Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse

2012 ◽  
Vol 112 (5) ◽  
pp. 918-925 ◽  
Author(s):  
B. R. Macias ◽  
J. M. Swift ◽  
M. I. Nilsson ◽  
H. A. Hogan ◽  
S. D. Bouse ◽  
...  
Keyword(s):  
Resistance Training ◽  
Bone Formation ◽  
Cortical Bone ◽  
Bone Growth ◽  
Formation Rate ◽  
Bone Geometry ◽  
Muscle Contractions ◽  
Hindlimb Unloading ◽  
Sprague Dawley ◽  
Cross Sectional

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days − 1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 μg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC ( P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces ( P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.

scholarly journals Sweep imaging with Fourier transform as a tool with MRI for evaluating the effect of teriparatide on cortical bone formation in an ovariectomized rat model

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yasutaka Sotozono ◽  
Kazuya Ikoma ◽  
Masamitsu Kido ◽  
Okihiro Onishi ◽  
Masataka Minami ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Bone Formation ◽  
Cortical Bone ◽  
Bone Histomorphometry ◽  
Signal To Noise Ratio ◽  
Formation Rate ◽  
Bound Water ◽  
Proton Density ◽  
Sprague Dawley ◽  
Bone Formation Rate

Abstract Background Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone quality. However, the effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating bound water of cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the consequences of the effect of TPTD on cortical bone formation using SWIFT. Methods Twelve-week-old female Sprague-Dawley rats (n = 36) were reared after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate the bone formation rate by bone histomorphometry. Measurements were compared using the Mann-Whitney U-test, and a P-value of < 0.05 was considered significant. Results PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate assessed by histomorphometry was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (P = 0.028, 1.98 ± 0.33 vs. 0.09 ± 0.05 μm3/μm2/day). Conclusions SWIFT could detect increased signals of bound water, reflecting the effect of TPTD on the cortical bone. The signal detected by SWIFT reflects a marked increase in the cortical bone formation rate.

scholarly journals Sweep Imaging with Fourier Transform as a Tool for Evaluating the Effect of Teriparatide on Cortical Bone Turnover in an Ovariectomized Rat Model

2021 ◽  
Author(s):  
Sotozono Yasutaka ◽  
Kazuya Ikoma ◽  
Masamitsu Kido ◽  
Okihiro Onishi ◽  
Masataka Minami ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Bone Formation ◽  
Bone Turnover ◽  
Cortical Bone ◽  
Bone Histomorphometry ◽  
Signal To Noise Ratio ◽  
Formation Rate ◽  
Proton Density ◽  
Sprague Dawley ◽  
Bone Formation Rate

Abstract Background: Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone turnover. However, the specific effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the effects of TPTD on cortical bone turnover using SWIFT in rats. Methods: Twelve-week-old female Sprague-Dawley rats (n=36) were reared for 12 weeks after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were extracted and evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate for the bone formation rate by bone histomorphometry . Measurements were compared using the Mann-Whitney U-test, and a P-value of <0.05 was considered significant. Results: PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (1.98±0.33 vs. 0.09±0.05 μm3/μm2/day).Conclusions: The marked increase of the bone formation rate in the cortical bone by TPTD could be measured using SWIFT. SWIFT could be an effective tool for evaluating the effects of TPTD on cortical bone turnover as images.

scholarly journals Growth Hormone and Mild Exercise in Combination Markedly Enhance Cortical Bone Formation and Strength in Old Rats*

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1899-1904 ◽  
Author(s):  
H. Oxlund ◽  
N. B. Andersen ◽  
G. Ørtoft ◽  
H. Ørskov ◽  
T. T. Andreassen
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Cortical Bone ◽  
Formation Rate ◽  
Breaking Load ◽  
Female Rats ◽  
Sectional Area ◽  
Cross Sectional ◽  
Bone Formation Rate ◽  
Factor I

Abstract The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected sc for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

Regulation of bone repletion in rats subjected to varying low-calcium stress

1984 ◽  
Vol 246 (2) ◽  
pp. R190-R196 ◽  
Author(s):  
R. H. Drivdahl ◽  
C. C. Liu ◽  
D. J. Baylink
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Bone Volume ◽  
Strong Positive Correlation ◽  
Sprague Dawley ◽  
Bone Formation Rate ◽  
Osteoblast Activity ◽  
Calcium Stress ◽  
Sprague Dawley Rats ◽  
Very High

Weanling Sprague-Dawley rats subjected to varying degrees of low-Ca dietary stress (depletion) showed graded increases in the rate of endosteal bone formation when normal dietary Ca was restored (repletion). There was a strong positive correlation between the rate of bone resorption in depletion and the rate of bone formation attained after 1 wk of repletion. However, bone formation declined rapidly within the first 4 wk of repletion, despite the persistence of a substantial endosteal bone volume deficit. Furthermore the medullary area (indicative of bone volume) did not by itself determine the bone formation rate. Bone volume in test groups was restored to control levels after 6 mo of repletion, and this result could be predicted by a kinetic analysis. Thus, although very high rates of formation in early repletion decline rapidly, smaller increments relative to controls must be sustained for long periods. Our data indicate that increased formation rats at all stages of repletion are a consequence of elevations in both osteoblast number and osteoblast activity.

The effects of loading and estrogen on rat bone growth

2010 ◽  
Vol 108 (6) ◽  
pp. 1737-1744 ◽  
Author(s):  
Olli V. Leppänen ◽  
Harri Sievänen ◽  
Jarkko Jokihaara ◽  
Ilari Pajamäki ◽  
Pekka Kannus ◽  
...  
Keyword(s):  
Bone Growth ◽  
Rat Femur ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Bone Mineral Mass ◽  
Sprague Dawley Rats ◽  
Sciatic Neurectomy ◽  
Periosteal Surface ◽  
Axial Growth ◽  
Mineral Mass

This study evaluated the contributions of locomotive loading and estrogen to the development of diaphysis of rat femur. A randomized 2 × 2 study design was used. Altogether, 70 female Sprague-Dawley rats were used, of which 10 were euthanized at entry. Of the remaining rats, 16 served as controls, and the rest, 44, underwent a unilateral sciatic neurectomy. The effect of estrogen was removed by ovariectomizing one-half of the neurectomized rats. After 27 wk, the animals were euthanized, and the femora were excised. Irrespective of loading or estrogen, the femur length and mineral mass increased by 142 and 687%, respectively. Axial growth was not modulated either by locomotive loading or estrogen, but the loading resulted in direction-specific changes in the cross-sectional geometry. The estrogen-related gains were evident on the endocortical surface, while the loading-related gains occurred on the periosteal surface. The loading and estrogen were significantly associated with increased bone strength (21 and 15%, respectively) in the mediolateral direction, but not in the anteroposterior direction. Axial growth and accrual of bone mineral mass of the rat femur are largely independent of locomotive loading or estrogen, whereas these factors specifically account for the femur function, as either a mechanical lever or a mineral reservoir for reproduction, respectively.

scholarly journals Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

2008 ◽  
Vol 205 (5) ◽  
pp. 1145-1153 ◽  
Author(s):  
Luc Malaval ◽  
Ndéyé Marième Wade-Guéye ◽  
Maya Boudiffa ◽  
Jia Fei ◽  
Ralph Zirngibl ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Growth ◽  
Formation Rate ◽  
Bone Sialoprotein ◽  
Tail Suspension ◽  
Wild Type ◽  
Hematopoietic Progenitors ◽  
Bone Formation Rate ◽  
Osteoblast Markers ◽  
Resorptive Activity

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (−/−) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP−/− mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (≥12 mo) BSP−/− mice. At 4 mo, BSP−/− mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP−/− versus WT bone marrow stromal cultures. BSP−/− hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP−/− mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN−/− mice.

scholarly journals PO-179 Prevention of sarcopenia and regulation of the ERK1/2 and p38MAPK phosphorylation by resistance training

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Hao Chen ◽  
Xiquan Weng ◽  
Wentao Lin ◽  
Sanhua Zhai
Keyword(s):  
Resistance Training ◽  
Middle Class ◽  
Cross Section ◽  
Skeletal Muscles ◽  
Pairwise Comparison ◽  
Treadmill Running ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Maximum Loading ◽  
The Difference

Objective Study of the effect of treadmill resistance training on the cross section and phosphorylation of ERK1/2 and p38MAPK of gastrocnemius of aging rats, and explore the role of resistance training in prevention and regulation of sarcopenia. Methods 11-month-old male Sprague-Dawley (SD) rats (n = 40, SPF grade, initial body weight 776.9 ± 50) were raised in various cages in a room with a room temperature of 23 ± 2°C, a humidity of 40–60%, and a natural light/dark cycle. After eight months, the treated rats were then divided into one sedentary group (control, n = 8/group) and four groups for resistance training (GRT 1-GRT 4, GRT for Group for Resistance Training, n = 8/group) lasting for 8 weeks. For resistance training, GRT1 to GRT4 carried no loading, 30% maximum loading, 50% maximum loading and 70% maximum loading, respectively. The protocol for treadmill running was as follows: 15m/min (speed), 35°C (slope), 15s each time, an interval for 30s between two runnings, four runnings as one training, an interval for 3mins between two training, three training as one cycle, two cycles one training day, and one-day break between two training days. The morphology and cross section of gastrocnemius and the phosphorylation of the ERK1/2、p38MAPK proteins in the rats were examined after 8 weeks’ training.  Results Compared with the control, GRT1-GRT4 displayed relatively better aligned muscles fibers and noticeably larger cross-sectional area (P＜0.05). The content of p-ERK1/2 (phosphorylated ERK1/2) displayed a descending trend as the loading increased compared with the control (GRT1 VS control, P＞0.05; GRT2 VS control, P＜0.05; GRT3 VS control, P＞0.05; GRT4 VS control, P＞0.05). However, the pairwise comparison revealed that only the difference between GRT1 and GRT2 was significant. Similarly, the content of p-p38MAPK (phosphorylated p38MAPK) displayed a descending trend as the loading increased compared with the control (GRT1 VS control, P＞0.05; GRT2 VS control, P＞0.05; GRT3 VS control, P＜0.01; GRT4 VS control, P＜0.01). Besides, the pairwise comparison revealed that the difference between GRT1 and GRT3 was significant (P＜0.05) and that between GRT1 and GRT4 was even highly significant (P＜0.01). Conclusions Resistance training with middle-class intensity or above can prevent sarcopenia. ERK1/2 and p38MAPK were subject to high-level phosphorylation in aging skeletal muscles, which resulted from the stress-like status of the aging body. Treadmill training of with middle-class intensity or above can reduce ERK1/2 and p38MAPK phosphorylation in aging skeletal muscles of rats, which indicates that resistance training can effectively prevent sarcopenia by inhibiting ERK1/2 and p38MAPK phosphorylation.

scholarly journals Sost deficiency leads to reduced mechanical strains at the tibia midshaft in strain-matched in vivo loading experiments in mice

2018 ◽  
Vol 15 (141) ◽  
pp. 20180012 ◽  
Author(s):  
Laia Albiol ◽  
Myriam Cilla ◽  
David Pflanz ◽  
Ina Kramer ◽  
Michaela Kneissel ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cortical Bone ◽  
Neutralizing Antibodies ◽  
Bone Geometry ◽  
Bone Adaptation ◽  
Mechanical Stimuli ◽  
Mineral Density ◽  
Littermate Control ◽  
Mechanical Environment

