Femoral Biomechanical Properties Research Articles

Effect of experimental pulmonary arterial hypertension on renal and bone parameters of rats submitted to resistance exercise training.

Pulmonary arterial hypertension (PAH) is characterized by right ventricular failure and diminished cardiac output, potentially leading to renal and bone impairments. In contrast, resistance exercise training (RT) offers cardiovascular and bone health benefits. This study aimed to assess the impacts of stable PAH induced by monocrotaline (MCT) and RT on renal morphometry, as well as bone morphometry and biomechanical properties in male Wistar rats. Four experimental groups, untrained control (UC, n=7), trained control (TC, n=7), untrained hypertensive (UH, n=7), trained hypertensive (TH, n=7), were defined. After the first MCT or saline injection (20 mg/kg), trained rats were submitted to a RT program (i.e., Ladder climbing), 5 times/week. Seven days later the rats received the second MCT or saline dose. After euthanasia, renal and femoral histomorphometry and femoral biomechanical properties were assessed. PAH reduced renal glomerular area and volume, which was prevented by the RT. While PAH did not harm the femoral morphometry, structural and mechanical properties, RT improved the femoral parameters (e.g., length, percentage of trabeculae and bone marrow, ultimte and yield loads). Experimental stable PAH promotes renal but not bone damages, whereas RT prevents renal deteriorations and improves the femoral morphological and biomechanical properties.

The combined treatment of insulin and naringin improves bone properties in rats with type 1 diabetes mellitus.

We have studied the effects of individual and combined treatment of insulin (I) and naringin (NAR) on the bone structure and biomechanical properties of femurs from streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into five groups: (1) controls, (2) STZ-induced diabetic rats, (3) STZ-induced diabetic rats treated with I, (4) STZ-induced diabetic rats treated with NAR, and (5) STZ-induced diabetic rats treated with I+NAR. Bone mineral density (BMD), bone histomorphometry, biomechanical testing, and bone biomarker expressions were accomplished in femur of all animals, as well as serum biochemical analyses. The combined treatment of I+NAR increased the body weight and the femur BMD from STZ-induced diabetic rats. The bone biomechanical properties and the bone morphology of the femurs from STZ-induced diabetic rats were also improved by the combined treatment. The increased number of osteoclasts in STZ-induced diabetic rats was partially prevented by I, NAR, or I+NAR. NAR or I+NAR completely blocked the decrease in the number of osteocalcin (+) cells in the femur from STZ-induced diabetic rats. RUNX family transcription factor 2 immunostaining was much lower in STZ-induced diabetic rats than in control animals; the combination of I+NAR totally blocked this effect. The combined treatment not only ameliorated bone quality and function, but also normalized the variables related to glucose metabolism. Therefore, the combination of I+NAR might be a better therapeutic strategy than the individual I or NAR administration to reduce bone complications in diabetic patients.

Integrated Dose-Effect Relationship of Near-Infrared Light-Emitting Diode Light on Bone Regeneration in Disuse Osteoporosis Rats.

Objective: To examine the integrated dose-effect relationship of near-infrared (NIR) light-emitting diode (LED) light therapy in promoting bone defect repair in the rat model for osteoporosis (OP). Background: Low-intensity laser therapy has been shown to promote bone regeneration in OP rats. However, its integrated dose-effect relationship is not clear. Methods: Twenty-week-old male Sprague-Dawley rats were randomly assigned to 11 groups: (1) no-treatment control group (C group), (2) tail suspension (TS)-induced disuse OP experimental group (TS-OP group), and (3) OP rats with LED light treatment at nine dosages (L1-L9 groups). The tail of the rat was tied and suspended on the beam of the cage to suspend their hind limbs to induce bone loss for 4 or 7 weeks. The rats were then released and returned to their regular positions. An NIR LED at 810 nm was used on the bilateral hind limbs daily for 4 weeks. The C group rats were not given any treatment. The TS-OP group rats were subjected to identical procedures with L groups, with the exception that the light power was not turned on. After the experiment, the dual-energy X-rays or the microcomputed tomography scan analysis was performed to evaluate bone tissue status. Data analysis was done using SPSS and the health scale. Results: The trabecular thickness, trabecular number, bone volume/total volume, and connectivity density of cancellous bone and the biomechanical properties of femur in light groups were significantly increased compared with the TS-OP group, while the trabecular separation and structure model index were significantly decreased. Conclusions: NIR LED light therapy may promote trabecular bone repair of TS-OP rats. Light intensity influences photobiomodulation. In our dose levels, the greater the light intensity, usually the more effective.

