Ezetimibe effect on bone mineral density and markers of bone formation and resorption.
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.


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 (beta-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/cm) and BMD-total femur (0.93 [0.12]-0.92 [0.12] g/cm) 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.
Sertbas
Yasar
Y
Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital, Bostanci-Kadikoy, Istanbul, Turkey. ysertbas@hotmail.com
Ersoy
Ugur
U
Ayter
Meltem
M
Gultekin Tirtil
Filiz
F
Kucukkaya
Belgin
B
D000469:Alkaline Phosphatase / Q000097:blood; D000924:Anticholesteremic Agents / Q000009:adverse effects*; D001384:Azetidines / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D024042:Collagen Type I; D008055:Lipids; D010446:Peptide Fragments; D000469:Alkaline Phosphatase; D000069438:Ezetimibe