<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "JATS-journalpublishing1.dtd">
<article xml:lang="EN" article-type="research-article">

<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Brain Neurorehabil</journal-id>
<journal-id journal-id-type="publisher-id">BN</journal-id>
<journal-title-group>
<journal-title>Brain &#x0026; Neurorehabilitation</journal-title>
</journal-title-group>
<issn pub-type="ppub">1976-8753</issn>
<issn pub-type="epub">2383-9910</issn>
<publisher>
<publisher-name>Korean Society for Neurorehabilitation</publisher-name>
</publisher>
</journal-meta>

<article-meta>
<article-id pub-id-type="publisher-id">2019120104</article-id>
<article-id pub-id-type="doi">10.12786/bn.2019.12.e5</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Vitamin D Status according to the Diseases in Hospitalized Rehabilitation Patients: Single Center Study</article-title>
</title-group>

<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-9032-7466</contrib-id>
<name>
<surname>Ko</surname>
<given-names>Hanbit</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>

<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-4170-9054</contrib-id>
<name>
<surname>Nam</surname>
<given-names>Jin Hee</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>

<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-8957-2827</contrib-id>
<name>
<surname>Bok</surname>
<given-names>Soo-kyung</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
</contrib-group>

<aff id="A1"><label>1</label>Department of Rehabilitation Medicine, Chungnam National University School of Medicine, Daejeon, <country>Korea</country>.</aff>
<aff id="A2"><label>2</label>Daejeon Chungcheong Regional Rehabilitation Center, Chungnam National University Hospital, Daejeon, <country>Korea</country>.</aff>

<author-notes>
<corresp>Correspondence to Soo-kyung Bok. Department of Rehabilitation Medicine, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea. <email>skbok@cnuh.co.kr</email>
</corresp>
</author-notes>

<pub-date pub-type="collection">
<month>03</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>02</day>
<month>04</month>
<year>2019</year>
</pub-date>
<volume>12</volume>
<issue>1</issue>
<elocation-id>e5</elocation-id>

<history>
<date date-type="received">
<day>03</day>
<month>03</month>
<year>2019</year>
</date>
<date date-type="rev-recd">
<day>29</day>
<month>03</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>31</day>
<month>03</month>
<year>2019</year>
</date>
</history>

<permissions>
<copyright-statement>Copyright &#x00A9; 2019. Korea Society for Neurorehabilitation</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Korea Society for Neurorehabilitation</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by-nc/4.0">
<license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://creativecommons.org/licenses/by-nc/4.0">https://creativecommons.org/licenses/by-nc/4.0</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>

<abstract>
<p>To investigate vitamin D status according to the diseases in patients admitted to the department of rehabilitation medicine. In total, 282 patients admitted to the department of rehabilitation medicine in our hospital were included. Patients were classified into 4 groups according to ailment: stroke, traumatic brain injury, spinal cord injury, and fracture. All patients were also classified as ambulatory or non-ambulatory. Serum 25-hydroxyvitamin D (25[OH]D) levels were estimated at admission and at discharge. Bone mineral density (BMD) and ionized calcium levels were also measured. All subjects completed the Desmond Fall Risk Questionnaire for fall risk assessment. In total, 92 patients (59 males and 33 females; mean age, 69.09 &#x00B1; 9.4 years) was enrolled. Low serum 25(OH)D levels (6&#x2013;28 ng/mL) were observed in all patients in this study, and these were lower in the group of fractures resulting from falls than in the group of strokes (p &#x003C; 0.05). Significant correlations were found between BMD and ionized calcium levels, Desmond Fall Risk Questionnaire scores and BMD, and questionnaire scores and serum 25(OH)D (p &#x003C; 0.05). Serum 25(OH)D levels were lower in the department of rehabilitation medicine inpatients in our study than in the general population. The ambulatory patients had higher serum 25(OH)D levels at discharge than the non-ambulatory patients'. The hospitalized rehabilitation patients had lower serum 25(OH)D compared with the community. There were lower serum 25(OH)D levels in patients with fractures and non-ambulatory groups. We should pay attention to serum vitamin D levels of rehabilitation center inpatients.</p>
</abstract>