Overall adjustment acupuncture improves osteoporosis and exerts an endocrine-modulating effect in ovariectomized rats.

Acupuncture is a widely practiced, convenient, and safe treatment modality within complementary and integrative medicine. Increasing studies have revealed the efficacy of acupuncture for the treatment of osteoporosis in both human and non-human subjects. The aim of the present study was to assess the improvement of osteoporosis after overall adjustment acupuncture (OA) as well as its endocrine-modulating effect in an ovariectomized rat model. In total, 32 female Sprague-Dawley (SD) rats were randomly divided into the sham, model, ovariectomy+estrogen (OVX+E), and OVX+OA (OVX+A) groups with eight rats in each group. The postmenopausal osteoporosis (PMOP) rat model was induced by bilateral ovariectomy. At 12 weeks after surgery, rats in the OVX+E group received estradiol (0.2 mg/kg/i.g./qod) for 12 weeks, and rats in the OVX+A group were treated with acupuncture at Zusanli (ST36), Shenshu (BL23), and Dazhu (BL11) points (qod) for 12 weeks. At the end of the treatment, all rats were sacrificed, and the body weight, uterus index, bone mineral density (BMD), bone mineral content (BMC), bone trabeculae structural parameters, femoral biomechanical properties, femoral histomorphology, and several hormone levels were examined. In OVX rats, OA abrogated the body weight gain and improved osteoporosis in terms of BMD, BMC, bone trabeculae structural parameters, bone strength, and bone tissue histomorphology. Moreover, OA modulated the serum levels of estradiol, corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). OA improves osteoporosis and exerts an endocrine-modulating effect in ovariectomized rats.

Do femoral biomechanical properties follow locomotor changes in primates? An ontogenetic study of olive baboons (Papio anubis)

AbstractObjectivesThe locomotor repertoire of the olive baboon (Papio anubis) changes during ontogeny from a diversified pattern in infancy to a stereotyped pattern in adults. On the assumption that the femoral diaphysis adapts to variations in the loading regime, we aimed to evaluate the impact of locomotor changes on femoral biomechanical properties during the ontogeny of olive baboons.Materials and MethodsWe used the cross‐sectional geometry of 50 three‐dimensional‐reconstructed olive baboon femora of an ontogenetic sample including individuals from birth to 28 years of age and belonging to a single social group. Cross section parameters were extracted, and cortical thickness maps were produced from 20% to 80% of the femoral length.ResultsNewborns present a distribution of cortical thickness that is longitudinally symmetric and anteroposterior shaped cross sections at midshaft. From this condition, infants, juveniles and adults femoral diaphyses are all characterized by a proximal shift in cortical thickness and a mediolateralization of bending rigidity and strength at midshaft.DiscussionAs soon as locomotor autonomy is established and despite a combination of several significant locomotor modes, the biomechanical pattern remains stable during ontogeny. Our results do not reflect the changes in locomotor repertoires that occur during ontogeny of Papio anubis. We therefore advise caution when inferring complex locomotor behavior from femoral biomechanical properties.

Influence of zoledronic acid in physicochemical and morphostructural parameters of bone and dental tissue of mice submitted to a jaw osteonecrosis model

