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 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 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 Serum sclerostin levels in men with idiopathic osteoporosis

2013 ◽  
Vol 168 (4) ◽  
pp. 615-620 ◽  
Author(s):  
B Lapauw ◽  
S Vandewalle ◽  
Y Taes ◽  
S Goemaere ◽  
H Zmierczak ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Mineral ◽  
Quantitative Computed Tomography ◽  
Whole Body ◽  
Control Group ◽  
Volumetric Bone Mineral Density ◽  
Low Bone Mass ◽  
Mineral Density ◽  
Bone Parameters ◽  
Idiopathic Osteoporosis

ObjectiveSclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass, this might be reflected in higher serum sclerostin levels.MethodsIn 116 men with idiopathic osteoporosis (≤65 years old), 40 of their sons and healthy controls, areal bone parameters were measured using dual-energy X-ray absorptiometry, and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays and estradiol (E2) levels using liquid chromatography–tandem mass spectrometry.ResultsMen with idiopathic low bone mass had lower levels of sclerostin than the controls (0.54±0.17 vs 0.66±0.23 ng/ml;P<0.001). In both groups, sclerostin levels were strongly associated with age; when adjusting for age, no associations with anthropometrics were observed (P>0.14). In multivariate analyses, sclerostin levels displayed a positive association with whole-body bone mineral content (BMC) and areal BMD (aBMD), as well as with trabecular and cortical volumetric bone mineral density (vBMD) at the tibia in the probands. No clear associations were observed in the control group, neither were sclerostin levels associated with BMC at the radius or lumbar spine (allP>0.11). Testosterone, but not E2, was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons when compared with their controls.ConclusionLower rather than higher serum sclerostin levels in the probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects.

scholarly journals Fat Mass Exerts a Greater Effect on Cortical Bone Mass in Girls than Boys

2010 ◽  
Vol 95 (2) ◽  
pp. 699-706 ◽  
Author(s):  
Adrian Sayers ◽  
Jonathan H. Tobias
Keyword(s):  
Bone Mineral Density ◽  
Bone Mass ◽  
Cortical Bone ◽  
Bone Mineral ◽  
Fat Mass ◽  
Quantitative Computed Tomography ◽  
Positive Association ◽  
Mineral Density ◽  
Cortical Bone Mineral Density ◽  
Cortical Bone Mass

Abstract Context: It is unclear whether fat mass (FM) and lean mass (LM) differ in the way they influence cortical bone development in boys and girls. Objective: The aim of the study was to investigate the contributions of total body FM and LM to parameters related to cortical bone mass and geometry. Design/Setting: We conducted a longitudinal birth cohort study, the Avon Longitudinal Study of Parents and Children. Participants: A total of 4005 boys and girls (mean age, 15.5 yr) participated in the study. Outcome Measures: We measured cortical bone mass, cortical bone mineral content (BMCC), cortical bone mineral density, periosteal circumference (PC), and endosteal circumference by tibial peripheral quantitative computed tomography. Results: LM had a similar positive association with BMCC in boys and girls [regression coefficients with 95% confidence interval (CI); P for gender interactions: boys/girls, 0.952 (0.908, 0.997); P = 0.85]. However, the mechanisms by which LM influenced bone mass differed according to gender because LM was positively associated with PC more strongly in girls [boys, 0.579 (0.522, 0.635); girls, 0.799 (0.722, 0.875); P &lt; 0.0001], but was only associated with cortical bone mineral density in boys [boys, 0.443 (0.382, 0.505); girls, 0.014 (−0.070, 0.097); P &lt; 0.0001]. There was a stronger positive association between FM and BMCC in girls [boys, 0.227 (0.185, 0.269); girls, 0.355 (0.319, 0.392); P &lt; 0.0001]. This reflected both a greater positive association of FM with PC in girls [boys, 0.213 (0.174, 0.253); girls, 0.312 (0.278, 0.347); P = 0.0002], and a stronger negative association with endosteal circumferencePC [boys, −0.059 (−0.096, 0.021); girls, −0.181 (−0.215, −0.146); P &lt; 0.0001]. Conclusions: Whereas LM stimulates the accrual of cortical bone mass to a similar extent in boys and girls, FM is a stronger stimulus for accrual of cortical bone mass in girls, reflecting a greater tendency in females for FM to stimulate periosteal growth and suppress endosteal expansion.

scholarly journals Three-Dimensional Characterization of Trabecular Bone Mineral Density of the Distal Radius Utilizing Quantitative Computed Tomography

