Figure 1 | Common pathogenetic mechanisms in vascular calcification and osteoporosis. BMPs participate in osteoblasts differentiation while they simultaneously produce ROS and increase the adhesiveness of monocytes on the vascular wall. Their action is blocked by MGP, a vitamin K-dependent protein, which also inhibits vascular mineralization as a co-factor of α -2-HS-glycoprotein (also known as fetuin-A). RANKL is a key factor of osteoclast maturation and also acts as an anticalcifying molecule. OPG prevents the interaction of RANKL with its receptor. Wnt signaling, which is important for osteoblast differentiation, is inhibited by sclerostin and DKK-1. On the vascular wall, Wnt is upregulated by the transcription factor MSX2, which blocks the inhibitory effect of DKK-1, resulting in increased vascular calcification. Phosphate, which penetrates the SMC wall through the Pit-1 co-transporter, directly stimulates vascular calcification whereas pyrophosphate acts as an inhibitor of calcification. OPN binds calcium and hydroxyapatite ions, thereby inhibiting crystal formation and vascular calcification; it interacts with integrin receptors resulting in osteoclast activation. PTH inhibits osteoblast activation and increases bone resorption; via PKA activation it induces osteoblastic differentiation and mineralization of vascular cells. Vitamin D increases the entry of calcium into vascular cells, resulting in calcification. Oxidized LDL cholesterol induces the expression of potent mediators of osteoclastic differentiation. Finally, angiotensin II participates in osteoclast activation. Abbreviations: BMP, bone morphogenetic protein; Ca2+, calcium; DKK-1, Dickkopf-1; E-NPP1, ectonucleotide pyrophosphatase/phosphodiesterase family member 1; M-CSF, macrophage-colony stimulating factor 1; MGP, matrix Gla protein; OPG, osteoprotegerin; OPN, osteopontin; Pi, inorganic phosphate; PPi, pyrophosphate; PKA, protein kinase A; PTH, parathyroid hormone; PTH1R, parathyroid hormone 1 receptor; RANKL, receptor activator of nuclear factor κB ligand; ROS, reactive oxygen species; RUNX2, runt-related transcription factor 2; SMC, smooth muscle cell; TRAP, tartrate-resistant acid phosphatase type 5.
As shown in Figure 1, during the 25 years of follow-up, the relative metacarpal cortical area decreased by 22.4% in women (from 79.6±7.8(SD) to 61.8±10.3) and by 13.3% in men (from 80.6±6.9 to 69.9±8.3). The aortic calcification score increased over eight-fold in women (from 1.2±2.7 (SD) to 9.9±6.7) and six-fold in men (from 1.6±2.8 to 9.6±6.3).
Figure 2 shows the adjusted change in the aortic calcification index according to the quartile of change in metacarpal cortical area for women and men separately. In women, there was a significant association in that women in the highest quartile of bone loss had significantly greater adjusted increase in the aortic calcification score than women in the lowest quartile (P = 0.02). In men, no asso ciation was apparent between the progression of bone loss and the progression of aortic calcification. To determine if men with greater bone loss might experience a significant progression of vascular calcification, we repeated our analy ses in the subgroup of men above the median value of bone loss and found no significant associations.