Zoledronic acid (ZA) leads to structural and physicochemical changes in mineralized tissues. The aim was to an- alyze physicochemical and morphostructural properties of bone and dental tissue of mice submitted to a model of ZA-related osteonecrosis of the jaws (OJ). This is a 2 × 2 factorial design experimental study, considering sex (male/female) and treatment (ZA/Saline). Lower left 2nd molar (day 42) extraction was performed after three ad- ministrations (days 0, 7, 14) of ZA 1.0 mg / kg or saline (n=8/group), with another administration on 49^th and eu- thanasia on 70^th day. Histological analysis, computerized microtomography, three-point bending test and Raman spectroscopy were performed. ANOVA 2-way/Bonferroni test was applied (p<0.05). Treatment with ZA promoted histological alterations in femoral epiphysis and increased bone necrosis signs (p <0.05) at sites of exodontia. Be- sides, ZA groups presented a lower number and greater separation of bone trabeculae, and smaller ratio bone/tissue volume in alveolar trabecular bone. Females presented a lower value of these parameters. In femoral bone, sex and treatment factors exerted an independent influence in mechanical parameters, on the cross-sectional area, maximum load, moment of inertia and work to fracture (p <0.05), being lower in females and increased in treated animals, which also presented higher flexural stiffness. Yield stress and flexural modulus were higher in females and lower with ZA treatment (p <0.05). Spectroscopic analysis showed increased crystallinity with ZA in cortical and medullar of right and left hemimandible, respectively, as well as femoral cortical. There was an increase of crys- tallinity in dental enamel and dentin with treatment. It is concluded that treatment with ZA, although associated with occurrence of OJ, modifies bone and dental mineral matrix, contributing to tissue biomechanics' improvement. Females present differences in femoral biomechanical properties and have a lower density of trabecular bone in the post-dental extraction socket, when compared to males.

Variation in cross-sectional indicator of femoral robusticity in Homo sapiens and Neandertals

Variations in the cross-sectional properties of long bones are used to reconstruct the activity of human groups and differences in their respective habitual behaviors. Knowledge of what factors influence bone structure in Homo sapiens and Neandertals is still insufficient thus, this study investigated which biological and environmental variables influence variations in the femoral robusticity indicator of these two species. The sample consisted of 13 adult Neandertals from the Middle Paleolithic and 1959 adult individuals of H. sapiens ranging chronologically from the Upper Paleolithic to recent times. The femoral biomechanical properties were derived from the European data set, the subject literature, and new CT scans. The material was tested using a Mantel test and statistical models. In the models, the polar moment of area (J) was the dependent variable; sex, age, chronological period, type of lifestyle, percentage of the cortical area (%CA), the ratio of second moment areas of inertia about the X and Y axes (Ix/Iy), and maximum slope of the terrain were independent covariates. The Mantel tests revealed spatial autocorrelation of the femoral index in H. sapiens but not in Neandertals. A generalized additive mixed model showed that sex, %CA, Ix/Iy, chronological period, and terrain significantly influenced variation in the robusticity indicator of H. sapiens femora. A linear mixed model revealed that none of the analyzed variables correlated with the femoral robusticity indicator of Neandertals. We did not confirm that the gradual decline in the femoral robusticity indicator of H. sapiens from the Middle Paleolithic to recent times is related to the type of lifestyle; however, it may be associated with lower levels of mechanical loading during adolescence. The lack of correlation between the analysed variables and the indicator of femoral robusticity in Neandertals may suggest that they needed a different level of mechanical stimulus to produce a morphological response in the long bone than H. sapiens.

Effect of Kelulut honey supplementation on bone health in male rats on high-carbohydrate high-fat diet

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To determine the effects of Kelulut honey (KH) on the bone health of rats with metabolic syndrome.&#x0D; Methods: Male Wistar rats were randomised into normal control and metabolic syndrome is fed with a diet enriched with carbohydrate and fat. The rats in the metabolic syndrome arm were further assigned into the negative control group and honey group supplemented orally with Kelulut honey (1g/kg) daily for eight weeks. After the rats were sacrificed, the trabecular and cortical micro-architecture of the harvested femur was analysed using X-ray micro-computed tomography, while histomorphometric method was used to determine bone cell indices. Femoral biomechanical properties were analysed using a universal mechanical tester.&#x0D; Results: Total cross-sectional area, osteoid surface and volume, displacement and strain reduced significantly, while eroded surface increased significantly in the rats with metabolic syndrome than the normal rats (p &lt; 0.05). The honey group showed a significant reduction in osteoclast surface than the normal healthy control (p &lt; 0.05). Other skeletal parameters did not show a significant intergroup difference.&#x0D; Conclusion: Metabolic syndrome is harmful to bone health and honey has limited effects in reversing these negative effects.&#x0D; &#x0D; &#x0D; &#x0D;

