IT IS WELL known that vitamin D deficiency decreases intestinal calcium absorption, leads to sec -ondary hyperparathyroidism, and accelerates bone loss [1]. In addition, vitamin D deficiency is associ -ated with decreased muscle strength and increased fall risk [2, 3]. Many studies have shown a positive asso -ciation between serum 25-hydroxyvitamin D [25(OH) D] and bone mineral density (BMD) [4]. Also, several cohort studies have reported that low serum 25(OH)D is associated with osteoporotic fractures in the elderly [5]. On the other hand, high serum parathyroid hor -mone (PTH) level has been associated with increased bone remodeling and increased fracture risk [6]. One
Effect of high parathyroid hormone level on bone mineral
density in a vitamin D-sufficient population: Korea National
Health and Nutrition Examination Survey 2008-2010
Se Hwa Kim1), Tae Ho Kim1) and Soo-Kyung Kim2)
1) Division of Endocrinology, Department of Internal Medicine, Catholic Kwandong University College of Medicine, International St. Mary’s Hospital, Incheon, Republic of Korea
2) Division of Endocrinology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
Abstract. The detrimental effect of high parathyroid hormone (PTH) on bone has not been adequately evaluated in vitamin D-sufficient Koreans. The aim of this study was to investigate the effect of high PTH on bone mineral density (BMD) in such a population. A total of 5,403 subjects (2,644 men and 2,759 postmenopausal women; ≥50 years old) were selected from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES). Subjects were divided into four groups according to vitamin D status (<20 and ≥20 ng/mL) and PTH levels (≤65 and >65 pg/mL). Total hip and spine BMD were evaluated in each group. High PTH level was found in 50% of vitamin D-deficient subjects and 35% of vitamin D-sufficient subjects. In the vitamin D-deficient group, subjects with normal PTH level had higher total hip and spine BMD than those with high PTH after adjusting for multiple confounding factors, regardless of gender. In the vitamin D-sufficient group, only women with high PTH showed lower total hip and spine BMD than those with normal PTH. Multivariable linear regression analysis found that PTH level was independently associated with total hip BMD in vitamin D-sufficient women as well as vitamin D-insufficient women, but no association was found in men. In conclusion, high serum PTH level has an additive detrimental effect on BMD in postmenopausal women even though they had sufficient vitamin D levels.
Key words: Bone mineral density, Parathyroid hormone, Vitamin D
recent study showed that serum PTH, but not 25(OH) D, predicts bone loss rate during a four-year follow-up study in the elderly [7].
Interestingly, not all patients with vitamin D defi -ciency develop secondary hyperparathyroidism. A pre -vious study by Sahota et al. [8] found that only one-third of vitamin D-deficient patients had a secondary hyperparathyroidism. These patients had a lower hip BMD compared to vitamin D-deficient patients with normal PTH level and to vitamin D-sufficient patients. On the contrary, it is unclear if all subjects with vita -min D sufficiency have a normal PTH level except for those with primary hyperparathyroidism or chronic kidney disease.
The authors of the present study hypothesized that a high PTH level has detrimental effects on BMD even in vitamin D-sufficient subjects. The results show that a substantial proportion of vitamin D-sufficient sub -jects had a high serum PTH level. Also, high PTH Submitted Jun. 25, 2014; Accepted Aug. 21, 2014 as EJ14-0287
Released online in J-STAGE as advance publication Sep. 20, 2014
Correspondence to: Soo-Kyung Kim, M.D., Ph.D., Division of Endocrinology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, Korea. E-mail: imdrksk@chollian.net
Endocrine Journal Advance Publication
Institute, Seoul, South Korea). All blood samples were analyzed within 24 hours of collection. Serum 25(OH) D concentration was measured with a radioimmuno -assay (DiaSorin Inc., Stillwater, MN, USA) using a gamma counter (1470 Wizard; PerkinElmer, Turku, Finland). According to an Endocrine Society Guideline for evaluation of vitamin D deficiency, vitamin D defi -ciency was defined as a 25(OH)D level below 20 ng/ mL [9]. A previous report using KNHANES data [10] demonstrated that only 13.2% of men and 6.7% of women had a serum 25(OH)D level greater than 30 ng/ mL. Therefore, we arbitrarily defined vitamin D suf -ficiency as a 25(OH)D greater than 20 ng/mL in the present study. Serum intact PTH was analyzed using a chemiluminescence assay (DiaSorin Inc., Stillwater, MN, USA). Serum creatinine was determined using a Hitachi automatic analyzer (Hitachi, Tokyo, Japan). Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cre -atinine equation.
