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darah tinggi sebabkan tulang reput
Long-term
effects of antihypertensive medications on bone mineral density in men older than
55 years
Abstract
Introduction
In this study, we
investigated the effects of long-term antihypertensive treatment with calcium
channel blockers or beta blockers on the bone mineral density of maxilla, as
determined by cone-beam computed tomography (CBCT).
Material
and methods
This retrospective study
was conducted on CBCT images of men older than 55 years who had received
different dental indications. Data were grouped into three categories according
to the antihypertensive medication history of the patients: group A included
patients who had been taking beta-blocker treatment for more than 5 years,
group B included patients who had been taking calcium channel blocker treatment
for more than 5 years, and the control group included patients who had never
used any hypertensive medications before.
Results
Statistically significant
differences were observed between the beta blocker and calcium channel blocker
groups.
Conclusion
In hypertension treatment, beta blockers may be preferred to
calcium channel blockers in patients at high risk for osteoporosis and bone
resorption.
Keywords: bone mineral density, CBCT, beta blockers, calcium channel
blockers
Introduction
Osteoporosis is a
metabolic bone disorder defined as “a skeletal disease, characterized by low
bone mass and microarchitectural deterioration of bone tissue, with a
consequent increase in bone fragility and susceptibility to fracture.”1 In
the elderly, with decreasing levels of estrogen and testosterone, bone
resorption exceeds bone formation; thus, the risk of osteoporosis increases. It
has been determined that every third postmenopausal woman and every fifth man
older than 50 years suffers from osteoporosis.2 In
contrast, about two-thirds of the adult population older than 60 years of age
are diagnosed with hypertension, and more than half of all older adults receive
antihypertensive medication.3 Osteoporosis
and hypertension, two very common diseases among adults, have been associated
with a low dairy intake, which could act as a possible pathogenic link between
these two diseases.4
At this time, there are many
classes of antihypertensive medication, and their effects on bone metabolism
have been extensively studied before. In the clinical aspect, beta blockers
have also been shown to improve bone mineral density (BMD) in some studies.5,6 Nevertheless,
Solomon et al did not determine any difference in fracture risk between users
and nonusers of beta blockers.7 In
contrast, the effects of calcium channel blockers, another very widely used
group of antihypertensive medications, on BMD are controversial. Zacharieva et
al found that 8 weeks of amlodipine treatment was not associated with a marked
influence on bone metabolism.8 However,
hypertension is a chronic disease, and these medications are generally used
throughout the life span. In that sense, 8 weeks of treatment may be too short
a time to determine the effects of these medications. Rejnmark et al reported
that the risk of hip fractures was reduced significantly (by 6%) in calcium
channel blocker users. They also reported that nondihydropyridine drugs were
associated with a larger risk reduction compared with dihydropyridine drugs.9 Nonetheless,
in a recent study, Takaoka et al argue that calcium channel blocker treatment
increases both vertebral and nonvertebral fracture risks in patients.10 Cone-beam
computed tomography (CBCT) is a gradually prevalent technology that can
generate high-resolution three-dimensional images of the head-and-neck region
with a short scan time and with greatly reduced radiation exposure compared
with conventional CT. CBCT has been reported to provide identical information
to multislice CT, with a considerable dose reduction.11 The
advantages of CBCT include a lower exposure dose, low cost, fast scanning time,
and lower number of image artifacts compared with CT. CBCT has been used in BMD
measurement in many recent studies.12,13 In
a study by Marquezan et al, a positive correlation was established between the
BMD of total bone block measured by dual-energy X-ray absorptiometry and the
one measured by CBCT.14
In CT imaging, Hounsfield units
(HU), which are the standardized numbers, are used to represent the relative
density of body tissues according to a calibrated gray-level scale, based on
values for air (−1,000 HU), water (0 HU), and bone density (+1,000 HU). HU have
been assessed in the jaw region in many studies and have been reported to be a
useful method of analyzing bone density.15
In this study, we aimed to
investigate the differences between the effects of long-term antihypertensive
treatment with calcium channel blockers and beta blockers on the BMD of maxilla
by using CBCT.
