Bone Stiffness Research Articles

Bone microarchitecture evaluated by HR-pQCT in Chinese adolescent and pediatric patients with X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Previous studies have found deteriorated bone microarchitecture in the XLH adults. Detailed studies on the skeletal microarchitecture of XLH adolescent and pediatric patients are still lacking. This study aimed to evaluate bone geometry, density, microarchitecture, stiffness in XLH adolescent and pediatric patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT).Method: This study utilized HR-pQCT to assess bone geometry, density, microarchitecture, and stiffness in 106 Chinese adolescent and pediatric patients with XLH. Compared with the sex- and age-matched controls, XLH patients had significantly higher trabecular area (Tb.Ar), lower total volumetric bone mineral density (Tot.vBMD), lower cortical volumetric BMD (Ct.vBMD), and lower stiffness at both the distal radius and the tibia after adjusting for height and weight. Alkaline phosphatase Z score (ALP-Z), a marker to reflect the disease activity of rickets, was negatively correlated with Ct.vBMD and cortical thickness (Ct.Th) at the distal radius, and Ct.vBMD at the distal tibia, and positively correlated with cortical porosity (Ct.Po) at the distal tibia. We developed an online calculator to estimate Tb.Ar, Ct.vBMD, and stiffness of the distal tibia of XLH adolescent and pediatric patients based on clinical general characteristic and biochemical indicators. The bone microarchitecture of XLH adolescent and pediatric patients was deteriorated, and ALP-Z was negatively correlated with the skeletal quality of XLH adolescent and pediatric patients, especially in the cortical bone. HR-pQCT parameters can be estimated using clinical characteristics and biochemical indicators, which may assist physicians to monitor the disease progression in areas without HR-pQCT access.

Slow H2S-Releasing Donors and 3D Printable Arrays Cellular Models in Osteo-Differentiation of Mesenchymal Stem Cells for Personalized Therapies

The effects of the hydrogen sulfide (H2S) slow-releasing donor, named GSGa, a glutathione-conjugate water-soluble garlic extract, on human mesenchymal stem cells (hMSCs) in both bidimensional (2D) and three-dimensional (3D) cultures were investigated, demonstrating increased expression of the antioxidant enzyme HO-1 and decreased expression of the pro-inflammatory cytokine interleukin-6 (IL-6). The administration of the H2S donor can therefore increase the expression of antioxidant enzymes, which may have potential therapeutic applications in osteoarthritis (OA). Moreover, GSGa was able to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but not of cardiac mesenchymal stem cells (cMSCs) in a 2D culture system. This result highlights the varying sensitivity of hMSCs to the H2S donor GSGa, suggesting that the induction of osteogenic differentiation in stem cells by chemical factors is dependent on the tissue of origin. Additionally, a 3D-printable mesenchymal stem cells–bone matrix array (MSCBM), designed to closely mimic the stiffness of bone tissue, was developed to serve as a versatile tool for evaluating the effects of drugs and stem cells on bone repair in chronic diseases, such as OA. We demonstrated that the osteogenic differentiation process in cMSCs can be induced just by simulating bone stiffness in a 3D system. The expression of osteocalcin, RUNX2, and antioxidant enzymes was also assessed after treating MSCs with GSGa and/or increasing the stiffness of the culture environment. The printability of the array may enable better customization of the cavities, enabling an accurate replication of real bone defects. This could optimize the BM array to mimic bone defects not only in terms of stiffness, but also in terms of shape. This culture system may enable a rapid screening of antioxidant and anti-inflammatory compounds, facilitating a more personalized approach to regenerative therapy.