Any unifying etiology to our findings of an association between bone loss and aortic calcification must account for the observed differences between men and women. One potential candidate is estrogen. In our analyses, estrogen replacement therapy was significantly associated with less progression of vascular calcification in bivariate analyses (r = -0.12, P = 0.02), yet in the multivariate model, the P-value was no longer statistically significant. Studies in animals demonstrate that estrogen reduces the size of vascular lesions in carotid arteries and the aorta and accelerates endothelial cell growth in vivo
Riesgo Cardiovascular y osteoporosis
Dr. Juan Carlos Vargas Decamps
Dr. Juan Carlos Vargas Decamps
VIII Congreso Nacional de Osteoporosis
VIII Congreso Nacional de Osteoporosis
Consejo Panameño de Osteoporosis
ño de Osteoporosis
Hard Rock, Panama
Hard Rock, Panama, 19 de Julio 2013
, 19 de Julio 2013
The osteoporosis/arterial calcification
syndrome. Computed tomography
demonstrating severe aortic calcification
(arrow) in a 71- year-old man with an
osteoporotic hip fracture (T score by DEXA:
−3.1 at the spine and −2.6 at the proximal
femur). His risk profile includes type 2 diabetes
mellitus, arterial hypertension and a 60-
packyear history of cigarette smoking
Es la probabilidad que tiene un individuo de contraer
una enfermedad cardiovascular en los próximos 10 años,
basado en el número de factores de riesgo presentes en el
mismo individuo (riesgo cualitativo) o teniendo en
cuenta la magnitud de cada uno de ellos (riesgo
Riesgo Cardiovascular y
•La enfermedad cardiovascular es la
principal causa de muerte en el mundo
•90% de los casos puede ser explicado
por la combinación de factores de riesgo
•El estudios Interheart avalaría la
universalidad de los factores de riesgo
•Factores de riesgo donde podemos
actuar ( dislipemia, tabaquismo, diabetes,
obesidad, sme metabólico, dieta aterogenica,
HDL < 40
Hx Fliar de EC prematura ( < 55 en hombres, < 65
Edad ( ≥45 en hombres/ ≥55 en mujeres)
HDL ≥60 ( resta un factor)
CT, HDL, LDL, TG a todos a partir de los 20ª;
repetir cada 5ª si son normales ( NCEP III)
Hombres a los 40 y mujeres a los 50; antes si
hay algun FRC, pedir CT, HDL, TG ( TWG)
Hombres a los 35 y mujeres a los 45; antes si
hay algun FRC , pedir CT y HDL ( Task Force)
La osteoporosis y las enfermedades cardiovasculares (ECV)
son de las principales preocupaciones de salud, así como
responsables de una gran proporción de la morbilidad y la
mortalidad entre los ancianos. La baja densidad mineral
ósea (DMO), especialmente entre las mujeres
posmenopáusicas, se asocia con una mayor mortalidad
debido a las fracturas osteoporóticas , derrames cerebrales
y enfermedades cardiovasculares La relación entre la
osteoporosis y las enfermedades cardiovasculares en las
mujeres ha sido reconocida por más de 30 años. Boukhris R,
Becker KL “Calcification of the aorta and osteoporosis. A roentgenographic study”. JAMA ,
Riesgo Cardiovascular y
De hecho, se ha estimado que las mujeres con masa ósea en
el cuartil más bajo (medida en la posmenopausia temprana)
tienen el doble de riesgo de muerte por ECV que los del
cuartil más alto
von der Recke P, Hansen MA, Hassager C “The association between low bone mass at the menopause
and cardiovascular mortality” . Am J Med 106:273–278, 1999.
Riesgo Cardiovascular y
Se especula que el mecanismo (s) que une la osteoporosis y
la aterosclerosis actúa a través de factores de riesgo comunes
1. Varios estudios epidemiológicos, han informado de la asociación entre
perfil de lípidos y la DMO. Adami et al, “Relationship between lipids and bone mass in 2 cohorts of
healthy women and men. Calcif Tissue Int 74:136–142, 2004.
2. El papel de la inflamación en la salud vascular y ósea también ha sido
estudiado. Se cree que la aterosclerosis se asocia con una respuesta
inflamatoria en curso, y la disminución de la DMO se ha visto en
individuos con diferentes condiciones inflamatorias crónica que incluye
enfermedades reumáticas, el lupus eritematoso, la enfermedad periodontal
y la enfermedad inflamatoria intestinal. Schett G, “Inflammation-induced bone loss in the
rheumatic diseases”. 2006.
Riesgo Cardiovascular y
Current data, described above, support the hypo- thesis that a common
metabolic pathway links osteoporosis and vascular calcification
1. These two conditions develop gradually with progression of age,
suggesting an inevitable and age -dependent association
2. A possible explanation for this connection is that vascular calcification
affects bone metabolism by reducing blood flow or by limiting physical
activity, leading in turn to bone loss
3. Studies in rats demonstrated that bisphosphonates, at doses comparable
to those that inhibit bone resorption, inhibit calcification of arteries and
valves without affect- ing serum levels of calcium or phosphate
4.This effect is attributable to the protective action of BIS on the vessel
wall; that is, by sensitizing macrophages to undergo apoptosis and by
preventing the formation of foam cells via inhibition of LDL cholesterol
5. In hypertensive rats, bisphosphonates reduced atherosclerosis and
vascular SMC proliferation.
1. In a prospective clinical study, bisphosphonates inhibited the
progression of plaques and abdominal aortic calcifica-tion (AAC) score in
women with osteoporosis whereas vascular calcification progressed in
healthy women who did not receive treatment, suggesting a protective role
for bisphosphonates against atherosclerosis.