<abstract abstract-type="key-points">
<title>Highlights</title>
<p>
<list list-type="simple">
  <list-item>
  <p>&#x2022; The hospitalized rehabilitation patients had lower serum 25 hydroxyvitamin D3 (25[OH]D3) compared with the community.</p>
  </list-item>
  <list-item>
  <p>&#x2022; Patients with fractures had lower serum 25(OH)D3 levels compared with those with other diseases.</p>
  </list-item>
  <list-item>
  <p>&#x2022; Non-ambulatory patients had significantly lower serum 25(OH)D3 levels at discharge compared with ambulatory patients.</p>
  </list-item>
  <list-item>
  <p>&#x2022; We should have a more interest of serum vitamin D in hospitalized rehabilitation patients.</p>
  </list-item>
</list>
</p>
</abstract>

<kwd-group kwd-group-type="author">
<kwd>Vitamin D</kwd>
<kwd>Bone Mineral Density</kwd>
<kwd>Accidental Falls</kwd>
<kwd>Fracture</kwd>
<kwd>Rehabilitation</kwd>
</kwd-group>

</article-meta>
</front>

<body>
<sec sec-type="intro">
<title>INTRODUCTION</title>
<p>Vitamin D is known to be important in optimizing the health of bones and can be obtained by exposing the skin to ultraviolet light in addition to diet [<xref ref-type="bibr" rid="B1">1</xref>]. Vitamin D level was reportedly the lowest in winter, highest in summer, and significantly higher in elderly individuals living at home than in those living in nursing homes [<xref ref-type="bibr" rid="B2">2</xref><xref ref-type="bibr" rid="B3">3</xref><xref ref-type="bibr" rid="B4">4</xref>]. Data from the National Health and Nutrition Examination Surveys for the years 2001&#x2013;2006 indicated that vitamin D levels were sufficient in 66% of the American population. Vitamin D sufficiency is defined by the Institute of Medicine as a serum 25-hydroxyvitamin D (25[OH]D) level of 50&#x2013;125 ng/mL. Approximately 25% of the population was at risk of vitamin D inadequacy, defined as serum 25(OH)D levels of 30&#x2013;49 ng/mL, while 8% were at risk of vitamin D deficiency, defined as serum 25(OH)D levels of &#x003C; 30 ng/mL [<xref ref-type="bibr" rid="B5">5</xref>].</p>
<p>The risk of vitamin D deficiency varies with age, sex, and race or ethnicity. The prevalence of vitamin D deficiency was lower in young, male, and non-Hispanic whites. Among females, the prevalence was lower in pregnant or lactating females [<xref ref-type="bibr" rid="B5">5</xref>]. In 2011, Choi et al. [<xref ref-type="bibr" rid="B6">6</xref>] reported that vitamin D insufficiency is very common in the Korean populations. In Korea, the prevalence of vitamin D deficiency was found in 47.3% of males and 64.5% of females. Dhesi et al. [<xref ref-type="bibr" rid="B7">7</xref>] reported that vitamin deficiency is very common, affecting at least 72% patients attending a falls clinic (25[OH]D &#x003C; 20 ng/mL). Of the total population, severe vitamin D deficiency (&#x003C; 12 ng/mL) was detected in 31.8% patients while moderate vitamin D deficiency (12.1&#x2013;20.0 ng/mL) was detected in 40.6%.</p>
<p>Supplementation with vitamin D metabolites in the elderly has been reported to decrease the incidence of falls [<xref ref-type="bibr" rid="B8">8</xref><xref ref-type="bibr" rid="B9">9</xref><xref ref-type="bibr" rid="B10">10</xref><xref ref-type="bibr" rid="B11">11</xref>]. No study has reported on vitamin D status according to disease groups and ambulatory status in hospitalized patients.</p>
<p>The aim of this study is to investigate the level of vitamin D in patients with subacute stage of admission to the department of rehabilitation medicine according to disease (stroke, traumatic brain injury [TBI], spinal cord injury [SCI], and fracture) and to determine the change of patient's vitamin D according to the availability of ambulation.</p>
</sec>

