Mechanical Properties Of Femur Research Articles

Digoxin attenuates bisphosphonate related osteonecrosis of the jaws by RORγt-dependent Th17 response in male rats

The study aimed to evaluate digoxin, an RORγt inhibitor, in Medication-Related Osteonecrosis of the Jaws (MRONJ) in male rats treated with zoledronic acid (ZA). Forty male Wistar rats were divided into a negative control group (0.1 mL/kg saline), a positive control group (ZA, 0.20 mg/kg), and three test groups treated with ZA and digoxin at 1 (DG1), 2 (DG2), or 4 (DG4) mg/kg. These groups received treatment three times weekly. ZA was administered intravenously on days 0, 7, and 14, followed by extraction of the left lower first molar on day 42, a final ZA dose on day 49, and euthanasia on day 70. Analyses included radiographic, histomorphometric, and immunohistochemical evaluation of the mandibles, western blotting of gingiva, and mechanical tests on femurs. Statistical analysis was performed using ANOVA/Bonferroni tests (P < .05). Digoxin reduced radiolucency of MRONJ (P < .001), inflammatory cells, empty osteocyte lacunae (P < .001), apoptotic osteoclasts (P < .001), and Caspase-3-positive osteocytes (P = .021). ZA increased immunoreactivity for most markers except c-Fos, while digoxin reduced interleukin 17, TNF-α, IL-6, IL-2, FOXP3, c-Jun, NFκB (P < .001), TGF-β (P = .009), RANKL (P = .035), and OPG (P = .034). Digoxin also reversed RORγt expression (P < .001), increased diarrhea scores (P = .028), renal and cardiac indexes (P < .001), and enhanced femur mechanical properties (P < .013). Digoxin attenuated MRONJ by inhibiting RORγt and reducing the Th17 response.

The combination of linagliptin and metformin rescues bone loss in type 2 diabetic osteoporosis

To develop an approach to reduce the type 2 diabetic osteoporosis, this study investigated the protective effects of the combination of linagliptin and metformin against osteoporosis. Micro-CT and dynamic biomechanical measurements were used to determine the bone microstructure in the type 2 diabetes mellitus (T2DM) rats. MC3T3-E1 cells were cultured in high glucose environments. In addition, we used qRT-PCR and Western blotting to assess osteogenic markers and p38 and extracellular signal-regulated kinase (ERK) protein expression. The combination of linagliptin and metformin treatment significantly restored bone micro-architecture and femoral mechanical properties in the T2DM rats. In contrast, bone markers including osteocalcin, NH2-terminal propeptide of type I procollagen, COOH-terminal telopeptide of type I collagen and tartrate-resistant acid phosphatase were significantly reduced by the combination of linagliptin and metformin treatment. We used high glucose treated MC3T3-E1 cells to mimic the condition of T2DM. Linagliptin combined with metformin treatment significantly inhibited the phosphorylation of p38 and ERK induced by high glucose treatment. In conclusion, the linagliptin combined with metformin treatment improved the rats’ bone mineral density, bone structure, and osteogenic markers. Both p38 and ERK phosphorylation were reduced in high glucose MC3T3-E1 cells. Our findings highlight the potential of linagliptin combined with metformin for the treatment of T2DM-related osteoporosis.

Characterization of the femur mechanical properties under different mechanical solicitations: A finite element investigation

Characterization of the femur mechanical properties under different mechanical solicitations: A finite element investigation

Biomedical response of femurs in male Wistar rat in chronic hypergravity environments

