scholarly journals Ibandronate Suppresses Changes in Apatite Orientation and Young's Modulus Caused by Estrogen Deficiency in Rat Vertebrae

2022 ◽  
Author(s):  
Takuya Ishimoto ◽  
Mitsuru Saito ◽  
Ryosuke Ozasa ◽  
Yoshihiro Matsumoto ◽  
Takayoshi Nakano
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Estrogen Deficiency ◽  
Dependent Manner ◽  
Mineral Density ◽  
Bone Material ◽  
Material Quality ◽  
Mechanical Integrity

AbstractBone material quality is important for evaluating the mechanical integrity of diseased and/or medically treated bones. However, compared to the knowledge accumulated regarding changes in bone mass, our understanding of the quality of bone material is lacking. In this study, we clarified the changes in bone material quality mainly characterized by the preferential orientation of the apatite c-axis associated with estrogen deficiency-induced osteoporosis, and their prevention using ibandronate (IBN), a nitrogen-containing bisphosphonate. IBN effectively prevented bone loss and degradation of whole bone strength in a dose-dependent manner. The estrogen-deficient condition abnormally increased the degree of apatite orientation along the craniocaudal axis in which principal stress is applied; IBN at higher doses played a role in maintaining the normal orientation of apatite but not at lower doses. The bone size-independent Young's modulus along the craniocaudal axis of the anterior cortical shell of the vertebra showed a significant and positive correlation with apatite orientation; therefore, the craniocaudal Young’s modulus abnormally increased under estrogen-deficient conditions, despite a significant decrease in volumetric bone mineral density. However, the abnormal increase in craniocaudal Young's modulus did not compensate for the degradation of whole bone mechanical properties due to the bone loss. In conclusion, it was clarified that changes in the material quality, which are hidden in bone mass evaluation, occur with estrogen deficiency-induced osteoporosis and IBN treatment. Here, IBN was shown to be a beneficial drug that suppresses abnormal changes in bone mechanical integrity caused by estrogen deficiency at both the whole bone and material levels.

scholarly journals Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen deficiency-induced bone loss

iScience ◽  
2021 ◽  
pp. 102224
Author(s):  
Juliane Lehmann ◽  
Sylvia Thiele ◽  
Ulrike Baschant ◽  
Tilman D. Rachner ◽  
Christof Niehrs ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Loss ◽  
Bone Mass ◽  
Estrogen Deficiency ◽  
High Bone Mass ◽  
High Bone

scholarly journals Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Bone Mineral ◽  
Combination Treatment ◽  
Mass Gain ◽  
Ovariectomized Rats ◽  
Concomitant Treatment ◽  
Mineral Density ◽  
Ovx Rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.

Young's modulus of trabecular and cortical bone material: Ultrasonic and microtensile measurements

1993 ◽  
Vol 26 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Jae Young Rho ◽  
Richard B. Ashman ◽  
Charles H. Turner
Keyword(s):  
Cortical Bone ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Bone Material

scholarly journals Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

scholarly journals MicroRNA-29a represses osteoclast formation and protects against osteoporosis by regulating PCAF-mediated RANKL and CXCL12

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Wei-Shiung Lian ◽  
Jih-Yang Ko ◽  
Yu-Shan Chen ◽  
Huei-Jing Ke ◽  
Chin-Kuei Hsieh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Estrogen Deficiency ◽  
Biomechanical Property ◽  
Mineral Density ◽  
Cxcl12 Expression ◽  
Osteogenic Cells

Abstract Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C–X–C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3′-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.

Iron Status Independently Associates With Bone Mineral Density At Population Level. Insights From The Val Borbera Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4672-4672
Author(s):  
Nicola Martinelli ◽  
Michela Traglia ◽  
Fabiana Busti ◽  
Marcella Sirtori ◽  
Natascia Campostrini ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Iron Overload ◽  
Bone Metabolism ◽  
Iron Status ◽  
Population Level ◽  
Mineral Density ◽  
Major Health Problem ◽  
T Score ◽  
Serum Hepcidin

