Category Archives: Dyslipidemia

Review: Dyslipidemia and Disabetes Associated with Fractures


[Bone diseases caused by impaired glucose and lipid metabolism].

The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

Kanazawa I, Sugimoto T
Clin Calcium Nov 2013
PMID: 24162600

Low LDL Associated with Osteoporosis in Type 2 Diabetics


Association of lower serum cholesterol levels with higher risk of osteoporosis in type 2 diabetes.

To determine whether a correlation exists between bone mineral density and circulating lipoprotein levels and whether these variables are independently associated with osteoporosis in patients with type 2 diabetes.
In a cross-sectional analysis, 159 patients with type 2 diabetes were compared with 70 patients without diabetes selected from an outpatient endocrinology clinic in a tertiary care institute during a 1-year period. Variables were gathered through history, physical examination, and laboratory findings, including blood chemistry studies and dual-energy x-ray absorptiometry.
Of the 229 study patients, 86 (37.6%) had osteoporosis. In the patients with diabetes, the mean +/- SD of age, weight, total cholesterol, and low-density lipoprotein (LDL) cholesterol in those with and without osteoporosis was 72.3 +/- 10.4 years versus 63.6 +/- 11.0 years, 74.2 +/- 14.4 kg versus 83.7 +/- 15.5 kg, 178.4 +/- 33.7 mg/dL versus 194.1 +/- 33.9 mg/dL, and 100.0 +/- 27.1 mg/dL versus 114.2 +/- 30.2 mg/dL, respectively (P<0.01 for all variables). After adjustment for other variables, multiple logistic regression analysis showed that the presence of diabetes was associated with a lower risk of osteoporosis. Similarly, older age and lower body weight, LDL levels, and serum calcium levels were independently associated with lumbar spine osteoporosis in patients with diabetes, in comparison with older age and lower weight in patients without diabetes. Lower weight and older age were associated with femoral neck and total hip osteoporosis in patients with diabetes, in comparison with only older age in patients without diabetes.
The presence of type 2 diabetes is associated with a lower risk of osteoporosis. In patients with type 2 diabetes, a lower LDL level is more likely to be associated with osteoporosis at the lumbar spine.

Afshinnia F, Chacko S, Zahedi T
Endocr Pract Oct 2007
PMID: 17954418

Oxidized Phospholipids May Interfere With Bone Growth


Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts.

Cardiovascular disease, such as atherosclerosis, has been associated with reduced bone mineral density and fracture risk. A major etiologic factor in atherogenesis is believed to be oxidized phospholipids. We previously found that these phospholipids inhibit spontaneous osteogenic differentiation of marrow stromal cells, suggesting that they may account for the clinical link between atherosclerosis and osteoporosis. Currently, anabolic agents that promote bone formation are increasingly used as a new treatment for osteoporosis. It is not known, however, whether atherogenic phospholipids alter the effects of bone anabolic agents, such as bone morphogenetic protein (BMP)-2 and parathyroid hormone (PTH). Therefore we investigated the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on osteogenic signaling induced by BMP-2 and PTH in MC3T3-E1 cells. Results showed that ox-PAPC attenuated BMP-2 induction of osteogenic markers alkaline phosphatase and osteocalcin. Ox-PAPC also inhibited both spontaneous and BMP-induced expression of PTH receptor. Consistently, pretreatment of cells with ox-PAPC inhibited PTH-induced cAMP production and expression of immediate early genes Nurr1 and IL-6. Results from immunofluorescence and Western blot analyses showed that inhibitory effects of ox-PAPC on BMP-2 signaling were associated with inhibition of SMAD 1/5/8 but not p38-MAPK activation. These effects appear to be due to ox-PAPC activation of the ERK pathway, as the ERK inhibitor PD98059 reversed ox-PAPC inhibitory effects on BMP-2-induced alkaline phosphatase activity, osteocalcin expression, and SMAD activation. These results suggest that atherogenic lipids inhibit osteogenic signaling induced by BMP-2 and PTH, raising the possibility that hyperlipidemia and atherogenic phospholipids may interfere with anabolic therapy.

