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2&#46;6&#41; being the previous fracture the more relevant risk factor for fractures &#40;HR&#58; 10&#46;37&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a> In addition&#44; RA is characterized by lower lean mass&#44; muscle strength and increased prevalence of sarcopenia&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Hand periarticular osteopenia is an early radiographic sign of RA&#46; This bilateral and symmetrical bone loss at the hand could appear despite clinical improvement and good control of inflammation through treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Despite digital X-ray radiogrammetry using conventional X-ray is a validated technique for the evaluation of hand BMD&#44;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13&#8211;15</span></a> dual-energy X-ray absorptiometry &#40;DXA&#41; from the lumbar spine &#40;LS&#41; and femoral neck &#40;FN&#41; is the gold standard imaging technique used for the diagnosis and monitoring of osteoporosis&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Whole-hand BMD assessment by DXA &#40;Lunar GE&#41; showed to be more sensitive than conventional radiology for measuring disease-related bone damage in early active RA&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> Hand BMD by DXA &#40;Lunar GE&#41; was validated for estimating BMD in healthy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>88&#41; and osteoarthritic women &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>46&#41; and potentially to be used for mass screening&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> A previous report carried out in 10 early arthritis and 17 healthy women showed lower cortical BMD at metacarpal bones&#44; especially after menopause using an adapted technique in HologicQDR-4500&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> However&#44; there is no specific software in Hologic devices and there are no unique standardized technique and reference values to compare hands&#46; Recently&#44; a study exploring the differences between dominant and non-dominant hands BMD by DXA was reported&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The main purpose of our study was to evaluate the hand BMD including the whole-hand&#44; carpus&#44; metacarpal bone and phalanges in RA patients compare to controls&#46; In addition&#44; we evaluated dominant and non-dominant hand BMD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Subjects and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Study population</span><p id="par0030" class="elsevierStylePara elsevierViewall">We performed a cross-sectional study in RA patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#41;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>18 years who fulfilled the RA classification criteria of the 2010 American College of Rheumatology&#47;European League Against Rheumatism &#40;ACR-EULAR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a> As a control group &#40;CG&#41;&#44; we included 44 healthy volunteers matched by age&#44; gender&#44; and body mass index &#40;BMI&#41;&#46; Exclusion criteria for both groups were pregnancy&#44; participants with a recent history &#40;last 12 months&#41; of immobilization&#44; or those who had a disease or were receiving drugs that could affect bone metabolism &#40;anticonvulsants&#44; bisphosphonates&#44; denosumab&#44; teriparatide&#44; raloxifene&#44; and hormonal replacement therapy&#44; except for corticosteroids&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">RA disease activity was assessed according to DAS-28 including erythrocyte sedimentation rate &#40;ESR&#41;&#44; the number of tenders and swollen joints &#40;28 joints&#41; and a visual analogue scale and Health Assessment Questionnaire Disability Index&#41; &#40;HAQ-I&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The study &#40;1MED486&#41; was approved by the Ethics Committee of the School of Medicine&#44; Rosario National University &#40;Argentina&#41; under the Declaration of Helsinki&#46; All participants gave written informed consent and were identified by a number to keep their identities confidential&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Lumbar spine BMD</span><p id="par0045" class="elsevierStylePara elsevierViewall">Weight and height were measured using a mechanical scale &#40;ROMA scale&#44; Argentina&#41;&#46; BMD &#40;g&#47;cm<span class="elsevierStyleSup">2</span>&#41; was measured by DXA &#40;Hologic Discovery Wi&#44; Hologic Inc&#46; Bedford&#44; MA&#41; on the LS &#40;L1-L4&#41; according to manufacturer recommendations&#46; Quality control was performed by the daily assessment of a phantom spine&#46; All scans were performed by the same certified physician&#44; with a coefficient of variation<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#37;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">DXA hands assessment</span><p id="par0050" class="elsevierStylePara elsevierViewall">Despite there being a specific software for hands in Lunar GE devices&#44; there is no software available in Hologic equipment&#44; which is widely distributed around the world&#46; Therefore&#44; we developed a technique to analyze the whole-hand and three regions of interest &#40;ROI&#41;&#58; carpus&#44; metacarpal bones and phalanges in Hologic Discovery Wi devices using the lumbar spine software&#46; To measure hands BMD&#44; both hands of each subject were placed palm-down on the table with the fingers extended&#44; as described by Deodhar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> We measure carpus as one&#44; the five metacarpal bones and the two proximal phalanges of fingers excluding the thumb and sesamoid bones &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; All determinations were made by the same bone densitometry-certified physician&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">The distribution of the data was evaluated with the Shapiro&#8211;Wilk test and the differences between groups were analyzed using the Student&#39;s <span class="elsevierStyleItalic">t</span>-test or the Mann&#8211;Whitney test&#44; as appropriate&#46; Pearson correlation test and linear regression were used to analyze LS and hand BMD&#46; Data were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 44 control subjects &#40;37 female and 7 male&#44; 49&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8 y&#41; and 60 with RA &#40;50 female and 10 male&#59; 52&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;7 years&#41; were included in this study &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Significant lower BMD in RA patients was found in LS &#40;&#8722;8&#46;7&#37;&#41;&#44; dominant whole-hand &#40;&#8722;9&#46;5&#37;&#41;&#44; carpus&#44; metacarpal bones&#44; and phalanges&#44; and non-dominant whole-hand &#40;&#8722;8&#46;7&#37;&#41;&#44; metacarpal bones&#44; and phalanges &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The intra-assay coefficient of variability &#40;CV&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10 for each region&#41; of whole-hand&#44; carpus&#44; metacarpal bones and phalanges BMD were 1&#46;2&#37;&#44; 0&#46;9&#37;&#44; 2&#46;8&#37; and 2&#46;1&#37; and the inter-assay CV &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; were&#58; 2&#46;7&#37;&#44; 2&#46;2&#37;&#44; 4&#46;3&#37; and 3&#46;7&#37; respectively&#46; Also&#44; the minimal detectable change for each region was calculated as 1&#46;96<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>&#8730;2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>SEM according to Bland and Altman &#40;1988&#41;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> based on duplicate DXA measures&#58; 0&#46;007&#44; 0&#46;010&#44; 0&#46;012&#44; and 0&#46;008<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span>&#44; respectively&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">A significant positive correlation was found between LS BMD and whole-hand BMD in both hands only in RA patients &#40;dominant <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;63&#44; non-dominant <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;67&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001 each&#41; without correlation in control subjects&#46; Linear regression of LS BMD and whole-hand BMD in controls and RA patients revealed a significant difference from zero only in RA patients &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Moreover&#44; there were significant differences between LS BMD and hands slope &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In addition&#44; a negative correlation between dominant and non-dominant hand BMD and age were found in RA patients &#40;dominant&#58; <span class="elsevierStyleItalic">r</span>&#58; &#8722;0&#46;32&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0148&#44; non-dominant&#58; <span class="elsevierStyleItalic">r</span>&#58; &#8722;0&#46;28&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0302&#41; without correlation with disease duration and disease activity parameters &#40;HAQ&#44; DAS28 and ESR&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Further&#44; we