Ross Ryan D, Anderson Kyle, Davison Reid, El-Masri Bilal M, Andreasen Christina M, Andersen Thomas L, Sumner Dale R
Department of Cell & Molecular Medicine Rush University Medical Center Chicago IL USA.
Department of Orthopedic Surgery Rush University Medical Center Chicago IL USA.
JBMR Plus. 2020 Feb 20;4(4):e10344. doi: 10.1002/jbm4.10344. eCollection 2020 Apr.
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. © 2020 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
为了测试骨质疏松药物在皮质骨重塑过程中如何影响骨基质成熟，72只怀孕大鼠在分娩时从0.4%钙饮食改为0.01%钙饮食，为期23天的哺乳期。断奶时，处死8只母鼠以建立基线值，其余母鼠恢复到0.4%钙饮食，并接受载体（生理盐水）、氟化钠（NaF）、唑来膦酸（ZA）或硬化蛋白抗体（Scl-Ab）治疗7天或28天（每个时间点每组8只动物）。通过μCT、动态组织形态计量学、傅里叶变换红外成像和缺口标本的三点弯曲对股骨进行检查。从基线到第28天，所有组的皮质孔隙率均降低。皮质内矿化表面（MS/BS）和矿化沉积率（MAR）以及矿物质与基质的比率不受治疗影响，但与载体相比，ZA组在第10天时皮质内结晶度增加。在28天内，所有组的皮质面积均增加，主要是因为在内皮质表面增加了骨量。各组间内皮质MS/BS无差异，但与载体相比，NaF组在第2天时内皮质MAR受到抑制，Scl-Ab组在第4天时内皮质MAR升高。与载体相比，NaF治疗后第5天和第10天内皮质矿物质与基质的比率增加，ZA治疗后第5天内皮质结晶度增加。各组间的断裂韧性无差异。因此，这些治疗在内皮质包膜处对基质成熟的影响比在皮质内更强烈。在这个诱导重塑模型中，骨形成阶段在多个部位同步，便于研究药物或其他骨靶向剂对基质成熟的影响，而不受其对重塑起始影响的干扰。©2020作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。
