Topically administered Risedronate shows powerful anti-osteoporosis effect in ovariectomized mouse model.
We investigated the therapeutic effect of topical Risedronate (RIS) on a mouse model of estrogen-deficient osteoporosis. Fourteen-week-old female mice were ovariectomized and assigned to 4 groups: SHAM-operated (SHAM), OVX mice treated with vehicle (OVX-V), OVX mice treated with 0.2% RIS (OVX-0.2% RIS), and OVX-mice treated with 0.02% RIS (OVX-0.02% RIS). Topical samples containing RIS were prepared in 10% (w/w) polyethylene glycol (PEG, MW 400) and 80 μg of sample was spread on the mice's mid-backs every 3 days for 5 weeks. Micro-CT analysis of femora demonstrated that OVX-0.2% RIS exhibited a 29% greater bone mineral density and 24% greater bone volume fraction than that of OVX-V group. Investigation of the trabecular bone in OVX-0.2% RIS revealed a 24% higher bone volume (BV/TV), 51% higher trabecular number (Tb.N), and 40% lower trabecular separation (Tb.Sp) compared to OVX-V mice. Additionally, bone phenotypes of tibiae were further confirmed by histological analysis. OVX-0.2% RIS group exhibited a 494% greater BV/TV, 464% less Tb.Sp, 81% greater active osteoclast surface (Oc.S/BS) and 26% less osteoclast number (N.Oc/BS) than that of OVX-V group. Collectively, these results indicated that topical delivery of RIS has powerful pharmaceutical effects on the prevention of osteoporosis and bone turnover.
Department of Chemistry, School of Natural Science, Seoul National University, Seoul, Republic of Korea.
So Hee
SH
Nam
Jae-Hwan
JH
Jeong
Xiangguo
X
Che
Kyung-Eun
KE
Lim
Hyemi
H
Nam
Jong-Sang
JS
Park
Je-Yong
JY
Choi
D000287:Administration, Topical; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D000068296:Risedronic Acid; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013977:Tibia / Q000187:drug effects / Q000648:ultrastructure; D055114:X-Ray Microtomography
D050071:Bone Density Conservation Agents; D000068296:Risedronic Acid; D012968:Etidronic Acid