Trabecular Bone Deterioration Research Articles

The Effects of Corticosteroid Administration and Treadmill Exercise on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in Rats.

We aimed to investigate the effects of short-term corticosteroid administration after anterior cruciate ligament (ACL) reconstruction on marrow adipose tissue (MAT) and trabecular bone mass, as well as to examine whether treadmill exercise can mitigate MAT increase and trabecular bone deterioration caused by corticosteroid. ACL-reconstructed rats were divided into groups: no intervention, daily treadmill exercise (60 min/day), administration of the steroidal drug dexamethasone (250 μg/kg on days 0-5, 7, and 9 post-operatively), or dexamethasone administration combined with treadmill exercise. Untreated rats were served as controls. At day 10 or 30 post-operatively, histological assessments were performed in the proximal tibial epiphysis. MAT accumulation and trabecular bone loss were observed after ACL reconstruction. Dexamethasone promoted MAT accumulation at day 10 post-operatively but did not affect the trabecular bone loss. The MAT accumulation caused by dexamethasone reversed within 21 days after discontinuation. Treadmill exercise did not influence the changes in the MAT and trabecular bone areas. Short-term corticosteroid administration after ACL reconstruction promoted MAT accumulation while not affecting trabecular bone area. The MAT accumulation resulting from corticosteroid administration was reversible after discontinuation. Treadmill exercise could not mitigate the accumulation of MAT caused by corticosteroid administration and did not affect trabecular bone area.

Dancr-BRG1 regulates Nfatc1 transcription and Pgc1β-dependent metabolic shifts in osteoclastogenesis

Long non-coding RNA (lncRNA) serves as a vital regulator of bone metabolism, but its role in pathologically overactive osteoclast differentiation remains elusive. Here, we identify lncRNA Dancr (Differentiation Antagonizing Non-protein Coding RNA) as a critical suppressor of osteoclastogenesis and bone resorption, which is down-regulated in response to estrogen deficiency. Global or osteoclast-specific Dancr Knockout mice display significant trabecular bone deterioration and enhanced osteoclast activity, but minimal alteration of bone formation. Moreover, the bone-targeted delivery of Dancr by Adeno-associated viral remarkably attenuates ovariectomy-induced osteopenia in mice. Mechanistically, Dancr establishes a direct interaction with Brahma-related gene 1 to prevent its binding and preserve H3K27me3 enrichment at the nuclear factor of activated T cells 1 and proliferator-activated receptor gamma coactivator 1-beta promoters, thereby maintaining appropriate expression of osteoclastic genes and metabolic programs during osteoclastogenesis. These results demonstrate that Dancr is a key molecule maintaining proper osteoclast differentiation and bone homeostasis under physiological conditions, and Dancr overexpression constitutes a potential strategy for treating osteoporosis.

Protective effect of vaginal resveratrol administration on joint tissues in ovariectomized rats: Targeting mTOR and сaspase 3

IntroductionEstrogens play a considerable role in maintaining bone and articular cartilage homeostasis. Menopause provokes joint disorders due to metabolic syndrome and altered signaling pathways. Phytoestrogen resveratrol was demonstrated to provide chondroprotective and osteoprotective effects. However, the mechanisms of such action of Resveratrol are still being explored. AimThe study aims to determine the effect of Resveratrol on the joints and its therapeutic mechanism in ovariectomized rats. Material and methodsThe study was carried out on Wistar female rats that were divided into three groups, including control animals; ovariectomized rats (OVX); and the OVX group treated with an intravaginal gel containing Resveratrol (0.5 % 0.1 mL, daily 28 days). Knee joint tissues (articular cartilage, subchondral plate, subchondral bone) were assessed by histomorphometry. The expression of mTOR, PTEN, Caspase 3 and BCL-2 in articular cartilage and subchondral bone were evaluated immunohistochemically. ResultsResveratrol treatment of OVX rats prevented weight gain by 17 % (P < 0.001), demonstrating the systemic effect on metabolic pathways. Although there were no statistically significant differences in the thickness of articular cartilage between groups, OVX rats possessed degenerative changes in chondrocytes, associated with the enhanced expression of mTOR (P < 0.001) and Casp-3 (P = 0.005). Resveratrol decreased mTOR (P = 0.007) and Casp-3 (P = 0.011) expression in chondrocytes, reducing degenerative changes. At the same time, resveratrol attenuated the deterioration of trabecular bone in OVX rats (P = 0.002). This effect was through the up-regulation of BCL-2 (P = 0.018) and down-regulation of Casp-3 expression (P < 0.001). ConclusionsIntravaginal administration of resveratrol provided systemic effects and ameliorated joint tissue structure and signaling in OVX rats through stimulation of BCL-2 and reduced Casp-3 expression.

