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ORIGINAL ARTICLE

ABSTRACT Aim: to obtain the prole of vitamin D deciency in

Indonesian elderly women. Methods: it is a cross-sectional study in 74 elderly

women from 4 randomly chosen institutionalized care units in two cities, Jakarta and Bekasi. Data collection included characteristics of subjects, 25(OH)D and PTH, concentration, skin type, nutrient intake including protein, calcium, and vitamin D, and use of sun screen.

Results: the prevalence of 25(OH)D deciency among Indonesian elderly women in institutionalized care is about 35.1%. Most of decient subjects went out-door only once a week (38.5%). Veil was the most sun protection worn by the subjects and most subjects had length of sun exposure 30-60 minutes a week. The mean daily intake of vitamin D was 0.6 IU, protein was 33.9 gr/day and calcium was 239.9 mg/day, and cut-off of serum 25(OH)D in Indonesian elderly women is (suspected) to be 75.9 nmol/L.

Conclusion: we conclude that the prevalence of 25(OH)D deciency among Indonesian elderly women in institutional-ized care is about 35.1% and cut-off of serum 25(OH)D in Indonesian elderly women is (suspected) to be 75.9 nmol/L. Population based study in Indonesia is needed to determine the normal value of 25(OH)D in Indonesian elderly women.

Key words: vitamin D, elderly women, institutionalized care.

Vitamin D Status Among Indonesian Elderly Women Living in Institutionalized Care Units Siti Setiati

Department of Internal Medicine, Faculty of Medicine, University of Indonesia-dr. Cipto Mangunkusumo Hospital, Jl. Diponegoro no. 71, Jakarta Pusat. E-mail: geriatri_fkuirscm@yahoo.com.

INTRODUCTIONIt is increasingly known that the combination of

vitamin D and calcium supplementation has an important role in preventing osteoporosis and fractures in the elderly. Vitamin D has also important role in many organ systems. Vitamin D deciency, recently, has been recognized as the risk factor of many diseases such as asthma, cancer, rheumatoid arthritis, diabetes, etc. Vitamin D deficiency in the elderly is a problem, not only in 4 season countries, but also in tropical countries.

The prevalence of hypovitaminosis D has been estimated in selected populations at particular risk of vitamin D deciency, such as residents of nursing homes and people over the age of 65, to be between 25 and 54 percent.1 Variation in 25(OH)D measurement is reported and confounds the diagnosis of vitamin D insufciency/deciency. Not surprisingly, much work has been focused on dening the optimal circulating concen-tration of 25(OH)D and determination of the required intake to achieve this concentration. Cut-off of vitamin D concentration which is based on the increase of PTH varies in several countries. In Boston, the seasonal variations of serum PTH were no longer visible when serum 25(OH)D was higher than 90 nmol/L leading to the conclusion that 25(OH)D should be higher than these levels to prevent secondary hyperparathyroidism. In a French population, serum PTH started to increase when 25(OH)D decreased below 78 nmol/L leading to a similar conclusion. However, in a large vitamin D study in Amsterdam, the negative relationship between serum PTH and serum 25(OH)D was signicant only when serum 25(OH)D was lower than 30 nmol/L.2 Need (2004) reported that PTH concentration started to increase when 25(OH)D was lower than 80 nmol/L.3

Data regarding prevalence of 25(OH)D deciency in Indonesian elderly are unavailable. The differences in normal vitamin D value in many countries lead to the assumption that there is also a certain normal value of vitamin D concentration in Indonesian elderly woman

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population. The aim of this study is to obtain the prole of vitamin D deciency and to dene the cut-off of 25(OH)D concentration in Indonesian elderly women.

METHODS

Patients, Materials, and MethodsIt is a cross-sectional study in elderly women from

4 randomly chosen institutionalized care units in two cities, Jakarta and Bekasi. Samples of study were elderly women, 60 years old and above, who met the inclusion criteria but had no exclusion criteria, i.e. remained independent, willing to be enrolled in this study, no liver abnormalities nor kidney failure, and free from steroid, phenobarbital and dilantin consumption. Sample size was determined by considering condence interval of 95% and study power of 90%. A total of 74 elderly subjects were recruited.

Data collection included characteristics of subjects, 25(OH)D, PTH, skin type, nutrient intake including protein, calcium, and vitamin D, and use of sun screen. Training about procedures and mechanism of the study for 4 research assistants was done earlier.

