month-old normal and ovariectomized rats treated by saline or zoledronate underwent controlled compressive loading on their right forelimb to create in vivo microdamage, which was then quantified by barium sulfate contrast-enhanced micro-CT imaging. Weekly in vivo micro-CT scans were taken to evaluate bone (re)modeling and to capture microstructural changes over time. After sacrifice, three-point-bending tests were performed to assess bone mechanical properties. Results show that the zoledronate treatment can reduce cortical microdamage accumulation in ovariectomized rats, which might be explained by the enhancement of several bone structural properties such as ultimate force, yield force, cortical bone area and volume. The rats showed increased bone formation volume and surface after the generation of microdamage, especially for the normal and the ovariectomized groups. Woven bone formation was also observed in loaded ulnae, which was most significant in ovariectomized rats. Although all the rats showed strong correlations between periosteal bone formation and microdamage accumulation, the correlation levels were lower for the zoledronate-treated groups, potentially because of their lower levels of microdamage. The present study provides insights to further investigations of pharmaceutical treatments for osteoporosis and osteopenia. The same experimental concept can be applied in future studies on microdamage and drug testing.

Early Osteogenic-Induced Adipose-Derived Stem Cells and Canine Bone Regeneration Potential Analyzed Using Biodegradable Scaffolds.

The complex process of bone regeneration is influenced by factors such as inflammatory responses, tissue interactions, and progenitor cells. Currently, multiple traumas can interfere with fracture healing, causing the prolonging or failure of healing. In these cases, bone grafting is the most effective treatment. However, there are several drawbacks, such as morbidity at the donor site and availability of suitable materials. Advantages have been provided in this field by a variety of stem cell types. Adipose-derived stem cells (ASCs) show promise. In the radiological examination of this study, it was confirmed that the C/S group showed faster regeneration than the other groups, and Micro-CT also showed that the degree of bone formation in the defect area was highest in the C/S group. Compared to the control group, the change in cortical bone area in the defect area decreased in the sham group (0.874), while it slightly increased in the C/S group (1.027). An increase in relative vascularity indicates a decrease in overall bone density, but a weak depression filled with fibrous tissue was observed outside the compact bone. It was confirmed that newly formed cortical bone showed a slight difference in bone density compared to surrounding normal bone tissue due to increased distribution of cortical bone. In this study, we investigated the effect of bone regeneration by ADMSCs measured by radiation and pathological effects. These data can ultimately be applied to humans with important clinical applications in various bone diseases, regenerative, and early stages of formative differentiation.

Pharmacologic Inhibition of Myostatin With a Myostatin Antibody Improves the Skeletal Muscle and Bone Phenotype of Male Insulin-Deficient Diabetic Mice.

Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin-deficient, streptozotocin (STZ)-induced diabetes is protective for bone and skeletal muscle. DBA/2J male mice were injected with low-dose STZ (diabetic) or vehicle (non-diabetic). Subsequently, insulin or palmitate Linbits were implanted and myostatin (REGN647-MyoAb) or control (REGN1945-ConAb) antibody was administered for 8 weeks. Body composition and contractile muscle function were assessed in vivo. Systemic myostatin, P1NP, CTX-I, and glycated hemoglobin (HbA1c) were quantified, and gastrocnemii were weighed and analyzed for muscle fiber composition and gene expression of selected genes. Cortical and trabecular parameters were analyzed (micro-computed tomography evaluations of femur) and cortical bone strength was assessed (three-point bending test of femur diaphysis). In diabetic mice, the combination of insulin/MyoAb treatment resulted in significantly higher lean mass and gastrocnemius weight compared with MyoAb or insulin treatment alone. Similarly, higher raw torque was observed in skeletal muscle of insulin/MyoAb-treated diabetic mice compared with MyoAb or insulin treatment. Additionally, muscle fiber cross-sectional area (CSA) was lower with diabetes and the combination treatment with insulin/MyoAb significantly improved CSA in type II fibers. Insulin, MyoAb, or insulin/MyoAb treatment improved several parameters of trabecular architecture (eg, bone volume fraction [BV/TV], trabecular connectivity density [Conn.D]) and cortical structure (eg, cortical bone area [Ct. Ar.], minimum moment of inertia [Imin]) in diabetic mice. Lastly, cortical bone biomechanical properties (stiffness and yield force) were also improved with insulin or MyoAb treatment. In conclusion, pharmacologic myostatin inhibition is beneficial for muscle mass, muscle function, and bone properties in this mouse model of T1D and its effects are both independent and additive to the positive effects of insulin. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Effect of high-fructose consumption in pregnancy on the bone growth of offspring rats.

