Sage Journals: Discover world-class research

Abstract

Blood samples from 126 menopausal women, seeking treatment for different ailments at a tertiary care, multidisciplinary hospital in Delhi, India, were examined for their vitamin D₃, quantified by 25-hydroxvitamin D (25-OH-D) level. Using a direct ELISA kit, the 25-OH-D levels were measured and were found to be sufficient in 30 (23.8%) cases, adequate in 10 cases (7.9%) and deficient in 86 cases (68.2%). Severe hypo-vitaminosis in menopausal women in the Indian subcontinent ought to be treated with oral or parenteral supplementation. Point-of-care assay formats are needed for quantification of 25-OH-D levels at healthcare centers.

Keywords

affluent patient fortified food menopausal women supplementation vitamin D3

Data available from several countries show that vitamin D₃ (25-hydroxvitamin D [25-OH-D]) deficiency has now emerged as a pandemic [1,2]. Inadequate levels of 25-OH-D are associated with secondary hyperparathyroidism, increased bone structural transformation and bone loss [3]. Severe 25-OH-D deficiency has been recorded in postmenopausal women with osteoporosis in Belgium, even after the 25-OH-D supplementation. The prevalence of hypovitaminosis of 25-OH-D among a total of 445 osteoporotic cases studied in Australia, Belgium, France, Germany, Hungary, Italy, Poland, Spain and the UK was highest in institutionalized women [4]. Non-uniform, epidemiological studies conducted in East Asian countries point towards a high prevalence of 25-OH-D inadequacy in postmenopausal women. Employing 25-OH-D serum levels of <30 ng/ml (75 nmol/l) to identify 25-OH-D deficiency, the prevalence rates were 47% in Thailand, 49% in Malaysia, 90% in Japan and 92% in South Korea [5]. To the best of our knowledge, similar investigations on menopausal women have not been conducted in countries of the Indian subcontinent. Investigations to assess 25-OH-D deficiency among women during the menopause in the Indian capital Delhi have revealed severe hypovitaminosis.

Materials & methods

From April to December 2010, 126 menopausal women who reported different ailments at a private, multidisciplinary, tertiary care hospital, Sant Parmanand Hospital (Delhi, India), had their vitamin D₃ concentrations measured. There were no inclusion or exclusion criteria. The women screened included 96 seeking treatments for orthopedic complaints and 30 for medical or gynecological complaints. No data on bone health or dietary 25-OH-D intake was assembled. This 140-bed hospital caters to the population in the capital as well as adjoining townships, including locations in Punjab, Haryana, Uttar Pradesh and the Bihar states.

The 25-OH-D levels were evaluated in the hospital laboratory using the 25(OH)-Vitamin D direct Elisa Kit (Immunodiagnostik; Bensheim, Germany), based on a competitive ELISA technique with a selected monoclonal antibody that recognizes 25(OH)-vitamin D. The individual assay runs were monitored by the inclusion of low- and high-level controls supplied by the manufacturer and Randox Laboratories (Crumlin, UK). The results were expressed, after point-to-point calculation, as nmol/l (with 1 nmol/l being equivalent to 2.5 ng/ml). Values ≥80 nmol/l (32 ng/ml) were defined as being at a sufficient level, while those of <50 nmol/l (20 ng/ml), as deficient, and 50–75 nmol/l (20–30 ng/ml) were labeled as with insufficient levels [6]. The percentage of variation was calculated by dividing the standard deviation by mean.

Statistical analysis was performed online using the GraphPad Quickcalcs online calculator.

Results

The mean age of the subjects was 64.8 years, the standard error was 0.6, the standard deviation was 7.6, the mode was 60 years, the minimum age was 52 years and the maximum was 84 years. The 25-OH-D level in all 126 cases ranged from 3.2 to 342 nmol/l (1.28–136.8 ng/ml), with a mean of 50.2 nmol/l (20.1 ng/ml), standard error of 4.8 nmol/l (1.9 ng/ml), standard deviation of 53.8 nmol/l (21.5 ng/ml)and mode of 14 nmol/l (5.6 ng/ml). In 30 cases, the 25-OH-D level exceeded 75 nmol/l (30 ng/ml), was between 50–70 nmol/l (20–28 ng/ml) in ten cases and less than 50 nmol/l (20 ng/ml) in 86 cases (Figure 1). Sufficient 25-OH-D level of >75 nmol/l (>30 ng/ml) was found in 30 (23.8%) cases, while the level was 50–75 nmol/l (20–20 ng/ml) in 10 cases (7.9%) and it was less than <50 nmol/l (<20 ng/ml) in 86 cases (68.2%) cases (Figures 1 & 2). No details about height, body weight and BMI were available.

Figure 1.

Vitamin D3 levels in menopausal women in Delhi, India (n = 126).

Figure 2.

Distribution of vitamin D3 levels amongst menopausal women in Delhi, India.

Discussion

The incidence of 25-OH-D deficiency in women in the Indian subcontinent has been determined only among women of child-bearing age. It was recorded in 74% of rural pregnant women in Northern India [7]. In a study at the Karachi Medical College, Pakistan, only 22% of pregnant women had sufficient levels of the 25-OH-D, while 78% had either insufficient or deficient levels [6]. Of 20 women giving birth in a tertiary care hospital in Delhi, more than 75% were 25-OH-D deficient [8]. Our results in menopausal women in Delhi are in no way different from the data in women of child-bearing age (Figures 1 & 2) [6 –8]. There was one outlier, an 80 year-old female, with a 25-OH-D level of 342 nmol/l (136 ng/ml). The corresponding values with the controls supplied by the manufacturer of the kit and those procured from an independent source, set up in parallel, were within the specified range. Serum aliquot was not available for a subsequent validation measurement of this value. The percentage variation with the internal control during this interval was 20.67%. We did not address any seasonal changes in 25-OH-D, although we acknowledge that seasonal changes may have an effect on serum 25-OH-D levels, as observed in studies conduced in other countries [9].