analyzed differences between dominant and non-dominant hands BMD in control subjects as an estimation of dominance differences&#46; More than 93&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41&#41; of the participants were right-handed&#46; The whole-hand&#44; metacarpal bones and carpus BMD were significantly higher in the dominant hand compared to the non-dominant hand without differences in the ROI phalanges &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The difference between the dominant and non-dominant sides were&#58; whole-hand BMD 0&#46;009<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> &#40;95&#37;CI 0&#46;014&#8211;0&#46;004&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0007&#41;&#44; carpus 0&#46;030<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> &#40;95&#37;CI 0&#46;045&#8211;0&#46;015&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0003&#41; and metacarpal bones 0&#46;009<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> &#40;95&#37;CI 0&#46;014&#8211;0&#46;004&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0003&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">RA is a chronic inflammatory disease that involves the joints and bones&#46; There is an increased prevalence of bone fragility fracture in RA patients compared to the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a> As hand periarticular osteopenia is an early radiographic sign of RA&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> the evaluation of BMD in the hands could be an early study with clinical value&#46; Therefore&#44; we evaluate a technique to measure whole-hand BMD and also three regions carpus&#44; metacarpal bone and phalanges in RA patients compare to controls in Hologic equipment&#46; This technique using a modified lumbar spine software in a Hologic device was previously described by Deodhar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> but they use an aluminium step wedge resembling the bone thicknesses for bone mineral content &#40;BMC&#41; measurement&#46; More recently&#44; Casta&#241;eda et al&#46; &#40;2007&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> and Llorente et al&#46; &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> also used a modified technique in Hologic device using the forearm software to juxta-articular BMD at metacarpophalangeal joints and metacarpal bones&#44; respectively&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">We found significantly lower BMD in RA patients in dominant whole-hand &#40;&#8722;9&#46;5&#37;&#41;&#44; carpus&#44; metacarpal bones&#44; and phalanges&#44; and non-dominant whole-hand &#40;&#8722;8&#46;7&#37;&#41;&#44; metacarpal bones&#44; and phalanges&#46; Our result adds additional evidence to a previous report who evaluated cortical BMD by DXA in 10 early arthritis and 17 healthy volunteers&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> Furthermore&#44; we found similar coefficients of variation compared to Llorente I et al&#46; &#40;2020&#41;&#58; 2&#46;25&#37;&#44; 2&#46;91&#37;&#44; 2&#46;85&#37;&#44; and 2&#46;07&#37; for metacarpal-2&#44; metacarpal-3&#44; metacarpal-4&#44; and mean metacarpal-second to fourth&#44; respectively and similar to Brownbill and Ilich &#40;2022&#41; for total hand &#40;0&#46;7&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> In addition&#44; the minimal detectable change at the different anatomical locations analyzed ranged were 0&#46;006<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> for whole-hand and from 0&#46;007 to 0&#46;022<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> for metacarpal bones in healthy controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; and 0&#46;009<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> for whole-hand and from 0&#46;005 to 0&#46;010<span class="elsevierStyleHsp" style=""></span>g&#47;cm<span class="elsevierStyleSup">2</span> for metacarpal bones in early arthritis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Moreover&#44; we found a significant positive correlation between LS BMD and whole-hand BMD in both hands only in RA patients without correlation in control subjects&#46; Finally&#44; we found a negative correlation between dominant and non-dominant hand BMD and age in RA patients without correlation with disease duration and disease activity parameters &#40;HAQ&#44; DAS28 and ESR&#41;&#46; Probably the initial DAS28 &#40;3&#46;7&#41; and HAQ &#40;1&#46;0&#41; values indicating a low&#47;moderate disease activity and adequate treatment are responsible&#44; at least in part&#44; for this lack of association&#46; However&#44; other studies found the disease activity &#40;among others&#58; age&#44; previous fracture&#44; parental hip fracture&#44; years since menopause&#44; erosions&#44; and cumulative dose of glucocorticoids&#41; as a risk factor for major osteoporotic fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a> In fact&#44; the inflammatory state in the early stages of RA mediated by proinflammatory interleukins and TNF-&#945; has been described to activate and differentiate osteoclasts leading to bone loss by different mechanisms &#40;RANK&#47;RANKL&#47;OPG and Wnt&#47;DKK1&#47;sclerostin pathways&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> Further&#44; anti-citrullinated protein antibodies and anti-carbamylated protein antibodies are independently associated with severe trabecular bone loss and increased risk of fracture in the next 10 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#44;27</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Previous studies showed that cortical thickness of the metacarpal bones by X-ray reflects BMD in patients with RA showing a good correlation with LS and FN BMD&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">28&#44;29</span></a> However&#44; the measurements in this study were performed manually and it was not suitable as a predictive marker for major osteoporotic fractures&#44; including vertebral&#44; hip&#44; humeral&#44; and wrist fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Further&#44; hand BMD by DXA was able to detect the increase in BMD in RA patients under 12 months under denosumab treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> Another study evaluates the relationship between BMD by DXA and the second metacarpal head microarchitecture by high-resolution peripheral quantitative computed tomography &#40;HR-pQCT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> HR-pQCT can provide a detailed quantitative assessment of periarticular cortical and trabecular bone loss&#44; however&#44; has a higher cost and is not available for clinical use&#46; Finally&#44; a report indicates that periarticular BMD by DXA seems not to be useful as diagnostic due to a strong overlap of BMD values between healthy controls&#44; established RA and early arthritis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> Despite the areas closest to the joint surface are more prone to BMD loss early&#44; the use of small ROIs and a periarticular measurement could not be accurate&#46; Moreover&#44; the authors indicated that the use of hand DXA without considering factors involved in bone loss as age&#44; sex and menopause does not improve the diagnosis in RA patients&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Also&#44; we found differences between dominant and non-dominant hands BMD in the whole-hand&#44; metacarpal bones&#44; and carpus without differences in the ROI of phalanges&#46; These data are consistent with a recent report which evaluated differences between dominant and non-dominant feet and hands BMD and bone mineral content &#40;BMC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a> The authors evaluated a total of 42 subjects &#40;11 men and 31 women&#41; with a mean age of 43&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;91 using 2 different approaches&#44; the whole region &#40;feet or hands&#41; and 2 specific ROIs and found higher BMD and BMC in the dominant hand in comparison with the non-dominant hand without significant differences in the foot&#46; Despite our difference between dominant and non-dominant whole-hand BMD was similar to data reported by Abdala R et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a> we can observe differences in the total hand BMD absolutes values which is assumed as a difference in the densitometer used &#40;Lunar Prodigy or Hologic Discovery Wi&#41;&#46; On the other hand&#44; Deodhar et al&#46; reported that hand dominance had no significant effect on hand BMC&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The limitations of our study include the need for technical training for hand and ROI positioning and&#44; there is no available specific software to measure hands and their different ROI in Hologic equipment&#46; Secondly&#44; the DXA measurements might be influenced by the presence of synovitis or bone erosions characteristics of RA&#46; However&#44; this non-invasive technique is easily adaptable and reproducible&#44; safe as the radiation effective dose is small with an acceptable and comparable coefficient of