Materials and methods
This study was conducted
at the Faculty of Dentistry, Department of Oral and Maxillofacial Surgery,
Dicle University, Diyarbakır, Turkey. The ethics committee at Dicle University
Faculty of Medicine approved the study (Protocol no 122). The retrospective
study was conducted on CBCT images of male patients older than 55 years who had
received different dental indications. In addition, it was a retrospective way
to determine the control group.
Cone-beam dental volumetric
tomography (I-Cat; Imaging Sciences International, Hatfield, PA, USA) was used
to take images of the maxilla-facial area at a setting of 120 kVp and 3.7 mÅ.
Images were obtained within 10 seconds (the actual exposure time was 9
seconds). Each scan involved a number of separate, small, individual exposures
(up to 440 frames) taken over 360° with a voxel size of 0.300 mm.
The tomography data were
grouped into three categories depending on the antihypertensive medication
history of the patients. Group A consisted of the patients who had been
receiving beta-blocker treatment for more than 5 years, group B comprised the
patients who had been receiving calcium channel blocker treatment for more than
5 years, and the control group included the patients who had never used any
hypertensive medications before. The patients who had a history of any cancers,
diabetes mellitus, Paget’s disease, thyroid dysfunctions, or osteoporosis or
who had received radiotherapy, chemotherapy, or any treatment for osteoporosis
before were excluded from the study. Moreover, the patients with a severe
pathology in their jaw region including defects, tumor, or cyst were also
excluded from the study. The patients with severe maxilla resorption and the
ones with insufficient distance for measurement between the sinus region and
teeth roots were not included in the study.
CBCT
procedure
A total of 294 dental
tomography scans of male patients older than 55 years, all of whom had been
performed for different indications, were evaluated. The CBCT scans were
obtained and reviewed by the same radiologist with the I-Cat Vision program.
The procedure began when all the scans were taken as preview screen images (Figure 1A and B), a 1.8
mm2 area was selected approximately 1 mm away from the apexes
of teeth, and the molar, premolar, canine, incisor teeth, and tuber regions of
maxilla (Figure 1Aand B) and
HU-statistic values were obtained from five different regions of the selected
area. The exact HU-statistic measurements were obtained from the apexes of
incisors (central and lateral), the apex of canine tooth, the apex of
premolars, the apex of molars, and the region of tuber maxilla. Moreover, mean
maxilla values were also determined via the means of these five determinants.
The measurements of patients with partial loss of teeth were also achieved from
the same regions.
Statistical
analysis
The statistical analyses
were performed using SPSS Statistics 18.0 software (IBM Corporation, Armonk,
NY, USA). For the comparison variables, it was used post hoc, as they were
homogeneous and the distribution was normal. Statistical significance level was
accepted at P<0.05.
Results
The subjects included men
older than 55 years; they had a mean age of 58 years. The radiographic
characteristics of all participants are summarized in Table 1. The incisor region of maxilla (P=0.034),
premolar region of maxilla (P=0.013),
and mean value of maxilla (P=0.008) presented significant
differences in the beta blocker and calcium channel blocker groups. The values
of the beta blocker group were better than the values of the calcium channel
blocker group. The values of the calcium channel blocker group were worse than
the control group in all measured areas, and there was no statistically
significant difference in any region between the control and study groups.
Discussion
In this study, by using
CBCT, we determined significantly better BMD values on maxilla among the
patients who had been receiving beta blocker treatment for at least 5 years
compared with the patients who had been receiving calcium channel blockers for
at least 5 years. Because osteoporosis is a very important health problem in
the elderly, especially because of the increased fracture risk, the difference
between these two widely used drug groups is of major importance. Moreover,
osteoporosis and hypertension coexist in many patients, and the use of antihypertensive
drugs could influence the potential effects of these diseases on the bones.