Lifestyle questionnaires and nutrition assessment Subjects were classified as regular exercisers if they exercised moderately for more than 30 min per session level had detrimental effects on BMD in postmeno
-pausal women, but not in men, even though the women were vitamin D-sufficient.
Materials and Methods
Study participants
This study is based on data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2008 to 2010. The KNHANES is a cross-sectional study regularly conducted by the Division of Chronic Disease Surveillance, Korea Centers for Disease Control and Prevention of the Ministry of Health and Welfare to examine the gen -eral health and nutritional status of the population of South Korea. The KNHANES database is publicly available at the KNHANES website (http://knhanes. cdc.go.kr, available in Korean). A total of 10,238 sub -jects ≥50 years of age participated in the KNHANES surveys from 2008 to 2010. Of these 10,238 partici -pants, 2,975 individuals were excluded from the pres -ent study because of incomplete BMD, serum PTH, or serum 25(OH)D data. Additionally, 1,860 individuals were excluded because they were premenopausal or had a history of osteoporosis medication, rheumatoid arthritis, asthma, cancer, serum PTH ≥150 or <10 pg/ mL, or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2. Finally, 2,644 men and 2,759 women were included in the study analysis (Fig. 1). All partic -ipants provided written informed consent.
Measurements of anthropometric parameters and bone mineral density
Height and body weight were measured using stan -dard methods while the participants were wearing light-weight clothes. Body mass index (BMI) was cal -culated as weight divided by height squared (kg/m2).
BMD values for the lumbar spine (L1-L4) and total hip were measured using dual-energy X-ray absorp -tiometry (DXA, Discovery QDR 4500; Hologic Inc., Waltham, MA, USA). The coefficients of variations (CVs) of the lumbar spine and total hip were 1.9%, and 1.8%, respectively.
Biochemistry assessment
As part of the KNHANES survey, blood samples were collected after an 8-hour fast and then immedi -ately processed, refrigerated, and transported in cold storage to the central laboratory (Neodin Medical
Excluded < 50 years old N=29,235 assessed for eligibility
KNHANES IV-2 (2008, n=9744) KNHANES IV-3 (2009, n=10533) KNHANES V-1 (2010, n=8958)
Excluded due to missing data serum 25(OH)D, n=1332 serum PTH, n=2534 BMD, n=2344
Excluded due to following conditions any cancer history, n=329
eGFR <60 ml/min/1.73m2, n=341 serum PTH ≥ 150 or ≤ 10pg/mL , n=116 premenopausal women, n=245 osteoporosis medication, n=373 History of rheumatoid arthritis, n=193 History of asthma, n=260 N=10,238 men (n=4384), women (n=5854) N=7,263 men (n=3146), women (n=4117) N=5,403 men (n=2644), women (n=2759)
Fig. 1 Schematic flow diagram of study subject selection and exclusion.
25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone; BMD, bone mineral density
Endocrine Journal Advance Publication
Endocrine Journal Advance Publication
P value <0.05 was considered significant. Statistical analyses were carried out using SPSS (version 19.0; SPSS Inc., Chicago, IL, USA).
Results
Characteristics of study participants
Clinical and biochemical characteristics of study subjects were shown in Table 1 and Table 2. Mean age was 62.9 ± 8.4 years and 51% of the subjects were women. Mean serum 25(OH)D concentrations were 20.6 ± 7.4 ng/mL and mean PTH levels were 64.3 ± 21.9 pg/mL. There were significant inverse correla -tions between serum 25(OH)D and PTH levels in men (r = -0.189, p < 0.001) and women (r = -0.189, p < 0.001) (Fig. 2).