variability&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD&#46; In addition&#44; the whole-hand&#44; metacarpal bones and carpus BMD were significantly higher in the dominant hand compared to the non-dominant hand without differences in the ROI phalanges&#46; We demonstrated that BMD measurements of the whole-hand&#44; and different ROI &#40;carpus&#44; metacarpal bones and phalanges&#41; by DXA would be an easily reproducible technique to evaluate the bone loss&#46; Nevertheless&#44; more data are necessary to consider as a screening tool for early bone loss in patients with RA&#46; A negative correlation between hand BMD and age in RA patients was found without correlation with disease duration and disease activity parameters &#40;HAQ&#44; DAS28 and ESR&#41;&#46; A study with a large sample considering the disease duration and other parameters for bone involvement would be necessary&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Authors&#8217; contributions</span><p id="par0125" class="elsevierStylePara elsevierViewall">Study design&#58; MLB and LRB&#46; Patient and data acquisition&#58; MLB&#44; AR&#44; BAPE&#44; NJQ&#44; MJ&#44; and GB&#46; Data analysis&#58; MLB&#44; AR and LRB&#46; Data interpretation and drafting of manuscript&#58; MLB&#44; and LRB&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ethics approval information</span><p id="par0130" class="elsevierStylePara elsevierViewall">Ethics Committee of the School of Medicine&#44; Rosario National University &#40;Argentina&#41; &#40;1MED486&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding statement</span><p id="par0135" class="elsevierStylePara elsevierViewall">This work was supported by a <span class="elsevierStyleGrantSponsor" id="gs1">Pan American League of Associations for Rheumatology &#40;PANLAR&#41;</span> Award to MLB and Rosario National University to LRB&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interests</span><p id="par0140" class="elsevierStylePara elsevierViewall">All authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "identificador" => "sec0035"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Authors&#8217; contributions"
        ]
        9 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Ethics approval information"
        ]
        10 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Funding statement"
        ]
        11 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflict of interests"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2022-12-09"
    "fechaAceptado" => "2023-04-22"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1778855"
          "palabras" => array:5 [
            0 => "Hands"
            1 => "Bone mineral density"
            2 => "Rheumatoid arthritis"
            3 => "Dominant hand"
            4 => "Non-dominant hand"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1778854"
          "palabras" => array:5 [
            0 => "Manos"
            1 => "Densidad mineral &#243;sea"
            2 => "Artritis reumatoide"
            3 => "Mano dominante"
            4 => "Mano no dominante"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity&#44; disability&#44; and osteoporosis&#46; We aimed to evaluate whole hand and regional BMD in RA patients compared to controls&#46; In addition&#44; we evaluated the BMD of dominant versus non-dominant hands in healthy subjects&#46; We included adult female and male RA patients and control subjects matched by age&#44; sex&#44; and BMI&#46; BMD &#40;g&#47;cm<span class="elsevierStyleSup">2</span>&#41; was measured by DXA in lumbar spine &#40;LS&#41;&#44; whole hand&#44; and three regions of interest&#58; carpus&#44; metacarpal bones&#44; and phalanges&#46; Results&#58; 44 control subjects &#40;49&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8 y&#41; and 60 with RA &#40;52&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;7 y&#41; were included&#46; Significant lower BMD in RA patients was found in LS &#40;&#8722;8&#46;7&#37;&#41;&#44; dominant whole hand &#40;&#8722;9&#46;5&#37;&#41;&#44; carpus&#44; metacarpal bones&#44; and phalanges&#44; and non-dominant whole hand &#40;&#8722;8&#46;7&#37;&#41;&#44; metacarpal bones&#44; and phalanges compared to controls&#46; A significant positive correlation was found between LS and whole-hand BMD &#40;dominant <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;63&#44; non-dominant <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;67&#41;&#46; Finally&#44; the whole hand&#44; metacarpal bones&#44; and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI&#46; In conclusion&#44; hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD&#46; We demonstrated that BMD measurements of the whole-hand&#44; and different ROI &#40;carpus&#44; metacarpal bones&#44; and phalanges&#41; by DXA would be an easily reproducible technique to evaluate bone loss&#46; In addition&#44; the whole hand&#44; metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La artritis reumatoide &#40;AR&#41; es una enfermedad autoinmune cr&#243;nica caracterizada por poliartritis sim&#233;trica que puede provocar deformidad e incapacidad articular y osteoporosis&#46; Nuestro objetivo fue evaluar la DMO de manos completa y por regiones en los pacientes con AR en comparaci&#243;n con los controles&#46; Se incluyeron pacientes adultos de ambos sexos con AR&#44; y sujetos controles de edad&#44; sexo e IMC similar&#46; La DMO se midi&#243; por DXA en columna lumbar &#40;CL&#41;&#44; manos completas y 3 regiones de inter&#233;s&#58; carpo&#44; metacarpianos y falanges&#46; Resultados&#58; se incluyeron 44 sujetos control &#40;49&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;8 a&#241;os&#41; y 60 con AR &#40;52&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;7 a&#241;os&#41;&#46; Se encontr&#243; una DMO significativamente m&#225;s baja en los pacientes con AR en CL &#40;&#8722;8&#44;7&#37;&#41;&#44; mano completa dominante &#40;&#8722;9&#44;5&#37;&#41; y mano completa no dominante &#40;&#8722;8&#44;7&#37;&#41; en comparaci&#243;n con los sujetos controles&#46; Se encontr&#243; una correlaci&#243;n positiva significativa entre la CL y la DMO de la mano completa &#40;dominante&#44; r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;63&#59; no dominante&#44; r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;67&#41;&#46; Finalmente&#44; la DMO de la mano completa&#44; los huesos metacarpianos y el carpo fueron significativamente m&#225;s altos en la mano dominante en comparaci&#243;n con la mano no dominante sin diferencias en la regi&#243;n de las falanges&#46; En conclusi&#243;n&#44; la DMO de la mano fue significativamente menor en los pacientes con AR en comparaci&#243;n con los sujetos controles&#44; y hubo una correlaci&#243;n significativa con la DMO de la CL&#46; Demostramos que las mediciones de la DMO de toda la mano y diferentes ROI &#40;carpo&#44; huesos metacarpianos y falanges&#41; por DXA ser&#237;an una t&#233;cnica f&#225;cilmente reproducible para evaluar la p&#233;rdida &#243;sea&#46; Adem&#225;s&#44; la DMO de la mano completa&#44; los huesos metacarpianos y el carpo fueron significativamente m&#225;s altos en la mano dominante en comparaci&#243;n con la mano no dominante&#46;</p></span>"
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Hand images derived from DXA showing three analyzed ROI using a modified technique in Hologic device&#58; &#40;A&#41; carpus&#46; &#40;B&#41; metacarpal bones and &#40;C&#41; phalanges&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Linear regression and 95&#37; CI for LS BMD versus whole-hand BMD in controls and RA patients&#46;</p>"
        ]
      ]
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Age&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Female&#47;male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disease duration&#44; years mean &#40;CI95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;4 &#40;5&#46;4&#8211;9&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HAQ score &#40;0&#8211;3&#41;&#44; mean&#40;CI95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;0 &#40;0&#46;8&#8211;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DAS28&#44; mean &#40;CI95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;7 &#40;3&#46;2&#8211;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ESR &#40;mm&#47;hour&#41;&#44; mean &#40;CI95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28&#46;3 &#40;20&#46;0&#8211;36&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of the included subjects&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BMD &#40;g&#47;cm<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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Vol. 19. Issue 10.
Pages 555-559 (December 2023)
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Vol. 19. Issue 10.
Pages 555-559 (December 2023)
Original article
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Whole-hand and regional bone mineral density involvement in rheumatoid arthritis
Compromiso de la densidad mineral ósea de la mano completa y regional en la artritis reumatoide
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María Lorena Brancea,b,c,
Corresponding author
lorenabrance@gmail.com