Protective effects of low-magnitude high-frequency vibration on high\xa0glucose-induced osteoblast dysfunction and bone loss in diabetic rats

ObjectiveLow-magnitude high-frequency vibration (LMHFV) has been reported to be capable of promoting osteoblast proliferation and differentiation. Reduced osteoblast activity and impaired bone formation were related to diabetic bone loss. We investigated the potential protective effects of LMHFV on high-glucose (HG)-induced osteoblasts in this study. In addition, the assessment of LMHFV treatment for bone loss attributed to diabetes was also performed in vivo.MethodMC3T3-E1 cells induced by HG only or treated with LMHFV were treated in vitro. The experiments performed in this study included the detection of cell proliferation, migration and differentiation, as well as protein expression. Diabetic bone loss induced by streptozotocin (STZ) in rats was established. Combined with bone morphometric, microstructure, biomechanical properties and matrix composition tests, the potential of LMHFV in treating diabetes bone loss was explored.ResultsAfter the application of LMHFV, the inhibiting effects of HG on the proliferation, migration and differentiation of osteoblasts were alleviated. The GSK3β/β-catenin pathway was involved in the protective effect of LMHFV. Impaired microstructure and biomechanical properties attributed to diabetes were ameliorated by LMHFV treatment. The improvement of femur biomechanical properties might be associated with the alteration of the matrix composition by the LMHFV.ConclusionLMHFV exhibited a protective effect on osteoblasts against HG by regulating the proliferation, migration and differentiation of osteoblasts. The function of promoting bone formation and reinforcing bone strength made it possible for LMHFV to alleviate diabetic bone loss.

Bone Status in a Mouse Model of Experimental Autoimmune-Orchitis.

Investigations in male patients with fertility disorders revealed a greater risk of osteoporosis. The rodent model of experimental autoimmune-orchitis (EAO) was established to analyze the underlying mechanisms of male infertility and causes of reduced testosterone concentration. Hence, we investigated the impact of testicular dysfunction in EAO on bone status. Male mice were immunized with testicular homogenate in adjuvant to induce EAO (n = 5). Age-matched mice were treated with adjuvant alone (adjuvant, n = 6) or remained untreated (control, n = 7). Fifty days after the first immunization specimens were harvested. Real-time reverse transcription-PCR indicated decreased bone metabolism by alkaline phosphatase and Cathepsin K as well as remodeling of cell-contacts by Connexin-43. Micro computed tomography demonstrated a loss of bone mass and mineralization. These findings were supported by histomorphometric results. Additionally, biomechanical properties of femora in a three-point bending test were significantly altered. In summary, the present study illustrates the induction of osteoporosis in the investigated mouse model. However, results suggest that the major effects on bone status were mainly caused by the complete Freund’s adjuvant rather than the autoimmune-orchitis itself. Therefore, the benefit of the EAO model to transfer laboratory findings regarding bone metabolism in context with orchitis into a clinical application is limited.

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice.

ABSTRACTPrevious studies proposed the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor expressed in myeloid cells including microglia in brain and osteoclasts in bone, as a link between brain and bone disease. The TREM2 R47H variant is a known risk factor for Alzheimer's disease (AD), the most common form of dementia. To investigate whether altered TREM2 signaling could contribute to bone and skeletal muscle loss, independently of central nervous system defects, we used mice globally hemizygous for the TREM2 R47H variant (TREM2R47H/+), which do not exhibit AD pathology, and wild‐type (WT) littermate control mice. Dxa/Piximus showed bone loss in female TREM2R47H/+ animals between 4 and 13 months of age and reduced cancellous and cortical bone (measured by micro‐computed tomography [μCT]) at 13 months, which stalled out by 20 months of age. In addition, they exhibited decreased femoral biomechanical properties measured by three‐point bending at 13 months of age, but not at 4 or 20 months. Male TREM2R47H/+ animals had decreased trabecular bone geometry but increased ultimate strain and failure force at 20 months of age versus WT. Only male TREM2R47H/+ osteoclasts differentiated more ex vivo after 7 days with receptor activator of nuclear factor κB ligand (RANKL)/macrophage colony‐stimulating factor (M‐CSF) compared to WT littermates. Yet, estrogen receptor alpha expression was higher in female and male TREM2R47H/+ osteoclasts compared to WT mice. However, female TREM2R47H/+ osteoclasts expressed less complement 3 (C3), an estrogen responsive element, and increased protein kinase B (Akt) activity, suggesting altered estrogen signaling in TREM2R47H/+ cells. Despite lower bone volume/strength in TREM2R47H/+ mice, skeletal muscle function measured by plantar flexion and muscle contractility was increased in 13‐month‐old female mutant mice. Overall, these data demonstrate that an AD‐associated TREM2 variant can alter bone and skeletal muscle strength in a sex‐dimorphic manner independent of central neuropathology, potentially mediated through changes in osteoclastic intracellular signaling. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Extracellular regulated kinase 5 mediates osteoporosis through modulating viability and apoptosis of osteoblasts in ovariectomized rats.