Huang MS, Morony S, Lu J, Zhang Z…
J. Biol. Chem. Jul 2007
PMID: 17522049 | Free Full Text

Review: Cardiovascular Disease and Osteoporosis


Cardiovascular disease and osteoporosis.

Cardiovascular disease (CVD) and osteoporosis (OP) are public health problems with numerous epidemiological links and important economic consequences. Recent studies have demonstrated that CVD and cardiovascular mortality are associated with reduced bone mineral density (BMD) and bone fractures. These two conditions may be sustained by similar or common pathophysiological mechanisms and risk factors. There are several matrix proteins, such as type 1 collagen, proteoglycan, osteopontin, and osteonectin, which are found in bone and vascular matrix components. Matrix proteins play an important role both in bone formation and in the development of atherosclerosis. Estrogens also play a role in both CVD and OP through their effects on cytokines, such as IL-1, IL-6 and TNF-alpha and osteoprotegerin (OPG). The lack of estrogens induces an increase in these cytokines and a decrease in OPG, both implicated in the mechanisms of bone loss and atherogenesis. An additional link between CVD and OP seems to be related to the action of some drugs, such as bisphosphonates, statins and raloxifene. Several studies suggest that the mechanism of action of these drugs at cellular level may not be mutually exclusive, acting either in bone or in atherosclerotic plaque. However, further studies are necessary to define the relationship between CVD and OP more specifically and to understand the complex interaction of similar or common risk factors and genetic or molecular determinants.

Baldini V, Mastropasqua M, Francucci CM, D’Erasmo E
J. Endocrinol. Invest. 2005
PMID: 16550727

Review: Arteries an Brittle Bones


Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?

Both osteoporosis and cardiovascular disease (CVD) are major public health problems leading to increased morbidity and mortality. Although traditionally viewed as separate disease entities that increase in prevalence with aging, accumulating evidence indicates that there are similar pathophysiological mechanisms underlying both diseases. In addition to menopause and advanced age, other risk factors for CVD such as dyslipidemia, oxidative stress, inflammation, hyperhomocystinemia, hypertension, and diabetes have also been associated with increased risk of low bone mineral density (LBMD). Elevated LDL and low HDL cholesterol are associated with LBMD, altered lipid metabolism is associated with both bone remodeling and the atherosclerotic process, which might explain, in part, the co-existence of osteoporosis and atherosclerosis in patients with dyslipidemia. Similarly, inflammation plays a pivotal role in both atherosclerosis and osteoporosis. Elevated plasma homocysteine levels are associated with both CVD and osteoporosis. Nitric oxide (NO), in addition to its known atheroprotective effects, appears to also play a role in osteoblast function and bone turnover. Supporting this notion, in a small randomized controlled trial, nitroglycerine (an NO donor) was found to be as effective as estrogen in preventing bone loss in women with surgical menopause. Statins, agents that reduce atherogenesis, also stimulate bone formation. Furthermore, bis- phosphonates, used in the treatment of osteoporosis, have been shown to inhibit atherogenesis. Intravenous bisphosphonate therapy significantly decreases serum LDL and increases HDL in postmenopausal women The exciting possibilities of newer pharmacological agents that effectively treat both osteoporosis and CVD hold considerable promise. However, it is important to emphasize that the current evidence linking both of these diseases is far from conclusive. Therefore, additional research is necessary to further characterize the relationship between these two common illnesses.

McFarlane SI, Muniyappa R, Shin JJ, Bahtiyar G…
Endocrine Feb 2004
PMID: 15034190

Review: Hearts and Bones


Hearts and bones.

Cardiovascular disease (CVD) and osteoporosis (OP) are two common degenerative processes that contribute in great measure to the decline in performance and quality of life of the elderly population. Traditionally, these disorders have been considered as distinct and unrelated entities. However, over the last few years, there has been increasing evidence supporting an important link between CVD and OP. Several genetic association and linkage studies have shown the existence of common genetic determinants for cardiovascular and skeletal diseases. These genes code for several key players on the metabolism of nutrients, such as lipids, calcium and folate, as well as other factors (e.g. sex hormone receptors) that are known to be subject to dietary modulation, suggesting the links at the level of dietary response. Some dietary factors have shown similarities in influencing the risks of both conditions. However, some others act differently in relation with their effects on the development of cardiovascular disease and osteoporosis. We therefore suggest that, any dietary and behavioral recommendations targeting to the ‘global health’ of the ageing population would take a comprehensive consideration of their potentially diverse effects (beneficial or deleterious) on the risks of various ageing related disorders, and would be tailored to the individual genetic background.

