Korean J Med.  2011 Jan;80(1):56-62.

The Effect of Pantoprazole on Bone Turnover in Ovariectomized ICR Mice

• Lim EH
• Kim KH
• Lee BJ
• Joo MK
• Koh JS
• Lee JY
• Lim SA
• Kim JH
• Yeon JE
• Park JJ
• Kim JS
• Byun KS
• Bak YT

Abstract

BACKGROUND/AIMS
Long-term exposure to proton pump inhibitors is associated with osteoporosis-related fractures; however, the mechanism is unknown. The purpose of this study was to evaluate the effect of pantoprazole on osteoporosis and bone turnover in ovariectomized ICR mice fed a calcium-free diet.
METHODS
Ovariectomized female ICR mice were divided into a pantoprazole group (n=10) and a control group (n=10). The mice in the pantoprazole group were given an intraperitoneal injection of pantoprazole at 20 mg/kg twice daily. After 4 weeks, the mice were humanely euthanized, and bone mineral density (BMD) and dry tibia weight were measured. Serum osteocalcin and CTX-1 levels were measured by enzyme-linked immunosorbent assay. The mRNA expression levels of cytokines that stimulate osteoclast differentiation were determined using RT-PCR. Serum calcium, phosphorus, and alkaline phosphatase (ALP) levels were also analyzed.
RESULTS
Serum osteocalcin concentration was significantly lower in the pantoprazole group compared with the control group (p=0.023). There was no difference in BMD, dry tibia weight, or serum ALP, calcium, phosphorus, or CTX-1 between the two groups. The expression of interleukin (IL)-1beta was lower in the pantoprazole group compared with the control group, but not significantly lower (p=0.058). The levels of tumor necrosis factor-alpha and IL-6 did not differ between the two groups.
CONCLUSIONS
Pantoprazole, a proton pump inhibitor, decreased serum osteocalcin and suppressed IL-1beta expression, suggesting that pantoprazole affects bone formation and resorption in ovariectomized ICR mice. Further studies using larger sample sizes are needed.

Keyword

Pantoprazole; Osteoporosis; Bone turnover

MeSH Terms

2-Pyridinylmethylsulfinylbenzimidazoles
Alkaline Phosphatase
Animals
Bone Density
Calcium
Cytokines
Enzyme-Linked Immunosorbent Assay
Female
Humans
Injections, Intraperitoneal
Interleukin-6
Interleukins
Mice
Mice, Inbred ICR
Osteocalcin
Osteoclasts
Osteogenesis
Osteoporosis
Phosphorus
Proton Pump Inhibitors
Proton Pumps
RNA, Messenger
Sample Size
Tibia
Tumor Necrosis Factor-alpha
2-Pyridinylmethylsulfinylbenzimidazoles
Alkaline Phosphatase
Calcium
Cytokines
Interleukin-6
Interleukins
Osteocalcin
Phosphorus
Proton Pump Inhibitors
Proton Pumps
RNA, Messenger
Tumor Necrosis Factor-alpha