Background and Aims Osteoporosis is a multifactorial major health problem affecting over 200 million people worldwide. It is long known as a complication of marked iron overload, both primary (i.e. genetic hemochromatosis) and secondary (i.e. transfusional iron overload), but only recently cellular and animal models have shed some light on the pathogenetic link between iron and bone metabolism. Iron has been shown to activate osteoclasts (Ishii KA, Nat Med 2009) and to inhibit osteoblasts (Yamasaki K, Toxicol Lett 2009), which express ferroportin regulated by hepcidin (Xu Y, Inflammation 2012). A murine model has shown that iron overload causes bone loss through induction of Reactive Oxygen Species (ROS) (Tsay J, Blood 2010). Of note, a recent longitudinal study in a Korean population has demonstrated that serum ferritin, even at concentrations generally not considered as “iron overload”, is an independent predictor of bone mass deterioration and incident vertebral fractures (Kim BJ, J Bone Miner Res 2012), an effect most prominent in women ≥ 45 years of age (Kim BJ, Osteoporos Int 2013). Taking advantage from the recently completed iron section of the Val Borbera Study (Traglia M, J Med Genet 2011), this study aimed to evaluate for the first time the association between iron status (including serum hepcidin levels) and bone mass in a Caucasian population. Subjects and Methods This survey included 921 subjects (564 females, 357 males) aged 53.8 ± 16.3 years for whom complete data regarding bone mass (measured by transportable Quantitative Ultrasonography, QUS-based approach) and iron status (including serum hepcidin-25 levels measured by Mass Spectrometry) were available. Subjects with known inflammatory and renal disorders, as well as hereditary hemochromatosis had been previously excluded. Analyses were performed separately in males and females, due to known gender-related differences in either iron or bone metabolism. Main Results No significant association was found in males, while in females both ferritin (r= -0.42, P<0.001) and hepcidin (r= -0.30, P<0.001) were inversely correlated with T-score at univariate analyses. However, after including both ferritin and hepcidin in an age-adjusted linear regression model, only ferritin remained a significant predictor of T-score variability (beta coefficient= -0.115, P=0.042). Subsequent regression models adjusted for age, BMI, and C-Reactive Protein highlighted ferritin levels as independent predictors of T-score in females. After stratification for age and ferritin categories, T-score decreased linearly with increasing ferritin levels especially in females aged 50-75 years (n=293), i.e. the age known to be at major risk of accelerated bone loss (P<0.001 – Figure 1). Conclusions This study confirms that iron status significantly associates with bone loss at population level even in Caucasians, particularly in post-menopausal women. Increasing iron stores, even not clearly “pathologic”, may influence bone metabolism through increased ROS and/or hepcidin-mediated altered iron handling of osteoblasts and osteoclasts. Disclosures: No relevant conflicts of interest to declare.

Risk of bone loss in men with multiple sclerosis

2004 ◽  
Vol 10 (2) ◽  
pp. 170-175 ◽  
Author(s):  
Bianca Weinstock-Guttman ◽  
Eileen Gallagher ◽  
Monika Baier ◽  
Lydia Green ◽  
Joan Feichter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
Bone Mass ◽  
Multivariate Linear Regression Analysis ◽  
Mineral Density ◽  
Factors Associated ◽  
Dexa Scan

Context: O steoporosis and the increased fracture risk associated with osteoporosis become apparent in men appro ximately 10 years later than women. However, in recent studies, appro ximately 20% of healthy men in the age range 55-64 years were found to be osteopenic. Emerging data suggest a significantly increased prevalence of osteoporosis in men and women with multiple sclerosis (MS) compared to age-matched controls, but no specific clinical testing recommendations are available for men. Objective: To determine the proportion of male MS patients with osteoporosis and to identify the factors associated with the reduction in bone mass. Design: C onsecutive male MS patients seen at our MS clinic were screened with dual-X-ray absorptiometry (DEXA) scan for determining the bone mineral density (BMD). A ll patients had neurological Expanded Disability Status Scale (EDSS) evaluation. The results were compared to healthy age-matched male reference population using the Z score and to a cohort of women MS patients and women controls. C alcium, total testosterone, sex-hormone binding globulin (SHBG), 25-hydro xy-vitamin-D, and parathyroid hormone (PTH) were evaluated in male patients with decreased BMD. Relevant data on body mass index (BMI), medicatio n, alcohol consumption, smoking, and sexual dysfunction were recorded. Setting: Academic MS C entre. Patients and other participants: Forty consecutive male MS patients, age mean 51.2±8.7 years, and mean EDSS of 5.8±1.9 were evaluated with DEXA scan. O f these, 17.5% patients were relapsing - remitting (RR) MS, 57.5% were secondary progressive (SP) MS and 25% were primary progressive (PP) MS. Main outcome measure: Proportion of male MS patients with reduced BMD at the lumbar spine and femoral neck. Results: Thirty-two (80%) of our patients had a reduced bone mass of either lumbar spine or the femoral neck; of these 17 patients (42.5%) had osteopenia and 15 patients (37.5%) had osteoporosis. Twenty-o ne per cent (eight out of 38 patients) had vertebral, rib or extremities fractures. Multivariate linear regression analysis indicated that the EDSS (P B-0.0001) and BMI (P =0.0004) were the important factors associated with low BMD at the femoral neck and the EDSS was the important factor (P =0.0017) associated with low BMD at the lumbar spine. The same factors emerged as significantly associated with the corresponding Z scores, which are corrected for age and sex. No clear association between intravenous steroid therapy and BMD was evident in the multivariate analysis. Low levels of 25-hydroxy-vitamin-D were seen in 37.5% of patients. Conclusions: The proportion of male MS patients with reduced bone mass is high and disproportionate to their age and ambulation, consistent with an association between the MS disease process and patho logical bone loss. Increased awareness and bone density screening of male and female MS patients over 40 years of age is warranted.