Bone is sensitive to mechanical stimulation and plays a loading-bearing role in the human body. However, regulation of bone biomechanical properties in chronic hypergravity environments is still unclear. In this study, male Wistar rats exposed to chronic hypergravity environments (4×g, 8×g, 10×g, and 20×g) for 4 weeks were set as the hypergravity groups, and rats exposed to the normal gravity as the control group. Morphology parameters and bone remodeling factors were obtained by means of micro-CT, Western blot, and q-PCR. Mechanical properties of femurs were measured utilizing three points bending test and creep test and were fitted into a viscoelastic-viscoplastic constitutive equation. The results indicate osteoporosis occurred in femurs of hypergravity groups. Accordingly, the protein and gene expressions of bone remodeling factors (OPG, RANKL, runx2) in hypergravity groups were significantly different from that in the control group, demonstrating that bone formation level increased and bone resorption level decreased. Meanwhile, mechanical properties of femurs in hypergravity groups showed that Young's modulus of femurs in the 20×g group was significantly higher than that in the control group. The viscoelastic-viscoplastic properties of bone tissue were changed in hypergravity environments. Among them, the 8×g group was closest to the control group in morphology and mechanical properties. To sum up, the biomechanical response regulation of rat femur under 4-20×g chronic hypergravity environments was presented. Hypergravity environments could lead to osteoporosis. The balance between bone formation and bone resorption would be disrupted in hypergravity groups due to bone adaptation. 20×g environment has a significant effect on elastic modulus on femurs. Due to the difference in biomechanical response of femurs, the viscoelastic-viscoplastic characteristics of femurs have a nonlinear relationship with hypergravity values. Bone tissue was least affected by 8×g hypergravity in morphology and mechanical properties.

Hind limb muscles influence the architectural properties of long bones in frogs.

The Mechanostat Theory states that osteocytes sense both the intensity and directionality of the strains induced by mechanical usage and modulate the bone design accordingly. In long bones, this process may adapt anterior-posterior and lateral-medial strength to their mechanical environment showing regional specificity. Anuran species are ideal for analyzing the muscle-bone relationships related to the different mechanical stresses induced by their many locomotor modes and habitat uses. This work aimed to explore the relationships between indicators of the force of the most relevant muscles to locomotion and the mechanical properties of femur and tibia fibula in preserved samples of three anuran species with different habitat use (aquatic, arboreal) and locomotion modes (swimmer, jumper, walker/climber). For that purpose, we measured the anatomical cross-sectional area of each dissected muscle and correlated it with the moments of inertia and bone strength indices. Significant, species-specific covariations between muscle and bone parameters were observed. Pseudis platensis, the aquatic swimmer, showed the largest muscles, followed by Boana faber, the jumper and Phyllomedusa sauvagii, the walker/climber. As we expected, bigger muscles correlate with bone parameters in all the species. Nevertheless, smaller muscles also play an important role in bone design. In aquatic species, muscle interaction enhances mostly lateral bending strength throughout the femur and lateral and antero-posterior bending strength in the tibia fibula. In the jumper species, muscles affected the femur and tibia fibula mostly in anterior-posterior bending. In the walker/climber species, responses involving both antero-posterior and lateral bending strengths were observed in the femur and tibia fibula. These results show that bones will be more or less resistant to lateral and antero-posterior bending according to the different mechanical challenges of locomotion in aquatic vs. arboreal habitats. This study provides new evidence of the muscle-bone relationships in three frog species associated with their different locomotion and habitat uses, highlighting the crucial role of muscle in determining the architectural properties of bones.

Mild-intensity physical activity prevents cardiac and osseous iron deposition without affecting bone mechanical property or porosity in thalassemic mice

Thalassemia causes anemia, ineffective erythropoiesis, bone loss and iron accumulation in several tissues, e.g., liver, bone and heart, the last of which leads to lethal cardiomyopathy and arrhythmia. Although exercise reportedly improves bone density in thalassemic mice, exercise performance is compromised and might pose risk of cardiovascular accident in thalassemic patients. Therefore, we sought to explore whether mild-intensity physical activity (MPA) with 30–50% of maximal oxygen consumption was sufficient to benefit the heart and bone. Herein, male hemizygous β-globin knockout (BKO) mice and wild-type littermates were subjected to voluntary wheel running 1 h/day, 5 days/week for 3 months (MPA group) or kept sedentary (SDN; control). As determined by atomic absorption spectroscopy, BKO-MPA mice had less iron accumulation in heart and bone tissues compared with BKO-SDN mice. Meanwhile, the circulating level of fibroblast growth factor-23—a factor known to reduce serum iron and intestinal calcium absorption—was increased early in young BKO-MPA mice. Nevertheless, MPA did not affect duodenal calcium transport or body calcium retention. Although MPA restored the aberrant bone calcium-phosphorus ratio to normal range, it did not change vertebral calcium content or femoral mechanical properties. Microstructural porosity in tibia of BKO-MPA mice remained unaltered as determined by synchrotron radiation X-ray tomographic microscopy. In conclusion, MPA prevents cardiac and bone iron accumulation, which is beneficial to thalassemic patients with limited physical fitness or deteriorated cardiac performance. However, in contrast to moderate-intensity exercise, MPA does not improve bone mechanical properties or reduce bone porosity.

