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Decreased serum vitamin D in idiopathic benign paroxysmal positional vertigo

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Previous studies have demonstrated an association of osteopenia/osteoporosis with idiopathic benign paroxysmal positional vertigo (BPPV). Since vitamin D takes part in the regulation of calcium and phosphorus found in the body and plays an important role in maintaining proper bone structure, decreased bone mineral density in patients with BPPV may be related to decreased serum vitamin D. We measured the serum levels of 25-hydroxyvitamin D in 100 patients (63 women and 37 men, mean age ± SD = 61.8 ± 11.6) with idiopathic BPPV and compared the data with those of 192 controls (101 women and 91 men, mean age ± SD = 60.3 ± 11.3) who had lived in the same community without dizziness or imbalance during the preceding year. The selection of the controls and acquisition of clinical information were done using the data from the Fourth Korean National Health and Nutrition Examination Survey, 2008. The serum level of 25-hydroxyvitamin D was lower in the patients with BPPV than in the controls (mean ± SD = 14.4 ± 8.4 versus 19.1 ± 6.8 ng/ml, p = 0.001). Furthermore, patients with BPPV showed a higher prevalence of decreased serum vitamin D (<20 ng/ml, 80.0 vs. 60.1 %, p < 0.001) than the controls. Multiple logistic regression analyses adjusted for age, sex, body mass index, hypertension, diabetes, proteinuria, regular exercise and the existence of decreased bone mineral density demonstrated that vitamin D insufficiency (10-20 ng/ml) and deficiency (<10 ng/ml) were associated with BPPV with the odds ratios of 3.8 (95 % confidence interval = 1.51-9.38, p = 0.004) and 23.0 (95 % confidence interval = 6.88-77.05, p < 0.001). Our study demonstrated an association between idiopathic BPPV and decreased serum vitamin D. Decreased serum vitamin D may be a risk factor of BPPV.
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ORIGINAL COMMUNICATION
Decreased serum vitamin D in idiopathic benign paroxysmal
positional vertigo
Seong-Hae Jeong Ji-Soo Kim Jong Wook Shin Sungbo Kim
Hajeong Lee Ae Young Lee Jae-Moon Kim Hyunjin Jo
Junghan Song Yuna Ghim
Received: 9 August 2012 / Revised: 3 October 2012 / Accepted: 5 October 2012
ÓSpringer-Verlag Berlin Heidelberg 2012
Abstract Previous studies have demonstrated an associ-
ation of osteopenia/osteoporosis with idiopathic benign
paroxysmal positional vertigo (BPPV). Since vitamin D
takes part in the regulation of calcium and phosphorus
found in the body and plays an important role in main-
taining proper bone structure, decreased bone mineral
density in patients with BPPV may be related to decreased
serum vitamin D. We measured the serum levels of
25-hydroxyvitamin D in 100 patients (63 women and 37
men, mean age ±SD =61.8 ±11.6) with idiopathic
BPPV and compared the data with those of 192 controls
(101 women and 91 men, mean age ±SD =60.3 ±11.3)
who had lived in the same community without dizziness or
imbalance during the preceding year. The selection of the
controls and acquisition of clinical information were done
using the data from the Fourth Korean National Health and
Nutrition Examination Survey, 2008. The serum level of
25-hydroxyvitamin D was lower in the patients with BPPV
than in the controls (mean ±SD =14.4 ±8.4 versus
19.1 ±6.8 ng/ml, p=0.001). Furthermore, patients with
BPPV showed a higher prevalence of decreased serum
vitamin D (\20 ng/ml, 80.0 vs. 60.1 %, p\0.001) than
the controls. Multiple logistic regression analyses adjusted
for age, sex, body mass index, hypertension, diabetes,
proteinuria, regular exercise and the existence of decreased
bone mineral density demonstrated that vitamin D insuffi-
ciency (10–20 ng/ml) and deficiency (\10 ng/ml) were
associated with BPPV with the odds ratios of 3.8 (95 %
confidence interval =1.51–9.38, p=0.004) and 23.0
(95 % confidence interval =6.88–77.05, p\0.001). Our
study demonstrated an association between idiopathic
BPPV and decreased serum vitamin D. Decreased serum
vitamin D may be a risk factor of BPPV.
Keywords Benign paroxysmal positional vertigo
Vertigo Nystagmus Vitamin D
Introduction
Benign paroxysmal positional vertigo (BPPV) is one of the
most common vestibular disorders [1]. The mechanism of
BPPV has well been established as free-floating otolith
debris (canalolithiasis) [2] or debris attached to the cupula
(cupulolithiasis) [3]. Until now, advanced age, head
trauma, various disorders affecting the inner ear, and
female sex are known predisposing factors of BPPV.
However, there is a paucity of data on the underlying cause
S.-H. Jeong J. W. Shin S. Kim A. Y. Lee J.-M. Kim
H. Jo
Department of Neurology, Chungnam National University
College of Medicine, Chungnam National University Hospital,
Daejeon, Korea
J.-S. Kim (&)
Department of Neurology, Seoul National University College
of Medicine, Seoul National University Bundang Hospital,
300 Gumi-dong, Bundang-gu, Seongnam-si,
Gyeonggi-do 463-707, Korea
e-mail: jisookim@snu.ac.kr
H. Lee
Department of Internal Medicine, Seoul National University
Hospital, Seoul, Korea
J. Song
Department of Laboratory Medicine, Seoul National
University College of Medicine, Seoul National University
Bundang Hospital, Seongnam, Korea
Y. Ghim
Division of Health and Nutrition Survey, Osong Health
Technology Administration Complex, Chungbuk, Korea
123
J Neurol
DOI 10.1007/s00415-012-6712-2
of otoconial degeneration and detachment from the
otoconial beds.
