Archives of Osteoporosis

, 10:19 | Cite as

High prevalence of hypovitaminosis D in Mexicans aged 14 years and older and its correlation with parathyroid hormone

  • Patricia Clark
  • Nalleli Vivanco-Muñoz
  • Juan Talavera Piña
  • Rodolfo Rivas-Ruiz
  • Gerardo Huitrón
  • Gabriela Chico-Barba
  • Alfredo A. Reza-Albarrán
Original Article

Abstract

Summary

A sample of 585 healthy subjects 14 years and older was studied to estimate the status of 25-hydroxyvitamin D (25(OH)D) and its correlation with parathyroid hormone in healthy Mexicans. In 43.6 % of the sample, levels of vitamin D were below 20 ng/mL and showed an inverse relationship with parathyroid hormone (PTH; p < 0.01).

Purpose

The purpose of the present study was to estimate the status of 25-hydroxyvitamin D (25(OH)D) and its correlation with parathyroid hormone in healthy Mexicans.

Methods

A cross-sectional study of 585 healthy subjects 14 years and older was carried out. A questionnaire including all relevant demographics, medical history, and lifestyle factors was applied by trained interviewers. Morning fasting blood was collected in all subjects for estimation of 25(OH)D using liquid chromatography-tandem mass spectrometry and PTH hormone–intact molecule by RIA.

Results

Of the group of 585 subjects, 54.1 % were women; the sample was divided in three age groups (14–29, 30–50, and >51). Only 9.6 % of the total sample had levels of 25(OH)D above 30 ng/mL; 46.8 % were between 20 and 29 ng/mL, and 43.6 % were below 20 ng/mL. Regarding PTH, a three-phase model was identified using regression smoothing scatterplot (LOESS), with two thresholds of 25(OH)D of 19 and 29 ng/mL. Phase 1 (25(OH)D <19 ng/mL) showed an inverse relationship with PTH (p < 0.01); phases 2 and 3 showed no significant relationship.

Conclusion

Our results show that 43.6 % of the Mexicans in this study have deficient concentration levels of vitamin D. The cutoff point of 20 ng/mL of 25(OH)D established by the Institute of Medicine has a biological and statistically significant relationship with PTH levels in the Mexican population, independently of principal confounding factors. Like many other countries, Mexico could be included in the global epidemic of hypovitaminosis D.

Keywords

Vitamin D Deficiency Parathyroid hormone Hypovitaminosis D 

Introduction

Vitamin D deficiency has been defined by the Institute of Medicine as a concentration of 25-hidroxyvitamin D (25(OH)D) of less than 20 ng/mL. According to this definition, it has been estimated that 20–100 % of US, Canadian, and European elderly men and women are vitamin D deficient. Children, the young, and middle-aged adults are at equally high risk for vitamin D deficiency worldwide. Vitamin D deficiency is common in Australia, the Middle East, India, Africa, and South America [1]. In developing countries, hypovitaminosis D is a widespread disorder across all age groups. There is a high prevalence of hypovitaminosis D even when a large number of these countries lie in latitudes with sufficient sunlight for vitamin D synthesis for most if not all of the year [2].

Vitamin D deficiency can result in abnormalities in calcium, phosphorus, and bone metabolism: In children, it is associated with rickets, and in childhood, the low levels of vitamin D can also interfere with the development of an optimal peak bone mass; in adults, it can lead to osteoporosis (OP) and fractures [1]. Although the deficiency has been linked with a wide range of diseases like hypertension, myopathic disorders, proneness to infection, autoimmune disorders, and cancer [3], two recent systematic reviews of observational and clinical trials were not able to determine a causal relationship between low levels of vitamin D and all these diseases. Since inflammation occurs with these disorders, and low levels of vitamin D accompany their clinical course, it has been suggested that vitamin D is more a marker of ill health than of being involved in a causal relationship [4, 5].

Several risk factors have been associated with vitamin D deficiency such as nutritional status, skin pigmentation, clothing style, and seasonal variation. Gender (females) and particular age groups (neonates, preschool children, or the elderly) have been the most consistently reported risk factors [2].

A lineal and inverse relationship between 25(OH)D and parathyroid hormone (PTH) has been established. Nevertheless, several studies demonstrate that as 25(OH)D increases, PTH levels reach a plateau. The 25(OH)D level where PTH starts this plateau is still to be determined.

Although there have been many publications about hypovitaminosis D in the adult population, few reports include the Mexican population and younger individuals and its relationship with PTH. Therefore, the aims of this study were to determine the prevalence of hypovitaminosis D in a sample of the Mexican population and to establish its correlation with PTH.

