Inhibition of sclerostin by treatment with anti-sclerostin antibody increased cancellous bone formation and decreased bone resorption in both high and low turnover bone sites in female rats

Bone ◽  
2008 ◽  
Vol 43 ◽  
pp. S29-S30 ◽  
Author(s):  
X.Y. Tian ◽  
W.S.S. Jee ◽  
R.B. Setterberg ◽  
M. Chen ◽  
X. Li ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Female Rats ◽  
Sclerostin Antibody

Prolonged intermittent but not continuous administration of oestradiol-17β increases bone volume in the rat

1993 ◽  
Vol 139 (2) ◽  
pp. 267-NP ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Volume ◽  
Female Rats ◽  
Continuous Treatment ◽  
Prolonged Treatment ◽  
Continuous Administration ◽  
Anabolic Action ◽  
Important Stimulus

ABSTRACT We have previously found that administration of oestradiol-17β (OE2) to intact adult female rats of 19 days stimulates cancellous bone formation. However, this effect is not observed following longer periods of OE2 treatment, suggesting that the responsiveness of the skeleton to oestrogen's anabolic action is reduced after prolonged administration. A possible explanation for this is that oestrogen also suppresses bone resorption, which is an important stimulus for bone formation. We therefore investigated the effect of omitting OE2 for short periods, on the proximal tibial metaphysis of intact female rats. We found that, unlike continuous treatment with OE2 (40 pg/kg) for 56 days, omission of OE2 for 4 days out of every 20 was associated with a significant increase in cancellous bone volume. Although continuous and intermittent OE2 were both associated with a reduction in osteoclast surface, a decrease in the proportion of double fluorochrome-labelled surface was only seen after continuous OE2 treatment. We then studied the effects of longer periods of OE2 omission by giving OE2 (40 pg/kg) for three repeated cycles of: (1) OE2 for 16 days/vehicle for 4 days, (2) OE2 for 12 days/vehicle for 8 days, (3) OE2 for 8 days/vehicle for 12 days, or (4) OE2 for 4 days/vehicle for 16 days. We found a significant increase in cancellous bone volume when OE2 was stopped for either 4 or 8 days at a time. However, longer periods of OE2 omission did not affect bone volume, possibly because these were associated with an increase in bone resorption and/or a reduction in bone formation during the OE2-free period. In conclusion, we observed an increase in cancellous bone volume after prolonged treatment with oestrogen only if OE2 was omitted for short periods. This may be due, at least in part, to bone formation being maintained at a higher rate by such treatment than by either continuous OE2 administration or by intermittent administration where OE2 is discontinued for longer periods. Journal of Endocrinology (1993) 139, 267–273

Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats

Bone ◽  
2010 ◽  
Vol 47 (3) ◽  
pp. 529-533 ◽  
Author(s):  
XiaoYan Tian ◽  
Rebecca B. Setterberg ◽  
Xiaodong Li ◽  
Chris Paszty ◽  
Hua Zhu Ke ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Cancellous Bone ◽  
Adult Female ◽  
Female Rats ◽  
Sclerostin Antibody

scholarly journals Negligible Effect of Estrogen Deficiency on Development of Skeletal Changes Induced by Type 1 Diabetes in Experimental Rat Models

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Aleksandra Janas ◽  
Ewa Kruczek ◽  
Piotr Londzin ◽  
Sławomir Borymski ◽  
Zenon P. Czuba ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Resorption ◽  
Bone Mass ◽  
Cancellous Bone ◽  
Maximum Load ◽  
Estrogen Deficiency ◽  
Female Rats ◽  
Skeletal System ◽  
Tibial Metaphysis ◽  
Ovx Rats