<sec sec-type="materials|methods">
<title>MATERIALS AND METHODS</title>
<p>The subjects were 282 patients admitted to the rehabilitation medicine clinic at our hospital for comprehensive rehabilitation from March 2012 to December 2012. Subjects who transferred or admitted to our department within 1 month from disease onset and were older than 50 years were included. Disease characteristics, age, sex, ambulatory status, and season were considered as potential confounders because of possible association with both vitamin D status and fall risk.</p>
<p>Patients were classified into 4 groups according to ailment: stroke, TBI, SCI, and fracture (<xref ref-type="table" rid="T1">Table 1</xref>). The fracture group included patients with fractures in the upper or lower extremities caused by falls only. Three seasonal periods were examined: March to June, July to September, and October to December. The baseline questionnaire collected information on age, sex, date of hospital admission, and date of discharge. All patients were also divided into 2 groups: ambulatory group who were able to gait using aid or who used wheelchairs as assistive gait devices and non-ambulatory group such as patients who have taken a wheelchair ride or in bedridden state.</p>
<table-wrap id="T1" position="float">
<?Table Large?>
<label>Table 1</label>
<caption>
<title>Characteristics of the subjects</title>
</caption>
<alternatives>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="bn-12-e5-i001"></graphic>
<table frame="hsides" rules="rows">
<col width="19.54%"/>
<col width="14.14%"/>
<col width="14.14%"/>
<col width="14.14%"/>
<col width="14.14%"/>
<col width="14.14%"/>
<col width="9.77%"/>
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Characteristics</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">SCI (n = 16)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Fracture (n = 14)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Stroke (n = 47)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">TBI (n = 15)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Total (n = 92)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">p value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Sex (male)</td>
<td valign="top" align="center" rowspan="1" colspan="1">12 (75)</td>
<td valign="top" align="center" rowspan="1" colspan="1">6 (42.85)</td>
<td valign="top" align="center" rowspan="1" colspan="1">29 (61.70)</td>
<td valign="top" align="center" rowspan="1" colspan="1">15 (80)</td>
<td valign="top" align="center" rowspan="1" colspan="1">59 (64.13)</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.104</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Ambulation</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">5</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">6</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">22</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">6</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">39</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.042</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Mean age (yr)</td>
<td valign="top" align="center" rowspan="1" colspan="1">65.4 &#x00b1; 7.96</td>
<td valign="top" align="center" rowspan="1" colspan="1">76.82 &#x00b1; 6.60</td>
<td valign="top" align="center" rowspan="1" colspan="1">69.45 &#x00b1; 9.37</td>
<td valign="top" align="center" rowspan="1" colspan="1">65.09 &#x00b1; 8.81</td>
<td valign="top" align="center" rowspan="1" colspan="1">69.09 &#x00b1; 9.40</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.001</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Serum 25(OH)D (ng/mL)</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">10.44 &#x00b1; 3.90</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">8.65 &#x00b1; 5.20</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">12.70 &#x00b1; 5.32</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">9.58 &#x00b1; 2.89</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">11.21 &#x00b1; 5.13</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.033</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">T-scores of BMD</td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;0.83 &#x00b1; 1.49</td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;2.76 &#x00b1; 1.54</td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;1.46 &#x00b1; 1.33</td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;1.58 &#x00b1; 1.21</td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;1.58 &#x00b1; 1.44</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.013</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Desmond fall score</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">3.22 &#x00b1; 2.1</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">6.14 &#x00b1; 2.6</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">5.56 &#x00b1; 3.31</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">3.0 &#x00b1; 2.1</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">5.02 &#x00b1; 3.0</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.156</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<p>Values are presented as mean &#x00B1; standard deviation or number (%). Baseline characteristics of all patients were tested using 1-way analysis of variance.</p>
<p>SCI, spinal cord injury; TBI, traumatic brain injury; BMD, bone mineral density.</p>
</table-wrap-foot>
</table-wrap>
<p>Patients were excluded if they had a history of taking medications that could affect bone and calcium metabolism (glucocorticoids, thiazide, and diuretics), had endocrine disease, chronic renal failure, or unable to ambulation for more than 2 months before illness.</p>
<p>Vitamin D levels were estimated according to serum 25(OH)D levels, ionized calcium levels, and bone mineral density (BMD). Serum 25(OH)D levels were measured twice at admission and at discharge (mean interval, 42 &#x00B1; 27 days). We compared serum 25(OH)D levels according to diseases and the correlations between ionized calcium and serum 25(OH)D levels and between BMD and serum 25(OH)D levels (<xref ref-type="table" rid="T2">Table 2</xref>). Furthermore, patients were divided into an ambulatory and a no ambulatory group, and serum 25(OH)D levels at admission and at discharge were measured in and compared between these 2 groups.</p>
<table-wrap id="T2" position="float">
<?Table Large?>
<label>Table 2</label>
<caption>
<title>Correlations analysis between serum 25 hydroxyvitamin D3, ionized calcium, BMD, falling score in Desmond fall risk questionnaire and age</title>
</caption>
<alternatives>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="bn-12-e5-i002"></graphic>
<table frame="hsides" rules="rows">
<col width="21.66%"/>