The otoconia are composed of calcium carbonate as
calcite crystals and an organic core consisting predomi-
nantly of glycoproteins [4,5]. Recently, we reported that
the prevalence of osteopenia/osteoporosis was higher in
both women and men with idiopathic BPPV than in con-
trols [6]. These findings suggest a deranged calcium
metabolism in idiopathic BPPV. In a number of epithelia,
transmural absorption of Ca
2?
is modulated by a set of
genes that encodes the epithelial Ca
2?
channel transport
system. This system includes the apical entry channels
(TRPV5 and TRPV6), the cytosolic Ca
2?
buffering pro-
teins (calbindin-D9 K and calbindin-D28 K), and the
basolateral Ca
2?-
extruding transporters (sodium–calcium
exchangers and plasma membrane calcium ATPases) [7].
A recent experimental study demonstrated that all com-
ponents of this epithelial Ca
2?
channel transport system are
expressed as transcripts in the semicircular canal duct and
cochlea. Even though lesser than the bone, the utricular
otolith is also generated by dynamic Ca
2?
uptake, and this
process is related to Ca
2?
-binding proteins that are
up-regulated by vitamin D. In addition, while the wild type
mice have robust vitamin D receptor expression in the
vestibular organs, the mice without vestibular D receptor
show vestibular dysfunction [810]. Based on these find-
ings, we hypothesized that low serum vitamin D could be
associated with development of BPPV.
Methods
Study design and patients
At the dizziness clinic of the Chungnam National Univer-
sity Hospital, 100 consecutive patients, 63 women (age
range =26–81 years, mean ±SD =60.0 ±12.2 years)
and 37 men (age range =42–83 years, mean ±SD =
64.8 ±9.7 years), with a diagnosis of idiopathic BPPV
had been recruited between September 2010 and May
2011, after excluding 26 patients with a history of inner ear
diseases, four patients with a history of head trauma during
the preceding month, and three patients who declined the
study. Eighty-four patients who reported a typical history
suggestive of BPPV but did not exhibit positional nystag-
mus during the positional maneuvers were also excluded.
We compared the serum levels of 25-hydroxyvitamin D in
the patients with those of 192 community-based controls
without dizziness or imbalance within 1 year. The control
data were obtained from the Fourth Korea National Health
and Nutrition Examination Survey, 2008, which had been
previously conducted by the Korea Centers for Disease
Control and Prevention. Since immobilization due to
dizziness itself may affect the serum vitamin D level, we
also compared serum vitamin D levels among the controls
and 397 persons who were excluded from the controls
because of a history of vertigo/dizziness or imbalance
during the preceding year. This comparison also allowed us
to determine the effect of possible selection bias from
excluding the controls with a history of dizziness and
imbalance irrespective of underlying etiologies. This study
received an approval from Institutional Review Board of
Chungnam National University Hospital.
Selection of the control group
The controls were selected from the data base of the
National Survey based on the following criteria: (1) no
history of vertigo/dizziness or imbalance within one year,
(2) measurement of bone mineral density and serum vita-
min D, and (3) living in Daejeon city and Chungchung
province. Of the 10,065 national survey responders (2008),
193 community-based controls met the above inclusion
criteria.
Neurotological evaluation
All patients underwent detailed evaluation for spontaneous
nystagmus, vibration-induced nystagmus, head-shaking
nystagmus, hyperventilation-induced nystagmus, and
positional nystagmus in addition to routine neurological
examination. Examinations of the patients were conducted
by a trained neurotologist (SHJ) and two residents (JWS
and SBK) who had training for more than three years in the
neurology department.
Positional maneuvers included (1) bending the head
toward the knees while sitting, (2) lying down from a
sitting upright posture, (3) turning the head to either side
while supine, (4) sitting up from supine, (5) straight head
hanging, and (6) the Dix-Hallpike maneuver to either
side.
A diagnosis of BPPV was based on (1) a history of a
brief episode of vertigo induced by head motion, (2) a
typical positioning nystagmus characteristic of BPPV, and
(3) no other identifiable disorders of the central nervous
system. When the nystagmus suggested that two or more
canals were involved (different patterns of nystagmus
depending on the provoking positional maneuvers), the
mixed type BPPV was diagnosed. When repeated canalith
repositioning maneuvers did not result in resolution of the
symptoms and positional nystagmus, brain imaging was
performed to rule out central pathologies [6].
Recurrent BPPV was defined when the patients reported
two or more previous episodes of positional vertigo similar
to those experienced at the time of diagnosis, at least
one month apart [6].
J Neurol
123
Measurement of serum vitamin D
Fasting early morning venous blood was collected from
patients and controls to measure serum 25-hydroxyvitamin
D. In the patients, the serum level of 25-hydroxyvitamin D
was measured using a chemiluminescence immunoassay
(CLIA) on Liaison equipment (Diasorin
Ò
, USA). Since the
serum concentration of 25-hydroxyvitamin D was measured
with
125
I-radioimmunoassay (RIA, Diasorin
Ò
, USA) in the
controls, we standardized the values using the central labo-
ratory data. For standardization, we got a regression equation
between the CLIA and LC–MS/MS by measuring serum
vitamin D in 40 samples using both methods and we also
obtained another regression equation between the RIA and
LC–MS/MS with the same procedures. Using both equations,
we finally deducted the regression equation between CLIA
and RIA methods, and converted the CLIA values to RIA
values using this final regression equation; CLIA =1.119 9
RIA -1.887. These standardization procedures followed
the CLSI EP-9 guidelines recommended by the Clinical and
Laboratory Standards Institute Consensus Process [11]. The
serum vitamin D level was classified as normal ([20 ng/ml),
insufficient (10–20 ng/ml), or deficient (\10 ng/ml) [1214].
