title: The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats.
abstract: Recent studies revealed that long-term intake of proton pump inhibitor (PPI) increases the risk of vertebral or hip fracture; however, the exact mechanism for this is not known. To evaluate the effect of long-term PPI therapy on bone turnover, we analyzed the signaling pathway involved in osteoclast differentiation and bone resorption/formation markers using ovariectomized rats. Six-week-old Sprague-Dawley (S-D) rats were ovariectomized, and two weeks later they were divided into four groups (group A, normal diet + placebo; group B, low calcium diet + placebo; group C, normal diet + PPI; and group D, low calcium diet + PPI). Omeprazole, at a concentration of 30 mg/kg, was administered orally for eight weeks and the rats were sacrificed when they were 16 weeks old. The relative expression levels of the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, c-Fos, nuclear factor of activated T cells c1 (NFATc1) and osteocalcin in femoral bone marrow cells were compared, and serum C-terminal cross-linking telopeptide of type I (CTX-1) levels were determined. The relative ratio of RANKL/OPG was increased in group D, and gene expression levels of c-Fos and NFATc1 were upregulated in groups B and D, which are involved in differentiation and activation of osteoclasts. Furthermore, expression levels of osteocalcin, a bone formation marker, were decreased and levels of serum CTX-1, a bone resorption marker, were increased in group D. Taken together, a low calcium diet and PPI administration are thought to collaborate in order to alter osteoclast activity and bone resorption signaling.
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152-703, Republic of Korea.
authors: Moon Kyung
authors: MK
authors: Joo
authors: Jong-Jae
authors: JJ
authors: Park
authors: Beom Jae
authors: BJ
authors: Lee
authors: Ji Hoon
authors: JH
authors: Kim
authors: Jong Eun
authors: JE
authors: Yeon
authors: Jae Seon
authors: JS
authors: Kim
authors: Kwan Soo
authors: KS
authors: Byun
authors: Young-Tae
authors: YT
authors: Bak
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin / Q000096:biosynthesis; D010052:Ovariectomy; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D053245:RANK Ligand / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053244:Osteoprotegerin; D054328:Proton Pump Inhibitors; D053245:RANK Ligand; D002118:Calcium