Enhancement of the adolescent murine musculoskeletal system using low-level mechanical vibrations

Mechanical signals are recognized as anabolic to both bone and muscle, but the specific parameters that are critical to this stimulus remain unknown. Here we examined the potential of extremely low-magnitude, high-frequency mechanical stimuli to enhance the quality of the adolescent musculoskeletal system. Eight-week-old female BALB/cByJ mice were divided into three groups: baseline controls (BC, n = 8), age-matched controls (AC, n = 12), and whole body vibration (WBV, n = 12) at 45 Hz (0.3 g) for 15 min/day. Following 6 wk of WBV, bone mineralizing surfaces of trabeculae in the proximal metaphysis of the tibia were 75% greater ( P < 0.05) than AC, while osteoclast activity was not significantly different. The tibial metaphysis of WBV mice had 14% greater trabecular bone volume ( P < 0.05) than AC, while periosteal bone area, bone marrow area, cortical bone area, and the moments of inertia of this region were all significantly greater (up to 29%, P < 0.05). The soleus muscle also realized gains by WBV, with total cross-sectional area as well as type I and type II fiber area as much as 29% greater ( P < 0.05) in mice that received the vibratory mechanical stimulus. The small magnitude and brief application of the noninvasive intervention emphasize that the mechanosensitive elements of the musculoskeletal system are not necessarily dependent on strenuous, long-term activity to initiate a structurally relevant response in the adolescent musculoskeletal system. If maintained into adulthood, the beneficial structural changes in trabecular bone, cortical bone, and muscle may serve to decrease the incidence of osteoporotic fractures and sarcopenia later in life.

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Interleukin (IL)-10 Is Important in the Maintenance of Trabecular and Cortical Bone and Protects Against Western Diet-Induced Disruption in Bone Remodeling in Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab061_021 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1137-1137

Author(s):

Leo Perez ◽

Sanmi Alake ◽

Payton Price ◽

Proapa Islam ◽

John Ice ◽

...

Keyword(s):

Body Weight ◽

Trabecular Bone ◽

Bone Metabolism ◽

Cortical Bone ◽

Structural Changes ◽

Western Diet ◽

Whole Body ◽

Strain Effect ◽

Type I ◽

X Ray

Abstract Objectives The purpose of this study was to investigate if consumption of a western diet (WD) exacerbates the effects of loss of function of IL-10, an anti-inflammatory cytokine, on biomarkers of bone metabolism and microarchitecture. Methods Six-week-old male B6.129P2-Il10tm1Cgn/J (IL-10 KO) and C57BL/6 mice (WT) were randomized to treatment in a 2 × 2 factorial with diet (AIN-93 control diet CD vs WD) and strain (IL-10 KO vs WT) as factors. Due to potential influence of high fat on intestinal Ca absorption, a WD diet with added Ca (1.2 g/kg) was used. After 12 wks, whole body dual-energy x-ray absorptiometry scans were performed to assess bone density and body composition, and micro-computed x-ray tomography was used to evaluate trabecular and cortical bone microarchitecture in the femur and lumbar vertebra. Serum biomarkers of bone formation, procollagen 1 intact N-terminal propeptide (P1NP), and resorption, c-terminal telopeptide of type I collagen (CTX-1) were assessed. Results Body weight, but not % body fat, was lower (P < 0.05) in IL-10 KO mice relative to WT controls. 12 weeks of WD increased (P < 0.05) body weight and % fat, but the response was not as great in the IL-10 KO mice. Bone mineral density and content were lower in IL-10 KO mice compared to WT, and the WD had no effect on these parameters. The IL-10 KO mice exhibited a decrease in trabecular bone volume, thickness, and number, and an increase in trabecular separation and structure model index compared to WT mice within the femur and vertebrae. The WD had no effect on these trabecular bone parameters. Cortical bone thickness and area were reduced (P < 0.05) and porosity increased in both the femur and vertebra of IL-10 KO mice relative to their WT counterparts. This strain effect was not altered by the WD. IL-10 KO mice exhibited a significantly lower serum PINP and higher CTX-1 compared to the WT mice. Despite the lack of structural changes in bone after 12 wks, the WD increased (P < 0.05) CTX-1 and tended to suppress P1NP (P = 0.051) in the IL-10 KO mice compared to WT. Conclusions We conclude that IL-10 plays an important role in bone metabolism and maintaining structural properties and in the absence of IL-10, WD negatively affects both osteoclast and osteoblast activity. Further studies are warranted to determine if structural changes occur with longer exposure to WD. Funding Sources Oklahoma Agricultural Experiment Station.

