Changes in micro-CT 3D bone parameters reflect effects of a potent cathepsin K inhibitor (SB-553484) on bone resorption and cortical bone formation in ovariectomized mice

Bone ◽  
2007 ◽  
Vol 40 (5) ◽  
pp. 1231-1237 ◽  
Author(s):  
Anbo Xiang ◽  
Masahiro Kanematsu ◽  
Sanjay Kumar ◽  
Dennis Yamashita ◽  
Toshihiko Kaise ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cortical Bone ◽  
Cathepsin K ◽  
Micro Ct ◽  
Bone Parameters ◽  
Cathepsin K Inhibitor ◽  
Ovariectomized Mice

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.

Overexpression of Fam20C in osteoblast in vivo leads to increased cortical bone formation and osteoclastic bone resorption

Bone ◽  
2020 ◽  
Vol 138 ◽  
pp. 115414
Author(s):  
Katsutoshi Hirose ◽  
Takuya Ishimoto ◽  
Yu Usami ◽  
Sunao Sato ◽  
Kaori Oya ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cortical Bone ◽  
Osteoclastic Bone Resorption

Erratum to “Overexpression of Fam20C in osteoblast in vivo leads to increased cortical bone formation and osteoclastic bone resorption” [Bone 138 (2020), 115414]

Bone ◽  
2021 ◽  
Vol 143 ◽  
pp. 115635
Author(s):  
Katsutoshi Hirose ◽  
Takuya Ishimoto ◽  
Yu Usami ◽  
Sunao Sato ◽  
Kaori Oya ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cortical Bone ◽  
Osteoclastic Bone Resorption

Inhibition of bone resorption by the cathepsin K inhibitor odanacatib is fully reversible

Bone ◽  
2014 ◽  
Vol 67 ◽  
pp. 269-280 ◽  
Author(s):  
Y. Zhuo ◽  
J.-Y. Gauthier ◽  
W.C. Black ◽  
M.D. Percival ◽  
L.T. Duong
Keyword(s):  
Bone Resorption ◽  
Cathepsin K ◽  
Cathepsin K Inhibitor

scholarly journals The Effect of the Cathepsin K Inhibitor ONO-5334 on Trabecular and Cortical Bone in Postmenopausal Osteoporosis: The OCEAN Study

2014 ◽  
Vol 29 (3) ◽  
pp. 629-638 ◽  
Author(s):  
Klaus Engelke ◽  
Shinichi Nagase ◽  
Thomas Fuerst ◽  
Maria Small ◽  
Tomohiro Kuwayama ◽  
...  
Keyword(s):  
Cortical Bone ◽  
Postmenopausal Osteoporosis ◽  
Cathepsin K ◽  
Cathepsin K Inhibitor ◽  
Ocean Study
Sign in / Sign up

Export Citation Format

Share Document