Characterization of pain-related behaviors, changes in bone microarchitecture and sensory innervation induced by chronic cadmium exposure in adult mice

Because of the relative lack of understanding of the neurobiological mechanisms that drive toxic effects of cadmium in bone, the purpose of this study was to characterize a preclinical model of chronic cadmium exposure. Adult male C57BL/6 J mice were exposed to cadmium 25 mg/L (as CdCl2) in drinking water for 16 weeks. During this time, pain-related behaviors including hindpaw mechanical sensitivity and vertical rears were evaluated every four weeks. We assessed changes in bone microarchitecture at the femoral neck and L5 vertebra by microcomputed tomography and quantified the density of nerve fibers expressing PGP 9.5 (a pan-neuronal marker) and CGRP (a marker of sensory nerve fibers subfamily) at the femoral neck and glabrous skin of the hindpaw using immunohistochemistry. Cadmium exposure produced mechanical hypersensitivity in both hindpaws along with decreased rearing activity (surrogate for musculoskeletal-related pain) without affecting the horizontal activity (a measure of locomotor behavior) in comparison to the control group. Intraperitoneal acute treatment with morphine and gabapentin reversed pain-related behaviors in cadmium-exposed mice. Furthermore, exposure to cadmium resulted in significant trabecular bone deterioration at the femoral neck and L5 vertebra. We also observed a significant reduction in the density of both CGRP+ and PGP 9.5+ nerve fibers in the femoral neck, but not in the hindpaw glabrous skin, suggesting tissue-dependent neurotoxicity. This model may help in developing a mechanism-based understanding of the factors that generate and maintain musculoskeletal pain and bone loss caused by chronic cadmium exposure and in translating these findings into new therapies for treating cadmium-induced bone toxicity.

Metabolomics and physiological analysis of the effect of calcium supplements on reducing bone loss in ovariectomized rats by increasing estradiol levels

BackgroundData from the 2010–2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen.ObjectiveThis study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats.MethodsForty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO3 (OVX-LC-H). CaCO3 or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed.ResultsThe OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO3 reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO3 supplementation (p < 0.01). The administration of 2800 mg/kg CaCO3 decreased serum triglyceride and high-density lipoprotein levels (p < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and β-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced.ConclusionsThe results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.

Grand multiparity associations with low bone mineral density and degraded trabecular bone pattern

IntroductionPregnancy is associated with changes in bone remodeling and calcium metabolism, which may increase the risk of fragility fracture after menopause. We hypothesized that in postmenopausal women, with history of grand multiparity, the magnitude of trabecular bone deterioration is associated with number of deliveries. Methods1217 women aged 69.2 ± 6.4 years, from the Bushehr Elderly Health (BEH) program were recruited. The areal bone mineral density (aBMD) of the lumbar spine and femoral neck and trabecular bone score (TBS) of 916 postmenopausal women, with grand multiparity defined as more than 4 deliveries, were compared with those of 301 postmenopausal women with 4 or fewer deliveries. The association of multiparity with aBMDs and TBS were evaluated after adjustment for possible confounders including age, years since menopause, body mass index, and other relevant parameters. ResultsThe aBMD of femoral neck (0.583 ± 0.110 vs. 0.603 ± 0.113 g/cm2), lumbar spine (0.805 ± 0.144 vs. 0.829 ± 0.140 g/cm2) and TBS (1.234 ± 0.086 vs. 1.260 ± 0.089) were significantly lower in women with history of grand multiparity than others. In the multiple regression analysis, after adjusting for confounders, the negative association did persist for lumbar spine aBMD (beta = −0.02, p value = 0.01), and the TBS (beta = −0.01, p value = 0.03), not for femoral neck aBMD. ConclusionWe infer that grand multiparity have deleterious effects on the aBMD and the trabecular pattern of the lumbar spine.