Postmenopausal osteoporosis is a common condition characterized by the increase and activation of osteoclasts. The present study aimed to investigate the effects of extracellular signal-regulated kinase (ERK) 5 (ERK-5) on postmenopausal osteoporosis by regulating the biological behaviors of osteoblasts. Sprague–Dawley (SD) rats were ovariectomized to develop an osteoporosis model. A lentivirus packaging system was employed to generate lentiviruses capable of up- or down-regulating the expression of ERK-5 in ovariectomized rats. The femoral biomechanical properties, bone mineral density (BMD), contents of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) and bone turnover markers in rats, as well as viability, cycle and apoptosis of osteoblasts and ALP activity in osteoblasts were measured in the ovariectomized rats so as to explore the functional significance of ERK-5 in postmenopausal osteoporosis. The femoral mechanical strength of ovariectomized rats was enhanced by overexpression of ERK-5. Meanwhile femoral BMD, and bone metabolism were increased, and bone turnover normalized in the ovariectomized rats when ERK-5 was overexpressed. Lentivirus-mediated ERK-5 overexpression in osteoblasts was observed to inhibit osteoblast apoptosis, and promote viability, accompanied with increased ALP activity. Taken together, ERK-5 could decelerate osteoblast apoptosis and improve postmenopausal osteoporosis by increasing osteoblast viability. Thus, our study provides further understanding on a promising therapeutic target for postmenopausal osteoporosis.

Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat Model of Postmenopausal Osteoporosis.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

Effect of Compound Medicine of Tanshinone 2A and Resveratrol on Peak Bone Mass in Growing Rats

Objective To study the effect of the compound medicine of tanshinone 2A and resveratrol on peak bone mass in growing rats and to explore its possible mechanism,so as to explore anti-osteoporosis mechanisms of new traditional Chinese medicine (TCM) drugs. Methods Totally 40 1-month-old female Wistar rats were randomly divided into tanshinone 2A group,resveratrol group,compound group (tanshinone 2A and resveratrol),and normal control group,with 10 rats in each group. Body weight was measured once every two weeks,and the whole body bone mineral density was measured with dual-energy X-ray monthly. When the whole-body bone mineral density became statistically significant between medication groups and control group,all animals were sacrificed to determine the bone mineral density of vertebrae and right femoral bone. The biomechanical properties of femur and vertebrae were measured by AGS-X series universal test,then the bone morphology was analyzed with Fuchsin picric acid staining. Finally,the levels of tartrate-resistant acid phosphatase 5b and osteocalcin were measured with enzyme-linked immunosorbent assay.Results The body weights were not statistically significant among all groups (P>0.05). The whole-body bone mineral density showed no significant difference (P>0.05) after feeding for 1 month;however,two months later,it was significantly different between medication groups and control group;in particular,the whole-body (P=0.016),femoral (P=0.001),and vertebral bone mineral density (P=0.034),bone trabecular number (P=0.024),thickness (P=0.040),and area (P=0.038) were significantly increased in the compound group,along with the significantly decreased trabecular separation degree (P=0.032). Compared with the control group,the compound group had significantly increased osteocalcin (P=0.033) and tartrate-resistant acid phosphatase 5b (P=0.028) levels in serum.Conclusion The compound of tanshinone 2 A and resveratrol can improve the bone density and bone quality in rats,and such effect is higher than either tanshinone 2 A monomer or resveratrolmonomer.