Corresponding author.
, Agustín Razzinia,b, Bernardo A. Pons-Esteld, Norberto J. Quagliatoe, Marisa Jorfenf, Guillermo Berbottog, Lucas R. Brunb,c
a Reumatología y Enfermedades Óseas, Rosario, Argentina
b Laboratorio de Biología Ósea, Universidad Nacional de Rosario, Argentina
c Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
d Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Rosario, Argentina
e Hospital Provincial Rosario, Argentina
f Red Municipal Rosario, Argentina
g Hospital Escuela Eva Perón, Granadero Baigorria, Argentina
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Table 1. Clinical characteristics of the included subjects.
Table 2. Differences in the lumbar spine and hands BMD between RA patients and control subjects.
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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity, disability, and osteoporosis. We aimed to evaluate whole hand and regional BMD in RA patients compared to controls. In addition, we evaluated the BMD of dominant versus non-dominant hands in healthy subjects. We included adult female and male RA patients and control subjects matched by age, sex, and BMI. BMD (g/cm2) was measured by DXA in lumbar spine (LS), whole hand, and three regions of interest: carpus, metacarpal bones, and phalanges. Results: 44 control subjects (49.5±11.8 y) and 60 with RA (52.7±12.7 y) were included. Significant lower BMD in RA patients was found in LS (−8.7%), dominant whole hand (−9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole hand (−8.7%), metacarpal bones, and phalanges compared to controls. A significant positive correlation was found between LS and whole-hand BMD (dominant r=.63, non-dominant r=.67). Finally, the whole hand, metacarpal bones, and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI. In conclusion, hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones, and phalanges) by DXA would be an easily reproducible technique to evaluate bone loss. In addition, the whole hand, metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges.