Analytical StudiesVenous blood was taken after the patients had fasted

for 12 h. Blood samples were stored in vacutainers without additives between 7 and 8 a.m. Plasma was separated and stored at -20oC until the biochemical analyses were performed. Serum 25(OH)D and PTH were measured by Enzyme-Linked Immuno Sorbent Assay (ELISA) method. Serum 25(OH)D and PTH test were performed in the clinical laboratory which is inter-nationally standardized (ISO 9001). The denition of 25(OH)D deciency is based on Lips’ criteria, that is mild deficiency for 25(OH)D level less than 50 nmol/L. Serum 25(OH)D lower than 25 nmol/L is called moderate vitamin D deciency and severe vitamin D deciency occurs when serum 25(OH)D is lower than 12.5 nmol/L. Secondary hyperparathyroidism is dened as PTH level increase 15% from normal level.

Nutritient IntakeSubjects were interviewed by dietitians to obtain

data on current nutrient intakes (protein, calcium, and vitamin D) by using 24-h food recall method and semi-quantitative food frequency questionnaire.

Statistical AnalysisThe data were entered and analyzed using stata

version 9.0. Numerical results were expressed as the mean (sd). In this study, an increase of 15% of normal PTH level is used as a gold standard to determine

the cut off of vitamin D deficiency. Correlation between 25(OH)D and PTH was tested by Pearson cor-relation. Sensitivity and specicity analysis was used to determine the cut-off of 25(OH)D concentration of Indonesian elderly women.

RESULTSThere were 74 subjects involved in this study. Most

of the subjects (77%) aged 60-75 years old and the rest were older, 76-90 years old. Characteristics of subjects were shown in table 1. Most of subjects went out-door 2 times or more a week (58.1%). Veil was the most sunscreen worn by the subjects when going out-door and most subjects had length of sun exposure less than 30 minutes a day (44.6%).

By using Lips criteria, in which vitamin D deciency is dened as 25(OH)D < 50 nmol/L, our study found the prevalence of vitamin D deciency in Indonesian elderly women was 35.1%. The characteristics of decient subjects were shown in table 2. The mean (SD) of 25(OH)D and PTH was 38.7 (5.2) nmol/L and 75.3 (27.1) pg/ml, respectively. Most of decient subjects went out-door only once a week (38.5%). Veil was the most sun protection worn by the subjects and most subjects had length of sun exposure 30-60 minutes a week. The mean (SD) daily intake of vitamin D was 0.6 IU, protein was 33.9 gr/day and calcium was 239.9 mg/day.

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There was signicant correlation between 25(OH)D level and PTH (r = -0.379; p = 0.001). Scatter diagram of correlation between 25(OH)D and PTH was shown in gure 1.

curve of 63.25%. (Table 3) The sensitivity and specic-ity of 75.9 nmol/l vitamin D was 93.8% and 32.8% respectively, if we counted by using 2x2 table. (Table 4)

Figure 1. Scatter diagram 25(OH)D and PTH

Cut-off of 25(OH)D concentration was obtained from sensitivity and specicity analysis by considering the wide area under ROC curve. The criteria for determining the best cut off was P value less than 0.05, high sensitivity and specicity value, and had the widest area under ROC curve. The best cut off tting to those criteria in this study was 75.9 nmol/L with area under

DISCUSSION The population of this study has represented the

age groups of the elderly. From lifestyle point of view, the lifestyle of most subjects is healthful with regard to vitamin D status. They remain independent, having outdoor activities and rarely using sunscreen, allowing them to get enough sun exposure. Vitamin D deciency is thought to be rare in Indonesian population as this country is exposed to sunlight all year long. However, this study revealed a high prevalence (35.1%) of 25(OH)D deficiency. In other studies of elderly housebound people and nursing home residents, one quarter and one half were vitamin D-decient.4,5,6 Low level of sun exposure and vitamin D intake are probably important factors that may explain why the prevalence of 25(OH)D of vitamin D deciency was high. The definition of vitamin D deficiency may also affect estimates of its prevalence.