To determine the effect of high PTH levels on BMD according to the vitamin D status, subjects were first divided into groups according to vitamin D status [defi -cient - 25(OH)D < 20ng/mL or suffi-cient - 25(OH)D ≥ 20ng/mL]. Subjects were further divided into groups according to PTH level (PTH ≤ 65pg/mL vs. PTH > 65pg/mL). Characteristics of study subjects accord -ing to vitamin D and PTH status were shown in men (Table 1) and women (Table 2). Forty three percent of men and 60% of women were classified as vitamin D-insufficient. Nearly half of the subjects in the vita -min D insufficiency group had normal PTH level (≤ 65pg/mL) (50.3%, n=572 in men and 50.3%, n=838 in women). Approximately 35% of the subjects in the more than five sessions per week or if they exercised
strenuously for more than 20 min per session more than three sessions per week. Current smokers were defined as those who had smoked more than five packs of cig -arettes during their life and were a current smoker. Alcohol consumption was defined as consuming more than one unit of alcohol per month. Daily calcium intake was assessed with a 24-hour dietary recall ques -tionnaire administered by a trained dietician. Fracture history was defined as having a history of clinical ver -tebral, hip, or forearm fracture.
Statistical analyses
Participants were classified into four groups accord -ing to vitamin D status and PTH level. Participant characteristics were compared using one-way analy -sis of variance (ANOVA) for continuous variables and Chi-square test for categorical variables. Mean BMD values of the four groups were compared by analysis of covariance (ANCOVA) after adjusting for age, BMI, smoking status, alcohol consumption, exercise habits, eGFR, history of hormone replacement therapy (HRT, for women), daily calcium intake, and fracture history. Separate multivariable logistic regression analysis was also performed for vitamin D-sufficient and -insuf -ficient subjects in order to identify independent factors for total hip BMD. Multivariable regression model included age, BMI, smoking, alcohol consumption, exercise, daily calcium intake, fracture history, 25(OH) D, PTH, eGFR, and history of HRT (for women). A
Table 1 Characteristics of male study subjects according to vitamin D status and PTH level
All subjects (n=2644) 25(OH)D < 20 ng/mL 25(OH)D ≥ 20 ng/mL P value PTH >65 pg/mL (n=563) PTH ≤65 pg/mL (n =572) PTH >65 pg/mL (n=543) PTH ≤65 pg/mL (n=966) Age (years) 62.6 ± 8.4 62.7 ± 8.6 61.6 ± 8.2 63.4 ± 8.9 62.8 ± 8.2 0.005 BMI (kg/m2) 23.7 ± 2.9 23.9 ± 3.2 23.6 ± 2.9 23.7 ± 2.9 23.6 ± 2.8 0.210 eGFR (ml/min/1.73m2) 86.3 ± 11.3 85.4 ± 11.5 86.4 ± 11.6 86.2 ± 11.2 86.7 ± 11.0 0.211 Total 25(OH)D (ng/mL) 22.1 ± 7.4 15.0 ± 3.2 15.9 ± 3.0 26.4 ± 4.9 27.4 ± 5.8 <0.001 PTH (pg/mL) 63.7 ± 21.6 85.5 ± 17.2 49.6 ± 10.3 81.8 ± 15.9 49.3 ± 10.8 <0.001 Calcium intake (mg/day) 545 ± 353 512 ± 334 561 ± 347 543 ± 366 554 ± 359 0.111
Current smoker (%) 34.9 38.0 36.3 32.8 33.3 0.182 Alcohol (%) 70.4 69.2 68.0 68.9 73.2 0.104 Regular exercise (%) 27.7 25.0 25.2 29.0 30.1 0.068 Hypertension (%) 45.4 51.4 44.7 46.1 41.9 0.005 Diabetes (%) 17.9 19.8 21.2 14.8 16.7 0.055 Fracture history (%) 1.6 1.4 1.2 0.9 2.2 0.228
Values are presented as the means ± SD or proportion (percent).
BMI, body mass index; eGFR, estimated glomerular filtration rate; 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone
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group, subjects with normal PTH had higher total hip BMD than those with high PTH, even after adjusting for age, history of HRT (for women), BMI, smoking status, alcohol consumption, exercise habits, daily cal -cium intake, a history of fracture, and eGFR in both men (0.925±0.005 vs. 0.907±0.005 g/cm2, p=0.009) (Fig.
3a) and women (0.785±0.003 vs. 0.771±0.003 g/cm2, p=0.002) (Fig. 3b). Furthermore, there was a signifi -cant difference in total hip BMD according to PTH sta -tus among vitamin D-sufficient women (0.792±0.003 vs. 0.779±0.005 g/cm2, p=0.033) (Fig. 3b). However,
in men who were vitamin D-sufficient, there was no vitamin D-sufficient group had high PTH level (36.0%,
n=563 in men and 32.5%, n=355 in women). The per -centage of subjects with hypertension was higher in subjects with high PTH than in those with normal PTH regardless of vitamin D status (Tables 1, 2).