In east Asian countries, dietary deficiency and inadequate exposure or reactivity to sunlight owing to lifestyle choices, cultural practices and/or aging were identified as important risk factors for 25-OH-D inadequacy [5]. This appears rather contradictory since there is sunshine almost all through the year in this region and 25-OH-D deficiency should have been much less common. In India, the intake of 25-OH-D-rich food is poor and 25-OH-D-fortified food is not available. In addition, affluent women prefer to avoid exposure to direct sunlight, using umbrellas or protective shields outdoors and thick curtains indoors, thus minimizing the production of 25-OH-D. It is likely that the situation in other countries with plenty of sunshine is similar.

To increase 25-OH-D levels among the deficient women, we plan to provide 25-OH-D supplementation and monitor its postsupplementation levels in order to identify any nonresponders (Figure 1). A daily oral supplementation of 1000 IU of 25-OH-D may fail to bring levels to a minimum of 75nmol/l (30 ng/ml) in 20–30% cases [10]. Alternatively, an intramuscular injection of 600,000 IU (15 mg) cholecalciferol vitamin D (vitamin D₃; Arachitol®, Solvay Pharma, India Ltd) might be suitable for all 25-OH-D-deficient women. This preparation is currently being used to treat vitamin 25-OH-D deficiency and its safety has been evaluated [11].

Conclusion

Severe 25-OH-D hypovitaminosis is also prevalent in the Indian subcontinent, similarly to countries in Europe [3, 4] and East Asia [5], among women in menopause, and requires priority attention. In view of the growing prevalence of the 25-OH-D deficiency among menopausal women globally, it would be desirable to initiate simple and rapid point-of-care assays for quantification of 25-OH-D level in the general population, both in urban and rural areas.

Future perspective

During the next decade the general public will be more familiar with the high global incidence of vitamin D deficiency. Fortified food should be introduced in several countries and international organizations associated with human nutrition should try to encourage fortified food. Rapid, point-of-care assay formats to measure 25-OH-D in healthcare centers, if available, will be useful to monitor 25-OH-D deficiency and the postsupplementation response.

Executive summary

Vitamin D3 level in blood can be quantified as 25-hydroxvitamin D (25-OH-D) using an ELISA kit.

In menopausal women presenting for orthopedic ailments at a tertiary care hospital in Delhi, India, more than 75% were found to be 25-OH-D deficient.

The postsupplementation response among 25-OH-D deficient individuals should be scrutinized to identify the nonresponders.

Simple, point-of-care diagnostic formats are required to quantify 25-OH-D levels at healthcare centers.

Footnotes

Acknowledgements

The authors would like to thank Beena Michael for her technical assistance.

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

References

Papers of special note have been highlighted as:

of interest

of considerable interest

Gibbs

. Rickets and the crippled child: an historical perspective. J. R. Soc. Med. 87(12), 729–732 (1994).

Discusses the historical background of vitamin D₃ deficiency in detail

Holick

Chen

. Vitamin D deficiency: a worldwide problem with health consequences. Am. J. Clin. Nutr. 87(Suppl.), S1080–S1086 (2008).

Describes developments in combatting vitamin D₃ deficiency during the past decade

Neuprez

Bruyère

Collette

Reginster

. Vitamin D inadequacy in Belgian postmenopausal osteoporotic women. BMC Public Health 7, 64 (2007).

Bruyere

Decock

Delhez

Collette

Reginster

. Highest prevalence of vitamin D inadequacy in institutionalized women compared with noninstitutionalized women: a case-control study. Women's Health (Lond. Engl.). 5(1), 49–54 (2009).

10.

Lim

Kung

Sompongse

Soontrapa

Tsai

. Vitamin D inadequacy in postmenopausal women in Eastern Asia. Curr. Med. Res. Opin. 24(1), 99–106 (2008).

11.

Vivid description of vitamin D₃ deficiency in menopausal women in Eastern Asia

12.

Karim

Nusrat

Aziz

. Vitamin D deficiency in pregnant women and their newborns as seen at a tertiary-care center in Karachi, Pakistan. Int. J. Gynaecol. Obstet. 112(1), 59–62 (2011).

13.

Sahu

Bhatia

Aggarwal

. Vitamin D deficiency in rural girls and pregnant women despite abundant sunshine in northern India. Clin. Endocrinol. (Oxf.) 70(5), 680–684 (2009).

14.

Agarwal

Arya

. Vitamin D3 level in pregnancy and newborns in a private tertiary care hospital in Delhi. Int. J. Gyn. Obst. 113(3), 240–241 (2011).

15.

Rylander

Lindqvist

. Eclampsia is more prevalent during the winter season in Sweden. Acta Obstet. Gynecol. Scand. 90(1), 114–117 (2011)

16.

Schwalfenberg

. A step in the right direction. CMAJ 182(16), 1763 (2010).

17.

Vieth

. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am. J. Clin. Nutr. 69, 842–856 (1999).

18.

Details issues relating to vitamin D supplementation

Hypovitaminosis D3 in Menopausal Women in a Tertiary Care Hospital in Delhi