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Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.
- Source :
-
Bone [Bone] 2016 Dec; Vol. 93, pp. 79-85. Date of Electronic Publication: 2016 Sep 15. - Publication Year :
- 2016
-
Abstract
- Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Antibodies pharmacology
Biomechanical Phenomena
Bone Resorption diagnostic imaging
Bone Resorption drug therapy
Bone Resorption pathology
Bone and Bones drug effects
Cortical Bone diagnostic imaging
Cortical Bone drug effects
Cortical Bone pathology
Diphosphonates pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Femur diagnostic imaging
Femur drug effects
Femur pathology
Intercellular Signaling Peptides and Proteins
Male
Organ Size drug effects
Osteoclasts drug effects
Osteoclasts metabolism
Osteoclasts pathology
Osteogenesis Imperfecta diagnostic imaging
Spectroscopy, Near-Infrared
X-Ray Microtomography
Antibodies therapeutic use
Bone and Bones pathology
Diphosphonates therapeutic use
Glycoproteins immunology
Osteogenesis Imperfecta drug therapy
Osteogenesis Imperfecta pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2763
- Volume :
- 93
- Database :
- MEDLINE
- Journal :
- Bone
- Publication Type :
- Academic Journal
- Accession number :
- 27641475
- Full Text :
- https://doi.org/10.1016/j.bone.2016.09.013