Relationships between BMD, vitamin D, and PTH concentration
Subjects who were vitamin D-deficient with high PTH had the lowest BMD, while subjects who were vitamin D-sufficient with normal PTH level had the highest BMD at each site. In the vitamin D-deficient
Fig. 2 Relationship between serum 25-hydroxyvitamin D [25(OH)D] and PTH concentration in men and women.
Table 2 Characteristics of female study subjects according to vitamin D status and PTH level
Variable All subjects(n=2759) PTH >65 pg/mL 25(OH)D < 20 ng/mL 25(OH)D ≥ 20 ng/mL P value (n=828) PTH ≤65 pg/mL(n=838) PTH >65 pg/mL(n=355) PTH ≤65 pg/mL(n=738) Age (years) 63.1 ± 8.4 64.3 ± 8.6 61.8 ± 8.2 64.2 ± 8.5 62.7 ± 8.1 <0.001 BMI (kg/m2) 24.2 ± 3.2 24.6 ± 3.3 24.0 ± 3.1 24.4 ± 3.5 23.9 ± 3.0 <0.001 eGFR (ml/min/1.73m2) 89.4 ± 7.0 88.5 ± 11.4 90.4 ± 11.1 88.3 ± 11.1 89.9 ± 11.0 0.001 Total 25(OH)D (ng/mL) 19.0 ± 7.0 14.0 ± 3.4 14.8 ± 3.4 25.8 ± 4.8 26.1 ± 5.0 <0.001 PTH (pg/mL) 64.8 ± 22.2 86.3 ± 18.4 50.4 ± 10.4 80.9 ± 14.9 49.3 ± 10.5 <0.001 Calcium intake (mg/day) 410 ± 288 386 ± 260 428 ± 308 408 ± 290 418 ± 292 0.030
Current smoker (%) 4.3 5.5 3.6 4.3 3.7 0.211 Alcohol (%) 25.5 23.9 27.2 24.8 25.8 0.479 Regular exercise (%) 23.9 20.5 24.6 23.7 27.1 0.023 Hypertension (%) 45.7 52.4 41.1 47.3 42.6 <0.001 Diabetes (%) 14.7 14.4 14.2 14.7 15.4 0.578 HRT (%) 17.0 15.1 18.5 17.2 17.2 0.680 Fracture history (%) 3.5 4.7 3.1 1.7 3.4 0.058
Values are presented as the means ± SD or proportion (percent).
BMI, body mass index; eGFR, estimated glomerular filtration rate; 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone; HRT, hormone replacement therapy
25(OH)D [ng/mL] 25(OH)D [ng/mL] Parathyroid hormone [pg/mL] Men Women r=-0.189, P < 0.001 rP =-0.223, < 0.001 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0.0 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0.0 50.0 30.0 60.0 10.0 20.0 40.0 0.0 0.0 10.0 20.0 30.0 40.0 50.0 60.0 Men Women r=-0.189, P < 0.001 r=-0.223, P < 0.001
Endocrine Journal Advance Publication
Endocrine Journal Advance Publication
well as vitamin D-deficiency (Table 3). On the other hand, PTH was independently associated with total hip BMD in women, regardless of vitamin D status. These data suggest that the detrimental effects of high PTH on BMD are more prominent in postmenopausal women than in men. Furthermore, serum 25(OH)D was not an independent factor for total hip BMD among vita -min D-sufficient men as well as vita-min D-sufficient women (Table 3). This result suggest that further increase of serum 25(OH)D may not have additional benefit on BMD in vitamin D-sufficient population.
Discussion
Both men and women with vitamin D deficiency and normal PTH level had higher BMD compared to those with vitamin D deficiency and high PTH. Interestingly, vitamin D-sufficient women with high PTH level had lower BMD compared to those with difference in total hip BMD according to PTH status
(0.937±0.004 vs. 0.932±0.005 g/cm2, p=0.341) (Fig.
3a). Similar results for lumbar spine BMD were seen in both men (Fig. 3c) and women (Fig. 3d).