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Hypergravity as a gravitational therapy mitigates the effects of knee osteoarthritis on the musculoskeletal system in a murine model

PLoS ONE ◽

10.1371/journal.pone.0243098 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243098

Author(s):

Benoit Dechaumet ◽

Damien Cleret ◽

Marie-Thérèse Linossier ◽

Arnaud Vanden-Bossche ◽

Stéphanie Chanon ◽

...

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Musculoskeletal System ◽

Tibialis Anterior ◽

Lipid Droplets ◽

Proximal Tibia ◽

Type I ◽

Negative Effects ◽

Positive Effects ◽

Resistance Exercises

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g). OA 1g displayed decreased trabecular bone in the proximal tibia metaphysis and increased osteoclastic activity and local TNFα gene expression, all entirely prevented by 2g gravitational therapy. However, while cortical bone of tibia midshaft was preserved in OA 1g (vs. ctrl), it is thinner in OA 2g (vs. OA 1g). In the hind limb, OA at 1g increased fibers with lipid droplets by 48% in the tibialis anterior, a fact fully prevented by 2g. In Ctrl, 2g increased soleus, tibialis anterior and gastrocnemius masses. In the soleus of both Ctrl and OA, 2g induced larger fibers and a switch from type-II to type-I fiber. Catabolic (myostatin and its receptor activin RIIb and visfatine) and anabolic (FNDC5) genes dramatically increased in Ctrl 2g and OA 2g (p<0.01 vs 1g). Nevertheless, the overexpression of FNDC5 (and follistatine) was smaller in OA 2g than in Ctrl 2g. Thus, hypergravity in OA mice produced positive effects for trabecular bone and muscle typology, similar to resistance exercises, but negative effects for cortical bone.

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Trends in Trabecular and Cortical Bone in the Radius Compared with Whole Body Calcium Balance in Osteoporosis

Clinical Science ◽

10.1042/cs0660109 ◽

1984 ◽

Vol 66 (1) ◽

pp. 109-112 ◽

Cited By ~ 6

Author(s):

R. Hesp ◽

A. C. Deacon ◽

Patricia Hulme ◽

J. Reeve

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Distal Radius ◽

Rate Of Change ◽

Whole Body ◽

Calcium Balance ◽

Total Absorption ◽

Balance Study ◽

Attenuation Coefficients ◽

Change Trend

1. Mean linear attenuation coefficients for trabecular bone (T) in the distal radius and total absorption coefficients (TA) in the radial mid-shafts of 22 patients with crush fracture osteoporosis were measured serially for a year by using computed tomography. After approximately 6 months, each patient was admitted to a metabolic ward for an 18-day calcium balance study. 2. The rate of change (trend) in trabecular bone (T) in the distal radius was a better predictor of calcium balance than the trend in mid-shaft cortical bone (TA). 3. The scatter in the regressions of the trends of T and TA on calcium balance could be accounted for by known methodological uncertainties.

