scholarly journals Bone Matrix Levels of Dickkopf and Sclerostin are Positively Correlated with Bone Mass and Strength in Postmenopausal Osteoporosis

2019 ◽  
Vol 20 (12) ◽  
pp. 2896 ◽  
Author(s):  
Thor Ueland ◽  
Lis Stilgren ◽  
Jens Bollerslev
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Postmenopausal Osteoporosis ◽  
Ethylenediaminetetraacetic Acid ◽  
Forearm Fracture ◽  
Guanidine Hydrochloride ◽  
Bone Matrix ◽  
Mineral Density ◽  
Protein Levels ◽  
Bone Volumetric Density

Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass inhibiting the canonical Wnt pathway. We evaluated whether bone protein content of secreted Wnt antagonists is related to age, bone mass, and strength in postmenopausal osteoporosis. We measured cortical and trabecular bone contents of SOST and Dickkopf-1 (DKK1) in combined extracts obtained after ethylenediaminetetraacetic acid and guanidine hydrochloride extraction in 56 postmenopausal women aged 47–74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. Our findings were (i) SOST and DKK1 protein levels were higher in trabecular bone, (ii) cortical and trabecular DKK1 and trabecular SOST correlated positively with bone matrix levels of osteocalcin (r between 0.28 and 0.45, p < 0.05), (iii) cortical DKK1 correlated with lumbar spine bone mineral density (BMD) (r = 0.32, p < 0.05) and femoral neck BMD (r = 0.41, p < 0.01), and (iv) cortical DKK1 and SOST correlated with apparent bone volumetric density and compressive strength (r between 0.34 and 0.51, p < 0.01). In conclusion, cortical bone matrix levels of DKK1 and SOST were positively correlated with bone mass and bone strength in postmenopausal osteoporotic women.

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.

scholarly journals Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2489-2499 ◽  
Author(s):  
Laura M. Calvi ◽  
Olga Bromberg ◽  
Yumie Rhee ◽  
Jonathan M. Weber ◽  
Julianne N. P. Smith ◽  
...  
Keyword(s):  
Stem Cells ◽  
Parathyroid Hormone ◽  
Bone Mass ◽  
Hematopoietic Stem Cells ◽  
Trabecular Bone ◽  
Bone Matrix ◽  
Osteoblastic Cells ◽  
Hematopoietic Stem ◽  
Parathyroid Hormone Receptor ◽  
Mineralized Bone Matrix

Abstract Microenvironmental expansion of hematopoietic stem cells (HSCs) is induced by treatment with parathyroid hormone (PTH) or activation of the PTH receptor (PTH1R) in osteoblastic cells; however, the osteoblastic subset mediating this action of PTH is unknown. Osteocytes are terminally differentiated osteoblasts embedded in mineralized bone matrix but are connected with the BM. Activation of PTH1R in osteocytes increases osteoblastic number and bone mass. To establish whether osteocyte-mediated PTH1R signaling expands HSCs, we studied mice expressing a constitutively active PTH1R in osteocytes (TG mice). Osteoblasts, osteoclasts, and trabecular bone were increased in TG mice without changes in BM phenotypic HSCs or HSC function. TG mice had progressively increased trabecular bone but decreased HSC function. In severely affected TG mice, phenotypic HSCs were decreased in the BM but increased in the spleen. TG osteocytes had no increase in signals associated with microenvironmental HSC support, and the spindle-shaped osteoblastic cells that increased with PTH treatment were not present in TG bones. These findings demonstrate that activation of PTH1R signaling in osteocytes does not expand BM HSCs, which are instead decreased in TG mice. Therefore, osteocytes do not mediate the HSC expansion induced by PTH1R signaling. Further, osteoblastic expansion is not sufficient to increase HSCs.

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 Mice Lacking β-Adrenergic Receptors Have Increased Bone Mass but Are Not Protected from Deleterious Skeletal Effects of Ovariectomy

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 144-152 ◽  
Author(s):  
M. L. Bouxsein ◽  
M. J. Devlin ◽  
V. Glatt ◽  
H. Dhillon ◽  
D. D. Pierroz ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Weight ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Adrenergic Receptors ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Mineral Density ◽  
Adrenergic Signaling ◽  
Β Adrenergic Receptors

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P &lt; 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P &lt; 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P &lt; 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling. Mice lacking ß-adrenergic receptors have increased body weight, bone mineral density, and bone turnover versus controls, but are not protected from bone loss due to deficiency of estrogens..