<col width="15.67%"/>
<col width="15.67%"/>
<col width="15.67%"/>
<col width="15.67%"/>
<col width="15.67%"/>
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Parameters</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Age (yr)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">BMD</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Serum 25(OH)D (ng/mL)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Ionized calcium (ng/mL)</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Fall score</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Age (yr)</td>
<td valign="top" align="center" rowspan="1" colspan="1">1</td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">BMD</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">&#x2212;0.41<sup>*</sup></td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">1</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)"></td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)"></td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)"></td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Serum 25(OH)D (ng/mL)</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.08</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.32<sup>*</sup></td>
<td valign="top" align="center" rowspan="1" colspan="1">1</td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Ionized calcium (ng/mL)</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">&#x2212;0.05</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.43<sup>*</sup></td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.091</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">1</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)"></td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Fall score</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.39<sup>*</sup></td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;0.191</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.137</td>
<td valign="top" align="center" rowspan="1" colspan="1">&#x2212;0.058</td>
<td valign="top" align="center" rowspan="1" colspan="1">1</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<p>25(OH)D, 25 hydroxyvitamin D; BMD, bone mineral density.</p>
<p><sup>*</sup>The p &#x003C; 0.05 by Pearson's correlation coefficient.</p>
</table-wrap-foot>
</table-wrap>
<p>BMD was estimated within 1 week from date of rehabilitation unit admission by dual-energy X-ray absorptiometry at the lumbar spine and femur. Lumbar spine was estimated from the first lumbar vertebra; fractured vertebrae were not included. The T-score of the femur neck was used.</p>
<p>Blood samples were obtained in the morning. Serum 25(OH)D samples collected at the study sites were measured using the Nichols Advantage System (Nichols Institute Diagnostics, San Clemente, CA, USA), which is a commercially available chemiluminescent assay in which 25(OH)D is released from vitamin D-binding proteins by a leasing agent. The competitive assay is completed automatically by the system. The self-reported Desmond Fall Risk Questionnaire for fall risk assessment was completed by all participants within 1 week from date of hospital admission. This questionnaire comprises 15 questions about fall experiences and falling sensations (<xref ref-type="table" rid="T3">Table 3</xref>) [<xref ref-type="bibr" rid="B12">12</xref><xref ref-type="bibr" rid="B13">13</xref>].</p>
<table-wrap id="T3" position="float">
<?Table Small?>
<label>Table 3</label>
<caption>
<title>Differences between ambulation and non-ambulation groups</title>
</caption>
<alternatives>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="bn-12-e5-i003"></graphic>
<table frame="hsides" rules="rows">
<col width="51.97%"/>
<col width="17.85%"/>
<col width="17.85%"/>
<col width="12.34%"/>
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)"></th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Non-ambulation</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Ambulation</th>
<th valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">p value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Age (yr)</td>
<td valign="top" align="center" rowspan="1" colspan="1">65.09 &#x00b1; 12.88</td>
<td valign="top" align="center" rowspan="1" colspan="1">61.12 &#x00b1; 17.20</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.23</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Onset to serum 25(OH)D test</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">17.75 &#x00b1; 12.31</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">14.84 &#x00b1; 11.15</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.25</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Length of stay in department of rehabilitation medicine<sup>*</sup></td>
<td valign="top" align="center" rowspan="1" colspan="1">52.32 &#x00b1; 18.63</td>
<td valign="top" align="center" rowspan="1" colspan="1">45.02 &#x00b1; 13.01</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.04</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">BMD</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">&#x2212;1.78 &#x00b1; 1.42</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">&#x2212;1.28 &#x00b1; 1.45</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.13</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Serum 25(OH)D (ng/mL) at admission</td>
<td valign="top" align="center" rowspan="1" colspan="1">10.63 &#x00b1; 4.83</td>
<td valign="top" align="center" rowspan="1" colspan="1">11.95 &#x00b1; 5.47</td>
<td valign="top" align="center" rowspan="1" colspan="1">0.24</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">Serum 25(OH)D (ng/mL) at discharge<sup>*</sup></td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">9.70 &#x00b1; 3.59</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">12.74 &#x00b1; 4.65</td>
<td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(245,235,243)">0.04</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot>
<p>Values are presented as mean &#x00B1; standard deviation or number (%). Independent t-test was used to compare groups.</p>
<p>BMD, bone mineral density; 25(OH)D, 25-hydroxyvitamin D.</p>
<p><sup>*</sup>The p &#x003C; 0.05.</p>
</table-wrap-foot>
</table-wrap>
<p>Statistical analysis was performed using SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA). Baseline data are presented as means &#x00B1; standard deviations. Baseline characteristics of all patients were tested using 1-way analysis of variance. Pearson's correlation coefficient was used as a linear correlation between serum 25(OH)D levels and other variables (age, BMD, ambulatory status, ionized calcium, and Desmond fall score). Independent t-test was performed to compare the differences between the ambulation group and the non-ambulation group.</p>
</sec>