2. The MESA abdominal aortic calcium study, for example, showed that,
after adjustment for age and risk factors, lower BMD is associated with
greater coronary artery calcium score among women and with greater
AAC score in both sexes
3. In a 9-year study of 236 women, loss of bone mass during menopause
was significantly greater in those with progression of aortic calcification
than those without.
4. In patients with renal failure undergoing haemodialysis, a significant
negative correlation has been noted between the rate of bone turnover, as
determined from bone biopsy samples, and cardiac calcification score
1.Low BMD in the hip seems to be a marker of advanced atherosclerosis in
2. Carotid intima–media thickness (IMT), a well- known cardiovascular
risk factor, has been related to osteoporosis in many studies.
3. Women with osteoporosis have impaired brachial arterial endothelial
function compared with healthy individuals, as depicted by flow -
mediated vasodilatation after reactive hyperaemia.
4. Arterial stiffness, measured by brachial– ankle pulse wave velocity, is
associated with osteoporosis and coronary artery atherosclerosis, as
determined by multidetector CT.
5. A number of clinical studies have also demonstrated associations
between vascular calcification and risk of osteoporotic fracture , and
between osteoporosis and cardiovascular events
6. In the MINOS Study, which followed 781 men aged ≥50 years for 10
years, higher AAC scores were associated with a twofold to threefold
increase in risk of fractures, regardless of BMD or history of falls.
1. In a group of 2,348 healthy postmenopausal women, degree of aortic
calcification (as measured by use of CT) was significantly and age-
independently associated with bone loss; furthermore, women with
calcification were five times more likely to experience a spine fracture and
three times more likely to have a hip fracture than those without
2. In a population- based cohort study of 2,662 healthy post- menopausal
women, advanced aortic calcification was associated with lower BMD and
a 2.3-fold increased risk of proximal femur fractures after 7.5 years of
observa-tion. An increased risk of fractures, especially vertebral fractures,
and the rate of BMD decline have also been positively associated with
progression of aortic calcifica-tion.
3. Women with osteoporosis have a 4.8- fold higher risk of stroke
compared with women with normal BMD.
4 In another study of the Framingham cohort, women with lower BMD
had greater progression of AAC over a 25-year follow- up period
A population -based cohort study of 16,294 patients showed that heart
failure is associated with factors that contribute to accelerated bone loss
and an increased risk of fractures, in particular a fourfold increase of hip
Osteoporotic fractures and acute cardiovascular events remain the predominant
contributors to morbidity and mortality among the elderly. Postmenopausal women
with osteoporosis are at increased risk for acute cardiovascular events independent of
their age and cardiovascular risk profile, and the increase in risk is proportional to the
severity of osteoporosis at the time of the diagnosis. Bone mineral density (BMD) at
the hip is inversely correlated with the severity of aorta calcification (AC) and hence
low hip BMD can be a surrogate marker of the atherosclerotic burden in elderly
Advanced AC is associated with increased risk of osteoporotic fractures. Collectively,
numerous epidemiological observations document an overlap between the
pathogenesis of the two diseases.
Conclusions:Conclusion The contribution of serum lipids to the modulators of BMD
seem to be via promotion of atherosclerosis, which in turn can affect bone
metabolism locally, especially when skeletal sites supplied by end-arteries are
Using a population-based cohort of older men and women, we tested the
hypothesis that the progression of vascular calcification of the abdominal
aorta should be greatest in those individuals with the greatest amount
of bone loss. From the original population-based Framingham Heart Study
cohort, 364 women and 190 men had lateral lumbar spine and hand
radiographs performed between 1966 and 1970 and repeated between
1992 and 1993. The lateral lumbar films were read for the presence of
aortic calcification using a semiquantitative method, and the hand films
were read for second metacarpal relative cortical area (MCA).
Using multivariate regression techniques, the 25-year progression of the
abdominal aortic calcification index was examined in relation to the change
in the MCA, while adjusting for recognized risk factors for atheroscle-
rotic cardiovascular disease.
During the 25 years of follow- up, the MCA decreased by 22.4% in women
(from 79.6 ± 7.8 (SD) to 61.8 ± 10.3) and by 13.3% in men (from 80.6 ± 6.9 to
69.9 ± 8.3). The aortic calcification score increased over eightfold in
women (from 1.2 ± 2.7 (SD) to 9.9 ± 6.7)
and six fold in men (from 1.6 ± 2.8 to 9.6 ± 6.3). There was a significant
association between percent change in MCA and change in aortic
calcification index (P = 0.01) in women after controlling for all potential
confounders. When we looked at the association between percent change
in metacarpal cortical area and change in aortic cal-cification index we
observed that for each percent decline in metacarpal cortical area, the
aortic calcification index in creased 7.3%. (P= 0.01) in women .