Bone densitometry
Bone densitometry (BMD) was performed using dual x-ray
absorptiometry (Hologic
Ò
, USA) in the lumbar spine and
femur. Detailed methods have been described previously
[6]. Osteoporosis was determined when the Tscore was
-2.5 or less [15].
Statistical analyses
Statistical analyses included v
2
test for dichotomous vari-
ables and ttest for continuous variables for comparison
among the groups. Multiple logistic regression analyses
were adjusted for the same relevant covariates. All tests
were performed using SPSS (version 17.0, SPSS, Chicago,
IL), and p\0.05 was considered significant.
Results
Demographic characteristics
The patients comprised of 63 women and 37 men (female-
to-male ratio =1.7:1). The patient age ranged from 26 to
83 years (mean age ±SD =61.8 ±11.6 years). The
BPPV most commonly occurred in the sixth decade of life
in both women and men, but the mean age was slightly
higher in men than in women (64.8 ±9.7 vs. 60.0 ±12.2,
p=0.044). The duration of symptoms until the initial
evaluation varied from 1 to 14 days (mean =5.8, med-
ian =1.0). Most (82 %) of the patients were evaluated
within a week from the symptom onset. There was no
difference either in the age and sex ratio between the
patients and controls (Table 1). The BMI was rather higher
in the patients (24.9 ±3.4 vs. 23.3 ±3.6, p=0.001).
Characteristics of BPPV
BPPV most commonly involved the posterior canal
(n=51, 51 %), which was followed by the horizontal
(n=39, 39 %) and anterior canal (n=8, 8 %). In two
patients (2 %), both posterior and horizontal canals were
affected. Isolated horizontal canal BPPV included 22
geotropic and 17 apogeotropic types. Recurrent attacks of
BPPV were reported in 44 patients.
25-hydroxyvitamin D
Serum level of 25-hydroxyvitamin D was lower in the
patients with BPPV than in the controls (mean ±SD
=14.4 ±8.4 vs. 19.0 ±6.8 ng/ml, p=0.001), both in
men (16.2 ±8.9 vs. 19.1 ±6.8 ng/ml, p=0.048) and
women (13.4 ±8.0 vs. 18.9 ±6.7 ng/ml, p\0.001).
Furthermore, the patients with BPPV showed a higher
prevalence of decreased serum vitamin D (\20 ng/ml, 80.0
vs. 60.4 %, p\0.001, Fig. 1) than the controls. However,
these features were not observed in the 397 community
inhabitants who were excluded from the controls due to an
experience of dizziness or imbalance during the preceding
year (mean ±SD =18.1 ±6.8 vs. 19.0 ±6.8 ng/ml,
p[0.05). In the patients, the vitamin D level did not differ
between the recurrent and de novo groups.
Bone mineral densitometry
The proportions of osteoporosis (Tscore B-2.5, 45.0 vs.
9.4 %, p\0.001) were higher in patients with BPPV than
in controls.
Multiple logistic regression analysis
Multiple logistic regression analyses adjusted for age, sex,
BMI, the existence of decreased bone mineral density,
vitamin supplements, diabetes, hypertension, proteinuria
and regular exercise demonstrated that vitamin D insuffi-
ciency and deficiency were associated with BPPV with the
odds ratios of 3.8 (95 % confidence interval =1.51–9.38,
p=0.004) and 23.0 (95 % confidence interval =
6.88–77.05, p\0.001). Osteoporosis and increased BMI
were also risk factors for BPPV (Table 2, Model 2).
Even after excluding the decreased BMD from the vari-
ables, the association between BPPV and vitamin D
J Neurol
123
insufficiency/deficiency remained significant. The C-sta-
tistic was measured at 0.852 for the multiple logistic
regression analysis model adopted in this study, which also
indicated the validity of our model.
Discussion
Even though the impact of vitamin D deficiency on muscu-
loskeletal health, and association of hypovitaminosis D with
cancer, cardiovascular disease, diabetes and autoimmune
disorders have been well established, the role of vitamin D in
the generation of BPPV has not been considered [16,17]. In
this study, we found that the serum level of vitamin D is
decreased in patients with idiopathic BPPV with an average
difference of 4.5 ng/ml. This finding was independent of age,
gender, BMI, and decreased BMD, which suggests that
decreased serum vitamin D could be a risk factor for BPPV.
Even though the clinical significance of the average differ-
ence at 4.5 ng/ml is unknown, a larger proportion of the
patients had vitamin D insufficiency than the normal controls
(80.0 vs. 60.4 %, p\0.001) with this average difference.
Indeed, according to a recent study, the vitamin D insuffi-
ciency is associated with a 24 % increase in the risk for
myocardial infarction, cancer, hip fracture, or death [18].
Correlation between BPPV and Vitamin D
BPPV is explained by otolithic debris dislodged from the
otoconial bed [19,20]. Since otoconia is composed of cal-
cium carbonate, normal otoconial formation requires locally
increased concentration of Ca
2?
and carbonate (CO
3-
)to
initiate crystal formation on the proteinaceous core [21].