Although postmenopausal osteoporosis often occurs concurrently with diabetes, little is known about interactions between estrogen deficiency and hyperglycemia in the skeletal system. In the present study, the effects of estrogen deficiency on the development of biochemical, microstructural, and mechanical changes induced by streptozotocin-induced diabetes mellitus (DM) in the rat skeletal system were investigated. The experiments were carried out on nonovariectomized (NOVX) and ovariectomized (OVX) control and diabetic mature female Wistar rats. Serum levels of bone turnover markers (CTX-I and osteocalcin) and 23 cytokines, bone mass and mineralization, histomorphometric parameters, and mechanical properties of cancellous and compact bone were determined. The results were subjected to two-way ANOVA and principal component analysis (PCA). Estrogen deficiency induced osteoporotic changes, with increased bone resorption and formation, and worsening of microstructure (femoral metaphyseal BV/TV decreased by 13.0%) and mechanical properties of cancellous bone (the maximum load in the proximal tibial metaphysis decreased by 34.2%). DM in both the NOVX and OVX rats decreased bone mass, increased bone resorption and decreased bone formation, and worsened cancellous bone microarchitecture (for example, the femoral metaphyseal BV/TV decreased by 17.3% and 18.1%, respectively, in relation to the NOVX controls) and strength (the maximum load in the proximal tibial metaphysis decreased by 35.4% and 48.1%, respectively, in relation to the NOVX controls). Only in the diabetic rats, profound increases in some cytokine levels were noted. In conclusion, the changes induced by DM in female rats were only slightly intensified by estrogen deficiency. Despite similar effects on bone microstructure and strength, the influence of DM on the skeletal system was based on more profound systemic homeostasis changes than those induced by estrogen deficiency.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats

2021 ◽  
pp. 1-22
Author(s):  
Jonathan M. Scott ◽  
Elizabeth A. Swallow ◽  
Corinne E. Metzger ◽  
Rachel Kohler ◽  
Joseph M. Wallace ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Resorption ◽  
Iron Deficiency ◽  
Bone Formation ◽  
High Intensity ◽  
Female Rats ◽  
Type I ◽  
Bone Resorption Markers ◽  
Iron Deficient ◽  
Tracp 5B

Abstract In the US, as many as 20% of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop iron deficiency upon completion of training. Iron is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesized iron deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: iron adequate sedentary, iron deficient sedentary, iron adequate exercise, and iron deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughness, and tibiae mineral composition and morphometry were measured. Iron deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, iron deficiency further increased bone TRAcP 5b, while in iron adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, iron deficiency increased the rate of bone formation, mineral apposition, and zinc content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by iron deficiency despite a decrease in tibiae iron content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats

1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Bone Volume ◽  
Ovariectomized Rats ◽  
Trabecular Thickness ◽  
Longitudinal Bone Growth ◽  
Periosteal Bone Formation

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.

Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model

Bone ◽  
2011 ◽  
Vol 48 (2) ◽  
pp. 197-201 ◽  
Author(s):  
XiaoYan Tian ◽  
Webster S.S. Jee ◽  
Xiaodong Li ◽  
Chris Paszty ◽  
Hua Zhu Ke
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Rat Model ◽  
Sclerostin Antibody

scholarly journals Alfacalcidol prevents aromatase inhibitor (Letrozole)-induced bone mineral loss in young growing female rats

2009 ◽  
Vol 202 (2) ◽  
pp. 317-325 ◽  
Author(s):  
Idris Mohamed ◽  
James K Yeh
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Oral Administration ◽  
Aromatase Inhibitor ◽  
Bone Mineral ◽  
Female Rats ◽  
Bone Area ◽  
Combined Intervention

Long-term aromatase inhibitor use causes bone loss and increases fracture risk secondary to induced estrogen deficiency. We postulated that alfacalcidol (A; vitamin D3 analog) could help prevent the Letrozole (L)-induced mineral bone loss. Fifty intact 1-month-old female rats were randomly divided into basal group; age-matched control group (AMC); L group: oral administration of 2 mg/kg per day; A group: oral administration of 0.1 μg/kg per day; and group L+A for a period of 8 weeks. Eight-week administration of L resulted in a significant increase in body weight, bone length, bone area, bone formation, and bone resorption activities when compared with the AMC group. However, the bone mass and bone mineral density (BMD) were significantly lower than the AMC group. Serum levels of testosterone, LH, FSH, and IGF-1 were significantly higher and serum estrone and estradiol were lower along with a decrease in ovary+uterus horn weight, when compared with the AMC groups. None of those parameters were affected by A treatment, except suppression of bone resorption activities and increased trabecular bone mass and femoral BMD, when compared with the AMC group. Results of L+A combined intervention showed that bone length, bone area, and bone formation activities were higher than the AMC group, and the bone resorption activities were lower and BMD was significantly higher than that of the L group. This study demonstrates that the combined intervention of L and A not only enhances bone growth, but also increases bone density, and the effects of L and A are independent and additive.

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