PMID- 23426758 OWN - NLM STAT- MEDLINE DCOM- 20140725 LR - 20130301 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 7 IP - 4 DP - 2013 Apr TI - The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats. PG - 1267-72 LID - 10.3892/mmr.2013.1327 [doi] AB - 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-kappaB 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. FAU - Joo, Moon Kyung AU - Joo MK AD - Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152-703, Republic of Korea. FAU - Park, Jong-Jae AU - Park JJ FAU - Lee, Beom Jae AU - Lee BJ FAU - Kim, Ji Hoon AU - Kim JH FAU - Yeon, Jong Eun AU - Yeon JE FAU - Kim, Jae Seon AU - Kim JS FAU - Byun, Kwan Soo AU - Byun KS FAU - Bak, Young-Tae AU - Bak YT LA - eng PT - Journal Article DEP - 20130219 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Osteoprotegerin) RN - 0 (Proton Pump Inhibitors) RN - 0 (RANK Ligand) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Bone Resorption/*metabolism/pathology MH - Bone and Bones/drug effects/*metabolism MH - Calcium/blood MH - Cell Differentiation/*drug effects MH - Gene Expression Regulation MH - Humans MH - Osteoclasts/drug effects/metabolism MH - Osteoprotegerin/biosynthesis MH - Ovariectomy MH - Proton Pump Inhibitors/*administration & dosage/adverse effects MH - RANK Ligand/biosynthesis MH - Rats MH - Signal Transduction/drug effects EDAT- 2013/02/22 06:00 MHDA- 2014/07/26 06:00 CRDT- 2013/02/22 06:00 PHST- 2012/10/30 00:00 [received] PHST- 2013/02/13 00:00 [accepted] PHST- 2013/02/22 06:00 [entrez] PHST- 2013/02/22 06:00 [pubmed] PHST- 2014/07/26 06:00 [medline] AID - 10.3892/mmr.2013.1327 [doi] PST - ppublish SO - Mol Med Rep. 2013 Apr;7(4):1267-72. doi: 10.3892/mmr.2013.1327. Epub 2013 Feb 19.