On the contrary, it is also important to maintain the
Table 1 Clinical characteristics
of patients and controls
BPPV benign paroxysmal
positional vertigo, BMI body
mass index, the body mass
index is the weight in kgs
divided by the square of the
height in meters. SD standard
deviation
pvalues were calculated using
independent ttest or Chi-square
test
Bold values indicate statistical
significance (p\0.05)
Characteristics BPPV (n=100) Controls (n=192) pvalue
Age, mean ±SD (years) 61.8 ±11.6 60.3 ±11.3 [0.05
Male sex (%) 37 (37.0) 92 (47.4) [0.05
BMI (kg/m
2
) 24.9 ±3.4 23.3 ±3.6 0.001
25-hydroxyvitamin D (ng/ml) 14.4 ±8.4 19.1 ±6.8 0.001
Bone mineral density <0.001
Normal 24 (24.0) 91 (47.4)
Osteopenia 31 (31.0) 83 (43.2)
Osteoporosis (%) 45 (45.0) 18 (9.4)
Vitamin supplements
Yes (%) 22/100 (22.0) 33/173 (19.1) [0.05
Missing 0 19
Diabetes
Yes (%) 10/100 (10.0) 21/192 (10.9) [0.05
Hypertension
Yes (%) 36 (36.0) 51/192 (26.6) [0.05
Proteinuria
Mild (trace to 1?) 10 (10) 15/183 (8.2) [0.05
Heavy (2?to 4?) 0 (0) 6/183 (3.3)
Missing 0 9
Regular exercise
Yes 28 (28.0) 43/192 (22.4) [0.05
Fig. 1 Proportion of vitamin D deficiency and insufficiency in the
patient and control groups. The proportions of vitamin D insufficiency
(10–20 ng/ml) and deficiency (\10 ng/ml) were higher in patients
with benign paroxysmal positional vertigo (BPPV) than in controls
(p\0.001)
J Neurol
123
Ca
2?
concentration low in the vestibular endolymph to pro-
hibit unnecessary mineralization of the rest of the endolymph
[10]. Our previous study indicated an association between
idiopathic BPPV and osteopenia/osteoporosis [6]. Also, it
was suggested that increased calcium resorption reduces the
capacity to dissolve the dislodged otoconia owing to
increased concentration of free calcium in the endolymph
[22]. Other experimental studies demonstrated an important
role of epithelial calcium channels (calbindins), Na
?
/Ca
2?
exchangers, and plasma membrane Ca
2?
pumps in transepi-
thelial absorption of Ca
2?
from the endolymph of the inner
ear [10]. These structures mainly contribute to temporal and
spatial modulation of Ca
2?
concentration in the endolymph to
maintain the environment adequate for calcium homeostasis.
Furthermore, the expression of some Ca
2?
binding proteins
(epithelial Ca
2?
channels such as calbindin-D9 k and cal-
bindin-D28 k) is up regulated by 1, 25-dihydroxyvitamin D
3
in the epithelial cells of rat semicircular canal ducts [10].
Therefore, we may assume that vitamin D deficiency con-
tributes to generation of BPPV via deranged calcium
metabolism in the vestibular organs [22,23]. However,
establishment of the causal link between BPPV and decreased
vitamin D would require animal experiments and eventuallya
clinical trial that looks for preventive effects of vitamin D
supplementation on recurrence of BPPV in patients with
BPPV and low serum vitamin D.
Vitamin D receptor in the vestibular organs
Vitamin D is best known for its role in homeostasis of
calcium and phosphorus. However, the vitamin D receptor
(VDR) is present in the cells throughout the body, and is
involved in cell proliferation and differentiation as well as
immunomodulation [24]. The functions of vitamin D are
mediated through the nuclear VDR. A previous study
detected the VDRs in the nuclei of the epithelium lining the
crista ampullaris, membranous semicircular canal, and the
surrounding osteocytes in mice [25]. Furthermore, VDR
mutant mice showed decreased performance during eval-
uation of the balance function using the accelerating rota-
rod, tilting platform, rotating tube, and the swim test, which
also suggests that decreased vitamin D could cause ves-
tibular dysfunction, likewise in BPPV [25].
Low vitamin D in BPPV; cause versus just bystander?
The serum level of vitamin D is influenced by various
factors including nutritional status and exposure to sun.
Accordingly, the nausea and vomiting frequently associ-
ated with vertigo attacks may have affected serum vitamin
D level in patients with BPPV. To assess possible effects of
malnutrition, we measured BMI in each group. However,
BMI was rather increased in patients BPPV. The recruit-
ment of controls from the local community may have
minimized the weather effects, if any. To avoid a bias from
diurnal fluctuation of serum vitamin D level, we obtained
the fast blood sample of the patients in the morning after
complete resolution of BPPV.
Also, the possible immobilization due to vertigo may
have affected serum vitamin D level in patients with
BPPV. To assess this effect, we also compared serum
vitamin D among the controls and 397 community resi-
dents who were excluded from the controls due to a history
of vertigo/dizziness or imbalance during the preceding
year. However, the serum vitamin D level did not differ
between the groups. This indicates that the presence of
dizziness/vertigo itself may have not caused low serum
vitamin D in our patients with BPPV.
