Bovine Lactoferrin Improves The Bone Mass And Microstructure Of Ovariectomized Rats Via The OPG/RANKL/RANK Pathway

Objective:The objective of this study was to evaluate the changes induced by lactoferrin （LF） inan ovariectomized （Ovx） rat model and to identify the pathways that mediate theanabolic action of lactoferrin in bone.Methods:Six-month-old female Sprague-Dawley rats （n=70） were randomly divided into thefollowing groups: Ovx untreated （Con）; sham-operated （Sham）; Ovx+17β-estradiol0.1mg/kg/wk, the positive control （E₂）; Ovx+LF10mg/kg/d （LF₁）; Ovx+LF100mg/kg/d（LF₂）; Ovx+LF1.0g/kg/d （LF₃）; and Ovx+LF2.0g/kg/d （LF₄）. After6months oftreatment, the bone mass and microstructure in the right femur and the L2-4vertebraewere scanned by micro-computed tomography （micro-CT）, and the levels ofosteoprotegerin （OPG） and the receptor-activator of nuclear factor κB ligand （RANKL）mRNA in the left femur were measured by quantitative real-time reverse transcriptionPCR （qRT-PCR）.Results:1.The body weights of the rats were not significantly different before the treatment（P>0.05, Table2）. By the end of the6-month experiment, all of the rats had increasedbody weight. The Con rats tended to gain more weight than the Sham rats （P<0.05）. Thefinal body weights of the LF-treated rats tended to be lower than those of the Con group;however, these differences were not statistically significant （P>0.05）. Estrogencompletely prevented the Ovx-induced weight gain.2. By the end of the6-month experiment,The Ovx-induced bone loss was completelyprevented in the E2group compared with the Con group （P<0.01）. The Ovx rats treatedwith LF had elevated bone volume （BV/TV）, trabecular thickness （Tb.Th.）, trabecularnumber （Tb.N.） and a reduction in trabecular separation （Tb.Sp.）.3. By the end of the6-month experiment,LF also increased the bone mineral density （BMD） at doses of1and2g/kg as compared with the Con group（P<0.01and P<0.05）,but this change did not occur in the rats treated with10and100mg/kg LF.3.Treatment with1and2g/kg LF caused a significant increase in the OPG mRNAlevels as compared with the Con group （P<0.05）. In addition, the RANKL mRNA levelsand the RANKL/OPG mRNA ratio were suppressed in the rats treated with1and2g/kgLF （P<0.05）.Conclusion:1. The replication animal model of osteoporosis was successful2. Oral LF both preserved bone mass and improved the bone microarchitecture.3. The increased bone mass and reduced bone loss of the ovariectomized rats treatedwith LF may have occurred via regulation of the OPG/RANKL/RANK pathway.