Impact of fluoride and aluminum co-exposure on bone growth and quality in juvenile rats: dose and duration effects

This study aimed to investigate the impact of the dosage and duration of fluoride and aluminum(F and Al) co-exposure on the skeletal growth and bone quality of juvenile rats. Forty-eight 8-week-old Sprague-Dawley rats were randomly assigned to normal control, low F and Al exposure, and high F and Al exposure groups, with 45-day and 90-day subgroups established for each. We measured body length, tibia length, conducted bone histomorphometric analysis of the proximal tibia, performed micro-CT scans and three-point bending tests of the femur. Compared to the age-matched control group, the low F and Al group at 45 days exhibited increased bone formation and stiffness; the low F and Al group at 90 days and the high F and Al group at 45 days showed increases in body length, tibia length, growth plate width, longitudinal bone growth rate, bone turnover, and improved microstructure. Notably, bone elastic stress only elevated in the high F and Al group at 45 days. Conversely, the high F and Al exposure group at 90 days experienced decreases in the aforementioned parameters, with the exception of growth plate width, and displayed abnormal hypertrophic chondrocyte morphology in the growth plate. In summary, long-term exposure to low levels of F and Al and short-term exposure to high levels of F and Al promote bone formation followed by bone resorption in juvenile rats, stimulating bone growth and enhancing bone quality. However, long-term exposure to high levels F and Al results in low bone turnover, slow bone growth, and reduced bone property.

Moderate-to-vigorous physical activity modulates the association between serum 25-hydroxyvitamin D and bone stiffness in European children and adolescents

It remains unclear how serum 25-hydroxyvitamin D (25(OH)D) concentrations relate to childhood bone health. We hypothesized that 25(OH)D was inversely associated with bone turnover biomarkers and positively associated with bone stiffness. Cross-sectional analyses were performed using data from participants (2-15-year-old, 51% boys) from the IDEFICS/I.Family cohort, comprising 3,638 serum 25(OH)D measurements collected in 2007/2008 and 2012/2013 across eight European countries. A biomarker of bone formation (serum osteocalcin), a biomarker of bone resorption (serum C-terminal telopeptides of type I collagen [CTx]), and stiffness index measured using calcaneal quantitative ultrasound were considered outcomes. Linear mixed-effects models were used to adjust for confounders (i.e., age, sex, parental education, time spent in sports club, dairy products consumption, sedentary behavior, height and weight z-scores), the cluster effect of country and repeated measurements. Interactions of calcium intake, moderate-to-vigorous physical activity (MVPA) and weight status with 25(OH)D on outcomes were tested. Only 1 in 3 participants reached the sufficient 25(OH) D concentration of 20 ng/ml. Sufficient 25(OH)D was associated with higher stiffness index if participants had MVPA ≥ 60 min/day (β = 12.14, p < 0.05). Moreover, 25(OH)D was inversely associated with CTx (β = -7.09, p < 0.05); this association was positive but not statistically significant among primary school children living with overweight/obesity. No interaction was observed for calcium intake. In conclusion, serum 25(OH)D and CTx were inversely associated. MVPA interacted the positive association between 25(OH)D and bone stiffness, highlighting the importance of promoting MVPA guidelines in future vitamin D and bone health interventions.

Bacillus licheniformis and phytase combination in broiler chicken diets: Effects on growth performance, digestibility coefficients, gut microbiome activities, and bone quality