This study also confirms our previous observation that
osteoporosis were associated with BPPV, which was the
result of a study conducted in another area of Korea [6,22,
26]. In that study, even though we did exclude the possible
confounding effects of known predisposing factors for
osteoporosis such as smoking, alcohol consumption, and
Table 2 Independent predictors of BPPV using multiple logistic
regression analyses
Model/variables Odds
ratio
pvalue 95 % CI
Model 1
Age (continuous) 1.0 [0.05 0.97–1.03
Female 1.7 [0.05 0.91–3.35
BMI (continuous) 1.2 0.002 1.06–1.28
Serum vitamin D
Insufficiency (10–19 ng/dl) 2.4 0.025 1.12–5.06
Deficiency (\10 ng/dl) 14.1 <0.001 5.17–38.33
Model 2
Age (continuous) 1.0 [0.05 0.95–1.02
Female 1.2 [0.05 0.58–2.54
BMI (continuous) 1.19 0.002 1.07–1.33
Serum vitamin D
Insufficiency (10–19 ng/dl) 3.8 0.004 1.51–9.38
Deficiency (\10 ng/dl) 23.0 <0.001 6.88–77.05
Bone mineral density
Osteopenia
(-2.5 \T-score \-1.0)
1.4 [0.05 0.61–3.31
Osteoporosis (T score B-2.5) 14.9 <0.001 5.19–42.70
BPPV benign paroxysmal positional vertigo, BMI body mass index,
the body mass index is the weight in kilograms divided by the square
of the height in meters
Model 1 age, sex, BMI, the existence of decreased bone mineral
density, vitamin supplements, diabetes, hypertension, proteinuria and
regular exercise
Model 2 included bone mineral density as a variable in addition to
those adopted in model 1
Bold values indicate statistical significance (p\0.05)
J Neurol
123
glucocorticoid medication, chronic renal failure, serum
levels of the calcium, phosphate, and uric acid, and
decreased BMI, we did not measure the serum level of the
vitamin D. The results of the current study suggest a
relationship between decreased serum vitamin D and an
association of osteoporosis with BPPV.
Of interest, patients with BPPV showed increased BMI
in this study. The association between BPPV and increased
BMI has been debated in the previous studies [6,27].
However, serum vitamin D decreases in obesity, and the
lower vitamin D would induce a compensatory increase in
serum parathyroid hormone. This in turn may promote
weight gain by increased calcium influx into adipocytes
and lipogenesis [2830]. Furthermore, obesity itself is also
considered to be a risk factor for hypovitaminosis D. One
of the most plausible explanations is enhanced uptake of
25-hydroxyvitamin D by the adipose tissue [31].
Our study showed that the prevalence of vitamin D
deficiency/insufficiency is around 60 % even in a ‘‘normal
population’’. Since the optimal concentration of serum
vitamin D is defined by the 25-hydroxyvitamin D level that
maximally suppresses secretion of the parathyroid hor-
mone, a large proportion of a normal population may have
serum vitamin D below the optimal level [32,33]. Indeed,
the proportion of vitamin D deficiency/insufficiency varied
from 8 to 90 % depending on the age, sex, and ethnicity. A
previous study also measured serum vitamin D less than
20 ng/ml in 47.3 % of Korean men and 64.5 % of Korean
woman, thus demonstrating that vitamin D insufficiency/
deficiency is also common in Koreans [34].
Acknowledgments Dr. J.S. Kim was supported by a grant of the
Korea Health 21 R&D Project, Ministry of Health and Welfare,
Republic of Korea (A080750). Dr. S-H. Jeong conducted the statis-
tical analyses with the help of the Chungnam National University
Hospital Research Institute of Clinical Medicine (Prof. Suk-Hoon Lee
and Jieun Shin).
Conflicts of interest All authors have no conflicts of interest.
Ethical standard All human study must state that have been
approved by the appropriate ethics committee and have, therefore,
been performed in accordance with the ethical standards laid down in
the 1964 Declaration of Helsinki.
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... As a result, vitamin D deficiency can change the dynamic turnover of otoconia, which is composed of calcium carbonate. Any change in otoconia's composition may lead to easier dislodgment and eventually the formation of the otolith, which could cause BPPV (12,13). This study aims to measure the vitamin D level in patients with BPPV who visited Loghman Hakim Hospital clinics and compare the results with controls. ...
... Therefore, vitamin D deficiency may predispose humans to impaired balance or posture control (18). Vitamin D is essential for calcium and bone homeostasis, so there is an association between bone marrow biomarkers and BPPV (13,19,20). Vitamin D supplemented also is more effective than calcium in reducing falling of elderly people through decreasing the recurrences of BPPV (21). ...
... In addition to increasing severity, the number of attacks, and symptoms, vitamin D deficiency can play a role as a risk factor for BPPV. Based on a case-control study consisting of 100 patients and 192 controls, low vitamin D levels were detected to be a risk factor for BPPV (13). Twenty nine patients with BPPV were included to assess the hypothesis that BPPV is an indicator of a decline in bone density. ...
... As a result, vitamin D deficiency can change the dynamic turnover of otoconia, which is composed of calcium carbonate. Any change in otoconia's composition may lead to easier dislodgment and eventually the formation of the otolith, which could cause BPPV (12,13). This study aims to measure the vitamin D level in patients with BPPV who visited Loghman Hakim Hospital clinics and compare the results with controls. ...
... Therefore, vitamin D deficiency may predispose humans to impaired balance or posture control (18). Vitamin D is essential for calcium and bone homeostasis, so there is an association between bone marrow biomarkers and BPPV (13,19,20). Vitamin D supplemented also is more effective than calcium in reducing falling of elderly people through decreasing the recurrences of BPPV (21). ...