Multi-centre study on postmenopausal women in 25 countries in 5 archipelagos found that the prevalence of 25(OH)D 25-50 nmol/L (mild deciency) was 24%. Elderly living in institutionalized care had the highest risk of 25(OH)D deciency. This group was reported to have higher prevalence of deciency, and mostly have

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severe deciency. The mean of 25(OH)D concentration was lower in inpatient elderly and those who live in insitutionalized care than in active elderly.2

Although the prevalence of 25(OH)D in this study was high, the deciency was still mild. We found no moderate and severe deciency in this study. Outdoor activities and routine mild outdoor sports which make subjects still exposed to sunlight may explain why the deciency was mild in this study. Given that sunshine exposure is the most important source of vitamin D, one should expect that vitamin D status depends upon geographic location relative to the equator, with vitamin D status being better in residents closer to the equator compared with those living at higher latitudes. Other factors also inuence vitamin D status, such as intake of high vitamin D containing food, use of vitamin D supplementation, and vitamin D fortication regulation. Length of sun exposure and time of day outdoor, habit of clothing, skin type and pigmentation also inuence the difference of vitamin D status among countries.2,7,8,9

Calcium and vitamin D intake have an important role in muscle and bone health. The requirements of cal-cium and vitamin D depend on difference of race and eth-nicity based on difference in calcium and vitamin D metab-olism between cultures.10 Previous studies has shown that calcium requirement depends on ethnicity group. As an example, white skin type group has a consumption habit of milk and other milk products which contain high calcium. Asian people are the example of population who have low consumption of milk and milk product. This group also has low intake of protein. Protein intake inuences excretion of calcium urine, therefore low protein intake is expected as protection factor in calcium economy in this population.11,12 Based on calcium economy principle, body will maintain calcium concentration in blood effectively by increasing calcium absorption on intestine and reducing calcium urine excretion. Calcium absorption in intestine which is regulated by vitamin D plays a role in calcium economy. Level of calcium absorption is inuenced by calcium intake and vitamin D concentration. Low calcium intake will increase calcium absorption in intestine and needs adequate vitamin D concentration.11,12,13 Based on calcium economy principle, low protein intake in this study (33.9 gram/day) acts as a protective factor because calcium intake is also low; therefore we will have much calcium excretion.12 Adequate vitamin D concentration is also needed to maintain optimal calcium absorption.

Calcium intake in this study (239.9 mg/day) is below the recommended calcium intake (1200 mg/day).14 Calcium intake is also lower compared to calcium intake among women in Europe (657 mg/day) and in

middle-east (684 mg/day).15 Daily vitamin D intake (23.6 IU) in this study is very low compared to the recommended vitamin d intake (400-800 IU/day).14,16,17 Lips reported that vitamin D intake among 4 seasons countries are relatively low (100 IU). The low intake of vitamin D in this study may be due to expensive price of food containing high vitamin D, limited fortied vitamin D food, and no vitamin D supplementation.2

The protein intake found in this study was also very low compared to the recommended protein intake (33.3 gr/day Vs 50 gr/day).18 The very low calcium and protein intake are risk factor of osteoporosis.19 Protein is an important structural component of bone, accounting for approximately half of bone volume and one fourth of bone mass, including the skeletal matrix. By inuencing the functionality of bone-related proteins, dietary protein may have considerable ramication for bone health beyond its effect on calcium. Dietary protein could also affect skeletal integrity through its inuence on the production of insulin-like growth factor I, which exerts several positive effects on the skeleton.20

The recent criteria for normal vitamin D concentration frequently used in many countries are the criteria dened by Lips.2 A serum 25(OH)D lower than 50 nmol/L is called mild vitamin D deciency which is associated with a slightly elevated serum PTH concentration. Serum 25(OH)D lower than 25 nmol/L is called moderate vitamin D deciency which is related to up to 30% of serum PTH elevation. Severe vitamin D deciency occurs when serum 25(OH)D is lower than 12.5 nmol/L, which is related to the increase of PTH concentration of more than 30%. In these cases, serum PTH might be related to a mineralization defect which ultimately leads to frank osteomalacia.2,4

An inverse correlation between PTH and 25(OH)D for the elderly was shown in many studies.21,22 In this study, an increase of 15% of normal PTH level is used as a gold standard to determine the cut off of vitamin D deciency.21,22,,23,24,25 By using sensitivity and specicity analysis, this study found that the cut off of vitamin D deciency was less than 75.9 nmol/L with an area under ROC of 63.25%. The data lead to the conclusion that PTH concentration will increase when 25(OH)D concentration is less than 75.9 nmol/L which is associated with increased bone resorption. Specicity of 75.9 nmol/L vitamin D in this study was 32.8%, meaning that there are some other factors that contribute to high level of normal value of 25(OH)D concentration such as age, kidney function, and estrogen status. This was also supported by the correlation coefcient of 25(OH)D and PTH level in this study, which was only 0.379.3,24,26,27 Low calcium intake