Subjects and methods

Study population

A cross-sectional study of 528 subjects from Toluca, the State of Mexico, was carried out between July 2010 and March 2011. Subjects were students, employees, teachers, and their relatives from several educational and retirement facilities who were invited to participate in this study focusing on vitamin D and factors related to bone health. Although the sample was not a true probability sample, care was taken to ensure representativeness of the general population, enrolling a certain number of participants per age category (13–24, 25–50, and ≥51 years old).

The ethics committee of the Centre for Medical Sciences Research (CICMED) reviewed and approved the study protocol, and a written consent for all participants was obtained before the study.

Baseline examinations

Demographics

All demographic characteristics (gender, age, education, and employment) and factors associated with bone health were evaluated by means of administered questionnaires, applied by trained interviewers.

Clinical factors

Weight (kg) was measured with a previous calibrated scale with participants being barefoot and wearing minimal clothing. Height (m) was measured using a conventional stadiometer while the participants were standing barefoot, with their shoulders in a normal position. Body mass index (BMI) was computed as a ratio of weight (kg) to height squared (m2) and was classified as follows: underweight (<18.5), normal (18.5–24.99), overweight (25–29.99), and obese (≥30) [6]. Skin tone (light and dark) was measured with a tone scale (Pantone 1215 and 159, respectively). Blood was drawn after a 12-h fast; 25(OH)D, PTH, alkaline phosphatase, calcium, and phosphorus were determined. For 25(OH)D determinations, a stable isotope–labeled internal standard was used in liquid chromatography-tandem mass spectrometry (LC-MS). [7] PTH was determined by RIA and the remaining elements with photometric assays (Siemens ADVIA chemistry systems) [8].

Statistical analysis

Initially, we calculated the mean ± standard deviation (SD) for continuous variables and frequencies for categorical variables to show population characteristics. Prevalence of 25(OH)D deficiency and insufficiency and PTH levels were calculated by sex and age group. A Pearson correlation and a regression smoothing scatterplot (LOESS) were performed to establish the possible relationship between 25(OH)D and PTH. In all cases, a p value of ≤0.05 was considered significant. All statistical analyses were made using the SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL).

Results

Of the total group of 585 subjects, 54.1 % were women and the sample was divided into three age groups (14–29, 30–50, and >51). Table 1 shows demographic and clinical characteristics by sex and in the total sample. The mean age (±SD) was 41.1 years (± 15). Most men reported performing office work (27.6 %), and the majority of women were housewives (34.7 %). The average monthly income was higher for men than for women. There was a high prevalence of overweight people in the total sample (41.4 %); however, more men were overweight (45.1 %), while more women were obese (21.1 %). The mean concentration of 25(OH)D was 23.2 and 19.3 ng/mL for men and women, respectively, reaching levels of deficiency in women. No difference was found in the concentration levels of 25(OH)D when overweight and obesity were contrasted with subjects with normal weight. The mean values of calcium, phosphorus, alkaline phosphatase, and PTH remained in normal ranges in both genders.
Table 1

Baseline characteristics

Variable

Men

N = 268

Women

N = 317

Total

N = 585

Age**

40.26 (15.15)

42.44 (15)

41.44 (15.09)

Education, n (%)

 Primary

32 (11.9)

47 (14.8)

79 (13.5)

 Junior high

58 (21.6)

50 (15.8)

108 (18.5)

 senior high

61 (22.8)

57 (18)

118 (20.2)

 Professional

117 (43.7)

163 (51.4)

280 (47.9)

BMI, n (%)

 Low weight

89 (33.2)

125 (39.4)

214 (36.6)

 Normal

8 (3)

4 (1.3)

12 (2.1)

 Overweight

121 (45.1)

121 (38.2)

242 (41.4)

 Obesity

50 (18.7)

67 (21.1)

117 (20)

Serum concentrations

 25(OH)D (ng/mL*)

23.2 (5.7–57.2)

19.3 (7.3–39.4)

20.9 (5.7–57.2)

 25(OH)D (nmol/mL*)

58 (14.3–142.8)

47.9 (18.3–98.3)

52.3 (14.3–142.8)

 Calcium (mg/dL*)

8.65 (7.7–11.68)

8.55 (2.2–10.49)

8.59 (2.2–11.68)

 Phosphorus (mg/dL*)

3.3 (0.98–6.09)

3.44 (1.7–4.98)

3.4 (0.98–6.09)

 Alkaline phosphatase (U/L+)

92 (4.47–57.2)

80 (24–236)

86 (4.47–567)

 PTH (pcg/mL*)

25.93 (5.55–227.9)

25.05 (5.68–174.62)

25.93 (5.55–227.9)