... In addition to increasing severity, the number of attacks, and symptoms, vitamin D deficiency can play a role as a risk factor for BPPV. Based on a case-control study consisting of 100 patients and 192 controls, low vitamin D levels were detected to be a risk factor for BPPV (13). Twenty nine patients with BPPV were included to assess the hypothesis that BPPV is an indicator of a decline in bone density. ...
Article
Background: Benign paroxysmal positional vertigo (BPV) is the most common cause of the high prevalence of vertigo. Today, BPV is caused by the separation of autochthonous particles from the macular atrial. As a result, these particles float in a semicircular canal and change position by gravity. The majority of vertigo causes arise from the inner ear. Aim: This study aims to measure the vitamin D level in patients with BPPV who visited Loghman Hakim Hospital clinics and compare the results with controls. Methods: This comparative study evaluated the effect of vitamin D on reducing BPV. Demographic information of patients was collected through interviews. The physical examinations were recorded through a questionnaire. For the group with BPPV, we did the Epley maneuver and measured the vitamin D level. We compared the vitamin D levels of these patients with the matched control group. Results: In this study, 148 patients were evaluated. Sixty-three patients were male, and 85 patients were female. All case and control patients were tested for vitamin D levels. Of 93 patients with benign vertigo, 39 (41.9%) patients had normal vitamin D levels, and 54(58.1%) patients had below normal. In the control group, 43 (78.2%) patients had normal vitamin D, and 12 (21.8%) patients had less than normal. There was a statistically significant difference between the two groups. Conclusion: The present study indicated that BPV was more prevalent in people with vitamin D deficiency, and vitamin D treatment could effectively control and reduce the prevalence of this disease.
... Several studies have observed the relationship between the deficit of theses micronutrients and BPPV. [7][8][9][10] The function of the semicircular canals and otoliths reduces with time. 11 With aging, there is a degeneration of the type I and II sensitivity ciliary cells. ...
... 3 Jeong et al. demonstrated that in patients with values between 10 and 20 ng/ml, the risk of having BPPV increased 3.8 times, while in patients with levels < 10 ng/ml, the risk was 23 times higher. 8 Sheikhzadeh et al. did an experimental study that became a role model for ours, in which he divided patients into two groups; the first was composed of patients with BPPV treated with both vitamin D supplements and repositioning maneu-vers and the second was a control group treated with the conventional maneuvers. The intensity of the disease was aggravated in the control group patients, compared with a state of stability without vertigo episodes during 6 months in the supplemented group (p ¼ 0.001). ...
Article
Introduction Benign paroxysmal positional vertigo (BPPV) appears during the same age group in which vitamin D and calcium deficiencies are evident. Vitamin D deficiency could predispose to BPPV, since these two entities share a demineralization process. Objective To establish the otological impact of vitamin D supplementation in patients with its deficiency who suffer from BPPV. Methods This was a randomized clinical trial. A total of 35 patients with vitamin D deficiency (< 30 ng/ml) and BPPV were divided into 2 groups: Group 1 (control group): treatment with repositioning maneuvers; and Group 2: treatment with repositioning maneuvers and vitamin D supplementation. Results A follow-up of between 6 and 13 months and a log rank test revealed that the probability of recurrence between the experimental groups was significantly different, with group 2 having a decreased recurrence of vertigo (p = 0.17). Scores in the Dizziness Handicap inventory (DHI) in patients treated with vitamin D supplementation were smaller (10 ± 9) when compared with a score of 36 ± 9 in the control group. Conclusion Plasmatic values of 25-hydroxyvitamin D have an impact in patients with BPPV, who present an improvement in their quality of life when their vitamin D levels are replaced with supplementation. Benign paroxysmal positional vertigo could stop being perceived as a purely otologic disease.
... This is achieved by the epithelial calcium channel transport system found in the labyrinth, which is maintained by vitamin D receptors. 18 Vitamin D deficiency leads to the production of abnormal otoconia, which results in otolith dysfunction. ...
Article
Full-text available
p>Vertigo is defined as a false sensation of movements where a patient gets a rotating perception of the environment or oneself. Vertigo and dizziness are commonly experienced during the pregnancy period and are among the most common complaint by pregnant women to the primary care physicians. Vertigo during pregnancy affects the quality of life of women and also has an impact on the fetus. Pregnancy is an important nine-month physiological period of female life. During pregnancy, the body of the female undergoes several physiological changes that affect all systems and organs, including sensory ones. There are significant changes during pregnancy including otological and neurotological manifestations. Vertigo/dizziness is a common complaint during pregnancy to the clinicians. Benign paroxysmal positional vertigo (BPPV), Meniere’s disease (MD), vestibular neuritis and vestibular migraine are common vestibular disorders result in vertigo during pregnancy. Vertigo during pregnancy directly affects the pregnant mother both mentally and physically. A multidisciplinary approach by otolaryngologists, neurologists, and gynaecologist and obstetricians is required for proper evaluation and management of vertigo in pregnant women. Currently, there are no guidelines for the management of vertigo in pregnancy. Little has been reported about vertigo during pregnancy. We performed a narrative review of vertigo in pregnant women.</p
... Furthermore, studies have examined the relationship between Ca-related diseases and BPPV [9]. In addition to studies indicating that BPPV patients have lower levels of vitamin D than controls, and some case studies have shown severe vitamin D deficiency in patients who chronically suffer from BPPV recurrence [10][11][12]. ...