Catalpol Protects Against High Glucose-Induced Bone Loss by Regulating Osteoblast Function.

Objective: The overall objective of this study was to investigate the effects of catalpol on bone remodeling of diabetic osteoporosis by regulating osteoblast differentiation and migration. Method: Using a murine model of diabetic osteoporosis, to detect the protective effects of catalpol on bone loss, architectural deterioration of trabecular bone and bone metabolism biomarkers were tested. A model of MC3T3-E1 cells was established by treatment with high glucose; the regulatory role of catalpol in the differentiation and migration was tested by Western blot, ALP staining, and Alizarin Red staining. Results: Catalpol treatment markedly ameliorated trabecular bone deterioration by reducing degenerative changes of the trabecular structure by improving the bone formation marker levels of ALP, osteopontin, type I collagen, and osteocalcin, as well as the level of OPG/RANKL. Catalpol enhanced cell motility and scattering following gap formation of MC3T3-E1 cells. Conclusion: The results indicated that catalpol exhibits a protective effect against diabetic osteoporosis by regulating the differentiation and migration of osteoblast.

Targeting autophagy by natural product Ursolic acid for prevention and treatment of osteoporosis

With the growth of the aging population, osteoporosis is becoming a global health problem. Ursolic acid (UA) is an active ingredient existed in a variety of foods and nature plants and owns plenty of pharmacological effects especially in treating metabolic disease. Our predication from network pharmacology hinted that UA has potential for ameliorating osteoporosis. Firstly through in vivo experiment, we confirmed that UA administration obviously protected against ovariectomy (OVX)-induced osteoporosis in rats by improving microarchitectural deterioration of trabecular bone (P < 0.001), decreasing numbers of TRAP positive osteoclast in vertebra (P < 0.001), as well as decreasing serum osteoclast-specific cytokines release (P < 0.001). Besides, UA ameliorated kidney damage secondary to OVX-induced osteoporosis by ameliorating glomerular atrophy, decreasing BUN and creatinine levels in OVX rats. In vitro, UA noticeably decreased osteoclastic-special marker proteins c-Fos and NFATc1 expressions (P < 0.001) in response to RANKL stimulation in macrophagy. Importantly, autophagy pathway was activated in the process of osteoclast differentiation and blocked by UA pretreatment. Furthermore, autophagy inhibitors suppressed osteoclast differentiation (P < 0.001). Collectively, UA may ameliorate osteoporosis by suppressing osteoclast differentiation mediated by autophagy. Our research provides scientific support for UA treating osteoporosis and offers an optimal dose for daily intake of UA safely to prevent bone diseases.

Trabecular bone deterioration in differentiated thyroid cancer: Impact of long-term TSH suppressive therapy.

BackgroundConflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long‐term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy.MethodsAbout 145 women with resected DTC and receiving long‐term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow‐up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual‐energy X‐ray absorptiometry (DXA) and TBS iNsight (Med‐Imaps), at baseline (1‐3 months after surgery) and at the final study visit.ResultsIn patients stratified by duration of TSH suppression therapy (Group I, 5‐10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS‐BMD and FN‐BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.‐0.5 or >0.5 µU/mL.ConclusionsWe found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5‐10 years of follow‐up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration.

Consequences of spinal ankylosis on bone trabecular fragility assessed on CT scans in patients with ankylosing spondylitis. A retrospective study.