The effects of beta blockers on
BMD have been formerly investigated in several studies. Inactivation of the
sympathetic nervous system impairs osteoclastic bone resorption, and thus
increases bone formation in animal models.16 The
data from human studies about the effects of beta blockers on osteoporosis is
almost the same. Although in some studies improvements on BMD with beta blocker
treatment have been proven,17 in
other studies no effects of these drugs on bone metabolism have been reported.18,19 Similarly,
the effects of beta blockers on fracture risk have also been studied, and they
were found to decrease fracture risk in some studies9,17 and
to be ineffective in others.20,21 In
a recent study, mice were intraperitoneally treated 3 days after ovariectomy,
using nifedipine, telmisartan, enalapril, propranolol, or hydrochlorothiazide
for 35 consecutive days. The study
revealed that the use of enalapril and propranolol compared with the control
group led to increased BMD loss in mice with atrophied uteri and that only
thiazide and telmisartan reduced bone loss and bone fraction in mice with
uterine atrophy compared with in the control group.22
Osteoporosis is the most common
metabolic bone disorder. It is an important public health problem not only
because of its high prevalence but also because of its main complication:
increased fracture risk. Osteoporotic fracture forces a considerable health
burden as a result of reduced mobility, increased requirements for
hospitalization, and increased risk for mortality.23 Hypertension
and osteoporosis coexist in many patients, and this coexistence has been
attributed not only to the high prevalence of both diseases but also to some
environmental, genetic, and dietary factors.24 Although
the data in the literature about the association of hypertension with
osteoporosis are controversial, recently, hypertension has been associated with
increased fracture risk in patients, independent of BMD, in a study.25 In
this respect, antihypertensive treatment gains more importance, and the effects
of these drugs on bone metabolism should be evaluated.
Kapitan-Malinowska et al report
that calcium channel blocker treatment increases serum calcium and inorganic
phosphate concentrations but has no effect on bone turnover markers or BMD.26 In
a study investigating whether amlodipine interferes with healing of rat
alveolar bone, a 20-30% decrease in bone volume fraction in the alveolus of
amlodipine-treated animals was reported, which may be a sign of decreased
osteoblastic activity.27
Takaoka
et al maintained that calcium channel blocker treatment significantly increases
fracture risks after adjustments for age, body mass index, serum creatinine,
and blood pressure levels in patients with type 2 diabetes mellitus.10
However, these significances
disappeared after an additional adjustment for a history of falls. Accordingly,
it can be concluded that calcium channel blocker treatment increases fracture
risks, possibly via falls.
In our
study, the patients receiving calcium channel blocker treatment provided worse
values in BMD than the control group did. However, the difference was not
statistically significant. When compared with beta blocker-treated patients,
beta blocker treatment has significantly positive effects on bone metabolism
compared with calcium channel blockers.
CBCT is a new technique with
lower radiation dosages, lower costs, and faster scanning in dental imaging. In
many studies, it has been used in the determination of bony structures,
especially in presurgical imaging for dental implant treatment and the
measurement of bone density.28,29 Yet
there is still no standardized method or standardized values for the evaluation
of osteoporosis with CBCT. Further studies are warranted to specify
standardized values. If a standardization was established, patients who had to
have a CBCT with dental indications might not need to have an extra dual-energy
X-ray absorptiometry measurement for the evaluation of osteoporosis, and in
this way, one CBCT may serve two purposes.
To the
best of our knowledge, this is the first study in literature comparing the
effects of these two groups of drugs on the bone metabolism of the jaw region
with CBCT.
There are several
limitations to this study. First, the blood pressures of participants were
regarded as normal and stable under drug treatment. Because hypertension itself
may also affect bone metabolism, the changes in blood pressures of participants
may also affect our results. In contrast, drug exposure data are based on
self-report of patients, though it is not the most reliable method in such
research.
Conclusion
It was revealed that the
BMD values on the jaw region with CBCT among patients receiving beta blocker
treatment for more than 5 years provide better results compared with those seen
for the patients treated with calcium channel blockers. Because hypertension
and osteoporosis are two very common diseases and their coexistence is also
very common, the results investigating the effects of different treatment
groups gain more importance. With these results, it can be concluded that in hypertension treatment, beta blockers
may be preferred to calcium channel blockers for patients at high risk for
osteoporosis.
Acknowledgments
The authors are grateful to the
Department of Oral and Maxillofacial Surgery, University of Dicle, Diyarbakır,
Turkey, for their valuable support.
Footnotes
Disclosure
The authors report no
conflicts of interest in this work.
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