In the present study, B. licheniformis was added to broiler chicken diets alone or in combination with 6-phytase and the effects on growth performance, coefficients of ileal nutrient digestibility, morphometrical measurements of selected internal organs, gut microbial activity, and bone quality were determined. Four hundred 1-day-old female birds (Ross 308) were randomly allotted to 4 dietary treatments (10 replicate pens, 10 birds each). The trial was set up as follows: negative control (NC), basal diet without any feed additive; NC+Pro, basal diet with B. licheniformis (500 g/t of diet); NC+Phy, basal diet with 6-phytase (400 g/t of diet); and NC+Pro+Phy, basal diet in which both experimental factors were added at the same levels as above. The interaction between treatments was noted in each evaluated period regarding BWG and FI. In the entire experiment, an increased body weight gain (P < 0.001) was observed in the NC+Pro+Phy treatment compared to the other groups. The birds that received both feed additives combined were characterized by an increased feed intake (P < 0.001), contrary to NC+Pro and NC+Phy. Moreover, in terms of microenvironment modulations, interactions (P < 0.05) were observed in the jejunal and cecal digesta pH, short-chain fatty acid (SCFA) level, and microbial enzyme activities. However, the impacts of B. licheniformis and phytase on cecal SCFA concentrations and bacterial enzymes were mainly opposite. There were no interactions (P < 0.05) in terms of geometrical, mechanical, and structural selected tibia and femur indices. However, 6-phytase addition improved bone structure, stiffness, and elasticity. In conclusion, the interactions between 6-phytase and B. licheniformis positively affect growth performance via microbial activity changes; however, the supportive bone quality maintenance properties are only connected to 6-phytase supplementation.

Fermented Rapeseed Meal as a Dietary Intervention to Improve Mineral Utilization and Bone Health in Weaned Piglets.

This study examined the effects of incorporating fermented rapeseed meal (FRSM) into the diet of newly weaned piglets on mineral digestibility and bone health. Experimental diets containing varying levels of FRSM (8%, 12%, 15%, and 25%) were introduced to the piglets at 18 days of age, prior to weaning at 28 days. These diets were continued until the piglets were euthanized at 42 days of age. Mineral absorption was assessed using the apparent total tract digestibility (ATTD) method and blood plasma element analysis, while bone mineral content and mechanical properties were evaluated through densitometry and three-point bending tests. The results showed that intermediate levels of FRSM (12-15%) significantly enhanced the digestibility of key minerals, including phosphorus, calcium, magnesium, copper, zinc, and iron. This improvement was linked to increased femoral mineral content and bone stiffness, as well as a higher yield point, likely due to enhanced collagen synthesis. Additionally, there was an increase in bone fracture load and fracture stress, potentially due to changes in the organization of the bone mineral phase, as no changes in bone mid-shaft mineral density or geometry were observed. These findings suggest FRSM as a promising dietary component for improving mineral bioavailability and bone health in piglets.

Bone turnover: the role of lipoproteins in a population-based study

BackgroundDyslipidemia has been associated with reduced bone mineral density and osteoporotic fractures, but the relation between lipid and bone metabolism remains poorly understood. Analysing the effects of lipoprotein subclasses on bone turnover may provide valuable insights into this association. We therefore examined whether lipoprotein subclasses, measured by proton nuclear magnetic resonance (1H-NMR) spectroscopy, are associated with bone turnover markers (BTMs) and with the ultrasound-based bone stiffness index.MethodsData from 1.349 men and 1.123 women, who participated in the population-based Study of Health in Pomerania-TREND were analysed. Serum intact amino-terminal propeptide of type I procollagen (P1NP, bone formation) and carboxy-terminal telopeptide of type I collagen (CTX, bone resorption) concentrations were measured. Associations between the lipoprotein data and the BTMs or the stiffness index were investigated using linear regression models.ResultsThe triglyceride or cholesterol content in very-low-density lipoprotein and intermediate-density lipoprotein particles was inversely associated with both BTMs, with effect estimates being slightly higher for CTX than for P1NP. The triglyceride content in low-density lipoprotein and high-density lipoprotein particles and the Apo-A2 content in high-density lipoprotein particles was further inversely associated with the BTMs. Associations with the ultrasound-based bone stiffness index were absent.ConclusionsConsistent inverse associations of triglycerides with bone turnover were observed, which argue for a protective effect on bone health, at least in the normal range. Yet, the presented associations did not translate into effects on the ultrasound-based bone stiffness. Further, there was no relevant gain of information by assessing the lipoprotein subclasses. Nevertheless, our study highlights the close relations between lipid and bone metabolism in the general population.