Ankylosing spondylitis (AS) patients seems to be at risk of osteoporosis but bone screening is not often performed. The objective was to evaluate the effect of vertebral ankylosis on scanographic bone attenuation coefficient (SBAC) on lumbar vertebrae in AS patients. This study included AS patients fulfilling New York criteria who underwent both thoraco-abdomino-pelvic computed tomography and X-rays during routine follow-up. The modified stoke ankylosing spondylitis spinal score (mSASSS) was scored on X-rays, and the presence of at least one syndesmophyte (mSASSS≥2) defined mSASSS+ patients. Ankylosis of a lumbar vertebra was defined by the presence of bone bridges to its two adjacent vertebrae. The SBAC was measured from L1 to L5, and the fracture threshold was set at SBAC≤145 HU. A total of 73 AS patients were included (mean age: 60.3 [±10.7] years, 65 men [89%]). Sixty patients (82.2%) were mSASSS+; 13 patients (17.8%) presented ankylosis of at least one lumbar vertebra. The SBAC of each lumbar vertebra was not significantly different between mSASSS- and mSASSS+ patients. The SBAC was lower for patients with at least one bone bridge than for patients without (P<0.05). Patients with lumbar vertebral ankylosis had a higher risk of presenting an SBAC≤145 HU (OR: 4.95 (95% CI: 1.1-17.4)). The presence of a bone bridge and complete ankylosis of lumbar vertebra were associated with a higher risk of SBAC under the fracture threshold, suggesting structural deterioration of trabecular bone in ankylosed vertebrae in AS patients.

Dose-dependent skeletal deficits due to varied reductions in mechanical loading in rats

Reduced skeletal loading leads to marked bone loss. Animal models of hindlimb suspension are widely used to assess alterations in skeleton during the course of complete unloading. More recently, the effects of partial unloading on the musculoskeletal system have been interrogated in mice and rats, revealing dose-dependent effects of partial weight bearing (PWB) on the skeleton and skeletal muscle. Here, we extended these studies to determine the structural and functional skeletal alterations in 14-week-old male Wister rats exposed to 20%, 40%, 70%, or 100% of body weight for 1, 2, or 4 weeks (n = 11–12/group). Using in vivo pQCT, we found that trabecular bone density at the proximal tibia declined in proportion to the degree of unloading and continued progressively with time, without evidence of a plateau by 4 weeks. Ex vivo measurements of trabecular microarchitecture in the distal femur by microcomputed tomography revealed deficits in bone volume fraction, 2 and 4 weeks after unloading. Histologic analyses of trabecular bone in the distal femur revealed the decreased osteoblast number and mineralizing surface in unloaded rats. Three-point bending of the femoral diaphysis indicated modest or no reductions in femoral stiffness and estimated modulus due to PWB. Our results suggest that this rat model of PWB leads to trabecular bone deterioration that is progressive and generally proportional to the degree of PWB, with minimal effects on cortical bone.

Vindoline Inhibits RANKL-Induced Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss in Mice.

Osteolytic bone diseases, for example postmenopausal osteoporosis, arise from the imbalances between osteoclasts and osteoblasts in the bone remodeling process, whereby osteoclastic bone resorption greatly exceeds osteoblastic bone formation resulting in severe bone loss and deterioration in bone structure and microarchitecture. Therefore, the identification of agents that can inhibit osteoclast formation and/or function for the treatment of osteolytic bone disease has been the focus of bone and orthopedic research. Vindoline (Vin), an indole alkaloid extracted from the medicinal plant Catharanthus roseus, has been shown to possess extensive biological and pharmacological benefits, but its effects on bone metabolism remains to be documented. Our study demonstrated for the first time, that Vin could inhibit osteoclast differentiation from bone marrow macrophages (BMMs) precursor cells as well as mature osteoclastic bone resorption. We further determined that the underlying molecular mechanism of action of Vin is in part due to its inhibitory effect against the activation of MAPK including p38, JNK, and ERK and intracellular reactive oxygen species (ROS) production. This effect ultimately suppressed the induction of c-Fos and NFATc1, which consequently downregulated the expression of the genes required for osteoclast formation and bone resorption. Consistent with our in vitro findings, in vivo administration of Vin protected mice against ovariectomy (OVX)-induced bone loss and trabecular bone deterioration. These results provided promising evidence for the potential therapeutic application of Vin as a novel treatment option against osteolytic diseases.