<sec sec-type="results">
<title>RESULTS</title>
<p>In total, 92 patients (59 males and 33 females; mean age, 69.09 &#x00B1; 9.4 years) was enrolled. The mean serum 25(OH)D level was 11.2 &#x00B1; 5.1 ng/mL, and mean BMD (T-score) was &#x2212;1.5 &#x00B1; 1.4 (<xref ref-type="table" rid="T1">Table 1</xref>). All patients showed low serum 25(OH)D levels (6&#x2013;28.6 ng/mL). Serum 25(OH)D levels according to disease group were as follows: SCI, 10.4 &#x00B1; 3.9 ng/mL; fracture, 8.6 &#x00B1; 5.2 ng/mL; stroke, 12.7 &#x00B1; 5.3 ng/mL, and TBI, 9.6 &#x00B1; 2.9 ng/mL (<xref ref-type="table" rid="T1">Table 1</xref>). Serum 25(OH)D levels were lower (mean, 8.7 &#x00B1; 5.2 ng/mL) in patients with fall-induced fractures than in those with stroke (mean, 12.7 &#x00B1; 5.3 ng/mL; p = 0.036; <xref ref-type="fig" rid="F1">Fig. 1</xref>).</p>
<fig id="F1" position="float" fig-type="figure">
<?Figure Large?>
<label>Fig. 1</label>
<caption>
<title>Baseline characteristics of 4 groups of disease at admission; 1 (A), mean age; 1 (B), serum 25(OH)D; 1 (C), BMD.</title>
<p>25(OH)D, 25-hydroxyvitamin D; BMD, bone mineral density; SCI, spinal cord injury; TBI, traumatic brain injury.</p>
<p><sup>*</sup>The p &#x003C; 0.05 by Tukey honestly significant difference in 1 way analysis of variance.</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="bn-12-e5-g001"></graphic>
</fig>
<p>T-score of BMD values according to disease were as follows: SCI, &#x2212;0.83 &#x00B1; 1.49; fracture, &#x2212;2.76 &#x00B1; 1.54; stroke, &#x2212;1.46 &#x00B1; 1.33; and TBI, &#x2212;1.58 &#x00B1; 1.21 (<xref ref-type="table" rid="T1">Table 1</xref>). BMD showed significant correlation with age (r = &#x2212;0.41, p &#x003C; 0.01), serum 25(OH)D (r = 0.32, p = 0.005), and ionized calcium (r = 0.43, p &#x003C; 0.01) (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
<p>Desmond Fall Risk Questionnaire score according to disease were as follows: SCI, 3.2 &#x00B1; 2.1; fracture, 6.1 &#x00B1; 2.6; stroke, 5.6&#x00B1;3.3; and TBI, 3.0 &#x00B1; 2.1 (<xref ref-type="table" rid="T1">Table 1</xref>). Desmond Fall Risk Questionnaire score was not significantly associated with characteristics of disease in patients admitted to a department of rehabilitation medicine.</p>
<p>Compared with the ambulatory group and the non-ambulatory group, there was no significant difference in the initial vitamin D levels between the 2 groups, but the vitamin D level at discharge was significantly higher in the ambulatory group (12.74 &#x00B1; 4.65, p = 0.04) and the length of stay was shorter in the ambulation group (45.02 &#x00B1; 13.01, p = 0.04), there were no significant difference in BMD between 2 groups (<xref ref-type="table" rid="T3">Table 3</xref>).</p>
</sec>