KNEE DEFORMITIES AND KNEE REPLACEMENTS IN SAUDI POPULATION: OUR EXPERIENCE AND LITERATURE REVIEW

It takes precise alignment, adequate balance, and deformity correction to accomplish a successful total knee arthroplasty (TKA). In main TKA, this can be successfully achieved with a posterior stabilized (PS) design, either with or without sub-periosteal release. However, severe abnormalities with a major bone defect, stiffness, and instability are often associated with these disorders in some circumstances, such as knee osteoarthritis. Additional restrictive prostheses are required since it is extremely difficult to balance these anomalies with soft tissue release alone, even after main TKA. In this situation, the constrained condylar knee (CCK) design is the optimum choice. This studys primary objectives were to characterize the clinical outcomes, function recovery, and complications of patients who underwent primary CCK-TKA for severe knee osteoarthritis related knee deformity. The secondary aim was to find out the mid-term prostheses survival. Methods: Between March 2021 and March 2022, 36 consecutive patients with knee osteoarthritis had cemented primary CCK-TKA. Twenty-Eight women and eight men, totaling 36 patients, had at least a 6 month follow-up for this retrospective analysis. We used the Knee Society Score (KSS), the Hospital for Special Surgery (HSS) score, and the roentgenographic evaluation form to assess the patients. The survival of prosthesis was assessed using Kaplan-Meiers survival analysis. The patients follow-up periods averaged 12 month. The KSS knee score rose from 44 points (23–68) to 91 points (76–100) following surgery [P &lt; 0.001]. Following the procedure, the mean KSS functional score rose from 20–75 points to 91 points (65–100) [P &lt; 0.001]. The average HSS score rose from 51 points (27–83) to 91 points (75–100) following surgery [P &lt; 0.001]. The average range of motion (ROM) also increased after surgery, going from 68.09° ± 35.99° (0°–120°) to 113.68° ± 8.90° (100°–130°) [P &lt; 0.001]. The average hip-knee-ankle (HKA) angle was 180.24° ± 1.77° (175°–184°) following surgery, compared to 176.88° ± 14.48° (135°–199°) before to surgery. Radiolucencies were seen in thirteen knees, mostly on the tibial side. After an average follow-up of 12 month, 94.7% of prosthesis were still in use. Despite severe deformity, instability, and stiffness at a relatively young age, the mid-term follow-up of primary CCK-TKA in knee osteoarthritis gives satisfactory clinical and functional outcomes with 94.7% prosthesis survival. However, there are a few issues.

Staged Management for Distal Femur Fractures: Impacts on Reoperation, Stiffness, and Overall Outcomes.

To evaluate the outcomes of staged management with external fixation (ex-fix) prior to definitive fixation of distal femur fractures. Design: Retrospective cohort. Single Level I Trauma Center. Adults treated operatively between 2004 and 2019 for distal femur fractures (OTA/AO 33A/33C) were identified using Current Procedural Terminology codes. Excluded cases were those with screw only fixation, acute distal femur replacement, 33B fracture pattern, no radiographs available, or did not have 6-months of follow-up. Postoperative complication rates including surgical site infection [SSI], reoperation to promote bone healing, final knee arc of motion <90 degrees, heterotopic ossification formation, and reoperation for stiffness were compared between patients treated with ex-fix prior to definitive fixation and those not requiring ex-fix. A total of 407 patients were included with a mean follow-up of 27 months (median [IQR] of 12 [7,33] months), (range 6-192 months). Most patients were male (52%) with an average age of 48 [Range: 18-92] years. Ex-fix was utilized in 150 (37%) cases and 257 (63%) cases underwent primary definitive fixation. There was no difference in SSI rates (p=0.12), final knee arc of motion <90 degrees (p=0.51), and reoperation for stiffness (p=0.41) between the ex-fix and no ex-fix groups. The 150 patients requiring ex-fix spent an average of 4.2 days (SD 3.3) in the ex-fix before definitive fixation. These patients were further analyzed by comparing the duration of time spent in ex-fix, <4 days (n=82) and ≥4 days (n=68). Despite longer time spent in ex-fix prior to definitive fixation, there was again no significant difference in any of the complication and reoperation rates when comparing the two groups, including final knee arc of motion <90 degrees (p=0.63), reoperation for stiffness (p=1.00), and SSI (p=0.79). Ex-fix of distal femur fractures as a means of temporary stabilization prior to definitive ORIF does not increase the risk of complications such as SSI, final knee arc of motion <90 degrees, or reoperations for bone healing or stiffness when compared to single stage ORIF of distal femur fractures. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Somatic Structure and Ultrasound Parameters of the Calcaneus Bone in Combat Sports Athletes in Relation to Vitamin D3 Levels.

