Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

Background.Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity.Methods.Female rats (25 days old) were assigned to a control (C) group (n= 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n= 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n= 15) and (G-R) (n= 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n= 15) and (G-OVX) (n= 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed.Results.GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the GnRH-a group compared to C, a similar deficit in BV/TV was also measured following recovery and post-OVX. The trabecular number and thickness were lower in the GnRH-a group compared to control.Conclusion.These data suggest that following a transient delay in pubertal onset, trabecular bone volume was significantly lower and no restoration of bone volume occurred following recovery or post-OVX surgery. However, cortical bone strength was maintained through architectural adaptations in the cortical bone envelope. An increase in the polar moment of inertia offset increased bone resorption. The current data are the first to suppress trabecular bone during growth, and then add an OVX protocol at maturity. Trabecular bone and cortical bone differed in their response to hypothalamic suppression during development; trabecular bone was more sensitive to the negative effects of hypothalamic suppression.

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

Journal of Endocrinology ◽

10.1530/joe-18-0153 ◽

2018 ◽

Vol 238 (1) ◽

pp. 13-23 ◽

Cited By ~ 12

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.

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A Comparison of Micro-CT and Dental CT in Assessing Cortical Bone Morphology and Trabecular Bone Microarchitecture

PLoS ONE ◽

10.1371/journal.pone.0107545 ◽

2014 ◽

Vol 9 (9) ◽

pp. e107545 ◽

Cited By ~ 19

Author(s):

Jui-Ting Hsu ◽

Ying-Ju Chen ◽

Jung-Ting Ho ◽

Heng-Li Huang ◽

Shun-Ping Wang ◽

...

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Bone Microarchitecture ◽

Micro Ct ◽

Bone Morphology ◽

Trabecular Bone Microarchitecture ◽

Dental Ct

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Bone microarchitecture and estimated bone strength in men with active acromegaly

Acta Endocrinologica ◽

10.1530/eje-17-0468 ◽

2017 ◽

Vol 177 (5) ◽

pp. 409-420 ◽

Cited By ~ 12

Author(s):

Paula P B Silva ◽

Fatemeh G Amlashi ◽

Elaine W Yu ◽

Karen J Pulaski-Liebert ◽

Anu V Gerweck ◽

...

Keyword(s):

Bone Density ◽

Trabecular Bone ◽

Cortical Bone ◽

Bone Strength ◽

Bone Microarchitecture ◽

Healthy Controls ◽

Trabecular Bone Density ◽

Trabecular Bone Microarchitecture ◽

Skeletal Site ◽

Active Acromegaly

Context Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). Objective To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. Design and subjects Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). Outcome measures Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. Results aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area (P < 0.0001), cortical thickness (P = 0.0038), cortical pore volume (P < 0.0001) and cortical porosity (P = 0.0008), but lower trabecular bone density (P = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density (P = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. Conclusions Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly.

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The assessment of trabecular bone parameters and cortical bone strength: A comparison of micro-CT and dental cone-beam CT

Journal of Biomechanics ◽

10.1016/j.jbiomech.2013.08.004 ◽

2013 ◽

Vol 46 (15) ◽

pp. 2611-2618 ◽

Cited By ~ 28

Author(s):

Jui-Ting Hsu ◽

Shun-Ping Wang ◽

Heng-Li Huang ◽

Ying-Ju Chen ◽

Jay Wu ◽

...

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Bone Strength ◽

Cone Beam Ct ◽

Cone Beam ◽

Micro Ct ◽

Bone Parameters

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A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover

Journal of Biomechanics ◽

10.1016/j.jbiomech.2007.05.013 ◽

2007 ◽

Vol 40 (15) ◽

pp. 3424-3431 ◽

Cited By ~ 18

Author(s):

Senthil K. Eswaran ◽

Matthew R. Allen ◽

David B. Burr ◽

Tony M. Keaveny

Keyword(s):

Bone Turnover ◽

Trabecular Bone ◽

Bone Strength ◽

Volume Fraction ◽

Bone Volume ◽

Trabecular Bone Volume ◽

Bone Volume Fraction ◽

Independent Contribution

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The Effect of the Supplementation of a Diet Low in Calcium and Phosphorus with Either Sheep Milk or Cow Milk on the Physical and Mechanical Characteristics of Bone using A Rat Model

Foods ◽

10.3390/foods9081070 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1070

Author(s):

Keegan Burrow ◽

Wayne Young ◽

Niels Hammer ◽

Sarah Safavi ◽

Mario Scholze ◽

...

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Rat Model ◽

Inductively Coupled Plasma ◽

Volume Ratio ◽

Bone Volume ◽

Cow Milk ◽

Bone Surface ◽

Sheep Milk ◽

Calcium And Phosphorus

This study assessed the effect of cow milk (CM) and sheep milk (SM) consumption on the micro-structure, mechanical function, and mineral composition of rat femora in a male weanling rat model. Male weanling rats were fed a basal diet with a 50% reduction in calcium and phosphorus content (low Ca/P-diet) supplemented with either SM or CM. Rats were fed for 28 days, after which the femora were harvested and stored. The femora were analyzed by μ-CT, three-point bending, and inductively coupled plasma–mass spectrometry (ICP-MS). The addition of either milk to the low Ca/P-diet significantly increased (p < 0.05) trabecular bone volume, trabecular bone surface density, trabecular number, cortical bone volume, and maximum force, when compared to rats that consumed only the low Ca/P-diet. The consumption of either milk resulted in a significant decrease (p < 0.05) in trabecular pattern factor, and cortical bone surface to volume ratio when compared to rats that consumed only the low Ca/P-diet. The results were achieved with a lower consumption of SM compared to that of CM (p < 0.05). This work indicates that SM and CM can help overcome the effects on bone of a restriction in calcium and phosphorus intake.