Disrupted radial and tibial microarchitecture in patients with monoclonal gammopathy of undetermined significance.

Fracture risk is elevated in patients with monoclonal gammopathy of undetermined significance (MGUS). However, the pathogenesis of bone disease in these patients is poorly understood. Prior work using high-resolution peripheral CT (HRpQCT) demonstrated abnormal microarchitecture at the radius, with predominantly cortical abnormalities. We hypothesized that patients with MGUS have abnormal microarchitecture at both radius and tibia compared to controls, reflecting global skeletal effects of the disease. This case-control study enrolled 36 subjects; patients with MGUS (n = 12) were matched 1:2 by age, sex, and race to controls (n = 24). Areal BMD (aBMD) was measured by DXA, vBMD, and microarchitecture by HRpQCT, and whole bone stiffness by finite element analysis. Serum was drawn for markers of bone metabolism and inflammation. By DXA, MGUS patients had lower aBMD at the lumbar spine, femoral neck, and 1/3 radius. Markers of bone metabolism and inflammation did not differ. By HRpQCT at the radius, MGUS patients had lower total, trabecular and cortical density, lower trabecular number, and greater trabecular separation and heterogeneity. At the tibia, MGUS patients had lower total and trabecular density, lower trabecular number, greater separation and heterogeneity, and lower whole bone stiffness. Patients with MGUS had lower vBMD, cortical, and trabecular abnormalities at the radius compared to matched controls. At the tibia, trabecular abnormalities predominated. These results suggest that in addition to previously described cortical deficits, deterioration of trabecular bone may contribute to a generalized skeletal fragility in patients with MGUS.

Low Muscle Strength and Mass Is Associated With the Accelerated Decline of Bone Microarchitecture at the Distal Radius in Older Men: the Prospective STRAMBO Study

Low muscle mass and strength are associated with poor bone microarchitecture. We studied the association of muscle mass and strength with changes in bone microarchitecture of distal radius in 821 older men during an 8-year prospective follow-up. Bone microarchitecture was assessed by high resolution peripheral quantitative computed tomography (XtremeCT-1, Scanco) at baseline, then after 4 and 8 years. Relative appendicular lean mass of the upper limbs (RALM-u.l.) was calculated as DXA-measured lean mass of upper limbs divided by (height)2 . Relative grip strength was calculated as grip strength divided by height. Decrease in bone mineral content (BMC), total volumetric bone mineral density (Tt.vBMD), cortical thickness (Ct.Th), cortical area (Ct.Ar) and cortical vBMD (Ct.vBMD) accelerated with age. Trabecular area (Tb.Ar) expansion and trabecular bone deterioration accelerated with age. Men in the first RALM-u.l. quartile had more rapid loss of BMC, Tt.vBMD, Ct.Th, Ct.vBMD and Ct.Ar vs. the highest quartile. They had more rapid increase in Tb.Ar. Men in the lowest quartile of grip strength had greater decrease in BMC, Tt.vBMD, Ct.Th, Ct.vBMD, Ct.Ar, and greater increase in Tb.Ar vs. the highest quartile. In the models including ALM-u.l. and grip strength (not corrected for height), both muscle-related variables were associated with more rapid bone microarchitectural deterioration (slightly more so for grip strength). Trabecular vBMD (Tb.vBMD) and Central.Tb.vBMD increased in men having higher muscle mass and strength. Trends in trabecular number and thickness did not differ across the groups in all the analyses. Thus, in men, aging-related deterioration of bone microarchitecture was most rapid after the age of 80. Low grip strength (and slightly more weakly low RALM-u.l.) is associated with the more rapid decrease in Tt.vBMD and cortical variables, and with greater Tb.Ar expansion. In conclusion, dynapenia and sarcopenia contribute to the deterioration of bone microarchitecture in older men. © 2018 American Society for Bone and Mineral Research.