<sec sec-type="discussion">
<title>DISCUSSION</title>
<p>In this study, serum 25(OH)D was found to be low in all patients admitted to the department of rehabilitation medicine, and serum 25(OH)D and BMD levels were significantly lower in patients with fractures.</p>
<p>Vitamin D deficiency has been the subject of attention because of the increased prevalence of osteoporotic fractures in the elderly. Sambrook et al. [<xref ref-type="bibr" rid="B14">14</xref>] reported low baseline serum 25(OH)D levels (median, 32.9 ng/mL) in elderly patients in Northern Sydney, Australia. In a study of hospitalized elderly patients in Iceland, Ramel et al. [<xref ref-type="bibr" rid="B3">3</xref>] observed serum 25(OH)D deficiency (serum 25(OH)D &#x003C; 25 ng/mL) in 12.3% patients and serum 25(OH)D insufficiency (serum 25(OH)D = 25&#x2013;75 ng/mL) in 71.9% patients. In an Italian study with a cutoff value of 20 ng/mL, the highest prevalence of vitamin D deficiency was found in a group of patients engaged in a long-term rehabilitation program. In these patients, vitamin D deficiency ranged from 57.8% in summer to 82.3% in winter [<xref ref-type="bibr" rid="B15">15</xref>]. In the present study, low serum 25(OH)D levels were found in rehabilitation patients (mean, 11.3 &#x00B1; 4.8 ng/mL). This level was extremely low compared with that in the general population [<xref ref-type="bibr" rid="B6">6</xref>]. We assumes that, this result was because rehabilitation patients had often received hospital treatment in many times because of other pain, muscle weakness, cognitive impairment, many underlying diseases. For future research, it would be relevant to investigate the cause that explains the association between serum 25(OH)D levels and rehabilitation patients through comparisons with other patients admitted in different departments and hospitalization period.</p>
<p>In the group of patients with fractures in our study, serum 25(OH)D (mean, 8.6 &#x00B1; 5.2 ng/mL) levels were lower than those in the other groups (mean, 11.2 &#x00B1; 5.1 ng/mL). Vitamin D status is associated with muscle strength, physical performance, and falls, as observed in many epidemiological studies [<xref ref-type="bibr" rid="B2">2</xref><xref ref-type="bibr" rid="B16">16</xref><xref ref-type="bibr" rid="B17">17</xref><xref ref-type="bibr" rid="B18">18</xref><xref ref-type="bibr" rid="B19">19</xref><xref ref-type="bibr" rid="B20">20</xref>]. Pfeifer et al. [<xref ref-type="bibr" rid="B21">21</xref>] found a significant decrease in fall incidence, significant improvements in quadriceps strength, decreased body sway, and decreased time required to perform the Time-Up-and-Go test in the vitamin D supplement group in their study. It may because low serum 25(OH)D levels plays an important role in balance control. Many studies have found that impaired gait, postural balance, and muscle strength are associated with fall risk and vitamin D level. For instance, in a population of 319 community-dwelling subjects (mean age, 75.9 years), Bischoff-Ferrari et al. observed a serum 25(OH)D level of &#x2264; 12 ng/mL, which was significantly correlated with decreased leg extension strength. This effect was less intense in females than in males [<xref ref-type="bibr" rid="B20">20</xref>]. Therefore, poor vitamin D status may influence fall risk by affecting muscle function. The active vitamin D metabolite, serum 25(OH)D, plays an important role in the regulation of calcium transport and protein synthesis in the muscle cell. It increases the calcium pool, which is essential for muscle contraction, and enhances the reflex protection mechanism. Therefore, low vitamin D levels may be associated with a high fall risk [<xref ref-type="bibr" rid="B21">21</xref>]. In this study, we once again confirmed that the vitamin D level was low in the fracture group, suggesting that patients with low vitamin D levels had a high fall risk and that the probability of fracture was high even though BMD was similar.</p>