Tea polysaccharide inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells and ameliorates ovariectomy-induced osteoporosis in rats

Background and purposeTea drinking has positive effects on bone health and may prevent and treat osteoporosis, especially in older and postmenopausal women. Tea polysaccharide (TPS) is a major bioactive constituent in tea. Despite its profound effects on human health, whether TPS has anti-osteoporotic effects remains largely unknown. As such, we investigated the anti-osteoporotic effects of TPS. MethodsIn vitro, TPS effects on osteoclastogenesis were examined using osteoclast precursor RAW264.7 cells. TPS effects on osteoclastogenesis-related expression of marker genes and proteins were determined by gene expression and immunoblotting analyses, respectively. For in vivo studies, 12-week-old female Wistar rats were divided randomly into a sham-operated group (sham) and four ovariectomized (OVX) subgroups: OVX with vehicle (model) and OVX with low-, medium-, and high-dose TPS (0.32, 0.64 and 1.28 g/kg body weight/day, respectively). TPS was administered intragastrically to rats for 13 weeks. Body weight, blood biochemical parameters, organ weight, organ coefficients, femoral length, bone mineral density (BMD), biomechanical properties, and bone microarchitecture were documented. ResultsTPS inhibited osteoclast differentiation significantly and dose-dependently, and its inhibitory effect was not due to toxicity to RAW264.7 cells. TPS suppressed expression of osteoclastogenesis-related marker genes and proteins significantly. In in vivo studies, medium-dose TPS treatment ameliorated OVX-induced calcium loss significantly. Low-dose TPS treatment decreased the activity of acid phosphatase (ACP) in OVX rats significantly. In addition, TPS treatment improved other blood biochemical parameters and femoral biomechanical properties to a certain extent. More importantly, TPS treatment ameliorated bone microarchitecture in OVX rats strikingly because of increased cortical bone thickness and trabecular bone area in the femur. ConclusionTPS can inhibit receptor activator nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells and ameliorate ovariectomy-induced osteoporosis in rats.

Flaxseed (linum usitatissimum) flour contributes to bone health in adult male rats.

This study evaluated effects of flaxseed flour diet on bone health in adult Wistar male rats at 180 d. After birth, pups were randomly assigned: Control (C, n = 12) and flaxseed flour (FF, n = 12) diet during lactation period. At 21 d, pups were weaned and they continued to receive the control and experimental diet, respectively. At 180 d, body length, total bone structure, and femur and lumbar vertebrae were evaluated by dual-energy X-ray absorptiometry. Femoral and lumbar vertebra dimensions, biomechanical properties of femur, and serum osteocalcin were measured. FF produced greater (P <0.05) total (+3.4%) and spine (+5.9%) bone mineral density, total (+10%) and spine (+12%) bone mineral content, total bone area (+8.7%), and osteocalcin (+82%). As to femur, FF produced greater (P <0.05) width of diaphysis (+8.1%), bone mineral density (+5.2%), maximum force (+10.6%), breaking strength (+12.9%), and stiffness (+23%). This experimental study found that a diet containing flaxseed flour contributed to bone mineral density and femur resistance at 180 d.

Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet induced Type 2 diabetes mellitus mouse model

BackgroundThis study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model.MethodsT2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test. The protein expression was detected by immunohistochemical staining and Western blot. The cell apoptosis was evaluated by TUNEL staining. The Bcl2, caspase 3, and osteoblast marker genes were detected by RT-qPCR.ResultsThe biomechanical properties of bones from DIO-FENO group were significantly lower than those in the control and DIO-PBS groups. Besides, the trabecular number was lower than those of the other groups, though the cortical porosity was decreased compared with that of DIO-PBS group because of the increase of apoptotic cells. The expression of osteocalcin and collagen I were decreased after treatment with fenofibrate in T2DM mice. Moreover, the cell viability was decreased after treated with different concentrations of fenofibrate, and the expression of Runx2 decreased after treated with high dose of fenofibrate.ConclusionFenofibrate decreases the bone quality of T2DM mice through decreasing the expression of collagen I and osteocalcin, which may be resulted from the down regulation of Runx2 expression.