Effect of tocotrienol from Bixa orellana (annatto) on bone microstructure, calcium content, and biomechanical strength in a model of male osteoporosis induced by buserelin.

BackgroundPatients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from Bixa orellana (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.MethodsForty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.ResultsAnnatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.ConclusionAnnatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.

Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model

This study aimed to investigate the bone quality in rats induced with metabolic syndrome (MetS) using high-carbohydrate high-fat (HCHF) diet. Male Wistar rats (n = 14) were randomized into two groups. The normal group was given standard rat chow. The MetS group was given HCHF diet. Diet regimen was assigned for a period of 20 weeks. Metabolic syndrome parameters were measured monthly until MetS was established. Left tibiae were scanned using micro-computed tomography at week 0, 8, 12, 16, and 20 to analyze the trabecular and cortical bone structure. At the end of the study, rats were euthanized and their bones were harvested for analysis. Metabolic syndrome was established at week 12 in the HCHF rats. Significant deterioration of trabecular bone was observed at week 20 in the HCHF group (p < 0.05). The HCHF diet also decreased cortical and tissue area significantly (p < 0.05), but did not affect cortical thickness and bone calcium content (p > 0.05). Femur length and width in the HCHF group were significantly shorter than the normal group (p < 0.05). The biomechanical strength test showed that the femur of the HCHF rats could endure significantly lower force, but significantly higher displacement and strain compared to the normal rats (p < 0.05). In conclusion, HCHF diet-induced MetS can cause adverse effects on the bone.

Moderate-intensity 4 mT static magnetic fields prevent bone architectural deterioration and strength reduction by stimulating bone formation in streptozotocin-treated diabetic rats

Type 1 diabetes mellitus (T1DM) has been associated with deterioration of bone microarchitecture and strength, resulting in increased fracture risk. Substantial studies have revealed the capacity of moderate-intensity static magnetic fields (SMF) on promoting osteoblastogenesis in vitro and stimulating bone growth and bone regeneration in vivo, whereas it is unknown whether SMF can resist T1DM-associated osteopenia/osteoporosis. We herein investigated the potential effects of whole-body SMF exposure with 4mT on bone loss in streptozotocin-induced T1DM rats. We found that SMF exposure for 16weeks inhibited architectural deterioration of trabecular bone and cortical bone and mechanical strength reduction in T1DM rats, as evidenced by the MicroCT and 3-point bending findings. Our serum biochemical, bone histomorphometric and PCR results revealed that SMF induced higher serum osteocalcin, mineral apposition rate and osteoblast number of trabecular bone, and higher skeletal osteocalcin, BMP2 and Runx2 gene expression in T1DM rats, whereas SMF showed no significant alteration in serum CTX, skeletal osteoclast number, or osteoclastogenesis-related RANKL-RANK signaling gene expression. Together, our findings suggest that moderate SMF prevented bone architectural deterioration and strength reduction by inhibiting the reduction of bone formation in T1DM rats, and indicate that SMF might become a promising biophysical countermeasure for T1DM-related osteopenia/osteoporosis.

