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 Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis*

2009 ◽  
Vol 24 (4) ◽  
pp. 578-588 ◽  
Author(s):  
Xiaodong Li ◽  
Michael S Ominsky ◽  
Kelly S Warmington ◽  
Sean Morony ◽  
Jianhua Gong ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Postmenopausal Osteoporosis ◽  
Bone Strength ◽  
Rat Model ◽  
Antibody Treatment ◽  
Sclerostin Antibody

scholarly journals Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2132-2140 ◽  
Author(s):  
Keiichiro Kitahara ◽  
Muneaki Ishijima ◽  
Susan R. Rittling ◽  
Kunikazu Tsuji ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Wild Type ◽  
Mineral Density ◽  
Cortical Bone Mass ◽  
Intermittent Pth

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.

scholarly journals Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Body Weight ◽  
Bone Loss ◽  
Bone Mass ◽  
Bone Turnover ◽  
Cancellous Bone ◽  
Mass Density ◽  
Female Rats ◽  
Bone Mass Density ◽  
Age Related

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

Sclerostin antibody improves phosphate metabolism hormones, bone formation rates, and bone mass in adult Hyp mice

Bone ◽  
2021 ◽  
pp. 116201
Author(s):  
Kelsey A. Carpenter ◽  
Reid Davison ◽  
Shruti Shakthivel ◽  
Kyle D. Anderson ◽  
Frank C. Ko ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Phosphate Metabolism ◽  
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.

Low turnover, fatty marrow cancellous bone was resistant to ovariectomy and raised cage exercise-induced bone changes in adult female rats

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S398
Author(s):  
Xiaoyan Tian ◽  
Rebecca B. Setterberg ◽  
Kevin Li ◽  
Kelly Li ◽  
Min Chen ◽  
...  
Keyword(s):  
Cancellous Bone ◽  
Adult Female ◽  
Female Rats ◽  
Bone Changes ◽  
Exercise Induced

scholarly journals Increased Bone Formation and Bone Mass Induced by Sclerostin Antibody Is Not Affected by Pretreatment or Cotreatment with Alendronate in Osteopenic, Ovariectomized Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3312-3322 ◽  
Author(s):  
Xiaodong Li ◽  
Michael S. Ominsky ◽  
Kelly S. Warmington ◽  
Qing-Tian Niu ◽  
Franklin J. Asuncion ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Ovariectomized Rats ◽  
Sclerostin Antibody
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