Abbreviations

1. 25(OH) D: 25-hydroxyvitamin D
2. IOM: Institute of Medicine
3. EFSA: European Food Safety Authority
4. ANSES: Agency for food, environmental and occupational health and safety
5. BMI: body mass index

1. Introduction

Vitamin D, a fat-soluble hormone, originates 80-90% from cutaneous biosynthesis under the effect of the ultraviolet rays of the sun. Only 10-20% of vitamin D is supplied by the absorption of food which naturally rich in this vitamin [1, 2]. The production of endogenous vitamin D is affected mainly by age, ethnic origin, availability of pro-vitamin D3, seasonal variations in sunlight, and the duration of exposure to the sun [3]. Main dietary vitamin D intakes include fatty fish, fish liver oil, eggs, cheese and milk products, particularly fortified products and certain mushrooms [4]. For adults, adequate intakes for vitamin D is set by the Institute of Medicine (IOM) and the European Food Safety Authority (EFSA) at 15 µg/day based on an adjusted model of the meta-regression analysis of serum 25-hydroxyvitamin D (25(OH)D) concentration according to total vitamin D intake [5, 6]. However, recommendations of dietary reference values for vitamin D for older adults aged over 65 range from 10 to 20 µg/day depending on the country [5]. In France, the National Agency for food, environmental and occupational health and safety (ANSES) reported actual nutritional reference of 15 µg/day for vitamin D [7]. At this vitamin D intake of 15 µ/day, the serum 25(OH)D concentration target was achieved at 20 µg/L (50 nmol/L) for the majority of the older population [5]. However, for patients with chronic diseases for which beneficial effects of vitamin D were suggested by observational studies, most experts were divided between setting a minimum concentration of 20 µg/L or 30 µg/L [8, 9]. Obtaining and maintaining a sufficient serum level of 25(OH)D remains crucial, since vitamin D has beneficial effects beyond musculoskeletal health, and potentially on other health aspects due to its immune modulatory properties, notably in older people with vitamin D deficiency [10]. For the elderly, the accent was placed on the reduction age-related loss of bone mass, the risk of bone fractures, skeletal muscle function and related risks of falls [5, 11]. Vitamin D is crucial to calcium and phosphorus homeostasis contributing to bone mineral density. Its deficiency in seniors that are often malnourished or at risk of becoming malnourished may contribute to the risk of fractures [12]. In addition to its known effects, vitamin D receptor is relatively ubiquitous in the organism and implicated in numerous physiological processes such as skeletal muscle development, cell regulation, immune system activity, autoimmune responses and inflammatory processes, brain development, peripheral neuronal activity, control of insulin secretion and the renin-angiotensin system, and cardiovascular function [13-21]. Older adults are prone to vitamin D hypovitaminosis because of low sun exposure notably in institutions, a poor diet, age-related physiological changes and medication such as antiepileptics and glucocorticoids [22]. With the negative consequences of vitamin D deficiency recognized for decades, studies and assessments are required, particularly for high-risk groups like elderly people who are hospitalized or institutionalized. The aim of this retrospective study was to determine the prevalence of vitamin D deficiency in older patients admitted to a French geriatric hospital.

2.Materials and Methods

2.1 Study design

An institutional board-approved retrospective review of older patients seen in our French geriatric hospital was performed from January 2019 to June 2023. Inclusion criteria included all patients up to 65 years old that had a vitamin D dosage at their hospital admission. The demographic data (age and sex), body mass index (BMI), presence of fracture, medication of antiepileptic and glucocorticoid, calcium and phosphorus blood values, serum albumin value, and vitamin D treatment initiation were performed during the study period.

2.2 Study protocol

Patients were selected using a patient cohort visualization tool (cohort360, health database of Assistance Publique des Hôpitaux de Paris declared with the French national data protection authority CNIL, authorization n° 1980120) which powerful queries directly in medical records. For the cohort, the physician requested vitamin D dosage routinely on patient admission. Its dosage guides vitamin D supplementation according to a local protocol. Patients who were vitamin D deficient (<30 µg/L) were treated with 100,000 IU of vitamin D3 (cholecalciferol) every two weeks. In our study, a vitamin D deficiency was defined by a vitamin D level ranged from 12 to 30 µg/L and a severe deficiency by a vitamin D level lower than 12 µg/L, according to the most frequently used thresholds [23].

2.3 Vitamin D determinations

Serum vitamin D (25(OH)D) was determined by electrochemiluminescence immunoassay (Elecsys vitamin D total III, Cobas Roche) from fasting venous blood samples. The lower limits of detection and quantitation for serum vitamin D was 3.0 µg/L and 6.0 µg/L, respectively. For patients in whom vitamin D levels were undetectable, a value of 3.0 µg/L was assigned for statistical calculations. Calcium (reference range 2.20-2.55 mmol/L) and phosphorus (reference range 0.81-1.45 mmol/L) levels were determined from blood serum samples.

2.4 Data analysis

Quantitative variables were reported as mean and standard deviation (SD) and qualitative variables as absolute proportion and percentage. The Pearson correlation coefficient was used to determine the correlation between vitamin D levels and age, BMI, and calcium and phosphorus levels. The Mann-Whitney test was used to compare the vitamin D level median according to sex. The alpha risk was set to 0.05. Statistical analysis was performed with Microsoft Excel 2016 (Microsoft Corporation, Santa Rosa, California). The percentage of patients according to categories of vitamin D status was calculated.

