Monthly Archives: March 2014

Review: Cardiovascular Disease and Osteoporosis Strategies

Abstract

Cardiovascular disease and osteoporosis: balancing risk management.

In this narrative review of the current literature, we examine the traditional risk factors and patient profiles leading to cardiovascular disease and osteoporosis. We discuss the interrelationships between risk factors and common pathophysiological mechanisms for cardiovascular disease and osteoporosis. We evaluate the increasing evidence that supports an association between these disabling conditions. We reveal that vascular health appears to have a strong effect on skeletal health, and vice versa. We highlight the importance of addressing the risk benefit of preventative interventions in both conditions. We discuss how both sexes are affected by these chronic conditions and the importance of considering the unique risk of the individual. We show that habitual physical activity is an effective primary and secondary preventative strategy for both cardiovascular disease and osteoporosis. We highlight how a holistic approach to the prevention and treatment of these chronic conditions is likely warranted.

Warburton DE, Nicol CW, Gatto SN, Bredin SS
Vasc Health Risk Manag 2007
PMID: 18078019 | Free Full Text

Review: Genetics of Cardiovascular Diseases and Osteoporosis

Abstract

Genetic determinants of osteoporosis: common bases to cardiovascular diseases?

Osteoporosis is the most common and serious age-related skeletal disorder, characterized by a low bone mass and bone microarchitectural deterioration, with a consequent increase in bone fragility and susceptibility to spontaneous fractures, and it represents a major worldwide health care problem with important implications for health care costs, morbidity and mortality. Today is well accepted that osteoporosis is a multifactorial disorder caused by the interaction between environment and genes that singularly exert modest effects on bone mass and other aspects of bone strength and fracture risk. The individuation of genetic factors responsible for osteoporosis predisposition and development is fundamental for the disease prevention and for the setting of novel therapies, before fracture occurrence. In the last decades the interest of the Scientific Community has been concentrated in the understanding the genetic bases of this disease but with controversial and/or inconclusive results. This review tries to summarize data on the most representative osteoporosis candidate genes. Moreover, since recently osteoporosis and cardiovascular diseases have shown to share common physiopathological mechanisms, this review also provides information on the current understanding of osteoporosis and cardiovascular diseases common genetic bases.

Marini F, Brandi ML
Int J Hypertens 2010
PMID: 20948561 | Free Full Text

Vitamin D in Atherosclerosis and Osteoporosis

Abstract

Association between atherosclerosis and osteoporosis, the role of vitamin D.

The latest data support the correlation of atherosclerosis and osteoporosis, indicating the parallel progression of two tissue destruction processes with increased fatal and non-fatal coronary events, as well as higher fracture risk. Vitamin D inadequacy associated with low bone mineral density increases fall and fracture risk, leads to secondary hyperparathyroidism, calcifies coronary arteries and significantly increases cardiovascular disease. Randomized clinical trial evidence related to extraskeletal vitamin D outcomes was limited and generally uninformative. A recent recommendation on vitamin D dietary requirements for bone health is 600 IU/d for ages 1-70 years and 800 IU/d for 71 years and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l). Further large randomized controlled trials are needed to reassess laboratory ranges for 25-hydroxyvitamin D in both diseases, in order to avoid under- and over-treatment problems, and completely clarify the relationship between atherosclerosis and osteoporosis.

Stojanovic OI, Lazovic M, Lazovic M, Vuceljic M
Arch Med Sci Apr 2011
PMID: 22291755 | Free Full Text

Oxidized Phospholipids May Interfere With Bone Growth

Abstract

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

Cardiovascular Disease Associated with Lower Bone Density

Abstract

The association of bone mineral density measures with incident cardiovascular disease in older adults.

The associations of volumetric and areal bone mineral density (BMD) measures with incident cardiovascular disease (CVD) were studied in a biracial cohort of 2,310 older adults. BMD measures were inversely related to CVD in women and white men, independent of age and shared risk factors for osteoporosis and CVD.
We investigated the associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with incident cardiovascular disease (CVD) in older adults enrolled in the Health, Aging, and Body Composition study.
The incidence of CVD was ascertained in 2,310 well-functioning white and black participants (42% black; 55% women), aged 68-80 years. aBMD measures of the hip were assessed using DXA. Spine trabecular, integral, and cortical vBMD measures were obtained using QCT.
During an average follow-up of 5.4 years, 23% of men and 14% of women had incident CVD. Spine vBMD measures were inversely associated with incident CVD in white men [HR(integral)=1.39, 95% CI 1.03-1.87; HR(cortical)=1.38, 95% CI 1.03-1.84], but not in black men. In women, aBMD measures of the total hip (HR = 1.36, 95% CI 1.03-1.78), femoral neck (HR = 1.44, 95% CI 1.10-1.90), and trochanter (HR = 1.34, 95% CI 1.04-1.72) exhibited significant associations with CVD in blacks, but not in whites. All associations were independent of age and shared risk factors between osteoporosis and CVD, and were not explained by inflammatory cytokines or oxidized LDL.
Our results provide support for an inverse association between BMD and incident CVD. Further research should elucidate possible pathophysiological mechanisms linking osteoporosis and CVD.

Farhat GN, Newman AB, Sutton-Tyrrell K, Matthews KA…
Osteoporos Int Jul 2007
PMID: 17285350

Review: Cardiovascular Disease and Osteoporosis

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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