Moderate Static Magnetic Fields Prevent Bone Architectural Deterioration and Strength Reduction in Ovariectomized Mice

Substantial studies have revealed the capacity of moderate-intensity static magnetic fields (SMFs) on promoting osteogenesis and inhibiting bone resorption. However, it is unknown whether moderate SMF can resist the deterioration of bone microarchitecture and strength induced by the reduction of estrogen in animal model for postmenopausal osteoporosis. Herein, the efficiency of moderate SMF of 0.2~0.4 T and SMF of 0.6 T on bone mineral density (BMD) and bone mineral content (BMC), bone microarchitecture, bone strength, and histological bone turnover was systematically investigated in ovariectomized (OVX) mice. OVX mice and sham mice were subjected to SMF exposure continuously for four weeks. Dual-energy X-ray absorptiometry (DEXA) data showed SMF prevented the reduction of BMD and BMC in OVX mice. Micro-computed tomography (Micro-CT) results revealed that SMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that SMF mitigated OVX-induced reduction in femoral mechanical properties, including stiffness, ultimate stress, and elasticity modulus. Moreover, bone histochemical analysis demonstrated that SMF decreased osteoclast formation in cancellous bone and cortical bone, while SMF increased osteoblast formation in trabecular bone. Together, these results demonstrate that moderate SMF alleviated menopause-induced bone loss effectively, and imply that moderate SMF might become a potential biophysical treatment modality for postmenopausal osteoporosis.

Disorder of Iron Metabolism Inhibits the Recovery of Unloading-Induced Bone Loss in Hypomagnetic Field

Exposure of humans and animals to microgravity in spaceflight results in various deleterious effects on bone health. In addition to microgravity, the hypomagnetic field (HyMF) is also an extreme environment in space, such as on the Moon and Mars; magnetic intensity is far weaker than the geomagnetic field (GMF) on Earth. Recently, we showed that HyMF promoted additional bone loss in hindlimb unloading-induced bone loss, and the underlying mechanism probably involved an increase of body iron storage. Numerous studies have indicated that bone loss induced by mechanical unloading can be largely restored after skeletal reloading in GMF conditions. However, it is unknown whether this bone deficit can return to a healthy state under HyMF condition. Therefore, the purpose of this study is to examine the effects of HyMF on the recovery of microgravity-induced bone loss, and illustrates the changes of body iron storage in this process. Our results showed that there was lower bone mineral content (BMC) in the HyMF reloading group compared to the GMF reloading group. Reloaded mice in the HyMF condition had a worse microstructure of femur than in the GMF condition. Femoral mechanical properties, including elastic modulus, stiffness, and ultimate stress, were poorer and toughness was higher in the HyMF group compared with the GMF group. Simultaneously, more iron content in serum, the tibia, liver, and spleen was found under HyMF reloading than GMF reloading. The iron chelator deferoxamine mesylate (DFO) decreased the iron content in the bone, liver, and spleen, and significantly relieved unloading-induced bone loss under HyMF reloading. These results showed that HyMF inhibits the recovery of microgravity-induced bone loss, probably by suppressing the elevated iron levels' return to physiological level. © 2019 American Society for Bone and Mineral Research.

Bone Health in Rats With Temporal Lobe Epilepsy in the Absence of Anti-Epileptic Drugs.