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in this population is suspected to contribute to high level of normal value of 25(OH)D concentration.28,29

Classication of 25(OH)D concentration is also based on muscle strength. Concentration of 25(OH)D less than 75 nmol/L is associated with reduced muscle strength. Holick considered the role of vitamin D in cellular growth and maturation as well as the muscular skeletal systems. He concluded that whereas secondary hyperparathyrodism could be avoided with 25(OH)D level of at least 50 nmol/L, 25(OH)D should probably be at least 75 nmol/L to maximize cellular health.30

Studies in older white population have shown that parathyroid hormone (PTH) concentrations rise when 25(OH)D concentrations fall below 37.5 nmol/L.1,6 A study of 35 patients aged 49-83 years indicated that PTH concentrations rise when 25(OH)D concentrations fall below 50 nmol/L, and a study on 1569 French adults aged 35-65 years found that serum intact PTH began to increase when serum 25(OH)D concentrations were < 78 nmol/L.22 Chapuy et al and Heaney have suggested that the optimal 25(OH)D serum concentration is approximately above 31-32 ng/ml (78-80 nmol/liter). It is often recommended that clinicians strive to maintain 25(OH)D concentration above 32 ng/ml in their patients to maximize bone health. 31

Study done by Thomas used another cut off of vitamin D. The denition of severe hypovitaminosis D was based on the lower limit of normal of 9 ng/mililiter (22 nmol/liter) for serum 25(OH)D concentrations in New England as measured by chromatography in the reference laboratory (Nichols Institute). The denition of moderate hypovitaminosis D was determined according to the Nichols Institute’s norms for serum 25(OH)D of 16 to 74 ng per mililiter (40-185 nmol per liter) in a competitive protein-binding assay & from the published data demonstrating that serum parathyroid hormone concentrations increased in patients who have serum 25(OH)D concentration less than or equal to 15 ng per mililiter.1 Study which was done by Sourbielle in 708 osteoporotic patients found that 26% patients having a serum 25(OH)D level < 30 nmol/liter had a serum PTH above 48 ng/liter, whereas only 7% had a PTH above 65 ng/liter.16 Another study done by Vieth in 1741 adults, found the exponential decay formula to estimate the PTH using 25(OH)D data. With this approach, the PTH concentration approached low plateau at 25(OH)D concentrations, more than 73 nmol/liter. 32

The differences in cut-off of 25(OH)D may be due to discrepancies among 25(OH)D assays and different calcium intake. The assay standardization is not simple

or inexpensive. The simplicity and low cost of its correction, and the potential, benecial, skeletal and non-skeletal consequences of doing so, it is essential that the medical community denes a threshold for optimal vitamin D status using accurate, reproducible assay. These assays must be internationally standardized and made available to practicing clinicians. International standardization of 25(OH)D measurement is essential before elimination of endemic hypovitaminosis D is achievable.33 A relatively high calcium intake, as usual in the Netherlands, may suppress serum PTH and inuence the serum 25(OH)D level at which secondary hyperparathyroidism becomes manifest.23

It is difcult to dene sharp diagnostic criteria for mild vitamin D deciency or insufciency. When the required serum 25(OH)D level is set too high, it will result in a clinically irrelevant diagnosis and unnecessary supplementation. When the required serum 25(OH)D level is set too low, unnecessary bone loss will occur in many patients.23

The limitation of this study is on the small number of sample size which inuences low specicity obtained. Although our data were limited by the small number of sample size (74 subjects), this is the first study which can give the description of prevalence and prole of 25(OH)D deciency and the cut-off of serum 25(OH)D in Indonesian elderly women. All samples were randomly chosen from 4 institutional care units, so it is assumed to represent the population of elderly women in Jakarta and Bekasi. This study is considered to be a preliminary study in determining the normal value of 259(OH)D in Indonesian elderly women.

CONCLUSIONWe conclude that the prevalence of 25(OH)D

deciency among Indonesian elderly women in institutionalized care is about 35.1% and cut-off of serum 25(OH)D in Indonesian elderly women is (suspected) to be 75.9 nmol/L. Population-based study in Indonesia is needed to determine the normal value of 25(OH)D in Indonesian elderly women.

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3. Need AG, O.L.P., Morris HA, Horowitz M, Nordin BEC. The effects of age and other variables on serum parathyroid

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33. Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, DeLuca HF, Drezner MK. Assay variation confounds the diagnosis of hypovitaminosis D: A call standardization. J Clin Endocrinol Metab. 2004;89:3152-7.