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Results From Demineralized Bone Creep Tests Suggest That Collagen Is Responsible for the Creep Behavior of Bone

Journal of Biomechanical Engineering ◽

10.1115/1.2835112 ◽

1999 ◽

Vol 121 (2) ◽

pp. 253-258 ◽

Cited By ~ 35

Author(s):

S. M. Bowman ◽

L. J. Gibson ◽

W. C. Hayes ◽

T. A. McMahon

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Power Law ◽

Creep Behavior ◽

Damage Accumulation ◽

Activation Energies ◽

Analysis Of Covariance ◽

Type I ◽

Creep Tests ◽

Demineralized Bone

Cortical and trabecular bone have similar creep behaviors that have been described by power-law relationships, with increases in temperature resulting in faster creep damage accumulation according to the usual Arrhenius (damage rate ~ exp (−Temp.−1)) relationship. In an attempt to determine the phase (collagen or hydroxyapatite) responsible for these similar creep behaviors, we investigated the creep behavior of demineralized cortical bone, recognizing that the organic (i.e., demineralized) matrix of both cortical and trabecular bone is composed primarily of type I collagen. We prepared waisted specimens of bovine cortical bone and demineralized them according to an established protocol. Creep tests were conducted on 18 specimens at various normalized stresses σ/E0 and temperatures using a noninvasive optical technique to measure strain. Denaturation tests were also conducted to investigate the effect of temperature on the structure of demineralized bone. The creep behavior was characterized by the three classical stages of decreasing, constant, and increasing creep rates at all applied normalized stresses and temperatures. Strong (r2 > 0.79) and significant (p < 0.01) power-law relationships were found between the damage accumulation parameters (steady-state creep rate dε/dt and time-to-failure tf) and the applied normalized stress σ/E0. The creep behavior was also a function of temperature, following an Arrhenius creep relationship with an activation energy Q = 113 kJ/mole, within the range of activation energies for cortical (44 kJ/ mole) and trabecular (136 kJ/mole) bone. The denaturation behavior was characterized by axial shrinkage at temperatures greater than approximately 56°C. Lastly, an analysis of covariance (ANCOVA) of our demineralized cortical bone regressions with those found in the literature for cortical and trabecular bone indicates that all three tissues creep with the same power-law exponents. These similar creep activation energies and exponents suggest that collagen is the phase responsible for creep in bone.

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The effects of estradiol are modulated in a tissue-specific manner in mice with inducible inactivation of ERα after sexual maturation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00018.2020 ◽

2020 ◽

Vol 318 (5) ◽

pp. E646-E654

Author(s):

Claes Ohlsson ◽

Helen H. Farman ◽

Karin L. Gustafsson ◽

Jianyao Wu ◽

Petra Henning ◽

...

Keyword(s):

Trabecular Bone ◽

Cortical Bone ◽

Fat Mass ◽

Sexual Maturation ◽

Volume Fraction ◽

Mrna Levels ◽

Uterine Weight ◽

Bone Area ◽

Estrogenic Effects ◽

Thymus Weight

Mouse models with lifelong inactivation of estrogen receptor-α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other nonskeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAGG-Cre-ER and ERαflox/flox mice. Tamoxifen-induced ERα inactivation after sexual maturation substantially reduced ERα mRNA levels in cortical bone, trabecular bone, thymus, uterus, gonadal fat, and hypothalamus, in CAGG-Cre-ERαflox/flox (inducible ERαKO) compared with ERαflox/flox (control) mice. 17β-estradiol (E2) treatment increased trabecular bone volume fraction (BV/TV), cortical bone area, and uterine weight, while it reduced thymus weight and fat mass in ovariectomized control mice. The estrogenic responses were substantially reduced in inducible ERαKO mice compared with control mice on BV/TV (−67%), uterine weight (−94%), thymus weight (−70%), and gonadal fat mass (−94%). In contrast, the estrogenic response on cortical bone area was unaffected in inducible ERαKO compared with control mice. In conclusion, using an inducible ERαKO model, not confounded by lack of ERα during development, we demonstrate that ERα expression in sexually mature female mice is required for normal E2 responses in most, but not all, tissues. The finding that cortical, but not trabecular bone, responds normally to E2 treatment in inducible ERαKO mice strengthens the idea of cortical and trabecular bone being regulated by estrogen via different mechanisms.