Rationale: Epilepsy patients often exhibit reduced bone mineral density and are at an increased risk of bone fracture. Whether these bone abnormalities are due to the use of anti-epileptic drugs (AED’s) or the disease itself is unknown. For example, although decreased bone health in epilepsy patients is generally attributed to the use of AED’s, seizures can also trigger a number of physiological processes that have the potential to affect bone. Therefore, to assess whether bone abnormalities occur in epilepsy in the absence of AED’s, the current study investigated mechanical characteristics and trabecular bone morphology in rats with chronic temporal lobe epilepsy. Methods: Ten-week old male Wistar rats underwent kainic acid-induced status epilepticus (SE; n = 7) or a sham procedure (n = 9). Rats were implanted with EEG recording electrodes at nine weeks post-SE, and video-EEG was continuously recorded for one week at 10- and 22-weeks post-SE to confirm that SE rats had spontaneous seizures. Open-field testing to assess locomotion was conducted at 23-weeks post-SE. At 24-weeks post-SE, rats were euthanized and tibia were extracted to determine trabecular morphology by micro-computed tomography (µCT), while femurs were used to investigate mechanical properties via 3-point bending. Results: All post-SE rats had spontaneous seizures at 10- and 22-weeks post-SE, while none of the sham rats had seizures. µCT trabecular analysis of tibia revealed no differences in total volume, bone volume, bone volume fraction, trabecular number, or trabecular separation between post-SE or sham rats, although post-SE rats did have increased trabecular thickness. There were also no group differences in total distance travelled in the open field suggesting that activity levels did not account for the increased trabecular thickness. In addition, no differences in mechanical properties of femurs were observed between the two groups. Conclusion: There was a lack of overt bone abnormalities in rats with chronic temporal lobe epilepsy in the absence of AED treatment. Although further studies are still needed, these findings may have important implications towards understanding the source (e.g., AED treatments) of bone abnormalities in epilepsy patients.

Femur Properties of Embryo in the Layer Hybrid and Pure Breeds

ABSTRACT Layer hybrids are more superior in the egg yield than pure breeds. But this superiority causes some problems in the bones during the production period. There are a lot of differences among genotypes in the production period that have been examined extensively, however, the differences throughout incubation period aren’t known yet. Thus, the objective of this study was to evaluate the differences in femur properties of pure breed and layer hybrid embryos during the incubation period. A total of 354 fresh hatching eggs were used from one hybrid (Lohman White) and two pure breeds (Denizli & Gerze). The eggs were incubated. Hatching eggs from each genotype at the beginning of embryonic days (E) 19 and E21 were examined. At these embryonic ages, 12 eggs were selected from each genotype. The eggs were opened and embryos were sacrificed by cervical dislocation. Both femurs were dissected from each embryo and then structure, mineral composition and mechanical properties of femur were determined. The genotype affected the length, width and Zn level in the femur of embryos. Weight, length, width, load of yield and ultimate, ash and all examined minerals increased with embryonic development. These results showed that some femur properties of embryos were influenced by the genotype and layer hybrid embryos are beginning to be advantageous in terms of Zn level in the femur at E21. This study leads to better understanding femur development during the incubation period in layer hybrid and pure breeds.

Ex Vivo Evaluation of Hip Fracture Risk by Proximal Femur Geometry and Bone Mineral Density in Elderly Chinese Women

BackgroundThe incidence of hip fracture is steadily increasing. We aimed to establish a creative approach to precisely estimate the risk of hip fracture by exploring the relationship between hip fracture and bone mineral density (BMD)/femur geometry.Material/MethodsSixteen samples of cadaveric female proximal femora were randomly selected. Experiments were performed experimental measurement of the femoral neck BMD and geometric parameters (including neck length, neck diameter, head diameter, and neck-shaft angle). In addition, the experimental measurements contain the failure load, which represents the mechanical strength of the femoral neck, and we calculated the correlation coefficient among BMD, geometric parameters, and failure load.ResultsSignificant correlations were discovered between femoral mechanical properties and femoral neck BMD (r=0.792, r2=0.628, P<0.001), trochanteric BMD (r=0.749, r2=0.560, P=0.001), and head diameter (r=0.706, r2=0.499, P=0.002). Multiple linear regression analyses indicated that the best predictor of hip fracture was the combination of femoral neck BMD, head diameter, and neck diameter (r2=0.844, P<0.001).ConclusionsThe results confirmed that, compared with BMD alone, the combination of BMD and geometric parameters of proximal femur is a better estimation of hip fracture. The geometry of the proximal femur played an important role in assessing the biomechanical strength of femur. This method greatly assists in predicting the risk of hip fracture in clinical trials and will assist studies on why the incidence of hip fracture varies among races.