Growing evidence suggests that bone health is programmed in early life. Maternal diet may influence the skeletal development of offspring. We aimed to determine the possible effects of high-fructose intake during pregnancy on different aspects of long bone morphology in the offspring of rats and to initially explore the possible mechanisms. Pregnant Sprague-Dawley rats were randomly divided into four groups and intragastrically administered the same dose of distilled water (CON, n = 12), 20 g/kg/day glucose (GLU, n = 12), 10 g/kg/day fructose (LFRU, n = 12), or 20 g/kg/day fructose (HFRU, n = 12) for 21 days during gestation. Computed tomography was used to analyze the cortical and cancellous bones of the distal femur of the offspring rats, and circulating bone metabolic biomarkers were measured using enzyme immunoassay. The results showed that high-fructose intake during pregnancy could decrease body weight, impair glucose metabolism, and increase serum leptin and uric acid in offspring. The offspring in the HFRU group had higher levels of the N-terminal propeptide of type I procollagen (PINP) and the C-telopeptide of type I collagen (CTX). The bone mean density (BMD), the total cross-sectional area inside the periosteal envelope (Tt.Ar), cortical bone area (Ct.Ar), medullary (or marrow) area (Ma.Ar), and trabecular mean density of the offspring in the HFRU group were lower than those in the CON group. Tartrate-resistant acid phosphatase (Trap) staining showed that high-fructose intake during pregnancy could increase the number of osteoclasts and increase the absorption area. Our results suggested that excessive fructose intake during pregnancy could inhibit skeletal development in offspring. Thus, attention to fructose intake during pregnancy is important for bone development in offspring.

Comparison of Bone Quality Among Winter Endurance Athletes with and Without Risk Factors for Relative Energy Deficiency in Sport (REDs): A Cross-Sectional Study.

Relative Energy Deficiency in Sport (REDs) is a syndrome describing the relationship between prolonged and/or severe low energy availability and negative health and performance outcomes. The high energy expenditures incurred during training and competition put endurance athletes at risk of REDs. The objective of this study was to investigate differences in bone quality in winter endurance athletes classified as either low-risk versus at-risk for REDs. Forty-four participants were recruited (M = 18; F = 26). Bone quality was assessed at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT), and at the hip and spine using dual X-ray absorptiometry (DXA). Finite element analysis was used to estimate bone strength. Participants were grouped using modified criteria from the REDs Clinical Assessment Tool Version 1. Fourteen participants (M = 3; F = 11), were classified as at-risk of REDs (≥ 3 risk factors). Measured with HR-pQCT, cortical bone area (radius) and bone strength (radius and tibia) were 6.8%, 13.1% and 10.3% lower (p = 0.025, p = 0.033, p = 0.027) respectively, in at-risk compared with low-risk participants. Using DXA, femoral neck areal bone density was 9.4% lower in at-risk compared with low-risk participants (p = 0.005). At-risk male participants had 21.9% lower femoral neck areal bone density (via DXA) than low-risk males (p = 0.020) with no significant differences in females. Overall, 33.3% of athletes were at-risk for REDs and had lower bone quality than those at low-risk.

Effects of Menaquinone-7 on the Bone Health of Growing Rats under Calcium Restriction: New Insights from Microbiome-Metabolomics.

Insufficient calcium intake during growth is a global public health concern. The aim of this study was to investigate the effects of dietary menaquinone-7 (MK-7) on bone accrual in growing Sprague-Dawley rats under calcium restriction. Following 13 weeks of treatment, various bone quality parameters, including microarchitecture, were measured. Fecal and cecal samples were subjected to microbiome (16S rRNA gene sequencing) analyses, while metabolomics analysis of the cecum and humerus samples was analyzed based on UHPLC-Q/TOF-MS. We found that calcium deficiency diminished the richness of the microbiome and disrupted microbiome composition, accompanied by an elevation in the relative abundance of Parasutterella. Furthermore, calcium insufficiency escalated the level of isovaleric acid and modified the metabolic profiles. MK-7 supplementation significantly increased the cortical thickness, cortical bone area, and the calcium content of the femur. Apart from improving bone calcium deposition and diminishing bone resorption, the mechanisms underlying the beneficial effects of MK on bone quality also involve the modulation of the host's metabolic pathways and the composition of gut microbiota. The gut-bone axis holds promise as an efficacious target for ameliorating calcium deficiency in children's bone quality, and MK-7 is a promising dietary supplement from this perspective.

Transcriptomic analysis the mechanisms of anti-osteoporosis of desert-living Cistanche herb in ovariectomized rats of postmenopausal osteoporosis.

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis.