Lack of effect of spaceflight on bone mass and bone formation in group-housed rats

1998 ◽  
Vol 85 (1) ◽  
pp. 279-285 ◽  
Author(s):  
T. J. Wronski ◽  
M. Li ◽  
Y. Shen ◽  
S. C. Miller ◽  
B. M. Bowman ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Cancellous Bone ◽  
Space Shuttle ◽  
Formation Rate ◽  
Lumbar Vertebrae ◽  
Sprague Dawley ◽  
Bone Formation Rate ◽  
Bone Changes ◽  
Space Shuttle Columbia

As part of an experiment to study the role of corticosteroids in bone changes during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs) aboard the space shuttle Columbia (STS-78). Control rats were group housed in a similar manner in ground-based AEMs or standard vivarium cages. Adrenal hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed a lack of significant changes in bone mass and bone formation in these animals. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were nearly the same in flight and ground-based rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation rate was found to be identical in flight and ground-based rats. The results indicate that, under conditions of group housing in AEMs, spaceflight has minimal effects on bone mass and bone formation in rapidly growing rats. These findings emphasize the need to investigate the importance of rat age, strain, and especially housing conditions for studies of the skeletal effects of spaceflight.

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.

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 Increased Marrow Adiposity in Premenopausal Women with Idiopathic Osteoporosis

2012 ◽  
Vol 97 (8) ◽  
pp. 2782-2791 ◽  
Author(s):  
Adi Cohen ◽  
David W. Dempster ◽  
Emily M. Stein ◽  
Thomas L. Nickolas ◽  
Hua Zhou ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Formation Rate ◽  
Premenopausal Women ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Marrow Fat ◽  
Bone Formation Rate ◽  
Idiopathic Osteoporosis ◽  
Marrow Adiposity

Abstract Context: We have previously reported that premenopausal women with idiopathic osteoporosis based on fractures (IOP) or idiopathic low bone mineral density (ILBMD) exhibit markedly reduced bone mass, profoundly abnormal trabecular microstructure, and significant deficits in trabecular bone stiffness. Bone remodeling was heterogeneous. Those with low bone turnover had evidence of osteoblast dysfunction and the most marked deficits in microstructure and stiffness. Objective: Because osteoblasts and marrow adipocytes derive from a common mesenchymal precursor and excess marrow fat has been implicated in the pathogenesis of bone fragility in anorexia nervosa, glucocorticoid excess, and thiazolidinedione exposure, we hypothesized that marrow adiposity would be higher in affected women and inversely related to bone mass, microarchitecture, bone formation rate, and osteoblast number. Design: We analyzed tetracycline-labeled transiliac biopsy specimens in 64 premenopausal women with IOP or ILBMD and 40 controls by three-dimensional micro-computed tomography and two-dimensional quantitative histomorphometry to assess marrow adipocyte number, perimeter, and area. Results: IOP and ILBMD subjects did not differ with regard to any adipocyte parameter, and thus results were combined. Subjects had substantially higher adipocyte number (by 22%), size (by 24%), and volume (by 26%) than controls (P &lt; 0.0001 for all). Results remained significant after adjusting for age, body mass index, and bone volume. Controls demonstrated expected direct associations between marrow adiposity and age and inverse relationships between marrow adiposity and bone formation, volume, and microstructure measures. No such relationships were observed in the subjects. Conclusions: Higher marrow adiposity and the absence of expected relationships between marrow adiposity and bone microstructure and remodeling in women with IOP or ILBMD suggest that the relationships between fat and bone are abnormal; excess marrow fat may not arise from a switch from the osteoblast to the adipocyte lineage in this disorder. Whether excess marrow fat contributes to the pathogenesis of this disorder remains unclear.

scholarly journals DSS-induced colitis produces inflammation-induced bone loss while irisin treatment mitigates the inflammatory state in both gut and bone

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Corinne E. Metzger ◽  
S. Anand Narayanan ◽  
Jon P. Elizondo ◽  
Anne Michal Carter ◽  
David C. Zawieja ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Therapeutic Potential ◽  
Negative Impact ◽  
Formation Rate ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Gut Inflammation

Abstract Chronic pediatric inflammatory bowel disease (IBD) leads to lack of bone accrual, bone loss, and increased fractures. Presently there is no cure, and many IBD treatments incur negative side effects. We previously discovered treatment with exogenous irisin resolved inflammatory changes in the colon, gut lymphatics, and bone in a mild IBD rodent model. Here we assess irisin treatment in severe IBD induced via dextran sodium sulfate (DSS). Male Sprague Dawley rats (2-mo-old) were untreated (Con) or given 2% DSS in drinking water. In week two, half of each group (Con + Ir and DSS + Ir) received injections of recombinant irisin (i.p., 2x/wk). After 4 weeks, gut inflammation was associated with declines in bone mineral density and cancellous bone volume. Furthermore, elevated osteocyte TNF-α, interleukin-6, RANKL, OPG, and sclerostin corresponded with higher osteoclast surfaces and lower bone formation rate in DSS animals as well as lower ultimate load. While irisin treatment improved colon inflammation, there were no improvements in bone density or bone mechanical properties; however, irisin elevated bone formation rate, decreased osteoclast surfaces, and reduced osteocyte pro-inflammatory factors. These data highlight the negative impact of chronic gut inflammation on bone as well as the therapeutic potential of irisin as an anti-inflammatory treatment.