<p>Recent studies showed that serum 25(OH)D levels were significantly higher in patients living at home than in those living in nursing homes [<xref ref-type="bibr" rid="B16">16</xref><xref ref-type="bibr" rid="B22">22</xref>]. This may be because patients living in nursing homes receive insufficient sunlight exposure and experience ambulatory difficulties. Sato et al. reported serum 25(OH)D deficiency in immobilized stroke patients in a cross-sectional study [<xref ref-type="bibr" rid="B4">4</xref>]. They suggested that vitamin D supplementation might be required in disabled elderly stroke patients with vitamin D deficiency in order to prevent hip fractures, which occur frequently in this population. The results of the present study showed that serum 25(OH)D levels at discharge were significantly higher in ambulatory patients than in non-ambulatory or bedridden patients (<xref ref-type="table" rid="T3">Table 3</xref>). One of the factors responsible for this result may be sunlight exposure, which the ambulatory patients received for a longer duration compared with the bedridden patients, and it is estimated that nutritional supplement such as meals was sufficient in the ambulation group compared with the non-ambulatory groups. In this study, Patients undergoing rehabilitation may have more ambulatory difficulties compared with the general population, resulting in less sunlight exposure and decreased serum 25(OH)D production. Also, it has been confirmed that serum 25(OH)D levels performed at discharge of non-ambulatory group showed decreasing trend, which is thought that patients with ambulatory difficulty in the department of rehabilitation medicine had less sunlight exposure and decreased serum 25(OH)D production. So, it seems to need a vitamin D supplement to patients during hospitalization period.</p>
<p>There are some limitations to this study. First, since this study was conducted as a single center study, it cannot be generalized through these results. In addition, there may be other factors that affect the vitamin D level, such as lifestyle or the sunlight exposure of each patient which we could not investigate. Since the analysis by groups, significant differences in the age of patients for each disease, there can be a limit to the interpretation of results. However, the difference in age was between the fracture group and the SCI and TBI groups, whereas the difference between serum 25(OH)D level and BMD was different in the stroke group in which age was not statistically significant. Finally, this study was initially aimed at assessing the association of the underlying disease and vitamin D levels in subacute stage patients, but did not yield significant results for each disease.</p>
</sec>

<sec sec-type="conclusions">
<title>CONCLUSION</title>
<p>The patients admitted to a department of rehabilitation medicine had lower serum 25(OH)D compared with the community. Patients with fractures had lower serum 25(OH)D levels compared with those with other diseases. Furthermore, non-ambulatory patients had significantly lower serum 25(OH)D levels at discharge compared with ambulatory patients (p &#x003C; 0.05).</p>
<p>Evaluation of baseline serum 25(OH)D levels and BMD may helpful in predicting the risk of falling. Also, evaluation of Desmond Fall Risk Questionnaire scores at admission is also useful for preventing recurrent falls in the hospital and for better rehabilitation outcomes.</p>
<p>Therefore, we should have a more interest of serum vitamin D in hospitalized rehabilitation patients and need to provide vitamin D supply to patients admitted in department of rehabilitation medicine, especially those with ambulation difficulty.</p>
</sec>
</body>

<back>
<fn-group>
<fn fn-type="conflict">
<label>Conflict of Interest</label>
<p>The authors have no potential conflicts of interest to disclose.</p>
</fn>
</fn-group>

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