Background/Objectives: Physical activity is widely recognized for its beneficial effects on bone density during adolescence, which could lead to enhanced bone density in later life, thus acting as a health-promoting activity with long-lasting implications. However, not all studies are conclusive regarding the type, intensity, duration, and frequency of the most effective physical activities. This study focuses on combat sports athletes and examines the relationship between their somatic build and heel bone parameters using ultrasound (USG) and their vitamin D3 levels. Methods: The study included 40 male athletes specializing in various combat sports. The measurements of body height, body mass, skinfold thickness, and bone widths at multiple sites were performed to estimate the somatic build. The USG parameters of the heel bone and the blood levels of vitamin D3 were also recorded. Statistical significance was determined using one-way ANOVA, with differences among sports disciplines also examined. Results: The study found significant differences in the body composition and USG bone parameters among athletes from different combat sports (p ≤ 0.05). The calcaneus stiffness index (SI) and speed of sound (SOS) were significantly higher in athletes with normal vitamin D3 levels compared to those with below-normal levels (p = 0.0015 and p = 0.001, respectively). These findings suggest that vitamin D3 may influence bone stiffness and density. Conclusions: The study underscores the importance of maintaining adequate vitamin D3 levels to support bone mineralization in athletes, particularly those training indoors with limited exposure to sunlight. It also highlights the potential of using USG as a non-invasive method to assess bone health, aiding in the optimization of training programs to prevent injuries and improve performance.

Finite element analysis of fixation stability according to reduction position for internal fixation of intertrochanteric fractures

In recent years, finite element analysis (FEA) has been instrumental in comparing the biomechanical stability of various implants for femur fracture treatment and in studying the advantages and disadvantages of different surgical techniques. This analysis has proven helpful for enhancing clinical treatment outcomes. Therefore, this study aimed to numerically analyze fixed stability according to location using FEA. In this study, a virtual finite element model was created based on a clinically anatomically reduced patient. It incorporated positive and negative support derived from intramedullary and extramedullary reduction from the anteroposterior (AP) view and neutral support from the lateral view. The generated model was analyzed to understand the biomechanical behavior occurring in each region under applied physiological loads. The simulation results of this study showed that the average von Mises stress (AVMS) of the nail when performing intramedullary reduction for femoral fixation was 187% of the anatomical reduction and 171% of the extramedullary reduction, and individually up to 2.5 times higher. In other words, intramedullary reduction had a very high possibility of fixation failure compared to other reduction methods. This risk is amplified significantly, especially in situations where bone strength is compromised due to factors such as old age or osteoporosis, which substantially affects the stability of fixation. Extramedullary reduction, when appropriately positioned, demonstrates greater stability than anatomical reduction. It exhibits stable fixation even in scenarios with diminished bone strength. In instances in which the bone density was low in the support position, as observed in the lateral view, the AVMS on the nail appeared to be relatively low, particularly in cases of positive support. Additionally, the femur experienced lower equivalent stress only in the extramedullary reduction-negative position. Moreover, by comparing different reduction methods and bone stiffness values using the same femoral shape, this study offers insights into the selection of appropriate reduction methods. These insights could significantly inform decision making regarding surgical strategies for intertrochanteric fractures.

