CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
AFRICA
295
Drug Trends in Cardiology
Osteoporosis: a cardiovascular risk factor equivalent to type 2
diabetes
An increasing body of research is showing
a link between osteoporosis and cardio-
vascular disease. The associations are
complex and, in some cases, not yet fully
understood, but the clinical implications
are that healthcare professionals need to
consider their osteoporosis patients as
having as high a risk for heart disease as
those with type 2 diabetes mellitus.
Prof Erik Eriksen, professor of
Endocrinology and Internal Medicine at
Oslo University Hospital, Aker, Norway,
explains further. He was in South Africa
recently at the invitation of Novartis.
‘Bone and blood vessels are closely
linked’, he told local general practitioners
and specialists. ‘To put it simplistically,
as the skeleton loses calcium, that calci-
um builds up in the arterial walls. This
phenomenon is what spurred the interest
in the relationship and led to research
initiatives.’
Bone remodelling – the process where-
by the skeleton constantly repairs itself
– is a dynamic process that becomes
accelerated in osteoporosis, leading to a
negative bone balance. The remodelling
process leads to the release of a variety of
substances (such as cytokines and growth
factors) linking bone to blood vessels.
These are potentially harmful in acceler-
ated states like osteoporosis. Prof Eriksen
quoted some startling findings from the
MORE study undertaken by Tanka
et al
.
in 2005:
•
Osteoporotic women have a 3.9-fold
increased risk of cardiovascular events
relative to women with osteopenia.
•
Each one standard deviation decrease
in bone-mineral density is associated
with a 70% increase in stroke risk.
•
Aortic calcification is an independ-
ent predictor of bone-mineral density
(BMD).
•
There is a graded relationship between
bone loss and progression to vascular
calcification.
•
There is a significant relationship
between risk of myocardial infarction
(MI) and low BMD.
The osteoprotegerin (OPG) and rank
ligand (RANKL) system is thought to
play a role in the relationship between
osteoporosis and cardiovascular disease.
RANKL has been implicated in poten-
tially catastrophic plaque rupture that
can lead to stroke or MI. ‘However, there
are currently some conflicting results in
respect of OPG, based on mouse models’,
said Prof Eriksen.
CTX-1, a bone marker, has also been
shown to have cardiovascular effects.
Prof Eriksen cited an Australian study
in which higher levels of CTX-1 were
associated with higher cardiovascular risk
as well as increased mortality. Conversely,
vitamin K would appear to have positive
effects on bone matrix proteins, so high
levels of vitamin K should be maintained.
There is increasing evidence that
vascular cells acquire osteoblast charac-
teristics and that arterial cells can differ-
entiate into osteoclasts. ‘This means that
when we treat high bone turnover with
anti-resorptive drugs, we also help to
treat cardiovascular disease’, said Prof
Eriksen. ‘Although we’re still not sure
why, we have found that zoledronic acid 5
mg reduces the risk of all-cause mortality
over time. A new study has shown that use
of bisphosphonate is significantly associ-
ated with reduced mortality in the first
three years after hip fracture, very possi-
bly a double effect in that it may also be
protecting against cardiovascular disease.’
In summary, Prof Eriksen reiterated
that, based on a coherent array of results
from animal studies and
in vitro
experi-
ments, numerous factors have been shown
to affect bone and vasculature and that
osteoporotic patients are at increased
cardiovascular risk as a result of their accel-
erated bone turnover. ‘Decarboxylation of
matrix proteins consequent on vitamin
K deficiency and high bone turnover
may constitute an important pathoge-
netic pathway. Treatment with bisphos-
phonates may therefore be of benefit’, he
concluded.
Peter Wagenaar, Gauteng correspondent