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 Evaluación de causas secundarias de baja masa ósea en mujeres colombianas con osteoporosis posmenopáusica

2017 ◽  
Vol 3 (4) ◽  
pp. 12-16
Author(s):  
Edwin Antonio Wandurraga ◽  
Lisseth Fernanda Marín Carrillo ◽  
Annie Katherine Natera Melo ◽  
Claudia Milena Gómez Giraldo ◽  
Juan Camilo Mendoza Díaz
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Loss ◽  
Bone Mass ◽  
Postmenopausal Osteoporosis ◽  
Inverse Correlation ◽  
Low Bone Mass ◽  
Mineral Density ◽  
History Of ◽  
Las Mujeres ◽  
Secondary Causes

Introducción: La osteoporosis posmenopáusica puede coexistir con otras entidades que aumentan la pérdida ósea.Objetivo: Determinar la frecuencia de causas secundarias de baja masa ósea en mujeres con osteoporosis posmenopáusica en una población colombiana.Diseño: Estudio descriptivo retrospectivo.Población: Mujeres mayores de 50 años con diagnóstico reciente de osteoporosis posmenopáusica antes de iniciar tratamiento.Mediciones: Se incluyeron variables demográficas, densitométricas y bioquímicas como hemoglobina, fosfatasa alcalina, transaminasas, creatinina, 25-hidroxivitamina D, calcio, fósforo, magnesio, calciuria en 24 horas, PTH y TSH.Resultados: Se incluyeron 129 mujeres con edad promedio de 67+/-8,8 años. Cuarenta y nueve mujeres (36%) presentaban antecedente de fractura por fragilidad. En el 86,8% se encontró al menos una alteración bioquímica asociada con pérdida de masa ósea, documentándose insuficiencia de vitamina D en 71,8%, hiperparatiroidismo normocalcémico en 18,1% e hipercalciuria en 6,4%. Las mujeres con antecedente de fractura presentaron valor promedio de fosfatasa alcalina superior (111,6 +/- 61,3 vs 87,1 +/- 30,4 U/L, p= 0,0143) y promedio de hemoglobina inferior (12,9 +/- 1,2 vs. 14,2 +/- 1,2gr/dl, p<0,0001) al compararse con las mujeres sin fractura. Se encontró correlación inversa entre los niveles de fosfatasa alcalina y la densidad mineral ósea de la columna lumbar (p<0,001) y la cadera (p=0,003).Conclusiones: Las causas secundarias de baja masa ósea en mujeres con OPM son frecuentes en nuestro medio. Con base en una frecuencia de alteraciones mayor al 5%, sugerimos la evaluación de toda mujer con OPM con hemoglobina, calcio, calciuria en 24 horas, 25-hidroxivitamina D, AST, PTH y TSH.Abstract Introduction: Postmenopausal osteoporosis can coexist with other entities that increase bone loss. Aim: To determine the frequency of secondary causes of low bone mass in women with postmenopausal osteoporosis in a Colombian population. Materials and methods: A retrospective descriptive study was conducted, including women over 50 years with newly diagnosed postmenopausal osteoporosis without treatment. Demographic, densitometric and biochemical variables such as hemoglobin, alkaline phosphatase, transaminases, creatinine, 25 hydroxivitamin D, calcium, phosphorus, magnesium, calciuria in 24 hours, PTH and TSH were evaluated.Results: 129 women with a mean age of 67 +/- 8,8 years were included. 49 patients (36%) had history of fragility fracture. At least one biochemical disorder associated with bone loss was reported in 86,8% of cases, vitamin D insufficiency was documented in 71,8%, normocalcemic hyperparathyroidism in 18,1% and hypercalciuria in 6,4%. Women with history of fracture showed higher average value of alkaline phosphatase (111,6 +/- 61,3 vs 87,1 +/- 30,4 U/L, p=0,0143) and lower mean hemoglobin (12,9 +/- 1,2 vs 14,2 +/- 1,2 gr/dl, p<0,0001) compared with women without fracture. Inverse correlation was found between levels of alkaline phosphatase and bone mineral density of lumbar spine (p<0,001) and hip (p=0,003). Conclusions: Secondary causes of low bone mass in women with PMO are frequent in our clinical practice. Based on a frequency of laboratory abnormalities greater than 5%, we suggest that all women with PMO should be studied with hemoglobin, serum calcium, urinary calcium in 24 hours, 25 hydroxivitamin D, AST, PTH and TSH. Keywords: ; ; etiology;; .

scholarly journals Effects of Estrogen with Micronized Progesterone on Cortical and Trabecular Bone Mass and Microstructure in Recently Postmenopausal Women

2013 ◽  
Vol 98 (2) ◽  
pp. E249-E257 ◽  
Author(s):  
Joshua N. Farr ◽  
Sundeep Khosla ◽  
Yuko Miyabara ◽  
Virginia M. Miller ◽  
Ann E. Kearns
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Distal Radius ◽  
Thoracic Spine ◽  
Quantitative Computed Tomography ◽  
Volumetric Bone Mineral Density ◽  
Mineral Density ◽  
Trabecular Microarchitecture ◽  
Micronized Progesterone