Multiple linear regression analysis
A multiple linear regression analysis was performed to identify independent factors for total hip BMD in all subjects. As expected, age, BMI, exercise, serum 25(OH)D, daily calcium intake, previous fracture his -tory, serum PTH, and eGFR were independent factors in men and women (Table 3). Use of HRT was an addi -tional independent factor for total hip BMD in women.
This study also explored whether PTH was indepen -dently associated with total hip BMD in subjects based on vitamin D status. Therefore, we analyzed our data separately for subjects with vitamin D-sufficiency and -deficiency. PTH was not an independent factor for total hip BMD in men with vitamin D-sufficiency as
Fig. 3 Bone mineral densities according to serum 25-hydroxyvitamin D and parathyroid hormone concentrations in men (a, c) and women (b, d). These data are adjusted for age, BMI, estimated glomerular filtration rate, smoking, alcohol consumption, exercise, history of HRT (for women), calcium intake, and previous fracture history. Error bar represents standard error.
0.88 0.89 0.9 0.91 0.92 0.93 0.94 0.95 0.96 PTH >65 PTH ≤65 PTH >65 PTH ≤65 0.74 0.75 0.76 0.77 0.78 0.79 0.8 0.81 0.82 PTH >65 PTH ≤65 PTH >65 PTH ≤65 Vitamin D deficiency Vitamin D deficiency 0.9 0.91 0.92 0.93 0.94 0.95 0.96 0.97 0.98 PTH >65 PTH ≤65 PTH >65 PTH ≤65 0.76 0.77 0.78 0.79 0.8 0.81 0.82 0.83 0.84 PTH >65 PTH ≤65 PTH >65 PTH ≤65 Vitamin D deficiency Vitamin D deficiency (a) (c) P < 0.001 (b) P =0.001 P = ns P = 0.009 P = ns Tota l hip BM D (g/c m 2) Vitamin D sufficiency Lumbar spine BM D (g/c m 2) P = 0.002 P = 0.073 P = ns P = 0.026 P = ns Vitamin D sufficiency P < 0.001 P = ns P = 0.033 P = 0.002 P = ns Vitamin D sufficiency P = 0.105 P = ns P =0.023 P = 0.032 P = 0.007 Vitamin D sufficiency (d)
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genders in the present study, which showed that nearly 50% of subjects with vitamin D deficiency (<20ng/mL) had normal PTH level. Our study also found that sub -jects with vitamin D deficiency and normal PTH level had higher total hip and lumbar spine BMD than those with vitamin D deficiency and high PTH level, even after adjusting for multiple confounding factors.
In the vitamin D-sufficient population, there were differences in BMD response between men and women according to PTH level. Women with high PTH had significantly lower total hip BMD compared to those with normal PTH. Moreover, serum PTH was an inde -pendent factor for total hip BMD in vitamin D suffi -cient women after adjusting for confounding factors. On the other hand, there was no significant difference in total hip BMD according to PTH level in men. These data suggest that the detrimental effects of high PTH on BMD are more prominent in postmenopausal women than in men; however, the reason for the observed vari -ation in these results remains unclear.
normal PTH. However, there was no significant dif -ference in BMD according to PTH status in men with vitamin D sufficiency.
