Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

Autor: Perosky JE; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States., Khoury BM; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States., Jenks TN; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States., Ward FS; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States., Cortright K; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States., Meyer B; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States., Barton DK; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States., Sinder BP; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States., Marini JC; Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Disorders, NIH, Bethesda, MD, United States., Caird MS; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States., Kozloff KM; University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States; University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States. Electronic address: kenkoz@umich.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2016 Dec; Vol. 93, pp. 79-85. Date of Electronic Publication: 2016 Sep 15.
DOI: 10.1016/j.bone.2016.09.013
Abstrakt: 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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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