Method and Instrumented Fixture for Femoral Fracture Testing in a Sideways Fall-on-the-Hip Position.

Mechanical testing of femora brings valuable insights into understanding the contribution of clinically-measureable variables such as bone mineral density distribution and geometry on the femoral mechanical properties. Currently, there is no standard protocol for mechanical testing of such geometrically complex bones to measure strength, and stiffness. To address this gap we have developed a protocol to test cadaveric femora to fracture and to measure their biomechanical parameters. This protocol describes a set of adaptable fixtures to accommodate the various load magnitudes and directions accounting for possible bone orientations in a fall on the hip configuration, test speed, bone size, and left leg-right leg variations. The femora were prepared for testing by cleaning, cutting, scanning, and potting the distal end and greater trochanter contact surfaces in poly(methyl methacrylate) (PMMA) as presented in a different protocol. The prepared specimens were placed in the testing fixture in a position mimicking a sideways fall on the hip and loaded to fracture. During testing, two load cells measured vertical forces applied to the femoral head and greater trochanter, a six-axis load cell measured forces and moments at the distal femoral shaft, and a displacement sensor measured differential displacement between the femoral head and trochanter contact supports. High speed video cameras were used to synchronously record the sequence of fracture events during testing. The reduction of this data allowed us to characterize the strength, stiffness, and fracture energy for nearly 200 osteoporotic, osteopenic, and normal cadaveric femora for further development of engineering-based diagnostic tools for osteoporosis research.

Upregulation of Akt signaling enhances femoral fracture healing by accelerating atrophic quadriceps recovery

Muscle damage and disuse muscular atrophy are detrimental for fracture healing. It has been reported that the Akt signaling pathway plays a role in skeletal muscle hypertrophy and atrophy. The aim of this study was to further investigate whether promoting local muscle function through regulating Akt signaling affects fracture healing. For this purpose, we combined a rat model of short-term atrophy of the quadriceps with a femoral fracture model. In brief, botulinum toxin-A (BTX) were administered locally into the quadriceps one week before femur osteotomy to induce muscle atrophy. For the following weeks after BTX treatment, animals received injection of the Akt activator SC79 (20mg/kg/week) or the Akt inhibitor MK2206 (100mg/kg/week). We found that SC79 significantly accelerated the recovery of quadriceps weight and fiber size after BTX treatment. Moreover, animals that received SC79 injection showed greater bone callus volumes and superior femur mechanical properties. Immunological analysis revealed that the expression levels of the muscle-specific marker myosin heavy chain (MHC) were increased while expression of a negative regulator of muscle mass and function, myostatin, was decreased after SC79 treatment. Furthermore, SC79 increased the mRNA levels of the myogenic regulatory factors MyoD, MRF4 and Myf5 and promoted myotube formation in vitro. Taken together, these findings reveal that SC79 could accelerate the recovery of reversible muscular atrophy induced by BTX and subsequently promote fracture healing through activation of the Akt signaling pathway, which suggests its therapeutic potential in orthopedics.

Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats

Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.