Article
Introduction Benign paroxysmal positional vertigo (BPPV) is a type of vertigo and its signs are short-time, severe attacks that occur in certain head and body positions. Recent studies have revealed that vitamin D deficiency correlates with BPPV and this is explained by cupulolithiasis and canalithiasis theories. Method In the present study, levels of serum vitamin D in the patients who were diagnosed as BPPV and those in the control group consisting of healthy individuals were investigated. In addition, it was examined whether vitamin D is influential on the rates of BPPV types. In our study, 258 patients who were diagnosed with BPPV after detailed ear-nose-throat and neurology examinations were examined. We compared the control group according to their ages, genders, and levels of vitamin D. In addition, we divided the BPPV group into two sub-groups according to their vitamin D levels (20-30 ng/ml and 20 g/ml lower), and each was compared by calculating vertigo types and ratios. Results The BPPV group included 187 females and 71 males, and their mean age was 43.70 ± 15.44. The control group consisted of 65 females and 35 males, and the mean age of this group was 44.63 ± 15.42. The mean vitamin D levels of the females and males were 18.42 ± 5.07 and 19.82 ± 5.11, respectively, in this study. On the other hand, the mean vitamin D levels of healthy females and males were found to be 30.88 ± 10.74. Conclusion Our study found that the vitamin D levels of the individuals in the BPPV group were statistically significantly lower than those of the individuals who were in the control group. However, it was observed that vitamin D did not affect the rate of vertigo subtypes.
... Benign paroxysmal positional vertigo recurrence refers to the occurrence of similar previous symptoms after successful repositioning. [18] The probability of BPPV recurrence after follow-up for one year is 15 to 20% and, therefore, the researchers have endeavored to predict its recurrence. [19] In this study, the plotted ROC curve exhibited that serum estradiol, calcium, and 25(OH)D levels had diagnostic values for BPPV recurrence in postmenopausal women. ...
Article
Full-text available
Objectives: This study aims to explore the predictive values of serum estradiol, calcium and 25-hydroxyvitamin D [25(OH)D] levels for benign paroxysmal positional vertigo (BPPV) recurrence in postmenopausal women. Patients and methods: A total of 156 postmenopausal women (mean age: 59.5±7.4 years; range, 46 to 75 years) diagnosed with primary BPPV between January 2015 and August 2018 were included. After follow-up for one year, they were divided into non-recurrence (n=126) and recurrence groups (n=30). Fifty healthy females (mean age: 60.3±7.4 years; range, 48 to 75 years) with natural menopause for over one year were enrolled as the control group. Serum estradiol, calcium and 25(OH)D levels were compared, and their correlations in the recurrence group were analyzed by Pearson method. The predictive values of these levels for recurrence were evaluated using the receiver operating characteristic curve. Predisposing factors were determined by univariate and multivariate logistic regression analyses. Results: Serum estradiol, calcium, and 25(OH)D levels of the control group were significantly higher than the non-recurrence and recurrence groups (p<0.05). The levels of recurrence group exceeded those of non-recurrence group (p<0.05). In recurrence group, estradiol level was positively correlated with those of calcium and 25(OH)D (r=0.7501, 0.7871, p<0.001), and calcium level was positively correlated with that of 25(OH)D (r=0.7904, p<0.001). The three levels had diagnostic values for recurrence. The maximum Youden’s index of their combination was 0.476, and the corresponding prognostic index was 13.04, suggesting a higher recurrence probability. Number of repositioning, Self-Rating Depression Scale score, levels of estradiol, calcium and 25(OH)D were predisposing factors for recurrence. Conclusion: Serum estradiol, calcium, and 25(OH)D levels are significantly positively correlated in postmenopausal women with BPPV recurrence and their combination can be used to predict recurrence.
Article
Amaç: Kliniğimize baş dönmesi şikâyeti ile başvurup idiopathic benign paroksismal pozisyonel vertigo (BPPV) tanısı alan hastalar ile baş dönmesi olmayan sağlıklı kontrol grubunun 25-hidroksi vitamin D (25-OH vitamin D) ve Ca2+ düzeylerinin karşılaştırılması Ca2+ ve 25-OH vitamin D’nin BPPV gelişimindeki rolünün araştırılmasıdır. Gereç ve Yöntem: Çalışmamız geriye dönük vaka kontrol çalışması olup, 01.01.2018-01.08.2021 arası Alanya Egitim ve Araştırma Hastanesi Nöroloji polikliniğine başvuran İdiopatik BPPV tanısı alan 409 hasta ile kontrol grubu olarak kliniğimize başvuru öncesi son 1 yıl içerisinde vertigo, dizziness ya da dengesizlik nedeniyle hekim başvurusu olmayan serum D vitamini düzeyi ölçümü yapılmış 338 hasta seçilerek oluşturuldu. İstatiksel değerlendirmeler için ki-kare ve T testi testi kullanıldı. Bulgular: Ortalama serum 25-OH vitamin D düzeyleri BPPV ve kontrol grubunda sırasıyla 15,74 ng/mL ve 17,91 ng/mL idi. Serum 25-OH vitamin D düzeyleri BPPV grubunda kontrol grubuna göre anlamlı derecede düşük bulundu ((p=0,01, p
Article