No association was observed in men (P= 0.50), including the 50% of men
with the greatest bone loss.
This is the first longitudinal study to show that women with the
greatest magnitude of bone loss also demonstrate the most severe
progression of abdominal aortic calcification, suggesting that the two
processes may be related,
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.
A decrease in femoral neck BMD by 1 SD below the mean was related to
a 24% increased risk for incident CVD among the women as a group.
In summary, we observed a longitudinal inverse association between
BMD measures and incident CVD in older women and white men with no
prior history of cardiovas- cular disease. These findings provide further
support for a relationship between osteoporosis and CVD that is inde-
pendent of age and shared risk factors.
In Black women , a 1 SD decrease in BMD of the total hip, femoral neck,
and trochanter was related to an increased CVD risk in the order of 36%,
44%, and 34%, respectively.
The association between bone mineral density (BMD) and
myocardial infarction (MI) was investigated in 6,872 men and
women. For both men and women, lower BMD in the femoral neck
and hip was associated with increased risk of MI largely
independent of smoking, hypertension, hypertriglyceridemia, and
Lower BMD of the femoral neck and total hip was associated with
increased risk of MI for both women [hazard ratio (HR) =1.33,
95% confidence interval (CI) 1.08–1.66 per SD decrease in FN BMD
and men (HR = 1.74, 95% CI 1.34–2.28 per SD decrease in total hip
Conclusion Lower BMD was associated with an increase in MI risk
for both men and women. Women had consistently lower HRs
compared to men in all models. Adjusting for smoking,
hypertension, hypertriglyceridemia, and diabetes did not
distinctively weaken these associations
From February 2006 to January 2007, 17,033 women aged 50 years (mean 71.8,
range 50–106) were recruited by 1,248 primary care practitioners and interviewed
by trained nurses. For each woman, 10-year probability of a future major
osteoporotic fracture was estimated using the World Health Organization Fracture
Risk Assessment Tool (FRAX). The study showed that the 10-year probability of a
major osteoporotic fracture was higher for 6,219 CVD women compared to 10,814
non CVD women after adjustment for age, BMI, current smoking, and alcohol use
With regard to high risk of fracture (i.e., 10-year probability 20%), the adjusted
odds ratio for CVD was 1.23 (95% CI 1.13–1.35, P 0.001)
What are cardiovascular diseases?
Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood
vessels and they include:
coronary heart disease – disease of the blood vessels supplying the heart
cerebrovascular disease - disease of the blood vessels supplying the brain;
peripheral arterial disease – disease of blood vessels supplying the arms and
rheumatic heart disease – damage to the heart muscle and heart valves from
rheumatic fever, caused by streptococcal bacteria;
congenital heart disease - malformations of heart structure existing at birth;
deep vein thrombosis and pulmonary embolism – blood clots in the leg veins,
which can dislodge and move to the heart and lungs.
Heart attacks and strokes are usually acute events and are mainly caused by a
blockage that prevents blood from flowing to the heart or brain. The most
common reason for this is a build-up of fatty deposits on the inner walls of the
blood vessels that supply the heart or brain. Strokes can also be caused by
bleeding from a blood vessel in the brain or from blood clots.
What are the risk factors for cardiovascular disease?
The most important behavioural risk factors of heart disease and stroke are
unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol.
Behavioural risk factors are responsible for about 80% of coronary
heart disease and cerebrovascular disease .
The effects of unhealthy diet and physical inactivity may show up in individuals
as raised blood pressure, raised blood glucose, raised blood lipids, and
overweight and obesity.
These “intermediate risks factors” can be measured in primary care facilities and
indicate an increased risk of developing a heart attack, stroke, heart failure and
Cessation of tobacco use, reduction of salt in the diet, consuming fruits and
vegetables, regular physical activity and avoiding harmful use of alcohol have
been shown to reduce the risk of cardiovascular disease.
What are the risk factors for cardiovascular disease?
The cardiovascular risk can also be reduced by preventing or treating
hypertension, diabetes and raised blood lipids.
Policies that create conducive environments for making healthy choices
affordable and available are essential for motivating people to adopt and sustain
There are also a number of underlying determinants of CVDs, or "the causes of
the causes". These are a reflection of the major forces driving social,
economic and cultural change – globalization, urbanization, and population
Other determinants of CVDs include poverty, stress and hereditary factors.