Impact of fractured tibia implant fixation devices on bone stiffness during bending test

This study focuses on evaluating the failure resistance of a previously reduced tibia with internal fixation implants as PLate (PL) or InterMedullary Nail (IMN), subjected later to a tibial lateral trauma. To replicate this type of trauma, which can be caused by a road accident, a three-point bending test is considered using experimental tests and numerical simulations.The withstand evaluation of the tibia-PL and tibia-IMN structures was conducted by following the load transfer through, the bone and the used implants. The analysis, up to tibia failure, required the use of an elasto-plastic behavior law coupled to damage. The model parameters were identified using experimental tests.Il was shown that the tibia-IMN structure provided a bending resistant load up to three-times higher than the tibia-PL. In fact, the used screws for plate fixation induced a high level of stress in the vicinity of threaded region, leading to a crack initiation and a damage propagation. However, in tibia-IMN structure the highest stress was generated in the trapped zone between the loader and the nail, promoting crack formation.From a biomechanical point of view, the structure with IMN is safer than the structure with PL, whose fixation induces earlier damage in bone.

Muscle Performance as a Predictor of Bone Health: Among Community-Dwelling Postmenopausal Japanese Women from Setagaya-Aoba Study.

Osteoporosis is a significant health concern for postmenopausal women, necessitating efficient screening methods for bone health. This study explores the potential of muscle function, assessed through the 30-s chair stand test (CS-30), as an indicator for low bone stiffness in this demographic, aiming to establish a practical threshold for large-scale fitness surveillance without the need for specialized tools. We analyzed data from 1055 community-dwelling postmenopausal Japanese women, aged 41-89years, collected between 2016 and 2019. Participants underwent CS-30 to evaluate muscle function alongside quantitative ultrasound (QUS) measurements to assess bone stiffness. The cohort was divided into two groups for the development and validation of a cutoff point for low bone stiffness, defined as a QUS speed of sound less than 1487.3m/s. The CS-30 cutoff was determined using receiver operating characteristic (ROC) curve analysis and validated through logistic regression, accounting for age, body mass index, and smoking status. Among 577 postmenopausal women, 16.0% exhibited low bone stiffness. In the development group (n = 382), ROC analysis identified a CS-30 cutoff of 25 repetitions for detecting low bone stiffness, with an area under the curve of 0.744 (P < 0.001). In the validation group (n = 195), participants performing ≥ 25 repetitions had a higher risk of low bone stiffness compared to those performing ≤ 24 repetitions. The CS-30 test is an effective preliminary screening tool for identifying postmenopausal women at risk of low bone stiffness, with a threshold of 25 repetitions. This method could facilitate early detection of individuals at higher osteoporosis risk, promoting timely intervention.

Sclerotic prostate cancer bone metastasis: woven bone lesions with a twist.

Bone metastases are the most severe and prevalent consequences of prostate cancer (PC), affecting more than 80% of patients with advanced PC. PCBMs generate pain, pathological fractures, and paralysis. As modern therapies increase survival, more patients are suffering from these catastrophic consequences. Radiographically, PCBMs are predominantly osteosclerotic, but the mechanisms of abnormal bone formation and how this pathological increase in bone density is related to fractures are unclear. In this study, we conducted a comprehensive analysis on a cohort of 76 cadaveric PCBM specimens and 12 cancer-free specimens as controls. We used micro-computed tomography to determine 3D organization and quantify bone characteristics, quantitative backscattering electron microscopy to characterize mineral content and details in bone structure, nanoindentation to determine mechanical properties, and histological and immunohistochemical analysis of bone structure and composition. We define 4 PCBM phenotypes: osteolytic, mixed lytic-sclerotic, and 2 subgroups of osteosclerotic lesions-those with residual trabeculae, and others without residual trabeculae. The osteosclerotic lesions are characterized by the presence of abnormal bone accumulated on trabeculae surfaces and within intertrabecular spaces. This abnormal bone is characterized by higher lacunae density, abnormal lacunae morphology, and irregular lacunae orientation. However, mineral content, hardness, and elastic modulus at micron-scale were indistinguishable between this irregular bone and residual trabeculae. The collagen matrix of this abnormal bone presents with irregular organization and a prominent collagen III composition. These characteristics suggest that osteosclerotic PCBMs initiate new bone deposition as woven bone; however, the lack of subsequent bone remodeling, absence of lamellar bone deposition on its surface, and presence of collagen III distinguish this pathologic matrix from conventional woven bone. Although the mineralized matrix retains normal bone hardness and stiffness properties, the lack of fibril anisotropy presents a compromised trabecular structure, which may have clinical implications.

