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Ezetimibe Effect on Bone Mineral Density and Markers of Bone Formation and Resorption
  1. Yasar Sertbas, MD*,
  2. Ugur Ersoy, MD,
  3. Meltem Ayter, MD*,
  4. Filiz Gultekin Tırtıl, MD*,
  5. Belgin Kucukkaya, MD*
  1. From the *Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital; and †Department of Internal Medicine, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.
  1. Received Febuary 11, 2009, and in revised form October 25, 2009.
  2. Accepted for publication October 26, 2009.
  3. Reprints: Yasar Sertbas, MD, Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital, Bostanci-Kadikoy, Istanbul, Turkey. E-mail: ysertbas{at}hotmail.com.

Abstract

Background Ezetimibe, as a lipid-lowering agent, inhibits the intestinal absorption of cholesterol and decreases low-density lipoprotein cholesterol (LDL-C) level in serum. It also up-regulates hepatic cholesterol biosynthesis and, by contrast to statins, increases serum mevalonate levels. Statins and biphosphonates decrease osteoclastic activity through the same mechanisms by inhibiting the mevalonate pathway. We therefore tested the effect of ezetimibe on bone turnover in hypercholesterolemic patients.

Subject and Methods In an open-label clinical trial, 54 hypercholesterolemic patients included in the study underwent 12 months of treatment with ezetimibe at a dosage of 10 mg/d. Before and after the 1-year ezetimibe treatment, bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry and serum samples taken for measurements of levels of total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol and LDL-C, serum calcium (Ca), serum phosphate, total and bone alkaline phosphatases (ALPs), and carboxyterminal fragment of type 1 collagen in the serum.

Results The hypercholesterolemic patients showed a significant reduction with respect to baseline TC and LDL-C serum levels: 20% for TC (270.18 [38.58]−214.46 [38] mg/dL) and 24% for LDL-C (189.57 [38.58]−144 [32.05] mg/dL). Biochemical markers of both bone formations (total ALP level, 65.50 [21.33]−66.27 [21.017] IU/L and bone ALP level, 55.93 [7.92]−56.25 [7.49] IU/L) and bone resorption (β-CTx, 0.44 [0.24]−0.46 [0.21] ng/mL) increased but did not show any significant change for the whole study period. At the end of 1 year, both BMD-lumbar spine (0.90 [0.12]−0.89 [0.08] g/cm2) and BMD-total femur (0.93 [0.12]−0.92 [0.12] g/cm2) showed a negative trend but without reaching statistical significance.

Conclusions Our study results showed a negative trend but did not demonstrate statistically significant changes of BMD and metabolic markers with the treatment of ezetimibe.

Key Words
  • ezetimibe
  • bone mineral density
  • hyperlipidemia

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