Keywords:
Hands
Bone mineral density
Rheumatoid arthritis
Dominant hand
Non-dominant hand
Resumen

La artritis reumatoide (AR) es una enfermedad autoinmune crónica caracterizada por poliartritis simétrica que puede provocar deformidad e incapacidad articular y osteoporosis. Nuestro objetivo fue evaluar la DMO de manos completa y por regiones en los pacientes con AR en comparación con los controles. Se incluyeron pacientes adultos de ambos sexos con AR, y sujetos controles de edad, sexo e IMC similar. La DMO se midió por DXA en columna lumbar (CL), manos completas y 3 regiones de interés: carpo, metacarpianos y falanges. Resultados: se incluyeron 44 sujetos control (49,5±11,8 años) y 60 con AR (52,7±12,7 años). Se encontró una DMO significativamente más baja en los pacientes con AR en CL (−8,7%), mano completa dominante (−9,5%) y mano completa no dominante (−8,7%) en comparación con los sujetos controles. Se encontró una correlación positiva significativa entre la CL y la DMO de la mano completa (dominante, r=0,63; no dominante, r=0,67). Finalmente, la DMO de la mano completa, los huesos metacarpianos y el carpo fueron significativamente más altos en la mano dominante en comparación con la mano no dominante sin diferencias en la región de las falanges. En conclusión, la DMO de la mano fue significativamente menor en los pacientes con AR en comparación con los sujetos controles, y hubo una correlación significativa con la DMO de la CL. Demostramos que las mediciones de la DMO de toda la mano y diferentes ROI (carpo, huesos metacarpianos y falanges) por DXA serían una técnica fácilmente reproducible para evaluar la pérdida ósea. Además, la DMO de la mano completa, los huesos metacarpianos y el carpo fueron significativamente más altos en la mano dominante en comparación con la mano no dominante.