Objective To examine the relationship of 25hydroxyvitamin D serum levels with BPPV incidence and recurrence rates. Methods A retrospective cross-sectional, case-controlled study with follow-up phone survey was performed on patients diagnosed with BPPV between 05/2017-05/2020, who had available 25hydroxyvitamin D serology. Patients were seen at a multidisciplinary, vestibular-focused, neurotology clinic at a tertiary referral center. Controls consisted of subjects from the National Health and Nutrition Examination Survey (NHANES), and a locoregional age, sex, and race-matched group of patients from our institution. Results Our BPPV cohort consisted of 173 patients (mean age 66.2 ± 11.8 years), who were predominately female (75.7%) and Caucasian (76.3%). Almost all age subgroups (BPPV, NHANES, and locoregional groups) ≤60 years old had insufficient levels of vitamin D. However, the overall BPPV cohort had a significantly higher vitamin D level than the NHANES control (31.4 ± 16.5 v. 26.0 ± 11.2 ng/mL, d=0.474 [0.323, 0.626]). There was no significant difference when compared to the overall locoregional control (31.4 ± 20.5 ng/mL). Migraines were significantly correlated to increased BPPV recurrence rates on univariate (beta=0.927, p=0.037, 95% CI: [0.057, 1.798]) and multiple regression analyses (beta=0.231, 95% CI: [0.024, 2.029], p=0.045). Furthermore, patients with BPPV recurrences had significantly lower levels of vitamin D at initial presentation when compared to patients with no recurrences (29.0 ± 12.0 v. 37.6 ± 18.3 ng/mL, d=0.571[0.139,1.001]). Conclusion Many BPPV patients in our cohort had insufficient vitamin D levels, and patients with BPPV recurrences had insufficient and significantly lower vitamin D levels than those without. As a readily available and affordable supplement, vitamin D may be used as an adjunct treatment but prospective studies should be done to confirm if it can prevent or reduce recurrence.
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Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration. To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D. Cohort study. The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis. 1621 white older adults. Serum 25-(OH)D concentration (using a high-performance liquid chromatography-tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards) and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death. Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137 hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of -0.54 best discriminated risk for the composite outcome and was associated with a 24% higher risk in adjusted analyses (95% CI, 9% to 42%). Corresponding season-specific 25-(OH)D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively. The observational study was restricted to white participants. Threshold concentrations of 25-(OH)D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH)D concentration may be more appropriate than static targets when evaluating health risk. National Institutes of Health.
Article
Vitamin D has attracted increasing attention in clinical medicine and research, in part because of its pleiotropic effects on biological processes other than calcium and bone homeostasis (1–3). Animal experimental studies demonstrate that 1,25-dihydroxyvitamin D, the active vitamin D hormone, suppresses the renin–angiotensin–aldosterone system, modulates immune cell function, and suppresses abnormal cell proliferation (4). Epidemiologic studies suggest that these actions may have clinical relevance, demonstrating that, in addition to fracture, vitamin D deficiency is associated with increased risks for coronary heart disease, cancer, and all-cause mortality (5–11). Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D], which reflect total vitamin D intake from cutaneous synthesis and dietary consumption, are used to define vitamin D deficiency (1–3). Biological 25-(OH)D thresholds below which adequate conversion to 1,25-dihydroxyvitamin D cannot be maintained may exist. Optimal concentrations of 25-(OH)D have been proposed on the basis of cross-sectional correlations with intermediate measures of bone and mineral metabolism, such as parathyroid hormone concentration, bone mineral density, and intestinal calcium absorption (1, 12–15). This approach relates biomarker levels to biological function, an important strength, but it also has several limitations. First, 25-(OH)D concentrations that are optimal for bone and mineral metabolism may not equal those for nonbone vitamin D activities. Second, current recommendations for target 25-(OH)D concentrations do not account for known seasonal variation in 25-(OH)D concentration (16–19). Third, existing recommendations are based on divergent 25-(OH)D assays, and Standard Reference Materials released by the National Institute of Standards and Technology (NIST) now permit reproducible 25-(OH)D testing to enhance external validity (20). In addition, 25-(OH)D targets are highly controversial—the Institute of Medicine (IOM) recently recommended a threshold of 50 nmol/L (20 ng/mL), substantially less than the 75-nmol/L (30-ng/mL) threshold recommended by other professional societies and expert panels (1, 12–15). The goal of this study was to examine the relationship of serum 25-(OH)D concentration to vitamin D in terms of risk for major clinical disease events of global pathophysiologic relevance, focusing on threshold concentrations associated with disease risk.
Article
The first part of this review deals with recent advances in the understanding of biochemical mechanisms of otoconial morphogenesis. Most important in this regard is the molecular characterization of otoconin 90, the principal matrix protein of mammalian calcitic otoconia, which was found to be a homologue of the phospholytic enzyme PLA2. The unique and unexpected expression pattern of this protein required radical rethinking of traditional concepts. The new data, when integrated with existing information, provide a rational basis for an explanation of the mechanisms leading to crystal nucleation and growth. Based on this information, a hypothetical model is presented that posits interaction of otoconin 90 with microvesicles derived from the supporting cells as a key event in the formation of otoconia. The second part of the review is directed at the controversial subject of maintenance of mature otoconia and systematically analyzes the available indirect information on this topic. A synthesis of these theoretical considerations is viewed in relation to the pathogenesis of the important otoneurologic entities of BPPN and senile otoconial degeneration. The last part of the review deals with several animal models that promise to help elucidate normal and abnormal mechanisms of otoconial morphogenesis, including mineral deficiencies, mutations with selective otoconial agenesis, as well as targeted disruption of essential genes.