scholarly journals Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats

2010 ◽  
Vol 25 (12) ◽  
pp. 2647-2656 ◽  
Author(s):  
Xiaodong Li ◽  
Kelly S Warmington ◽  
Qing-Tian Niu ◽  
Franklin J Asuncion ◽  
Mauricio Barrero ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Strength ◽  
Male Rats

scholarly journals Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass and Bone Strength of Intact Bones in Adult Male Rats

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Pui Kit Suen ◽  
Tracy Y. Zhu ◽  
Dick Ho Kiu Chow ◽  
Le Huang ◽  
Li-Zhen Zheng ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Strength ◽  
Adult Male ◽  
Male Rats ◽  
Antibody Treatment ◽  
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 Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

scholarly journals A western-style diet reduces bone mass and biomechanical bone strength to a greater extent in male compared with female rats during development

2003 ◽  
Vol 90 (3) ◽  
pp. 589-595 ◽  
Author(s):  
Wendy E. Ward ◽  
Susie Kim ◽  
W. Robert Bruce
Keyword(s):  
Folic Acid ◽  
Weight Gain ◽  
Bone Mass ◽  
Bone Strength ◽  
Control Diet ◽  
Biomechanical Properties ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Male And Female Rats

Evidence from epidemiological and animal-feeding trials suggests that a western-style diet that is high in fat, and low in Ca, vitamin D and folic acid may result in low bone mass and poor bone quality: this leads to an increased risk of fragility fracture. The overall objective of the present study was to determine the effect of feeding a western-style diet (low in Ca (0·4 g/kg diet, Ca:P ratio 1:10), cholecalciferol (3 μg/kg diet), folic acid (0·23 mg/kg diet) and fibre (20 g/kg diet), and high in fat (200 g/kg diet)) for 17 weeks on bone mineral content (BMC) and the biomechanical bone strength of rat femurs. A secondary objective was to determine whether femurs from male and female rats (seven to eight rats per group) respond differently to the western-style diet. Male and female rats weighing 150–180 g were fed a western-style diet or a control diet for 17 weeks. At the end of the feeding trial, femur BMC was measured by ashing, and biomechanical properties were determined by three-point bending. Femur BMC and the majority of biomechanical properties measured were lower (P<0·05) among male and female rats fed a western-style diet compared with a control diet, despite similar weight gain and final body weight within genders. However, the western-style diet had a greater negative effect on femur BMC and biomechanical strength properties among male rats compared with females. This may be because male rats experienced greater overall body growth, as assessed by weight gain, than female rats, and suggests that the nutrient composition of the western-style diet did not support the development of strong femurs.

Time course of disassociation of bone formation signals with bone mass and bone strength in sclerostin antibody treated ovariectomized rats

Bone ◽  
2017 ◽  
Vol 97 ◽  
pp. 20-28 ◽  
Author(s):  
Yanfei L Ma ◽  
Matthew Hamang ◽  
Jonathan Lucchesi ◽  
Nicoletta Bivi ◽  
Qianqiang Zeng ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Strength ◽  
Time Course ◽  
Ovariectomized Rats ◽  
Sclerostin Antibody

scholarly journals Sclerostin and Dickkopf-1 as Therapeutic Targets in Bone Diseases

2012 ◽  
Vol 33 (5) ◽  
pp. 747-783 ◽  
Author(s):  
Hua Zhu Ke ◽  
William G. Richards ◽  
Xiaodong Li ◽  
Michael S. Ominsky
Keyword(s):  
Monoclonal Antibody ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Repair ◽  
Wnt Pathway ◽  
Bone Growth ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Metabolic Bone Diseases ◽  
Dickkopf 1

The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.

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