Abstract Context: In women, cortical bone mass decreases significantly at menopause. By contrast, loss of trabecular bone begins in the third decade and accelerates after menopause. Objective: The aim of the study was to investigate the effects of estrogen on cortical and trabecular bone. Design: The Kronos Early Estrogen Prevention Study is a double-blind, randomized, placebo-controlled trial of menopausal hormone treatment (MHT) in women, enrolled within 6–36 months of their final menstrual period. Setting: The study was conducted at the Mayo Clinic, Rochester, Minnesota. Intervention: Subjects were treated with placebo (n = 31), or .45 mg/d conjugated equine estrogens (n = 20), or transdermal 50 μg/d 17β-estradiol (n = 25) with pulsed micronized progesterone. Main Outcome Measures: Cortical and trabecular microarchitecture at the distal radius was assessed by high-resolution peripheral quantitative computed tomography. Results: At the distal radius, cortical volumetric bone mineral density (vBMD) decreased, and cortical porosity increased in the placebo group; MHT prevented these changes. By contrast, MHT did not prevent decreases in trabecular microarchitecture at the radius. However, MHT prevented decreases in trabecular vBMD at the thoracic spine (assessed in a subset of subjects; n = 51). These results indicate that MHT prevents deterioration in radial cortical vBMD and porosity in recently menopausal women. Conclusion: The maintenance of cortical bone in response to estrogen likely has important clinical implications because cortical bone morphology plays an important role in bone strength. However, effects of MHT on trabecular bone at the radius differ from those at the thoracic spine. Underlying mechanisms for these site-specific effects of MHT on cortical vs trabecular bone require further investigation.

scholarly journals Hubungan fraksi area trabekula anterior mandibula dengan kepadatan tulang lumbar spine untuk deteksi dini osteoporosis

2017 ◽  
Vol 3 (1) ◽  
pp. 43
Author(s):  
Sri Lestari ◽  
Rini Widyaningrum
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Bone Mineral ◽  
Mass Density ◽  
Area Fraction ◽  
Bone Mass Density ◽  
Mineral Density ◽  
Anterior Mandible

The relationship of anterior mandible trabecular area with bone mass density of lumbar spine for early detection of osteoporosis. Bone mineral density is an indicator of osteoporosis, including the bone mineral density of lumbar spine. The decrease of lumbar spine bone mass density will cause an alteration in another site, including the mandibular. The aim of this research is to determine the predictor of lumbar spine bone mineral density using trabecular bone image of anterior mandible on periapical radiographs. The research was conducted by extracting the area fraction at mandible trabecular bone using digital periapical radiograph from 25 subjects. Canny edge detection was used in digital image processing for each radiograph. The regions of interest were selected from the image obtained by canny edge detection, so that the area fraction could be measured. A linier regression test was applied to determine a relationship between the area fractions of mandible trabecular bone with the bone mineral density of lumbar spine. The result of linear regression test showed that the area fraction of mandible trabecular bone had a moderate negative correlation with bone mass density of lumbar spine (α = 0.046; R = -0.403). The direction of the correlation was negative (b = -0.145). The area fraction of mandible trabecular bone on periapical radiographs could be used as the predictor for bone mass density of lumbar spine.ABSTRAKKepadatan tulang merupakan indikator osteoporosis, salah satu diantaranya adalah kepadatan tulang pada lumbar spine. Penurunan kepadatan tulang pada lumbar spine mempengaruhi kondisi tulang lain, termasuk tulang rahang bawah (mandibula). Tujuan penelitian ini adalah untuk menentukan prediktor densitas mineral tulang menggunakan citra radiograf periapikal tulang trabekula pada regio anterior rahang bawah. Penelitian dilakukan dengan ekstraksi fraksi area tulang trabekula mandibula yang tercitrakan pada radiograf periapikal digital dari 25 subjek. Pengolahan citra digital pada radiograf periapikal dilakukan dengan menggunakan metode deteksi tepi canny terhadap masing-masing citra radiograf. Region of Interest diseleksi dari citra hasil deteksi canny, sehingga dapat dilakukan pengukuran fraksi area. Uji regresi linier dilakukan untuk mengetahui hubungan antara nilai fraksi area trabekula mandibula dengan tingkat kepadatan tulang pada lumbar spine. Hasil uji regresi linier menunjukkan bahwa nilai fraksi area trabekula mandibula berkorelasi negatif dengan kepadatan tulang dengan kekuatan sedang (α = 0,046; R = -0,403). Adapun arah korelasi antara nilai fraksi area trabekula mandibula dengan kepadatan tulang adalah negatif (b = -0,145). Fraksi area tulang trabekula pada citra radiograf periapikal dapat digunakan sebagai prediktor kepadatan tulang pada lumbar spine.

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