Palabras clave:
Manos
Densidad mineral ósea
Artritis reumatoide
Mano dominante
Mano no dominante
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Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity and disability. Chronic inflammation in RA has a detrimental effect on bone mass even in premenopausal women and can lead to focal or generalized osteoporosis.1–4 Moreover, several other factors, such as female sex, age, corticosteroid therapy, disease activity itself, and immobility due to pain, among others increase bone loss in RA patients.5,6 An increase in trabecular and cortical bone involvement and risk of vertebral and non-vertebral fractures have been reported in RA patients.7,8 A high incidence of clinical fragility fractures in postmenopausal Spanish women with RA was recently described where the incidence of major osteoporotic fracture was 3.55 per 100 patient-year in RA patients and 0.72 in controls (HR: 2.6) being the previous fracture the more relevant risk factor for fractures (HR: 10.37).9 In addition, RA is characterized by lower lean mass, muscle strength and increased prevalence of sarcopenia.10,11

Hand periarticular osteopenia is an early radiographic sign of RA. This bilateral and symmetrical bone loss at the hand could appear despite clinical improvement and good control of inflammation through treatment.12

Despite digital X-ray radiogrammetry using conventional X-ray is a validated technique for the evaluation of hand BMD,13–15 dual-energy X-ray absorptiometry (DXA) from the lumbar spine (LS) and femoral neck (FN) is the gold standard imaging technique used for the diagnosis and monitoring of osteoporosis.16

Whole-hand BMD assessment by DXA (Lunar GE) showed to be more sensitive than conventional radiology for measuring disease-related bone damage in early active RA.17 Hand BMD by DXA (Lunar GE) was validated for estimating BMD in healthy (n=88) and osteoarthritic women (n=46) and potentially to be used for mass screening.18 A previous report carried out in 10 early arthritis and 17 healthy women showed lower cortical BMD at metacarpal bones, especially after menopause using an adapted technique in HologicQDR-4500.19 However, there is no specific software in Hologic devices and there are no unique standardized technique and reference values to compare hands. Recently, a study exploring the differences between dominant and non-dominant hands BMD by DXA was reported.20

The main purpose of our study was to evaluate the hand BMD including the whole-hand, carpus, metacarpal bone and phalanges in RA patients compare to controls. In addition, we evaluated dominant and non-dominant hand BMD.

Subjects and methodsStudy population

We performed a cross-sectional study in RA patients (n=60)>18 years who fulfilled the RA classification criteria of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR-EULAR).21 As a control group (CG), we included 44 healthy volunteers matched by age, gender, and body mass index (BMI). Exclusion criteria for both groups were pregnancy, participants with a recent history (last 12 months) of immobilization, or those who had a disease or were receiving drugs that could affect bone metabolism (anticonvulsants, bisphosphonates, denosumab, teriparatide, raloxifene, and hormonal replacement therapy, except for corticosteroids).

RA disease activity was assessed according to DAS-28 including erythrocyte sedimentation rate (ESR), the number of tenders and swollen joints (28 joints) and a visual analogue scale and Health Assessment Questionnaire Disability Index) (HAQ-I).22,23

The study (1MED486) was approved by the Ethics Committee of the School of Medicine, Rosario National University (Argentina) under the Declaration of Helsinki. All participants gave written informed consent and were identified by a number to keep their identities confidential.

Lumbar spine BMD

Weight and height were measured using a mechanical scale (ROMA scale, Argentina). BMD (g/cm2) was measured by DXA (Hologic Discovery Wi, Hologic Inc. Bedford, MA) on the LS (L1-L4) according to manufacturer recommendations. Quality control was performed by the daily assessment of a phantom spine. All scans were performed by the same certified physician, with a coefficient of variation<1%.

DXA hands assessment

Despite there being a specific software for hands in Lunar GE devices, there is no software available in Hologic equipment, which is widely distributed around the world. Therefore, we developed a technique to analyze the whole-hand and three regions of interest (ROI): carpus, metacarpal bones and phalanges in Hologic Discovery Wi devices using the lumbar spine software. To measure hands BMD, both hands of each subject were placed palm-down on the table with the fingers extended, as described by Deodhar et al.24 We measure carpus as one, the five metacarpal bones and the two proximal phalanges of fingers excluding the thumb and sesamoid bones (Fig. 1). All determinations were made by the same bone densitometry-certified physician.

Fig. 1.

Hand images derived from DXA showing three analyzed ROI using a modified technique in Hologic device: (A) carpus. (B) metacarpal bones and (C) phalanges.

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Statistical analysis

The distribution of the data was evaluated with the Shapiro–Wilk test and the differences between groups were analyzed using the Student's t-test or the Mann–Whitney test, as appropriate. Pearson correlation test and linear regression were used to analyze LS and hand BMD. Data were expressed as mean±SD and p<0.05 was considered significant.

Results

A total of 44 control subjects (37 female and 7 male, 49.5±11.8 y) and 60 with RA (50 female and 10 male; 52.7±12.7 years) were included in this study (Table 1). Significant lower BMD in RA patients was found in LS (−8.7%), dominant whole-hand (−9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole-hand (−8.7%), metacarpal bones, and phalanges (Table 2).