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Hemoglobin Levels and Bone Density in Older Persons: Results from the Inchianti Study.

Blood ◽

10.1182/blood.v104.11.1630.1630 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1630-1630

Author(s):

Matteo Cesari ◽

Marco Pahor ◽

Fulvio Lauretani ◽

Brenda W.H.J. Penninx ◽

Benedetta Bartali ◽

...

Keyword(s):

Bone Density ◽

Linear Regression ◽

Bone Loss ◽

Trabecular Bone ◽

Cortical Bone ◽

Trabecular Bone Density ◽

Regression Analyses ◽

Bone Area ◽

Cortical Bone Density ◽

Relationship Of

Abstract Background: Hypoxemia has been recognized as a risk factor for bone loss. The aim of the present study is to investigate the relationship of anemia and hemoglobin levels with bone mass and density measures in a large sample of older community-dwelling persons. Methods: The present study is based on data from 950 participants enrolled in the “Invecchiare in Chianti” (Aging in the Chianti area, InCHIANTI) study. All the analyses were performed considering continuous hemoglobin levels as well as the dichotomous anemia variable (defined according to WHO criteria as hemoglobin <12 g/dL in women and <13 g/dL in men). A peripheral quantitative computerized tomography (pQCT) scan of the right calf was performed in all participants to evaluate total bone density, trabecular bone density, cortical bone density, and the ratio between cortical and total bone area. Linear regression analyses were used to assess the multivariate relationship of pQCT bone measures with anemia and hemoglobin levels after adjustment for demographics, chronic conditions, muscle strength and biological variables. Results: Participants were 75.0 (SD 6.9) years old. In our sample, 101 participants (10.6%) were anemic. In women, coefficients from adjusted linear regression analyses evaluating the association between pQCT bone measures (per SD increase) and hemoglobin levels/anemia showed significant associations of anemia with total bone density (ß=−0.335, SE=0.163; p=0.04), and cortical bone density (ß=−0.428, SE=0.160; p=0.008). Relationships with borderline significance were found for the associations of anemia with trabecular bone density and the ratio between cortical and total bone area. Significant associations were found between hemoglobin levels and trabecular bone density (ß=0.112, SE=0.049; p=0.02), total bone density (ß=0.101, SE=0.046; p=0.03), cortical bone density (ß=0.100, SE=0.046; p=0.03), and the ratio between cortical bone and total area (ß=0.092, SE=0.045; p=0.04). In men, significant associations were found for the associations of hemoglobin levels with total bone density (ß=0.076, SE=0.036; p=0.03) and cortical bone density (ß=0.095, SE= 0.41; p=0.02). A borderline significance was reported for the association between anemia and cortical bone density. Conclusion: Anemia and low hemoglobin levels are negatively and independently associated with bone mass and density. The bone loss associated with hemoglobin levels mainly occurs in the cortical bone. Women with lower hemoglobin levels demonstrate a higher bone loss than men.

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A Densitometric and Morphometric Analysis of the Skeleton in Adults with Varying Degrees of Growth Hormone Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0897 ◽

2006 ◽

Vol 91 (2) ◽

pp. 432-438 ◽

Cited By ~ 41

Author(s):

Robert D. Murray ◽

Judith E. Adams ◽

Stephen M. Shalet

Keyword(s):