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The Effects of Cortical Bone Thickness and Trabecular Bone Strength on Noninvasive Measures of the Implant Primary Stability Using Synthetic Bone Models

Clinical Implant Dentistry and Related Research ◽

10.1111/j.1708-8208.2011.00349.x ◽

2011 ◽

Vol 15 (2) ◽

pp. 251-261 ◽

Cited By ~ 33

Author(s):

Jui-Ting Hsu ◽

Lih-Jyh Fuh ◽

Ming-Gene Tu ◽

Yu-Fen Li ◽

Kuan-Ting Chen ◽

...

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Bone Strength ◽

Primary Stability ◽

Bone Thickness ◽

Synthetic Bone ◽

Cortical Bone Thickness

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Mechanical Loading-Related Bone Gain Is Enhanced by Tamoxifen but Unaffected by Fulvestrant in Female Mice

Endocrinology ◽

10.1210/en.2010-0645 ◽

2010 ◽

Vol 151 (12) ◽

pp. 5582-5590 ◽

Cited By ~ 33

Author(s):

Toshihiro Sugiyama ◽

Gabriel L. Galea ◽

Lance E. Lanyon ◽

Joanna S. Price

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Mechanical Loading ◽

Bone Volume ◽

Trabecular Bone Volume ◽

Trabecular Thickness ◽

Female Mice ◽

Short Period ◽

Bone Gain ◽

The Right

Accumulating evidence indicates that estrogen receptors (ERs) are involved in the mechano-adaptive mechanisms by which loading influences the mass and architecture of bones to establish and maintain their structural load-bearing competence. In the present study, we assessed the effects of the ER modulators tamoxifen and fulvestrant (ICI 182,780) on loading-related changes in the volume and structure of trabecular and cortical bone in the tibiae of female mice. Ten days after actual or sham ovariectomy, 17-wk-old female C57BL/6 mice were treated with vehicle (peanut oil), tamoxifen (0.02, 0.2, or 2 mg/kg · d), fulvestrant (4 mg/kg · d), or their combination and the right tibiae subjected to a short period of noninvasive axial loading (40 cycles/d) on 5 d during the subsequent 2 wk. In the left control tibiae, ovariectomy, tamoxifen, or fulvestrant did not have any significant effect on cortical bone volume, whereas trabecular bone volume was decreased by ovariectomy, increased by tamoxifen, and unaffected by fulvestrant. In the right tibiae, loading was associated with increases in both trabecular and cortical bone volume. Notably, the medium dose of tamoxifen synergistically enhanced loading-related gain in trabecular bone volume through an increase in trabecular thickness. Fulvestrant had no influence on the effects of loading but abrogated the enhancement of loading-related bone gain by tamoxifen. These data demonstrate that, at least in female mice, the adaptive response to mechanical loading of trabecular bone can be enhanced by ER modulators, in this case by tamoxifen.

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The use of high-resolution computed tomography to explore age-related trabecular change in human ribs

10.1101/2021.07.12.452053 ◽

2021 ◽

Author(s):

Sophia Mavroudas ◽

Victoria M Dominguez

Keyword(s):

Computed Tomography ◽

High Resolution ◽

Trabecular Bone ◽

Cortical Bone ◽

Volume Fraction ◽

Bone Volume ◽

3D Analysis ◽

High Resolution Computed Tomography ◽

Trabecular Thickness ◽

Age Related

High-resolution computed tomography was used to explore age-related trabecular change in male human ribs ranging in age from 20–95 years (Mean=55 years, SD=21.634 years) from the Texas State Donated Skeletal Collection (TXSTDSC). Two regions of interest (ROIs), midshaft (50%) and anterior (75%) were extracted from each scan to analyze age-related trabecular change. Dragonfly V4.1 was used to isolate cortical bone volumes of interest (VOIs) and three trabecular VOIs for each ROI; one each along the cutaneous cortex, the center of the medullary cavity, and the pleural cortex. Each trabecular VOI was analyzed for bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular spacing (TbSp), connectivity density (Conn.D), and degree of anisotropy (DA), within and between the 50 and 75% ROIs. Overall, the cutaneous VOIs at both the 50% and 75% ROIs exhibited greater BV/TV, TbTh, and Conn.D when compared to the center and pleural VOIs. All results are consistent with expected biomechanical strain on human ribs. Both trabecular variables and cortical bone volume are only weakly associated with age. These results show that 3D analysis of trabecular bone volume does not improve visualization or understanding of trabecular bone changes with age over traditional 2D methods. Future research should incorporate female samples to explore sex-related trabecular change variation.

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