Evaluation of bone density and microarchitecture in adult patients with X-linked hypophosphatemic rickets: A pilot longitudinal study

X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and biomechanical properties are poorly known. Our aim was to analyze bone properties in the appendicular and axial skeleton of adults with XLH. In this observational case-control study, each affected patient (N = 14; 9 females; age 50 ± 15 years) was matched by sex, age and body mass index to a minimum of two healthy controls (N = 34). Dual-energy X-ray Absorptiometry (DXA) analyses revealed that areal bone mineral density (aBMD) was higher in XLH patients at the lumbar spine (Z score mean difference = +2.47 SD, P value = 1.4 × 10−3). Trabecular Bone Score was also higher at the lumbar spine (P value = 1.0 × 10−4). High Resolution peripheral Quantitative Computed Tomography (HRpQCT) demonstrated that bone cross-sectional area was larger at the distal radius (P value = 6 × 10−3). Total and trabecular volumetric BMD were lower at both sites. Trabecular bone volume fraction was also lower with fewer trabecular numbers at both sites. However, bone strength evaluated by micro-finite element analyzes revealed unaffected bone stiffness and maximum failure load. Evaluation of bone mineralization with aBMD by DXA at the distal radius correlated with vBMD by HRpQCT measurements at both sites. PTH levels were inversely correlated with trabecular vBMD and BV/TV at the tibia. We then followed a subset of nine patients (median follow-up of 4 years) and reassessed HRpQCT. At the tibia, we observed a greater decrease than expected from an age and sex standardized normal population in total and cortical vBMD as well as a trabecularization of the cortical compartment. In conclusion, in adult patients with XLH, bone mineral density is high at the axial skeleton but low at the appendicular skeleton. With time, microarchitectural alterations worsen. We propose that noninvasive evaluation methods of bone mineralization such as DXA including the radius should be part of the management of XLH patients. Larger studies are needed to evaluate the clinical significance of BMD changes in XLH patients under conventional or targeted therapies.

Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton

BackgroundPrenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton.MethodsPregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology.ResultsOsteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤ 30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals.ConclusionsEvidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD.

Multifunctional Design of Triply Periodic Minimal Surface Structures for Temporary Pediatric Fixation Devices

Fracture fixation and limb deformity correction in pediatric orthopedics often use temporary metallic fixation devices. These devices’ higher stiffness compared to cortical bone leads to stress shielding, causing significant bone density reduction, periprosthetic loosening, and bone growth interference. The 3D‐printed triply periodic minimal surface (TPMS) structures present a promising engineering solution to match bone stiffness while ensuring reliable implant strength. In this study, finite‐element modeling and experimental testing are employed to identify optimal multifunctional TPMS‐based lattices that meet the required design constraints of 1) stiffness in the range of cortical bone, 2) strength in the range of cortical bone, 3) minimum osteointegration to facilitate the implant removal after healing, and 4) manufacturability with limited defect sensitivity. Six different types of TPMS structures in Ti–6Al–4V material manufactured via laser powder bed fusion are evaluated for their ability to target the lower and upper bounds of pediatric cortical bone stiffness. Lattices based on the Primitive unit cell design are superior, demonstrating the highest strength/stiffness ratio, best manufacturability, and potentially reduced osteointegration due to larger pore size, smaller surface area, and smallest negative Gaussian curvature compared to other investigated TPMS types.