Effects of diisononyl phthalate on osteopenia in intact mice

Osteopenia is characterized by bone loss and deterioration of trabecular bone, which leads to osteoporotic fractures. This disease is highly prevalent in industrialized areas and is associated with exposure to endocrine disrupting chemicals (EDCs). Diisononyl phthalate (DINP) is one of these EDCs and is mainly used as a plasticizer in flexible polyvinyl chloride (PVC) products. Although it is well known that exposure to DINP is harmful to humans, no studies have been reported concerning its contribution to osteopenia. Therefore, in this study, we injected DINP (2, 20, and 200mg/kg) into C3H/HeN mice for 6weeks and found that the uterus weight, bone (femur and tibia) weight, and bone length of the DINP-exposed mice were reduced compared to those of the SHAM group. On the other hand, body weight, the serum alkaline phosphatase (ALP) and inorganic phosphorus (IP) levels in the DINP treated mice were increased compared with those of the SHAM group. The tartrate-resistant acid phosphatase (TRAP) activity (bone resorption marker) was increased and the bone alkaline phosphatase (BALP) activity was lowered by the treatment with DINP as compared with the SHAM group. Furthermore, the microarchitecture of the femur and tibia in the intact mice was destroyed by the DINP injection. The tissue volume (TV), bone volume (BV), BV/TV, bone surface (BS), BS/TV, trabecular thickness (Tb.Th), and trabecular number (Tb.N) were reduced and the trabecular pattern factor (Tb.Pf), structure model index (SMI), and trabecular separation (Tb.Sp) were increased by the DINP injection. The bone mineral density (BMD) of the femur and tibia was lower in the DINP group than in the SHAM group. These results indicate that DINP contributes to an increased risk of osteopenia via destruction of the microarchitecture and enhancement of osteoclast activity.

Total Flavonoids of Drynariae Rhizoma Prevent Bone Loss Induced by Hindlimb Unloading in Rats.

Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized rats. However, the beneficial effects of the total flavonoids of Drynariae Rhizoma on osteoporosis caused by microgravity or mechanical inactivity remain unknown. This study assessed the effects of total Drynariae Rhizoma flavonoids (DRTF, Qihuang, Beijing, China, national medicine permit No. Z20030007, number of production: 04080081, content of DRTF ≥80%) against bone loss induced by simulated microgravity. A hindlimb unloading tail-suspended rat model was established to determine the effect of DRTF on bone mineral density (BMD), biomechanical strength and trabecular bone microarchitecture. Twenty-eight male Sprague–Dawley rats were divided into four groups: the baseline, control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with DRTF (HLU–DRTF, 75 mg/kg/day) groups. Oral DRTF was administered for 4 weeks. The underlying mechanisms of the DRTF actions on disuse-induced osteoporosis are discussed. The results showed that DRTF treatment significantly increased the BMD and mechanical strength of tail-suspended rats. Enhanced bone turnover markers with HLU treatment were attenuated by DRTF administration. Deterioration of trabecular bone induced by HLU was prevented through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). The present study provides the first evidence that DRTF prevents bone loss induced by HLU treatment, indicating its potential application in the treatment of disuse-induced osteoporosis.

Decreased trabecular bone deterioration of proximal tibiae and lumbar vertebrae in postmenopausal women with osteoarthritis.

Osteoporosis and osteoarthritis (OA) are two common age-related skeletal disorders, which are associated with substantial morbidity and disability, particularly among elderly women. The present study was performed to investigate the trabecular bone deterioration of proximal tibiae and lumbar vertebrae in postmenopausal women with OA. The results demonstrated that the histomorphometric section of trabecular bone below the growth plate was markedly different between the healthy control and OA group. However, the loss of trabecular bone underneath the growth plate in the healthy control group was significantly worse than that of the OA group. Hematoxylin and eosin staining demonstrated the increased disconnection and separation of the trabecular bone network as well as the reduction of trabecular bone mass of primary and secondary spongiosa throughout the proximal metaphysis of tibia in the healthy control compared to the OA group; similar results were found when the same experiment was repeated on the lumbar vertebrae of healthy control subjects and OA patients from postmenopausal women. The biological properties of trabecular bone in the proximal tibia and lumbar vertebrae were measured in postmenopausal women with OA. Spearman's rank correlation analysis revealed that the bone volume fraction was both positively correlated with radiographic severity and Western Ontario McMaster University Osteoarthritis Index scores in in the proximal tibia and lumbar vertebrae from postmenopausal women with OA. In conclusion, the structural properties of the proximal tibia and lumbar vertebrae supported that an inverse correlation existed between postmenopausal women with OA and healthy controls. Moreover, there is an important protective mechanism of OA on trabecular microstructure in proximal tibiae and lumbar vertebrae from postmenopausal women.