BMI body mass index, PTH parathyroid hormone, 25(OH)D 25-hydroxyvitamin D

*Data is presented as median (min-max)

**Mean and SD

In Table 2, we present the different cutoff points accepted in the literature for 25(OH)D. Levels of deficiency were found in 43.6 % of the sample.
Table 2

Vitamin D status in the healthy Mexican population

 

Men

N = 268

Women

N = 317

Total

N = 585

Groups of age (years)

14–29

n (%)

30–50

n (%)

>51

n (%)

14–29

n (%)

30–50

n (%)

>51

n (%)

14–29

n (%)

30–50

n (%)

>51

n (%)

>30 ng/mL

9 (12)

18 (14.6)

10 (14.5)

5 (7)

3 (1.9)

11 (12.9)

14 (9.6)

21 (7.4)

21 (13.6)

29–20

39 (52)

63 (51.2)

44 (63.8)

29 (40.8)

68 (42.2)

30 (35.3)

68 (46.6)

131 (46.1)

74 (48.1)

19–10

26 (34.7)

40 (32.5)

14 (20.3)

37 (52.1)

84 (52.2)

42 (49.4)

63 (43.2)

124 (43.7)

56 (36.4)

<10

1 (1.3)

2 (1.6)

1 (1.4)

0

6 (3.7)

2 (2.4)

1 (0.7)

8 (2.8)

3 (1.9)

PTH levels are shown in Table 3. Most people had normal levels; however, those under 29 years had a higher proportion of low concentrations. When performing a Pearson correlation of concentrations of 25(OH)D with PTH, we observe a weak and negative correlation that is statistically significant (r = −0.085, p = 0.039). A three-phase model was identified using regression smoothing scatterplot LOESS, with two thresholds of 25(OH)D of 19 and 29 ng/mL. Phase 1 (25(OH)D <19 ng/mL) showed an inverse relationship with PTH (p < 0.01), phase 2 (25(OH)D 20–29 ng/mL) had a smooth non-significant direct relationship (p = 0.122), and phase 3 (25(OH)D >29 ng/mL) also showed no relationship (p = 0.312; Fig. 1).
Table 3

PTH concentration levels in the sample

 

Low

<11 pcg/mL

Normal

11–62 pcg/mL

High

>62 pcg/mL

Total

n (%)

n (%)

n (%)

 14–29 years old

15 (9.2)

147 (90.2)

1 (0.6)

 30–50 years old

8 (2.8)

272 (95.8)

4 (1.4)

 ≥51 years old

0 (0)

133 (96.4)

5 (3.6)

Men

 14–29 years old

9 (11)

72 (87.8)

1 (1.2)

 30–50 years old

2 (1.6)

120 (97.6)

1 (0.8)

 ≥51 years old

0 (0)

61 (96.8)

2 (3.2)

Women

 14–29 years old

6 (7.4)

75 (92.6)

0 (0)

 30–50 years old

6 (3.7)

152 (94.4

3 (1.9)

 ≥51 years old

0 (0)

72 (96)

3 (4)

Fig. 1

Three-phase model of 25(OH)D and PTH using regression smoothing scatterplot (LOESS)

Discussion

Our study reveals a high prevalence of vitamin D deficiency levels in this healthy sample of Mexican men and women. Almost half the sample (43.6 %) had less than 20 ng/mL, and our results found a statistically inverse relationship with PTH levels among the group who presented vitamin D deficiency. Different figures of prevalence of hypovitaminosis D have been reported in children and adults across the world that ranges from the lowest of 3.5 % to the highest of 92 % depending on the country, population selected, and cutoff points used.

The variation in the cutoff points of the different reports published is an important issue if we want to make comparisons; Guardia et al. [9] reported that the prevalence of vitamin D depletion changed in the same group from 15 % with a cutoff point of 15 ng/mL, to 32 % taking the cutoff point of 20 ng/mL, and as high as 72 % taking the cutoff point of 30 ng/mL.

Also, another important factor to take into account when comparing results is the diversity of methods for determination the levels of 25(OH)D. ELISA, radioimmunoassay, chemiluminescent assay, high-performance liquid chromatography, and liquid chromatography-mass spectrometry are used to determine the concentration levels of 25(OH)D among the different reports, and variations up to 20–40 % in the serum 25(OH)D levels have been found depending upon which assay is used [10, 11, 12, 13, 14].

Finally, last but not the least are some other factors that might influence these disparities as age, race, diet, sun exposure, and clothing, among others [15, 16].