3. Results

Based on collected data, a total amount of 149 patients were included in the study. The study population was between 65 to 100 years old with a mean age of 83.9 ± 7.8 years. The gender balance was 95 women (64%) and 54 men (36%). Demographic and clinical characteristics of the study sample are supplied in Table 1. The study sample had a mean vitamin D level of 18.7 ± 11.8 µg/L with extrema from 3.0 to 91.2 µg/L. In total, 44 (29.5%) patients demonstrated severe vitamin D deficiency (<12.0 µg/L) of which 8 patients presented undetectable levels (<3.0 µg/L) and 88 (59%) patients demonstrated vitamin D deficiency (12-30 µg/L). The mean and the median of the serum vitamin D level were higher in women than in men (p = 0.025) (Fig. 1). Pearson correlation results between vitamin D levels and demographic data or other laboratory analyses such as calcium and phosphorus levels are reported in Table 2. Marked values are statistically significant. Statistical significant correlation was found between the calcium and vitamin D level (Pearson coefficient=0.2669, p=0.006982) and gender and vitamin D level (Mann-Whitney test, p=0.04). This relationship between the calcium and vitamin D level was showed in Fig. 2. There was no significant correlation between age, BMI or phosphorus level. Most patients (86.6%) had serum calcium levels within the normal range. However, hypocalcaemia (<2.2 mmol/L) was found in 11.4%, whereas just three patients (2.0%) were affected by hypercalcemia (>2.55 mmol/L). In all, 8 patients had a fracture, 3 patients received antiepileptic treatment (lamotrigine, phenobarbital, carbamazepine, levetiracetam) and 1 patient took steroid (prednisone). For many patients (76%), vitamin D supplementation was initiated according to the local protocol (100,000 IU of cholecalciferol every 15 days for 2 months) (Table 3). For 14 (9%) patients, no supplementation was introduced regardless of drug level (Table 3). For any patient, vitamin D blood control was performed.

Table 1: Characteristics of patients

Table 2: Correlation results between the selected variables and the vitamin D level.

Table 3: Vitamin D supplementation according drug level.

^*Local protocol=100,000 IU cholecalciferol every 15 days for 2 months

Figure 1: Graphical representation of mean vitamin D level by sex.

Figure 2: Relationship between calcium and vitamin D level

4. Discussion

The principal aim of this study was to determine the prevalence of vitamin D deficiency among older adults in a French geriatric hospital. Overall, 88.6% of patients had insufficient serum levels of vitamin D (<30 µg/L), and over 29.5% of participants had a severe vitamin D deficiency (<12 µg/L). Low vitamin D levels, especially among the elderly, has been shown to cause severely impaired muscle function by interfering with specific nuclear receptor in muscle and mineralization disorders such as osteopenia and osteomalacia [22, 27, 28]. Moreover, the dose-response of vitamin D level could be associated with higher risk of injurious falls in older population [29]. An American study including 4,100 older adults showed that low levels of vitamin D prolonged time to completion on the 8-foot walk test and the sit-to-stand test [30]. Sun exposure and optimization of the diet with few vitamin D-rich foods are the major ways to increase vitamin D level in seniors [31, 32]. However, older people in institution or in long-term care unit are deemed to have a higher risk of vitamin D deficiency due to low exposure to sunlight, a diet poor in vitamin D, or poly-pathological health status. In order to supplement a deficiency in vitamin D, cholecalciferol was routinely prescribed using a specific protocol (100,000 IU every 15 days during 2 months) in our hospital regardless of the blood levels of this drug. In this case, the vitamin D supplementation corresponded to a daily dose of 7000 IU according the recommendations for curative treatment of the available commercial drug (Uvedose 100,000 IU, Crinex, France). Currently, there is no French national consensus of the optimal level for vitamin D supplementation. Although the European Food Safety Authority advises a maximum of 4000 IU/day, many countries have adopted a conservative upper limit of 2000 IU/day for adults [23, 33]. The upper daily limit given by the Endocrine Society is 10,000 IU [8]. Vitamin D toxicity is rare and occurred for serum levels of 25(OH)D concentration often exceeded 150 µg/L. The characteristic signs of vitamin D toxicity are hypercalcemia and hypercaliuria [34]. In our study, any vitamin D serum level was prescribed to control efficacy or toxicity of the local protocol. Due to the high prevalence of vitamin D deficiency among older adults and the adoption of a supplementation protocol irrespective of the 25(OH)D serum level, strategies to identify patients at higher risk for vitamin D deficiency are challenging. The team of Deschasaux et al had developed simple scoring system based on easy-to assess individual characteristics to predict a vitamin D Insufficiency [35]. This score used information on individual characteristics of patients such as sex, BMI, physical activity, residential latitude, and usual sun exposure. This useful tool could be integrated in our clinical practice to obviate unnecessary supplementation and blood testing.

5. Conclusion

In conclusion, prevalence of vitamin D deficiency in the older adults hospitalized in our hospital was high with vitamin D serum level correlated with the calcium level of the patients. The supplementation of a dose of 7000 IU vitamin D3 per day during 2 months was routinely prescribed regardless the 25(OH)D serum level. To check efficacy of the supplementation, a blood test should be scheduled at the end of protocol.

Funding

The authors declare that funding was not utilized for the preparation of this manuscript.

Data availability

All relevant data has been presented in the manuscript and further inquiry can be directed to the corresponding author.

Contributions

JS, decided study design and concept, drafted manuscript; DLL, revised manuscript. All authors have read and approve the final manuscript.

Ethics declarations

Ethics approval and consent to participate

The requirement for informed consent was waived by the Ethic Committee of the Paul Doumer Hospital because of the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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