Increased Bone Turnover in Patients with Hypercholesterolemia

Majima, T.; Shimatsu, Akira; Komatsu, Yasato; Satoh, Noriko; Fukao, Akira; Ninomiya, Kiyoshi; Matsumura, Tadashi; Nakao, Kazuwa

doi:10.1507/endocrj.k07e-004

Cited by 34 publications

(34 citation statements)

References 39 publications

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“…In our clinical studies, we observed that postmenopausal women with hypercholesterolaemia showed increased bone Acta Pharmacologica Sinica npg turnover and lower BMD, which is consistent with the data reported in other clinical studies [2][3][4] . We thus hypothesise that a high cholesterol diet induces or promotes the development of osteoporosis.…”

Section: Discussionsupporting

confidence: 92%

“…Femurs and 1-4 lumbar vertebrae (LV) were also excised. The whole left femur and lumbar vertebrae (1)(2)(3)(4) were used for further analysis. The bone mineral content and area was measured, and BMD was automatically calculated via dual-energy X-ray absorptiometry (HOLOGIC, MA, USA).…”

Section: Animals and Experimental Treatmentmentioning

confidence: 99%

“…It was reported that postmenopausal women with hypercholesterolaemia have a significantly higher serum bone-specific alkaline phosphatase (BAP) level compared with postmenopausal women with a normal lipid profile [2] . In addition, both BAP and the N-terminal telopeptide of type I collagen (NTx) are significantly and positively correlated with both serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in women.…”

Section: Introductionmentioning

confidence: 99%

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High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Sheng

Tang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Methods: Female Sprague-Dawley rats were randomly separated into 3 groups: (1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet. Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol (E2), osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells (MC3T3-E1) were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. Results: In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol (12.5-50 μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1, and increased the oxidative injury in MC3T3-E1 cells. Conclusion:The results suggest a close correlation between hypercholesterolaemia and osteoporosis. High cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts.

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Section: Discussionsupporting

confidence: 92%

Section: Animals and Experimental Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Sheng

Tang

et al. 2011

Acta Pharmacol Sin

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“…Participants were measured for serum total calcium (TCa), phosphate, glucose, creatinine, TC (TC), HDL-cholesterol (HDL-C), LDLcholesterol (LDL-C) (calculated using the friedewald formula), triglycerides, albumin, and total alkaline phosphatase by standard automated methods in a Technicon Dax autoanalyser (Technicon instruments, Co. USA). Hypercholesterolemia was defined as fasting serum TC levels greater than 220 mg/dL or an elevated serum LDL-C level greater than 140 mg/dL [26].…”

Section: Laboratory Measurementsmentioning

confidence: 99%

Serum Lipids and Bone Metabolism in Spanish Men: The Camargo Cohort Study

et al. 2010

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Abstract. There is growing evidence of a link between lipid and bone metabolism, although data on this association in European men are scarce. This cross-sectional study from a community-based prospective cohort aims to explore the association of serum lipids with different aspects of bone metabolism in spanish men. Demographic and anthropometric measurements, biochemical parameters including serum lipids, bone remodelling markers and calciotropic hormones, bone mineral density (BMD) assessed by dual X-ray absorptiometry and heel quantitative ultrasound, and prevalent vertebral and non-vertebral fractures, were evaluated in 289 men. Calciotropic hormones or bone markers were not associated with serum lipids. serum total (TC) and LDL cholesterol, as well as LDL/HDL ratio were positively correlated to BMD at lumbar spine and hip. No significant correlation was noted for triglycerides or HDL. We observed a positive association between triglycerides, LDL/HDL ratio and Bua, and between TC/HDL ratio and both, Qui and Bua. BMD at the femoral neck and total hip was significantly higher in men with hypercholesterolemia after controlling for all the covariates (p=0.007). We did not observe any association between serum lipids and prevalent vertebral fractures. However, we found that TC (p=0.03) and LDL (p=0.04) were lower in subjects with non-vertebral fractures. in conclusion, we have found that a more unfavorable lipid profile (mainly higher LDL-C levels) is associated with higher BMD at lumbar spine and hip in spanish men. Moreover, we did not observe any association between hypercholesterolemia and prevalent vertebral fractures, but we found lower serum TC and LDL-C levels in men with prevalent non-vertebral fractures.

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“…Oxidized lipids, characteristic of hyperlipidemia, modulate the resorptive effects of parathyroid hormone (PTH) (17), inducing the expression of RANKL (18) and suppressing the differentiation of bone marrow stromal cells to osteoblasts (19). In this study, we sought to gain additional information beyond what has been reported so far (20)(21)(22) on bone mineral density among postmenopausal women with osteo-porosis based upon their history of statin use and fragility fractures. We conducted this test of the hypothesis because new preclinical evidence has been published recently, while clinical studies, especially on a population such as ours, are lacking.…”

Section: Introductionmentioning

confidence: 99%

New Clues that May Link Osteoporosis to the Circulating Lipid Profile

et al. 2013

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Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination: 610 women with osteoporosis (mean lumbar spine T-score -3.16±0.81, mean yrs. since menopause 15.79±8.9) were grouped according to age at evaluation (< 50 years, 51-60 years, 61-70 years, > 70 years), the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index (BMI: P>0.05, r 2 <0.02). However, when BMD was correlated with both BMI and the lipid profile (Triglycerides, Cholesterol, LDLc, HDLc), significant correlations were found in 5 cohorts: 51-60 years with fractures (n=61, r 2 =0.14, P<0.01), 61-70 years (n=201, r 2 =0.09, P<0.01) with fractures (n=88, r 2 =0.14, P<0.01) or without fractures (n=113, r 2 =0.24, P=0.02) and over 70 years (n=247, r 2 =0.11, P<0.01).

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Increased Bone Turnover in Patients with Hypercholesterolemia

Cited by 34 publications

References 39 publications

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Serum Lipids and Bone Metabolism in Spanish Men: The Camargo Cohort Study

New Clues that May Link Osteoporosis to the Circulating Lipid Profile

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