Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

Ross, Ryan D.; Anderson, Kyle; Davison, Reid; El‐Masri, Bilal M.; Andreasen, Christina M.; Andersen, Thomas L.; Sumner, Dale R.

doi:10.1002/jbm4.10344

Title: Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

Journal Article · 23 January 2020 · JBMR Plus

DOI: https://doi.org/10.1002/jbm4.10344 · OSTI ID:1608144

^[1]; Anderson, Kyle ^[2]; Davison, Reid ^[2]; El‐Masri, Bilal M. ^[3];

^[3];

^[3]; Sumner, Dale R. ^[1]

Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Cell & Molecular Medicine; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Orthopedic Surgery
Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Cell & Molecular Medicine
Odense Univ. Hospital (Denmark). Dept. of Pathology; Univ. of Southern Denmark, Odense (Denmark). Dept. of Clinical Research. Research Unit of Pathology. Clinical Cell Biology; Univ. of Southern Denmark, Odense (Denmark). Dept. of Molecular Medicine

To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23-day lactation period. At weaning, eight dams were sacrificed to establish baseline values, while the remaining dams were returned to 0.4% calcium and treated with vehicle (saline), sodium fluoride (NaF), zoledronic acid (ZA), or sclerostin antibody (Scl-Ab) for either 7 or 28 days (eight animals per group per time point). Femora were examined by μCT, dynamic histomorphometry, Fourier transform infrared imaging, and three-point bending of notched specimens. Cortical porosity decreased in all groups from baseline to day 28. Intracortical mineralizing surface (MS/BS) and mineral apposition rate (MAR), as well as the mineral-to-matrix ratio were unaffected by treatment, but intracortical crystallinity was increased in the ZA group at day 10 compared with vehicle. Cortical area increased in all groups over 28 days mainly because of an addition of bone at the endocortical surface. Endocortical MS/BS did not vary among the groups, but endocortical MAR was suppressed in the NaF group at day 2 and elevated in the Scl-Ab group at day 4 compared with vehicle. Endocortical mineral-to-matrix ratio was increased at days 5 and 10 following NaF treatment and endocortical crystallinity was increased at day 5 following ZA treatment compared with vehicle. Fracture toughness did not differ among the groups. Thus, the treatments affected matrix maturation more strongly at the endocortical then intracortical envelope. In this model of induced remodeling, the bone formation phase is synchronized at multiple sites, facilitating study of the effects of drugs or other bone-targeting agents on matrix maturation independent of their effects on the initiation of remodeling.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231; DE‐AC02‐05CH11231

OSTI ID:: 1608144

Alternate ID(s):: OSTI ID: 1608145; OSTI ID: 1629976

Journal Information:: JBMR Plus, Vol. 4, Issue 4; ISSN 2473-4039

Publisher:: Wiley - American Society for Bone and Mineral ResearchCopyright Statement

Country of Publication:: United States

Language:: English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
bisphosphonate
bone remodeling
intracortical
lactation
mineralization
sclerostin

Title: Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

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