Morphological, densitometric and mechanical properties of pelvic limb bones in 14-month-old female ostriches (Struthio camelus)

Limited information on physiological characteristic of bones in ostrich skeleton are available, even though bone weaknesses in ostriches are commonplace. Thus, the aim of this study was to evaluate morphological, densitometric, and mechanical properties of pelvic limb long bones (femur, tibia, and tarsometatarsus) in 14-month-old female ostriches (Struthio camelus var. domesticus). After the slaughter procedure, all bones were isolated, cleaned of soft tissues, and bone weight and length were determined. Using dual energy X-ray absorptiometry (DEXA) bone mineral density (BMD) and bone mineral content (BMC) were determined. Volumetric bone mineral density (vBMD) and geometrical parameters of the bones were determined using the quantitative computed tomography (QCT) method. Maximum elastic strength and ultimate strength of the bones were determined using three-point bending test. Significant differences were revealed between morphological, densitometric, and mechanical properties of femur, tibia, and tarsometatarsus in female ostriches at the slaughter age of 14 months. Elaborated experimental model and determination of morphological, densitometric, and mechanical properties of femur, tibia, and tarsometatarsus in female ostriches may serve for further studies on metabolic regulation of skeletal system properties with environmental, physiological, dietary, pharmacological, and toxicological factors.

Assessing the inter- and intra-animal variability of in vivo OsteoProbe skeletal measures in untreated dogs

The OsteoProbe is a second-generation reference point indentation (RPI) device without a reference probe that is designed to simplify RPI testing for clinical use. Successful clinical implementation of the OsteoProbe would benefit from a better understanding of how its output, bone material strength index (BMSi), relates to the material properties of bone and under what conditions it reliably correlates with fracture risk. Large animal models have the potential to help fill this knowledge gap, as cadaveric studies are retrospective and limited by incomplete patient histories (including the potential use of bone matrix altering drugs such as bisphosphonates). The goal of this study was to assess the intra and inter-animal variability of OsteoProbe measures in untreated beagle dogs (n=12), and to evaluate this variability in comparison to traditional mechanical testing. OsteoProbe measurements were performed in vivo on the left tibia of each dog and repeated 6months later on the day of sacrifice. Within-animal variation of BMSi (CV of 5–10 indents) averaged 8.9 and 9.0% at the first and second timepoints, respectively. In contrast, inter-animal variation of BMSi increased from 5.3% to 9.1%. The group variation of BMSi was on par with that of traditional 3-point mechanical testing; inter-animal variation was 10% for ultimate force, 13% for stiffness, and 12% for total work as measured on the femur. There was no significant change in mean BMSi after 6months, but the individual change with time across the 12 dogs was highly variable, ranging from −12.4% to +21.7% (mean 1.6%, SD 10.6%). No significant correlations were found between in vivo tibia BMSi and femur mechanical properties measured by ex vivo 3-pt bending, but this may be a limitation of sample size or the tests being performed on different bones. No relationship was found between BMSi and tissue mineral density, but a strong positive correlation was found between BMSi and tibia cortical thickness (ρ=0.706, p=0.010). This report shows that while the OsteoProbe device has inter-individual variability quite similar to that of traditional mechanical testing, the longitudinal changes show high levels of heterogeneity across subjects. We further highlight the need for standardization in post-testing data processing and further study of the relationships between OsteoProbe and traditional mechanical testing.

Maternal dietary vitamin D carry-over alters offspring growth, skeletal mineralisation and tissue mRNA expressions of genes related to vitamin D, calcium and phosphorus homoeostasis in swine.

Maternal dietary vitamin D carry-over effects were assessed in young pigs to characterise skeletal abnormalities in a diet-induced model of kyphosis. Bone abnormalities were previously induced and bone mineral density (BMD) reduced in offspring from sows fed diets with inadequate vitamin D3. In a nested design, pigs from sows (n 23) fed diets with 0 (-D), 8·125 (+D) or 43·750 (++D) µg D3/kg from breeding through lactation were weaned and, within litter, fed nursery diets arranged as a 2×2 factorial design with 0 (-D) or 7·0 (+D) µg D3/kg, each with 95 % (95P) or 120 % (120P) of P requirements. Selected pigs were euthanised before colostrum consumption at birth (0 weeks, n 23), weaning (3 weeks, n 22) and after a growth period (8 weeks, n 185) for BMD, bone mechanical tests and tissue mRNA analysis. Pigs produced by +D or ++D sows had increased gain at 3 weeks (P<0·05), and at 8 weeks had increased BMD and improved femur mechanical properties. However, responses to nursery diets depended on maternal diets (P<0·05). Relative mRNA expressions of genes revealed a maternal dietary influence at birth in bone osteocalcin and at weaning in kidney 24-hydroxylase (P<0·05). Nursery treatments affected mRNA expressions at 8 weeks. Detection of a maternal and nursery diet interaction (P<0·05) provided insights into the long-term effects of maternal nutritional inputs. Characterising early stages of bone abnormalities provided inferences for humans and animals about maternal dietary influence on offspring skeletal health.