According to the international cutoff points (IOM and Endocrine Society), the prevalence of 25(OH)D deficiency (≤20 ng/mL) in the total sample was 43.5 %. When analyzing the sample by different age groups (14–29, 30–50, and >51 years), the prevalence of deficiency reached 43.6, 46.5, and 37.7 %, respectively. In both genders, the group older than 50 years presented the lowest frequency of vitamin D deficiency. Three studies have reported the concentration levels of 25(OH)D in Mexicans: Elizondo-Alanis LJ [17] found 31.2 % 25(OH)D levels lower than 20 ng/mL in a sample of postmenopausal women in Mexico, Lips et al. [18] reported an international study in which a sample of Mexican population was included in which levels of deficiency of 25(OH)D were present in 29.5 % prevalence of the postmenopausal women of the sample (<20 ng/mL), and finally in a subsample of the 2006 Mexican Nutrition Survey, Flores et al. [19] reported lower figures in the adult population and only 9.2 % were reported as deficient.

Our figures are higher than the data reported in these studies, and differences are likely be attributed, as previously mentioned in the text, to the laboratory method used for determination levels of 25(OH)D. Elizondo-Alanis et al. and Lips et al. used the Nichols Advantage competitive binding chemiluminescence immunoassay, who has been criticized for overestimating serum 25(OH)D levels when compared with a gold standard high-performance liquid chromatography method [11, 12, 20, 21]. Thus, the prevalence of vitamin D inadequacy could be higher than reported by these authors. Flores et al.’s determinations were performed with ELISA (25(OH)-Vitamin D direct ELISA Kit) also known to have a low sensitivity.

Currently, liquid chromatography-tandem mass spectrometry (LC-MS) is the leading reference standard since it can measure vitamin D metabolites (vitamin D2 and vitamin D3) [22] and was the method used in this study for determining 25(OH)D; therefore, comparisons with studies not using the same method can lead to an erroneous conclusions. However, besides the method used and the variations in the prevalence, the fact is that three out of four studies are consistent with the finding of high prevalence of hypovitaminosis D in our population.

We found a weak but statistically significant negative correlation between 25(OH)D and PTH. Low 25(OH)D increases PTH activity to maintain calcium homeostasis. When performing LOESS, the cutoff point of 20 ng/mL of 25(OH)D, established by the Institute of Medicine, has a biological and statistically significant relationship with PTH levels in the Mexican population, independently of principal confounding factors as age, weight, skin color, or diet. Other cutoff points proposed by other authors have no statistical relationships.

The present study has certain limitations. The sample is not representative of the entire Mexican population. Nevertheless, it represents a predominantly urban working-class population. Toluca, the city where the study was performed, is a medium-size city near Mexico City that, with four other states, represents around one fourth of the population of Mexico [23, 24].

Conclusions

A high prevalence of hypovitaminosis D in Mexicans is presented in this study. The need for nutritional public health awareness campaigns about the importance of vitamin D is pressing, specifically in developing countries where the prevalence of hypovitaminosis D is high as in Mexico.

A review of the evidence on the safety and efficacy of vitamin D supplementation from published studies as well as the different guidelines published regarding the supplementation of vitamin D from the public health perspective is needed in order to define the type of supplementation if supplementation is needed as well as the definition of vulnerable populations to be the target for such intervention. These policies would, however, require further revisions based on evidence from locally conducted studies [2].

Notes

Acknowledgments

This study was supported by the CONACyT grant: Salud-01-114965. The authors are grateful to Dr. Francisco Velázquez Forero for running the intact PTH at the Bone and Mineral Metabolism Laboratory at the Hospital Infantil Federico Gómez, Mexico City, Mexico, and to Dr. Juan A. Tamayo for his support of this work.

Conflict of interest

Patricia Clark, Nalleli Vivanco-Muñoz, Juan Talavera-Piña, Rodolfo Rivas-Ruiz, Gerardo Huitron-Bravo, Gabriela Chico-Barba, and Alfredo A Reza-Albarrán do not have any conflict of interest to declare.

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • Patricia Clark
    • 1
  • Nalleli Vivanco-Muñoz
    • 1
  • Juan Talavera Piña
    • 2
  • Rodolfo Rivas-Ruiz
    • 1
  • Gerardo Huitrón
    • 3
  • Gabriela Chico-Barba
    • 1
  • Alfredo A. Reza-Albarrán
    • 4
  1. 1.Clinical Epidemiology UnitHospital Infantil Federico Gómez-Facultad de Medina UNAMMéxicoMexico
  2. 2.Coordination of ResearchCMN Siglo XXI and Universidad Autónoma del Estado de MéxicoTolucaMexico
  3. 3.Center of Research in Medical SciencesUniversidad Autónoma del Estado de MéxicoTolucaMexico
  4. 4.Parathyroid and Bone Clinic, Department of EndocrinologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexicoMexico

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