Histomorphometric analysis of rat skeleton following spaceflight

1987 ◽  
Vol 252 (2) ◽  
pp. R252-R255 ◽  
Author(s):  
T. J. Wronski ◽  
E. R. Morey-Holton ◽  
S. B. Doty ◽  
A. C. Maese ◽  
C. C. Walsh
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Proximal Tibia ◽  
Space Shuttle ◽  
Lumbar Vertebrae ◽  
Lumbar Vertebra ◽  
Histomorphometric Analysis ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Trabecular Bone Mass

Male Sprague-Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared with data derived from ground-based control rats. Trabecular bone mass was not altered during the 1st wk of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. For the most part, histological indexes of bone resorption were normal in flight rats. The results indicate that 7 days of weightlessness are not of sufficient duration to induce histologically detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the 1st wk of spaceflight.

scholarly journals Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

2014 ◽  
Vol 222 (2) ◽  
pp. 277-288 ◽  
Author(s):  
Corine Martineau ◽  
Louise Martin-Falstrault ◽  
Louise Brissette ◽  
Robert Moreau
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Metabolism ◽  
Plasma Levels ◽  
Formation Rate ◽  
Estrogen Metabolism ◽  
Type I ◽  
Bone Formation Rate ◽  
Hdl Metabolism ◽  
Gender Specific

A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product ofScarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism inScarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations inScarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-oldScarb1-null females. No such alteration was seen in males, indicating gender- and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in bothScarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in femaleScarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in femaleScarb1-null mice only.In vitroexposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression ofosterixandcollagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of femaleScarb1-null mice.

β-Blocker and Other Analogous Treatments that Affect Bone Mass and Sympathetic Nerve Activity in Ovariectomized Rats

2007 ◽  
Vol 35 (01) ◽  
pp. 89-101 ◽  
Author(s):  
Wenping Zhang ◽  
Masayuki Kanehara ◽  
Yanjun Zhang ◽  
Xiaoming Wang ◽  
Torao Ishida
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Formation Rate ◽  
Chinese Herbs ◽  
Ovariectomized Rats ◽  
Mineral Apposition Rate ◽  
Control Group ◽  
Bone Formation Rate ◽  
Ovx Rats ◽  
Bone Formation Markers

We investigated whether treatments with beta-blockers or other administrations that have similar actions to β-blockers, such as Chinese herbs or needling, were effective in treating osteoporosis induced by ovariectomy (OVX). Female Wister rats were divided into five groups: a sham-operated control group treated with vehicle (Sham, n = 8), an ovariectomized (OVX) group treated with vehicle (Model, n = 8), an OVX group administered with propranolol (Pro, n = 10), an OVX group administered an ethanol extract of Fructus Citri Sarcodactylis (Fcs, n = 9), and an OVX punctured at Sanyinjiao (SP-6) and Neiguan (PC-6) (Needling, n = 8). The treatment started when rats were 12 weeks old and continued for 24 weeks. Serum osteocalcin and urinary deoxypyridinoline (Dpd) levels were upregulated in rats in response to OVX, together with a significantly decreased BMD and trabecular bone area. The Pro, Fcs and Needling treatment improved the decreased BMD and the trabecular area, increased the trabecular number, lowered the trabecular separation to some extent as well as significantly depressed the urinary Dpd levels ( p < 0.05). The bone formation markers, such as the mineralizing surface, mineral apposition rate and bone formation rate were not significantly changed, along with a slightly higher trend of osteocalcin levels when compared with the Model rats. The slower heart rate and lower plasma NE levels in these therapeutic groups were also found. Our results suggested that propranolol, Fcs and needling on Sanyinjiao (SP-6) and Neiguan (PC-6) may improve the bone mass of OVX rats, and it provides an alternative and potential therapy for the prevention of postmenopausal osteoporosis.

Effects of disrupted β1-integrin function on the skeletal response to short-term hindlimb unloading in mice

2005 ◽  
Vol 98 (2) ◽  
pp. 690-696 ◽  
Author(s):  
U. T. Iwaniec ◽  
T. J. Wronski ◽  
D. Amblard ◽  
Y. Nishimura ◽  
M. C. H. van der Meulen ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cancellous Bone ◽  
Formation Rate ◽  
Dominant Negative ◽  
Hindlimb Unloading ◽  
Femoral Diaphysis ◽  
Short Term ◽  
Bone Formation Rate ◽  
Mechanical Unloading ◽  
Lumbar Vertebral Body

The study was designed to determine whether β1-integrin plays a role in mediating the acute skeletal response to mechanical unloading. Transgenic (TG) mice were generated to express a dominant negative form of β1-integrin under the control of the osteocalcin promoter, which targets expression of the transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice were subjected to hindlimb unloading by tail suspension for 1 wk. Pair-fed, normally loaded WT and TG mice served as age-matched controls. Bone samples from each mouse were processed for quantitative bone histomorphometry and biomechanical testing. The skeletal phenotype of TG mice was characterized by lower cancellous bone mass in the distal femoral metaphysis (−52%) and lumbar vertebral body (−20%), reduced curvature of the proximal tibia (−20%), and decreased bone strength (−20%) and stiffness (−23%) of the femoral diaphysis with relatively normal indexes of cancellous bone turnover. Hindlimb unloading for only 1 wk induced a 10% decline in tibial curvature and a 30% loss of cancellous bone in the distal femur due to a combination of increased bone resorption and decreased bone formation in both WT and TG mice. However, the strength and stiffness of the femoral diaphysis were unaffected by short-term hindlimb unloading in both genotypes. The observed increase in osteoclast surface was greater in unloaded TG mice (92%) than in unloaded WT mice (52%). Cancellous bone formation rate was decreased in unloaded WT (−29%) and TG (−15%) mice, but, in contrast to osteoclast surface, the genotype by loading interaction was not statistically significant. The results indicate that altered integrin function in mature osteoblasts may enhance the osteoclastic response to mechanical unloading but that it does not have a major effect on the development of cancellous osteopenia in mice during the early stages of hindlimb unloading.

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