Table 1.

Clinical characteristics of the included subjects.

Characteristics  Control (n=44)  RA (n=60)  p 
Age, mean±SD, years  49.5±11.8  52.7±12.7  ns 
Female/male  37/7  50/10  ns 
BMI, mean±SD, kg/m2  26.3±4.5  27.9±4.9  ns 
Disease duration, years mean (CI95%)  –  7.4 (5.4–9.3)  – 
HAQ score (0–3), mean(CI95%)  –  1.0 (0.8–1.2)  – 
DAS28, mean (CI95%)  –  3.7 (3.2–4.2)  – 
ESR (mm/hour), mean (CI95%)  –  28.3 (20.0–36.5)  – 
Table 2.

Differences in the lumbar spine and hands BMD between RA patients and control subjects.

BMD (g/cm2Control (n=44)  RA (n=60)  p 
Lumbar spine BMD  1.014±0.122  0.926±0.140*  −8.7  0.0032 
Dominant hand BMD
Total hand  0.296±0.030  0.268±0.036*  −9.5  0.0003 
Carpus  0.423±0.061  0.391±0.059*  −7.6  0.0113 
Metacarpal bones  0.293±0.029  0.261±0.039*  −10.9  <0.0001 
Phalanges  0.242±0.030  0.223±0.036*  −7.8  0.0114 
Non-dominant hand BMD
Total hand  0.286±0.026#  0.261±0.036*  −8.7  0.0005 
Carpus  0.394±0.038#  0.382±0.073  −3.0  ns 
Metacarpal bones  0.285±0.028#  0.252±0.034*  −11.6  <0.0001 
Phalanges  0.239±0.028  0.219±0.036*  −8.4  0.0059 
*

Indicates significant differences versus controls (p<0.05).

#

Indicates significant differences versus the dominant hand (p<0.05).

The intra-assay coefficient of variability (CV) (n=10 for each region) of whole-hand, carpus, metacarpal bones and phalanges BMD were 1.2%, 0.9%, 2.8% and 2.1% and the inter-assay CV (n=10) were: 2.7%, 2.2%, 4.3% and 3.7% respectively. Also, the minimal detectable change for each region was calculated as 1.96×√2×SEM according to Bland and Altman (1988)25 based on duplicate DXA measures: 0.007, 0.010, 0.012, and 0.008g/cm2, respectively.

A significant positive correlation was found between LS BMD and whole-hand BMD in both hands only in RA patients (dominant r=0.63, non-dominant r=0.67; p<0.0001 each) without correlation in control subjects. Linear regression of LS BMD and whole-hand BMD in controls and RA patients revealed a significant difference from zero only in RA patients (Fig. 2). Moreover, there were significant differences between LS BMD and hands slope (p<0.05).

Fig. 2.

Linear regression and 95% CI for LS BMD versus whole-hand BMD in controls and RA patients.

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In addition, a negative correlation between dominant and non-dominant hand BMD and age were found in RA patients (dominant: r: −0.32, p=0.0148, non-dominant: r: −0.28, p=0.0302) without correlation with disease duration and disease activity parameters (HAQ, DAS28 and ESR).

Further, we analyzed differences between dominant and non-dominant hands BMD in control subjects as an estimation of dominance differences. More than 93% (n=41) of the participants were right-handed. The whole-hand, metacarpal bones and carpus BMD were significantly higher in the dominant hand compared to the non-dominant hand without differences in the ROI phalanges (Table 1). The difference between the dominant and non-dominant sides were: whole-hand BMD 0.009g/cm2 (95%CI 0.014–0.004, p=0.0007), carpus 0.030g/cm2 (95%CI 0.045–0.015, p=0.0003) and metacarpal bones 0.009g/cm2 (95%CI 0.014–0.004, p=0.0003).

Discussion

RA is a chronic inflammatory disease that involves the joints and bones. There is an increased prevalence of bone fragility fracture in RA patients compared to the general population.8 As hand periarticular osteopenia is an early radiographic sign of RA,12 the evaluation of BMD in the hands could be an early study with clinical value. Therefore, we evaluate a technique to measure whole-hand BMD and also three regions carpus, metacarpal bone and phalanges in RA patients compare to controls in Hologic equipment. This technique using a modified lumbar spine software in a Hologic device was previously described by Deodhar et al.24 but they use an aluminium step wedge resembling the bone thicknesses for bone mineral content (BMC) measurement. More recently, Castañeda et al. (2007)26 and Llorente et al. (2019)19 also used a modified technique in Hologic device using the forearm software to juxta-articular BMD at metacarpophalangeal joints and metacarpal bones, respectively.

