J Korean Endocr Soc.  2007 Feb;22(1):19-25. 10.3803/jkes.2007.22.1.19.

Lipid Profile Changes in Postmenopausal Korean Women Treated with Alendronate (10 mg) for 2 Years: Comparing with Control Group

• Joo IW
• Oh HJ

• KMID: 2178238
• DOI: http://doi.org/10.3803/jkes.2007.22.1.19

Abstract

BACKGROUND: Bisphosphonate, which has been used for prevention and treatment of osteoporosis with the mechanism of inhibiting bone resorption, also has an association with the cholesterol synthethic process. This suggests that bisphosphonate might have benefit to improve the lipid profile in humans through a process that blocks the mevalonate-squalene pathway. However, few reports have revealed the relationship between the action of bisphosphonate and lipid metabolism in postmenopausal Korean women. We planned this study to determine the effect of alendronate (10 mg) on the serum lipid level in postmenopausal Korean women. Subjects and METHODS: We retrospectively evaluated the postmenopausal Korean women (aged over 50) who visited the Osteoporosis clinic in the Health Care Center in Seoul from March of 2003 to October of 2005. The changes of the serum lipid levels, including total cholesterol, triglyceride, and HDL cholesterol, after 2-years of alendronate 10 mg administration were evaluated and comparing to a control group.
RESULTS
After 2-years alendronate (10 mg) administration, the total cholesterol was decreased by 11.8 +/- 3.7 mg/dL, and the HDL cholesterol was increased by 5.2 +/-1.4 mg/dL as compared to the baseline lipid level. Both of these results showed statistical significance. Changes of the triglyceride and fasting blood glucose also showed a decline by 15.4 +/-9.8 mg/dL and 6.0 +/-1.4 mg/dL, respectively, but this was not statistically significant. However, in the control group, the total cholesterol was increased by 9.4 +/-8.8 mg/dL, and the triglyceride was increased by 10.5 +/-7.2 mg/dL as compared to the baseline lipid level. Both of the results showed statistical significance.
CONCLUSION
Alendronate might have a beneficial effect on lipid metabolism to decrease cholesterol and increase HDL. Taking into consideration about the postmenopausal increase in the cholesterol level, alendronate is recommended for the prevention of hyperlipidemia in postmenopausal women, in addition to preventing and treating osteoporosi

Keyword

Alendronate; Total cholesterol; HDL cholesterol; Triglyceride

MeSH Terms

Alendronate*
Blood Glucose
Bone Resorption
Cholesterol
Cholesterol, HDL
Delivery of Health Care
Fasting
Female
Humans
Hyperlipidemias
Lipid Metabolism
Osteoporosis
Retrospective Studies
Seoul
Triglycerides
Alendronate
Blood Glucose
Cholesterol
Cholesterol, HDL

Figure

• 

  Fig. 1 Serum cholesterol level after 2-year alendronate (10 mg) administration. After 2-year alendronate (10 mg) administration, total cholesterol level was decreased by 11.8 ± 3.7 mg/dL with compared to the baseline lipid level with statistical significance (P < 0.05).

• 

  Fig. 2 Serum HDL level after 2-year alendronate (10 mg) administration. After 2-year alendronate (10 mg) administration, HDL level was increased by 5.2 ± 1.4 mg/dL compared to the baseline lipid level with statistical significance (P < 0.05).

• 

  Fig. 3 Serum triglyceride level after 2-year alendronate (10 mg) administration. After 2-year alendronate (10 mg) administration, changes of triglyceride showed a declined pattern by 15.4 ± 9.8 mg/dL, but statistically not significant.

Reference

1. Fleisch N, Russel RG, Straumann F. Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature. 1966. 212:901–903.

2. Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hoghes DE, Masarachia PJ, et al. Alendronate mechanism of action:geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci USA. 1999. 96:133–138.

3. Benford HL, McGowan NWA, Helfrich MH, Nuttall ME, Rogers MJ. Visualization of bisphosphonateinduced caspase-3 activity in apoptotic osteoclasts in vitro. Bone. 2001. 28:465–473.

4. Reszka AA, Halasy-Nagy JM, Masarachia PJ, Rodan GA. Bisphosphonates act directly on the osteoclast to induce caspase cleavage of Mst kinase during apoptosis. J Biol Chem. 2001. 274:34967–34973.

5. Mansfield K, Teixeira CC, Adams CS, Shapiro IM. Phosphonate ions mediated chondrocyte apoptosis through a plasma membrane transporter mechanism. Bone. 2001. 28:1–8.

6. van Beek E, Lowik C, Van der Pluijim G, Papapoulos S. The role of geranylgeranylation in bone resorption and its suppression by bisphosphonate in fetal bone explants in vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner res. 1999. 14:722–729.

7. Montagnani A, Gonnelli S, Cepollaro C, Campagna MS, Franci MB, Pacini S, Gennari C. Changes in serum HDL and LDL cholesterol in patients with Paget\'s disease treated with pamidronate. Bone. 2003. 32:15–19.

8. Strobach D, Lorenz RL. The bisphosphonate ibandronate stimulates reverse cholesterol transport out of monocytoid cells by enhanced ABCA1 transcription. Biochem Biophys Res Commun. 2003. 307:23–30.

9. Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, et al. Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res. 1992. 33:1657–1663.

10. Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S. Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen and alendronate. Bone. 1996. 18:621–627.

11. Mori H, Yamaguchi K, Fukushima H, Kato N, Wakamatsu T, Uzawa H. Extensive arterial calcification of unknown etiology in a 29-year-old male. Heart Vessels. 1992. 7:211–214.

12. Price PA, Faus SA, Williamson MK. Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. Arterioscler Thromb Vasc Biol. 2001. 21:817–824.

13. Ylitalo R. Bisphosphonates and atherosclerosis. Gen Pharmacol. 2000. 35:287–296.

14. Adami S, Braga V, Guidi G, Gatti D, Gerardi D, Fracassi E. Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. J Bone Miner res. 2000. 15:599–604.

15. Berkhout TA, Simon HM, Patel DD, Bentzen C, Niesor E, Jackson B, Suckling KE. The novel cholesterol-lowering drug SR-12813 inhibit cholesterol via an increased degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem. 1996. 271:14376–14382.