Sclerostin, a product of the Sost gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear. Sost knockout (KO) mice were examined to gain insight into how long-term Sost deficiency alters the local mechanical environment within the bone. This knowledge is crucial as the strain environment regulates bone adaptation. We characterized the bone geometry at the tibial midshaft of young and adult Sost KO and age-matched littermate control (LC) mice using microcomputed tomography imaging. The cortical area and the minimal and maximal moment of inertia were higher in Sost KO than in LC mice, whereas no difference was detected in either the anterior–posterior or medio-lateral bone curvature. Differences observed between age-matched genotypes were greater in adult mice. We analysed the local mechanical environment in the bone using finite-element models (FEMs), which showed that strains in the tibiae of Sost KO mice are lower than in age-matched LC mice at the diaphyseal midshaft, a region commonly used to assess cortical bone formation and resorption. Our FEMs also suggested that tissue mineral density is only a minor contributor to the strain distribution in tibial cortical bone from Sost KO mice compared to bone geometry. Furthermore, they indicated that although strain gauging experiments matched strains at the gauge site, strains along the tibial length were not comparable between age-matched Sost KO and LC mice or between young and adult animals within the same genotype.

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

1996 ◽  
Vol 270 (1) ◽  
pp. E51-E59 ◽  
Author(s):  
D. A. Martinez ◽  
M. W. Orth ◽  
K. E. Carr ◽  
R. Vanderby ◽  
A. C. Vailas
Keyword(s):  
Growth Hormone ◽  
Bone Formation ◽  
Cortical Bone ◽  
Rapid Growth ◽  
Crystal Size ◽  
Bone Growth ◽  
Recombinant Human Growth Hormone ◽  
Bone Collagen ◽  
Bone Maturation ◽  
Hydroxyapatite Crystal

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

scholarly journals Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Glucocorticoid Induced Osteoporosis by Inhibiting Osteoclastogenesis

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Lianjie Shi ◽  
Ying Ning ◽  
Liling Xu ◽  
Jianhong Li ◽  
Xuewu Zhang
Keyword(s):  
Cortical Bone ◽  
Bone Microarchitecture ◽  
Osteoclast Differentiation ◽  
Bone Geometry ◽  
Negative Control ◽  
High Dose ◽  
Micro Ct ◽  
Sprague Dawley ◽  
Blank Group ◽  
Methylene Diphosphonate

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) is an effective anti-inflammatory drug in treating rheumatoid arthritis (RA) for over 15 years in China. However, as a special form of bisphosphonate, the antiosteoporotic effect of99Tc-MDP is unclear. We systematically investigated the effects of99Tc-MDP on cancellous and cortical bone, respectively, in glucocorticoid induced osteoporosis (GIO) animal models. Forty-eight Sprague-Dawley rats were randomly divided into six groups: blank, negative control, high dose, medium dose, low dose, and positive control groups. After dexamethasone was given to all groups except the blank group to induce osteoporosis, the rats in different groups were treated with saline, MDP, or different doses of99Tc-MDP. After treatment, all rats were sacrificed, and their tibiae and femora were analyzed with microcomputed tomography (micro-CT), histology and biomechanics. Micro-CT analyses showed that (1)99Tc-MDP reversed glucocorticoid induced bone microarchitecture destruction by increasing BV/TV, Tb.Th, and Tb.N and decreasing BS/BV, Tb.Sp, and TBPf; (2) effect of99Tc-MDP increased as its dosage increased; and (3)99Tc-MDP could improve cortical bone thickness while MDP failed to do so. Micro-CT spatial structure analysis and histology also yielded consistent results, indicating that99Tc-MDP increased trabecular number and connectivity morphologically. Secondly, biomechanics revealed that99Tc-MDP can enhance the extrinsic stiffness of bone by changing bone geometry. Finally,99Tc-MDP could inhibit osteoclastogenesis in PBMCs in human. In conclusion,99Tc-MDP exerted antiosteoporotic effect by improving both cancellous and cortical bone, as well as increasing extrinsic bone stiffness which might be attributed to the its inhibition of osteoclast differentiation. The antiosteoporotic effect of99Tc-MDP may suggest a potential clinical application for patients with GIO.

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