Qi L, Shen H, Ordovas JM
Nutr Metab Cardiovasc Dis Jun 2003
PMID: 12955798

Review: Lipids and Bone


Cardiovascular disease and osteoporosis: is there a link between lipids and bone?

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.

Burnett JR, Vasikaran SD
Ann. Clin. Biochem. May 2002
PMID: 12038594

High Cholesterol Promotes Osteoclasts in Mice


Hypercholesterolemia promotes an osteoporotic phenotype.

A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health.

Pelton K, Krieder J, Joiner D, Freeman MR…
Am. J. Pathol. Sep 2012
PMID: 22770664 | Free Full Text

Lipids not Associated with Bone Density in Korean Women


Association between Serum Cholesterol Level and Bone Mineral Density at Lumbar Spine and Femur Neck in Postmenopausal Korean Women.

Blood lipid profiles have been suggested to be a risk factor for osteoporosis. However, the association between lipid profiles and bone mineral density (BMD) is still unclear. This study aimed to evaluate an association between blood lipid profiles and BMD through both a cross-sectional and a longitudinal study.
Study subjects were 958 postmenopausal Korean women who have repeatedly undertaken laboratory tests and BMD measurements at lumbar spine and femur neck with an interval of 7.1 years. The associations between lipid profiles and BMD were examined using Spearman correlation analysis with an adjustment for age, smoking, alcohol drinking, physical activity, body mass index, and follow-up duration.
Lumbar spine BMD was not associated with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HLD-C) regardless of when the measurement was performed. In an analysis using data measured at the beginning of the study, femur neck BMD was not associated with TC and LDL-C. However, femur neck BMD showed weak but significantly positive correlation with HDL-C (correlation coefficient, 0.077; 95% confidence interval, 0.005 to 0.149). When the analysis was repeated with data measured at the end of the follow-up, there was no significant correlation between femur neck BMD and any lipid profile. In addition, change in femur neck BMD during follow-up was not associated with the change in lipid profiles.
Although further study with a consideration of calcium intake and osteoporosis medication seems necessary, this study found no association between serum lipid profiles and BMD in postmenopausal Korean women.

Go JH, Song YM, Park JH, Park JY…
Korean J Fam Med May 2012
PMID: 22787539 | Free Full Text

Lipids, Obesity, and Bone Density


Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study.

Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data relate bone density, lipid profile and anthropometric measures.
To investigate these relationships in a large, well-characterized cohort of men and women (The Hertfordshire Cohort Study).Men (n = 465) and women (n = 448) from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur.
BMD at the lumbar spine (males r = 0.15, p = 0.001; females r = 0.14, p = 0.003) and total femoral region (males r = 0.18, p = 0.0001; females r = 0.16, p = 0.0008) was related to serum triglyceride level, even after adjustment for waist-hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r = -0.15, p = 0.001) and total femoral BMD in both sexes (males r = -0.15, p = 0.002; females r = -0.23, p < 0.0001); these relationships were also attenuated by adjustment for body fat percentage but not waist-hip ratio. No relationships were seen between total or LDL cholesterol with BMD.
In this cohort, relationships between lipid profile and BMD were robust to adjustment for one measure of central obesity (waist-hip ratio), but not total body fat. This broadly supports the idea that adiposity may confound the relationship between lipids and bone mass.

Dennison EM, Syddall HE, Aihie Sayer A, Martin HJ…
QJM May 2007
PMID: 17449479 | Free Full Text

A number of studies have suggested a positive relationship between BMD and triglyceride level, in concordance with our own findings [10,13], while the literature concerning relationships between HDL cholesterol levels and BMD is conflicting [12, 13,15,15, 18,19]. While D’Amelio et al [12] found an inverse relationship similar to our own results, Yamaguchi et al [14] described a positive relationship, and Cui et al [13] and Poli et al [15] described no relationship.