scholarly journals The bone-sparing effects of estrogen and WNT16 are independent of each other

2015 ◽  
Vol 112 (48) ◽  
pp. 14972-14977 ◽  
Author(s):  
Sofia Movérare-Skrtic ◽  
Jianyao Wu ◽  
Petra Henning ◽  
Karin L. Gustafsson ◽  
Klara Sjögren ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Integration Site ◽  
Mineral Density ◽  
Trabecular Bone Mass ◽  
Sparing Effect ◽  
Total Body ◽  
Cortical Bone Mass

Wingless-type MMTV integration site family (WNT)16 is a key regulator of bone mass with high expression in cortical bone, and Wnt16−/− mice have reduced cortical bone mass. As Wnt16 expression is enhanced by estradiol treatment, we hypothesized that the bone-sparing effect of estrogen in females is WNT16-dependent. This hypothesis was tested in mechanistic studies using two genetically modified mouse models with either constantly high osteoblastic Wnt16 expression or no Wnt16 expression. We developed a mouse model with osteoblast-specific Wnt16 overexpression (Obl-Wnt16). These mice had several-fold elevated Wnt16 expression in both trabecular and cortical bone compared with wild type (WT) mice. Obl-Wnt16 mice displayed increased total body bone mineral density (BMD), surprisingly caused mainly by a substantial increase in trabecular bone mass, resulting in improved bone strength of vertebrae L3. Ovariectomy (ovx) reduced the total body BMD and the trabecular bone mass to the same degree in Obl-Wnt16 mice and WT mice, suggesting that the bone-sparing effect of estrogen is WNT16-independent. However, these bone parameters were similar in ovx Obl-Wnt16 mice and sham operated WT mice. The role of WNT16 for the bone-sparing effect of estrogen was also evaluated in Wnt16−/− mice. Treatment with estradiol increased the trabecular and cortical bone mass to a similar extent in both Wnt16−/− and WT mice. In conclusion, the bone-sparing effects of estrogen and WNT16 are independent of each other. Furthermore, loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. WNT16-targeted therapies might be useful for treatment of postmenopausal trabecular bone loss.

scholarly journals Improvement of bone properties and enhancement of mineralization by ethanol extract of Fructus Ligustri Lucidi

2008 ◽  
Vol 99 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Yan Zhang ◽  
Ping-Chung Leung ◽  
Chun-Tao Che ◽  
Hung-Kay Chow ◽  
Chun-Fu Wu ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mineral ◽  
Sham Operation ◽  
Dependent Manner ◽  
Aged Rats ◽  
Mineral Density ◽  
Fructus Ligustri Lucidi ◽  
Bone Properties ◽  
Ovx Rats ◽  
Umr 106

Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herb, was shown to regulate Ca balance in ovariectomized (OVX) rats in our previous study. This study investigated whether it could improve bone properties in aged normal and OVX rats and increase osteoblastic differentiation in rat osteoblast-like UMR-106 cells. Ten-month-old aged rats underwent sham-operation or ovariectomy, were orally administered with FLL extracts or its vehicle and fed with diets containing different levels of Ca (LCD, 0·1 % Ca; MCD, 0·6 % Ca; HCD, 1·2 % Ca) for 12 weeks. Ovariectomy induced bone loss at multiple-sites of both tibia and femur in all rats being studied. FLL extract increased bone mineral density and bone mineral content at both tibial and femoral diaphysis as well as the lumbar vertebra (LV-2) in rats fed either LCD or MCD. In addition, FLL increased biomechanical strength of the tibial diaphysis in these rats. Combination of FLL and high-Ca diet significantly improved bone mass of cortical and trabecular bone at appendicular bones and LV-2 and decreased bone loss associated with ovarietomy and low-Ca feeding. Treatment of UMR-106 cells with FLL extracts accelerated the formation of calcified matrix and increased extracellular Ca and P depositions in time- and dose-dependent manner. The level of mineralization reached a maximum by 6 d incubation at the dosage of 10 μg FLL extract/ml. Our study indicated that FLL extract could improve bone properties in aged rats possibly via its direct action on osteoblastic cells by enhancement of the mineralization process.

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