Development of Transdermal Formulation Based on Nanotechnology and Elucidation of Its Drug Delivery Pathways

Transdermal drug delivery is a formulation in which the drug is absorbed through the skin for systemic action. Its advantages include avoidance of first-pass effects, sustained drug supply, and ease of administration and discontinuation. Drugs administered transdermally transfer into the blood circulation through the stratum corneum, epidermis, and dermis. The stratum corneum on the skin surface plays a barrier function in skin absorption. Therefore, developing of transdermal drug delivery systems requires innovations that overcome the barrier function of the stratum corneum and improve skin permeation. This review examines the usefulness of transdermal formulations based on solid nanoparticles using raloxifene. Milled raloxifene was gelled with (mRal-NPs) or without menthol (Ral-NPs) using Carbopol. The drug release and transdermal penetration were measured using a Franz diffusion cell, and the therapeutic evaluation of osteoporosis was determined in an ovariectomized rat model. Although the raloxifene released from Ral-NPs remained in the nanoparticle state, the skin penetration of raloxifene nanoparticles was prevented by the stratum corneum in rat. The inclusion of menthol in the formulation attenuated the barrier function of the stratum corneum and permitted raloxifene nanoparticles to penetrate through the skin. Moreover, macropinocytosis relates to the formulation's skin penetration, including menthol (mRal-NPs). Applying mRal-NPs attenuated the decreases in calcium level and stiffness of bones of ovariectomized rats. This information can support future studies aimed at designing novel transdermal formulations.

Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Early manifestation of hypophosphatemic rickets in goslings: a potential role of insufficient muscular adenosine triphosphate in motility impairment of early P-deficient geese

We aimed to determine the onset time of hypophosphatemic rickets and investigate the mechanism of motility impairment through adenosine triphosphate (ATP) production in goslings. Two hundred and sixteen 1-day-old male Jiangnan white geese were randomly divided into 3 groups, with 6 replicates and 12 geese per replicate. Birds were fed on 3 diets: a control diet (nonphytic phosphorus, NPP, 0.38%), a P-deficient diet (PD; NPP, 0.08%), and a high P diet (HP; NPP, 0.80%) for 14 d. Subsequently, all birds were shifted to the control diet for an additional 14 d. The cumulative incidence of lameness increased significantly (P < 0.01) starting on d 4, reaching over 80% on d 7 and 100% on d 12 in the PD group. Drinking and eating frequency decreased from d 4 and d 5, respectively, in the PD group compared to the other groups (most P < 0.01). The PD group exhibited shorter and narrower beaks, higher (worse) curvature scores of the beak and costochondral junctions, swelling caput costae, and dirtier feathers since d 4, in contrast to the control and HP groups (most P < 0.01). The HP had bigger (P < 0.05) beak and sternum sizes than the control groups on d 4 to 11. Leg muscle ATP levels were lower (P < 0.01 or 0.05) on d 4 to 11; in contrast, adenosine diphosphate (d 7-11) was higher in PD compared to the control (P < 0.05). Leg muscle ATP level had positive linear (R2 > 0.40) correlations (r > 0.60) with eating and drinking frequencies on d 7 and 11 (P < 0.01). Bone stiffness, feather cleanliness, and ATP levels recovered (P > 0.05) to the control level, whereas bone size did not recover (P < 0.05) in PD and HP after eating the control diet for 2 wk. The onset time of hypophosphatemic rickets was around 4 d in goslings, and insufficient leg muscle ATP was related to the impaired motility observed in early P-deficient geese.