Bone Mineral Density ◽

Bone Density ◽

Cortical Bone ◽

Bone Mineral ◽

Cortical Thickness ◽

Controlled Study ◽

Bone Area ◽

Mineral Density ◽

Cross Sectional ◽

Cortical Density

Context: Low bone mass is a characteristic feature of the adult GH deficiency (GHD) syndrome, but recent dual-energy x-ray absorptiometry (DXA) studies in patients with GH-receptor and GHRH-receptor gene mutations suggest that the situation is more complex. Objective: The objective was to define bone areal and volumetric densities and morphometry in hypopituitary adults. Design: The study was a cross-sectional case-controlled study performed between 1999 and 2001. Setting: The study was undertaken at an endocrine tertiary referral center. Patients: Thirty patients with GHD, 24 with GH insufficiency (GHI) [peak GH, 3–7 μg/liter (9–21 mU/liter)], and 30 age- and sex-matched controls were included for study. Main Outcome Measures: DXA and peripheral quantitative computed tomography (pQCT) derived bone density and morphometry were measured. Results: No densitometric or morphometric abnormalities were detected in GHD patients who acquired their deficiency during adult life. GHD adults of childhood-onset (CO-GHD) showed decreased bone mineral density at the lumbar spine and hip on DXA. pQCT of the radius showed that CO-GHD patients have normal trabecular bone mineral density and only a 2% decrease in cortical density. Radial bone area was reduced 14.5%, cortical thickness 20%, and cortical cross-sectional area 23%, culminating in a reduction in cortical bone of 25%. The “apparent” low DXA bone density in CO-GHD adults therefore relates primarily to reduced cortical thickness and smaller bone area. DXA and pQCT data derived from adults with GHI revealed no evidence of densitometric or morphometric abnormalities. Conclusions: 1) Adult-onset GHD patients have normal bone density and size. 2) CO-GHD adults have marginally reduced cortical density but significantly reduced cortical bone as a result of reduced cortical thickness and bone size. 3) GHI has no measurable impact on the skeleton.

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Structural Changes in Trabecular Bone, Cortical Bone and Hyaline Cartilage as Well as Disturbances in Bone Metabolism and Mineralization in an Animal Model of Secondary Osteoporosis in Clostridium perfringens Infection

Journal of Clinical Medicine ◽

10.3390/jcm11010205 ◽

2021 ◽

Vol 11 (1) ◽

pp. 205

Author(s):

Agnieszka Tomczyk-Warunek ◽

Tomasz Blicharski ◽

Siemowit Muszyński ◽

Ewa Tomaszewska ◽

Piotr Dobrowolski ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Trabecular Bone ◽

Cortical Bone ◽

Clostridium Perfringens ◽

Broiler Chickens ◽

Structural Changes ◽

Hyaline Cartilage ◽

Structural Parameters ◽

Metabolic Bone ◽

Turnover Markers

There is no information regarding whether changes in the microbiological balance of the gastrointestinal tract as a result of an infection with Clostridium perfringens influence the development of metabolic bone disorders. The experiment was carried out on male broiler chickens divided into two groups: control (n = 10) and experimental (n = 10). The experimental animals were infected with Clostridium perfringens between 17 and 20 days of age. The animals were euthanized at 42 days of age. The structural parameters of the trabecular bone, cortical bone, and hyaline cartilage as well as the mineralization of the bone were determined. The metabolism of the skeletal system was assessed by determining the levels of bone turnover markers, hormones, and minerals in the blood serum. The results confirm that the disturbed composition of the gastrointestinal microflora has an impact on the mineralization and metabolism of bone tissue, leading to the structural changes in cortical bone, trabecular bone, and hyaline cartilage. On the basis of the obtained results, it can be concluded that changes in the microenvironment of the gastrointestinal tract by infection with C. perfringens may have an impact on the earlier development of osteoporosis.