Alterations in geometry, biomechanics, and mineral composition of juvenile rat femur induced by nonplanar PCB-155 and/or planar PCB-169.

Exposure to widespread lipophilic and bioaccumulative polychlorinated biphenyls (PCBs) induces diverse biochemical and toxicological responses in various organs, including the bone. The aim of this study was to evaluate the changes in growth rate, geometry, serum, and bone biochemical parameters and biomechanics of juvenile rat femur induced by lactational exposure to nonplanar PCB-155 and planar PCB-169 individually and in combination. Fifteen lactating Wistar rats were divided into four groups (PCB-169, PCB-155, PCB-155+169, and control), and PCBs were administered intraperitoneally at different time points after delivery. Femurs from 22-day-old offspring were analyzed by microCT, three-point bending test and inductively coupled plasma-mass spectrometry (ICP-MS) to obtain data on bone geometry, biomechanics and mineral composition. The serum levels of calcium, phosphate and alkaline phosphatase were also determined. Lactational exposure to planar PCB-169 resulted in shorter and thinner femurs, reduced endosteal and periosteal perimeters, smaller total cross-sectional and medullary areas, and lowered serum bone marker levels and calcium levels in the bone, while femur mechanical properties were not significantly altered. The changes observed in the combination exposure (PCB-155+169) group were similar to those observed in the PCB-169 group but were less pronounced. In summary, our results demonstrate that alterations in lactationally exposed offspring were primarily induced by planar PCB-169. The milder outcome in the combined group suggested that the PCB-169-mediated toxic effects on the bone might be reduced by a nonplanar PCB-155 congener. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1135-1146, 2017.

Effects of doxorubicin administration on bone strength and quality in sedentary and physically active Wistar rats.

Bone growth in pre-pubertal years critically influences adult fracture risk. DOX is widely used in the treatment of pediatric cancers, but there is limited evidence on its potential negative effects on bone growth. Exercise improves bone growth in children, but there is no evidence if it protects against DOX-induced bone toxicity. This study investigates the early and intermediate effects of a 7-week course of DOX on bone histomorphometry and strength in sedentary and exercised growing animal models. Sixty-eight male Wistar rats (8weeks) were treated with DOX (2mgkg-1) or vehicle for 7weeks and afterward housed in standard cages or in cages with a running wheel and killed 2 or 10weeks after last DOX administration. Femurs and blood were collected for assaying geometry, trabecular microarchitecture (histology), biomechanical properties (three-point bending and shearing of the femoral neck), bone calcium content and density (atomic absorption spectroscopy), and bone turnover markers (ELISA). DOX treatment reduced the femur diaphysis radial growth, with DOX-treated animals having a lower tissue area, cortical area, cortical thickness, and moment of inertia. DOX also decreased distal femur trabecular bone volume and trabecular number and increased trabecular separation. Femur diaphysis stiffness and maximum load were also reduced in past DOX-treated animals. Exercise was shown to worsen the effects of past DOX treatment on the femur diaphysis mechanical properties. DOX negatively affects bone geometry, trabecular microarchitecture, and femur mechanical properties in growing Wistar rats. Exercise further aggravates the detrimental effects of past DOX treatment on bone mechanical properties.

Interrelationships between morphometric, densitometric and mechanical properties of femur in ostriches (Struthio Camelus)

Interrelationships between morphometric, densitometric and mechanical properties of femur in ostriches (<i>Struthio Camelus</i>)