Effect of subclinical hypothyroidism on the skeletal system and improvement with short-term thyroxine therapy.

The purpose of the study was to observe changes in the skeletal system of rats with subclinical hypothyroidism (SCH) and to determine whether L-thyroxine (L-T4) administration suppresses those changes. Sixty male Wistar rats were randomly divided into control, SCH, and SCH+T4 groups. SCH was induced in rats by administration of methimazole (MMI), and rats in the SCH+T4 group were treated with L-T4 after 45 days of MMI administration. The SCH group had higher thyroid-stimulating hormone (TSH) level than the control and SCH+T4 groups. There were no differences in serum thyroid hormone (FT4 and FT3) levels among the three groups. Bone mineral density; serum levels of BALP and TRACP-5b, two bone metabolic markers; and the biomechanical properties of the femurs were lower in the SCH group than in the control group. After L-T4 treatment, serum BALP and TRACP-5b levels and the femur biomechanical properties were higher in the SCH+T4 than the SCH group. Histopathological examination revealed damage to the structure of the femur trabecular bone network in rats with SCH, and L-T4 treatment improved this condition to some extent. These findings demonstrate that L-T4 treatment ameliorates the destructive effects of SCH on the skeletal system in rats.

Insulin‐Stimulated Bone Blood Flow and Bone Biomechanical Properties Are Compromised in Obese, Type 2 Diabetic OLETF Rats

Type 2 diabetes (T2D) increases skeletal fragility and fracture risk; however, the underlying mechanisms remain to be identified. Impaired bone vascular function, in particular insulin‐stimulated vasodilation and blood flow is a potential, yet unexplored mechanism. The purpose of this study was to determine the effects of T2D on femoral biomechanical properties, trabecular microarchitecture, and insulin‐stimulated bone vasodilation by comparison of hyperphagic Otsuka Long‐Evans Tokushima Fatty (OLETF) rats with normoglycemic control OLETF rats. Four‐week old, male OLETF rats were randomized to two groups: type 2 diabetes (O‐T2D) or normoglycemic control (O‐CON). O‐T2D were allowed ad libitum access to a rodent chow diet and O‐CON underwent moderate caloric restriction (30% restriction relative to intake of O‐T2D) to maintain normal body weight (BW) and glycemia until 40 weeks of age. Hyperphagic O‐T2D rats had significantly greater BW, body fat, and blood glucose than O‐CON. Total cross‐sectional area (Tt.Ar), cortical area (Ct.Ar), Ct.Ar/Tt.Ar, and polar moment of inertia of the mid‐diaphyseal femur adjusted for BW were greater in O‐T2D rats versus O‐CON. Whole‐bone biomechanical properties of the femur assessed by torsional loading to failure did not differ between O‐T2D and O‐CON, but tissue‐level strength and stiffness adjusted for BW were reduced in O‐T2D relative to O‐CON. Micro–computed tomography (μCT) of the distal epiphysis showed that O‐T2D rats had reduced percent bone volume, trabecular number, and connectivity density, and greater trabecular spacing compared with O‐CON. Basal tibial blood flow assessed by microsphere infusion was similar in O‐T2D and O‐CON, but the blood flow response to insulin stimulation in both the proximal epiphysis and diaphyseal marrow was lesser in O‐T2D compared to O‐CON. In summary, impaired insulin‐stimulated bone blood flow is associated with deleterious changes in bone trabecular microarchitecture and cortical biomechanical properties in T2D, suggesting that vascular dysfunction might play a causal role in diabetic bone fragility. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Protective Effect of Chokeberry (Aronia melanocarpa L.) Extract against Cadmium Impact on the Biomechanical Properties of the Femur: A Study in a Rat Model of Low and Moderate Lifetime Women Exposure to This Heavy Metal.

The hypothesis that the consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased the procollagen I concentration in the bone tissue and weakened the biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that the consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for skeletal protection under low-level and moderate chronic exposure to Cd.