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Reciprocal Relation between Marrow Adiposity and the Amount of Bone in the Axial and Appendicular Skeleton of Young Adults

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2691 ◽

2008 ◽

Vol 93 (6) ◽

pp. 2281-2286 ◽

Cited By ~ 106

Author(s):

Natascia Di Iorgi ◽

Michael Rosol ◽

Steven D. Mittelman ◽

Vicente Gilsanz

Keyword(s):

Cortical Bone ◽

Progenitor Cell ◽

Dual Energy ◽

Reciprocal Relation ◽

Appendicular Skeleton ◽

Sectional Area ◽

Bone Area ◽

Cross Sectional ◽

X Ray ◽

Marrow Adiposity

Abstract Background: Studies in the elderly suggest a reciprocal relation between increased marrow adiposity and bone loss, supporting basic research data indicating that osteoblasts and adipocytes share a common progenitor cell. However, whether this relation represents a preferential differentiation of stromal cells from osteoblasts to adipocytes or whether a passive accumulation of fat as bone is lost and marrow space increases with aging is unknown. To address this question and avoid the confounding effect of bone loss, we examined teenagers and young adults. Methods: Using computed tomography, we obtained measurements of bone density and cross-sectional area of the lumbar vertebral bodies and cortical bone area, cross-sectional area, marrow canal area, and fat density in the marrow of the femurs in 255 sexually mature subjects (126 females, 129 males; 15–24.9 yr of age). Additionally, values for total body fat were obtained with dual-energy x-ray absorptiometry. Results: Regardless of gender, reciprocal relations were found between fat density and measures of vertebral bone density and femoral cortical bone area (r = 0.19–0.39; all P values ≤ .03). In contrast, there was no relation between marrow canal area and cortical bone area in the femurs, neither between fat density and the cross-sectional dimensions of the bones. We also found no relation between anthropometric or dual-energy x-ray absorptiometry fat values and measures for marrow fat density. Conclusions: Our results indicate an inverse relation between bone marrow adiposity and the amount of bone in the axial and appendicular skeleton and support the notion of a common progenitor cell capable of mutually exclusive differentiation into the cell lineages responsible for bone and fat formation.

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Sex Hormone-Binding Globulin as an Independent Determinant of Cortical Bone Status in Men at the Age of Peak Bone Mass

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2189 ◽

2010 ◽

Vol 95 (4) ◽

pp. 1579-1586 ◽

Cited By ~ 12

Author(s):

Griet Vanbillemont ◽

Bruno Lapauw ◽

Veerle Bogaert ◽

Stefan Goemaere ◽

Hans-Georg Zmierczak ◽

...

Keyword(s):

Bone Mass ◽

Cortical Bone ◽

Peak Bone Mass ◽

Bone Size ◽

Whole Body ◽

Sex Steroid ◽

Bone Area ◽

Mineral Density ◽

Bone Parameters ◽

Volumetric Bmd

Abstract Context: Sex steroids are important determinants of the skeletal development, growth, and maintenance after achievement of peak bone mass. A large fraction of these hormones are bound by SHBG, and previous studies have shown that SHBG could be a determinant of bone characteristics. Objective: We investigated associations of serum SHBG levels with cortical and trabecular bone characteristics in young healthy men. Design and Settings: A total of 677 healthy male siblings aged 25–45 yr were recruited in a cross-sectional, population-based study. Main Outcomes: Areal bone parameters were assessed using dual-energy x-ray absorptiometry. Cortical bone parameters at the tibia and radius and trabecular vBMD at the radius were assessed using peripheral quantitative computed tomography. Serum testosterone, estradiol, and SHBG levels were measured using immunoassays. Results: Regression models including age, height, and weight showed that SHBG levels were positively associated with bone area at the hip and the whole body, but not with areal bone mineral density (BMD). Higher SHBG levels were associated with a larger cortical bone area and periosteal and endosteal circumferences at both the tibia and the radius, whereas trabecular volumetric BMD at the radius was negatively associated with SHBG levels. Associations persisted after adjustment for (free) sex steroid levels. No associations were found with cortical volumetric BMD or cortical thickness. Conclusion: In this population of healthy adult men at the age of peak bone mass, SHBG levels were positively associated with cortical bone size, independently from sex-steroid levels. This suggests a possible independent role of SHBG in the determination of adult bone size.

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