We found significantly lower BMD in RA patients in dominant whole-hand (−9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole-hand (−8.7%), metacarpal bones, and phalanges. Our result adds additional evidence to a previous report who evaluated cortical BMD by DXA in 10 early arthritis and 17 healthy volunteers.19 Furthermore, we found similar coefficients of variation compared to Llorente I et al. (2020): 2.25%, 2.91%, 2.85%, and 2.07% for metacarpal-2, metacarpal-3, metacarpal-4, and mean metacarpal-second to fourth, respectively and similar to Brownbill and Ilich (2022) for total hand (0.7%).18 In addition, the minimal detectable change at the different anatomical locations analyzed ranged were 0.006g/cm2 for whole-hand and from 0.007 to 0.022g/cm2 for metacarpal bones in healthy controls (n=16) and 0.009g/cm2 for whole-hand and from 0.005 to 0.010g/cm2 for metacarpal bones in early arthritis (n=22).26

Moreover, we found a significant positive correlation between LS BMD and whole-hand BMD in both hands only in RA patients without correlation in control subjects. Finally, we found a negative correlation between dominant and non-dominant hand BMD and age in RA patients without correlation with disease duration and disease activity parameters (HAQ, DAS28 and ESR). Probably the initial DAS28 (3.7) and HAQ (1.0) values indicating a low/moderate disease activity and adequate treatment are responsible, at least in part, for this lack of association. However, other studies found the disease activity (among others: age, previous fracture, parental hip fracture, years since menopause, erosions, and cumulative dose of glucocorticoids) as a risk factor for major osteoporotic fractures.9 In fact, the inflammatory state in the early stages of RA mediated by proinflammatory interleukins and TNF-α has been described to activate and differentiate osteoclasts leading to bone loss by different mechanisms (RANK/RANKL/OPG and Wnt/DKK1/sclerostin pathways).4 Further, anti-citrullinated protein antibodies and anti-carbamylated protein antibodies are independently associated with severe trabecular bone loss and increased risk of fracture in the next 10 years.4,27

Previous studies showed that cortical thickness of the metacarpal bones by X-ray reflects BMD in patients with RA showing a good correlation with LS and FN BMD.28,29 However, the measurements in this study were performed manually and it was not suitable as a predictive marker for major osteoporotic fractures, including vertebral, hip, humeral, and wrist fractures.30

Further, hand BMD by DXA was able to detect the increase in BMD in RA patients under 12 months under denosumab treatment.31 Another study evaluates the relationship between BMD by DXA and the second metacarpal head microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT).32 HR-pQCT can provide a detailed quantitative assessment of periarticular cortical and trabecular bone loss, however, has a higher cost and is not available for clinical use. Finally, a report indicates that periarticular BMD by DXA seems not to be useful as diagnostic due to a strong overlap of BMD values between healthy controls, established RA and early arthritis patients.33 Despite the areas closest to the joint surface are more prone to BMD loss early, the use of small ROIs and a periarticular measurement could not be accurate. Moreover, the authors indicated that the use of hand DXA without considering factors involved in bone loss as age, sex and menopause does not improve the diagnosis in RA patients.

Also, we found differences between dominant and non-dominant hands BMD in the whole-hand, metacarpal bones, and carpus without differences in the ROI of phalanges. These data are consistent with a recent report which evaluated differences between dominant and non-dominant feet and hands BMD and bone mineral content (BMC).20 The authors evaluated a total of 42 subjects (11 men and 31 women) with a mean age of 43.82±9.91 using 2 different approaches, the whole region (feet or hands) and 2 specific ROIs and found higher BMD and BMC in the dominant hand in comparison with the non-dominant hand without significant differences in the foot. Despite our difference between dominant and non-dominant whole-hand BMD was similar to data reported by Abdala R et al.20 we can observe differences in the total hand BMD absolutes values which is assumed as a difference in the densitometer used (Lunar Prodigy or Hologic Discovery Wi). On the other hand, Deodhar et al. reported that hand dominance had no significant effect on hand BMC.24

The limitations of our study include the need for technical training for hand and ROI positioning and, there is no available specific software to measure hands and their different ROI in Hologic equipment. Secondly, the DXA measurements might be influenced by the presence of synovitis or bone erosions characteristics of RA. However, this non-invasive technique is easily adaptable and reproducible, safe as the radiation effective dose is small with an acceptable and comparable coefficient of variability.

In conclusion hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. In addition, the whole-hand, metacarpal bones and carpus BMD were significantly higher in the dominant hand compared to the non-dominant hand without differences in the ROI phalanges. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones and phalanges) by DXA would be an easily reproducible technique to evaluate the bone loss. Nevertheless, more data are necessary to consider as a screening tool for early bone loss in patients with RA. A negative correlation between hand BMD and age in RA patients was found without correlation with disease duration and disease activity parameters (HAQ, DAS28 and ESR). A study with a large sample considering the disease duration and other parameters for bone involvement would be necessary.

Authors’ contributions

Study design: MLB and LRB. Patient and data acquisition: MLB, AR, BAPE, NJQ, MJ, and GB. Data analysis: MLB, AR and LRB. Data interpretation and drafting of manuscript: MLB, and LRB. All authors read and approved the final manuscript.

Ethics approval information

Ethics Committee of the School of Medicine, Rosario National University (Argentina) (1MED486).

Funding statement

This work was supported by a Pan American League of Associations for Rheumatology (PANLAR) Award to MLB and Rosario National University to LRB.

Conflict of interests

All authors declare that they have no conflict of interest.

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