It is well known that vitamin D deficiency causes secondary hyperparathyroidism and bone loss [1]. However, some studies have shown that patients with vitamin D deficiency can have a normal PTH level [7, 8]. Sahota et al. [8] reported that normal serum PTH was present in 67% of subjects with hypovitaminosis D (defined as a 25OHD ≤ 12 ng/mL). They also found that patients with hypovitaminosis D and normal PTH level had higher BMD compared to those with hypo -vitaminosis D and secondary hyperparathyroidism. Similarly, Arabi et al. [7] conducted a study of elderly men and women that included a four-year follow-up and found that the rate of bone loss was higher in sub -jects who were vitamin D-insufficient (<20ng/mL) and had high PTH level, compared to subjects who were vitamin D-insufficient and had normal PTH level. These findings were consistent with results from both
Table 3 Multivariable linear regression analysis to identify factors associated with total hip BMD in men and women
Subjects with 25(OH)D <
20 ng/mL Subjects with 25(OH)D ≥ 20 ng/mL All subjects
β P value β P value β P value
I. Men Model R2 0.311 0.273 0.288 Age (year) -0.309 <0.001 -0.256 <0.001 -0.279 <0.001 BMI (kg/m2) 0.354 <0.001 0.368 <0.001 0.365 <0.001 Smoking (yes/no) -0.025 0.371 -0.019 0.422 -0.026 0.152 Alcohol (yes/no) 0.018 0.499 0.063 0.008 0.045 0.012 Exercise (yes/no) 0.086 0.002 0.030 0.208 0.052 0.003
Daily calcium intake (mg) 0.093 0.001 0.075 0.002 0.082 <0.001 Fracture history (yes/no) -0.033 0.213 -0.042 0.073 -0.040 0.024
25(OH)D (ng/mL) 0.057 0.037 0.013 0.587 0.068 <0.001 PTH (pg/mL) -0.042 0.124 -0.025 0.292 -0.036 0.043 eGFR (ml/min/1.73m2) -0.046 0.120 -0.054 0.037 -0.050 0.010 II. Women Model R2 0.424 0.395 0.410 Age (year) -0.545 <0.001 -0.477 <0.001 -0.518 <0.001 BMI (kg/m2) 0.288 <0.001 0.325 <0.001 0.301 <0.001 Smoking (yes/no) -0.038 0.056 -0.022 0.367 -0.033 0.035 Alcohol (yes/no) 0.024 0.220 0.030 0.233 0.027 0.078 Exercise (yes/no) 0.021 0.295 0.085 0.001 0.047 0.003
Daily calcium intake (mg) 0.052 0.009 0.015 0.545 0.039 0.013 Fracture history (yes/no) -0.048 0.015 -0.023 0.362 -0.039 0.011
25(OH)D (ng/mL) 0.028 0.159 0.022 0.374 0.037 0.021
PTH (pg/mL) -0.074 <0.001 -0.068 0.007 -0.075 <0.001 eGFR (ml/min/1.73m2) -0.057 0.013 -0.008 0.774 -0.037 0.042
HRT (yes/no) 0.055 0.006 0.004 0.882 0.037 0.017
BMI, body mass index; eGFR, estimated glomerular filtration rate; 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone
Endocrine Journal Advance Publication
Endocrine Journal Advance Publication
high cardiovascular morbidity and mortality [13-15]. PTH receptors are expressed in the vessel wall and myocardium and may be involved in the pathological process of cardiovascular disease.
An important limitation of this study was that serum calcium and phosphorus levels were not mea -sured. Thus, subjects with primary hyperparathyroid -ism may be included in the study. However, recent study reported the incidence of primary hyperpara -thyroidism was 66 per 100,000 person-years among women, and 25 per 100,000 person-years among men [16]. The incidence of primary hyperparathyroidism was highest among blacks, followed by whites, Asians, and Hispanics. Therefore, these findings suggest the potential for bias in our study would be minimal.
In conclusion, serum PTH is a significant determinant of BMD in subjects with vitamin D sufficiency as well as vitamin D deficiency, especially in postmenopausal women. Measuring serum PTH level may help identify individuals who are at risk of osteoporosis even if they have normal renal function and are vitamin D-sufficient, especially in postmenopausal Korean women.
Disclosure Summary
The authors have nothing to declare. Sahota et al. [8] did not compare BMD according toPTH level among vitamin D-sufficient patients because only a few of these patients had high serum PTH level. In the present study, 35% of the population with vita -min D sufficiency (≥20ng/mL) showed high PTH con -centration (>65 pg/mL). When the cut-off value for vitamin D sufficiency is defined as 30ng/mL, 32% of the population showed high PTH levels in our study (data not shown). The causes of this high prevalence of increased serum PTH levels in vitamin D-sufficient population are unknown. Firstly, very low dietary cal -cium intake may lead to secondary hyperparathyroid -ism despite vitamin D sufficiency. Mean dietary cal -cium intake was 545 mg/day for men and 410 mg/day for women. These values are substantially lower than values reported by other studies conducted in pop -ulations of different ethnicities [11, 12]. Secondly, subjects with primary hyperparathyroidism may be included in the study. Because we exclude CKD stage 3 or more, renal dysfunction could not be a factor for high prevalence of increased PTH.
Interestingly, the percentage of subjects with hyper -tension was higher in groups with high PTH than in those with normal PTH regardless of vitamin D status in our study. Previous studies have shown that serum PTH concentration is associated with hypertension,
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