Telmisartan alleviates rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats.
In the present study, we systematically examined telmisartan, an angiotensin AT(1) receptor antagonist, on rosiglitazone-induced bone loss in ovariectomized spontaneously hypertensive rats. Telmisartan (5 mg/kg/d, 90 days) was found to be able to significantly alleviate rosiglitazone (10 mg/kg/d, 90 days)-induced decrease in BMD of femur and lumbar vertebrae. The BMD changes were associated with positive biomechanical changes of lumbar vertebrae, improvements in microarchitecture of tibial metaphysic and normalized serum osteocalcin (OC) levels and urinary deoxypyridinoline/creatinine (DPD/Cr) ratio. MicroCT analysis of the tibial metaphysis showed that telmisartan significantly prevented the decreases in bone volume/tissue volume (BV/TV), connect density (Conn. D.), trabecular number (Tb. N.) and trabecular thickness (Tb. Th.), and increase in trabecular separation (Tb. Sp.) induced by rosiglitazone. Histomorphometric analysis also showed that telmisartan had protective effects on rosiglitazone-reduced bone formation indices such as histomorphometric bone volume fraction (BV/TV-Histo), mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR/BS). Our study clearly showed that telmisartan alleviated rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats. The relief of bone loss provides a possible therapeutic application of telmisartan with rosiglitazone for the treatment of elderly women patients afflicted with metabolic syndrome.
Ma
L
L
Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, 210009 Nanjing, P.R. China.
Ji
J L
JL
Ji
H
H
Yu
X
X
Ding
L J
LJ
Liu
K
K
Li
Y Q
YQ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR; D000077154:Rosiglitazone; D013599:Systole / Q000187:drug effects; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000009:adverse effects*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D055114:X-Ray Microtomography
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D015415:Biomarkers; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077333:Telmisartan