Hand ◽  
2018 ◽  
Vol 15 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Tyler S. Pidgeon ◽  
Katia A. DaSilva ◽  
Joseph J. Crisco ◽  
Eric C. Johnson ◽  
Alison B. Chambers ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Mineral Density ◽  
Trabecular Bone ◽  
Distal Radius ◽  
Bone Mineral ◽  
Quantitative Computed Tomography ◽  
Three Dimensional ◽  
Mineral Density ◽  
Quantitative Ct ◽  
Trabecular Bone Mineral Density

Background: Distal radius (DR) fractures demonstrate patterns of predictable fragments. Bone mineral density (BMD) measurements of these regions of interest (ROIs) may guide more precise treatment. Methods: Computed tomography (CT) scans of the DR of 42 healthy volunteers (23 female) were analyzed using quantitative CT software, measuring BMD within trabecular bone. Seven ROIs were described by alignment with the distal (volar ulnar distal [VUD], dorsal ulnar distal [DUD], volar radial distal [VRD], and dorsal radial distal [DRD]) or proximal (middle ulnar proximal [MUP], middle proximal [MP], and middle radial proximal [MRP]) sigmoid notch. Additional ROIs were the radial styloid (RS) and metadiaphysis (MD). A general estimation equation assessed subject’s BMDs with predictive factors of gender, ROI, and age. The interaction between gender, ROI, and age was included in the model to allow for differences in ROI to vary with gender and/or age. Results: Comparing ROIs within the same gender and, separately, within the same age group revealed significantly higher BMD adjacent to the radioulnar and radiocarpal joints. Male and female individuals aged ≥50 years (mean: 172.7 mg/cm3 ± 6.1) had significantly lower BMD than those aged <50 years (mean: 202.7 mg/cm3 ± 5.8) when all ROIs were considered. Males had higher mean BMD at each ROI compared with females; these differences were significant in 5 of the 9 ROIs: VUD, DUD, DRD, RS, MUP. Conclusions: Trabecular BMD of the DR is highest adjacent to the radioulnar and radiocarpal joints. Female patients and those ≥50 years have lower trabecular BMD.

scholarly journals Astragalus Extract Mixture HT042 Improves Bone Growth, Mass, and Microarchitecture in Prepubertal Female Rats: A Microcomputed Tomographic Study

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Jungbin Song ◽  
Sung Hyun Lee ◽  
Donghun Lee ◽  
Hocheol Kim
Keyword(s):  
Bone Mass ◽  
Cortical Bone ◽  
Bone Growth ◽  
Volume Fraction ◽  
Control Diet ◽  
Female Rats ◽  
Volumetric Bone Mineral Density ◽  
Mineral Density ◽  
Longitudinal Bone Growth ◽  
Tibial Length

Astragalus extract mixture HT042 is a standardized multiherbal mixture comprising Astragalus membranaceus, Eleutherococcus senticosus, and Phlomis umbrosa, which has proven to promote children’s height growth. The aim of this study was to investigate the effects of HT042 on longitudinal bone growth, bone mass, and bone microstructure in growing rats using a high-resolution microcomputed tomography system. Four-week-old female rats were fed an HT042-containing diet for 2 weeks. Tibial length was measured at baseline and weekly in vivo. At the end of the study, volumetric bone mineral density (vBMD) and microarchitectural parameters were estimated in the trabecular and cortical bone of the tibia. Tibial length gain was significantly increased by HT042 compared to that reported with the control diet. In the proximal tibial metaphysis, HT042-treated rats had significantly higher trabecular vBMD, bone volume fraction, and trabecular number and lower trabecular separation, trabecular pattern factor, and structure model index values than control rats did. Total cross-sectional area and bone area of the cortical bone in the tibial diaphysis also increased. These findings suggest that HT042 increases longitudinal bone growth rate, improves trabecular bone mass, and enhances the microarchitecture of trabecular and cortical bone during growth.

Quantitative computed tomography in measurement of vertebral trabecular bone mass

1988 ◽  
Vol 29 (6) ◽  
pp. 719-725 ◽  
Author(s):  
M. Nilsson ◽  
O. Johnell ◽  
K. Jonsson ◽  
I. Redlund-Johnell
Keyword(s):  
Computed Tomography ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Quantitative Computed Tomography ◽  
Vertebral Trabecular Bone ◽  
Trabecular Bone Mass

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.

Ischemic heart disease is associated with lower cortical volumetric bone mineral density of distal radius

2015 ◽  
Vol 26 (7) ◽  
pp. 1893-1901 ◽  
Author(s):  
J. Paccou ◽  
M. H. Edwards ◽  
K. A. Ward ◽  
K. A. Jameson ◽  
C. L. Moss ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Distal Radius ◽  
Bone Mineral ◽  
Ischemic Heart ◽  
Volumetric Bone Mineral Density ◽  
Mineral Density
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