SAT0460 Low Bone Mass in Patients with Systemic Sclerosis: Relationships with Dickkopf-1 Levels and 25-Hydroxyvitamin D Status
Authors: B. Seriolo, R. Brizzolara, S. Soldano, A. Casabella, L. Molfetta, S. Paolino, M.A. Cimmino, G. Botticella, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients (pts) affected by systemic sclerosis (SSc) show increased risk of bone loss as a result of the chronic inflammatory state, physical inactivity, gut malabsorption or malnutrition, decrease activation of vitamin D in the altered fibrotic skin<sup>1</sup>. Dickkopf-1 (Dkk-1) is recognized as a key regulator of bone remodeling by inhibition of the Wnt signalling required for new bone formation and is increased in postmenopausal pts. <h3>Objectives</h3> In this study, bone mineral density (BMD), 25-hydroxyvitamin D [25(OH) D] status and Dkk-1 serum levels were evaluated in order to investigate in SSc pts a possible association between systemic osteoporosis and/or osteopenia, and Dkk-1 concentrations, based on different 25(OH) D status <h3>Methods</h3> 64 postmenopausal pts (mean age 63±7 ys) affected by SSc (mean disease duration 6±3 ys) and 43 age-matched healthy controls (mean age 62±5 ys) were evaluated during their regular screenings and after informed consent in different periods of the year. Pts were not treated with vitamin D addiction or bone remodelling drugs. BMD (g/cm<sup>2</sup>) of the lumbar spine (L<sub>1</sub>-L<sub>4</sub>) and total hip was analyzed using dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy, GE, USA). Dkk-1 serum levels were measured using an enzyme-linked immunosorbent assay and 25(OH)D3 serum levels were evaluated by radioimmunoassay. Vitamin D levels were classified as normal (&gt;30 ng/ml), insufficient (&lt;30 and &gt;10 ng/ml), and deficient &lt;10 ng/ml) <h3>Results</h3> 47 of the SSc pts enrolled (73%) presented bone loss, in particular 24 pts (51%) showed osteoporosis and 23 osteopenia. BMD was found significantly lower in the SSc pts than in control group (lumbar spine: 0.990±0.192 g/cm<sup>2</sup> vs 1.039±0.18 g/cm<sup>2</sup> and total hip 0.809±0.125 g/cm<sup>2</sup> vs 0.903±0.11 g/cm<sup>2</sup>, both p&lt;0.001). Dkk-1 levels were significantly higher in SSc pts than in control group (2,702±910 pg/mL vs 2,164±662 pg/mL, p&lt;0.007). Vitamin D levels were found lower in SSc patients than in controls (22.6+ 11 ng/ml vs 49.8+ 10 ng/ml). Interestingly, BMD at lumbar spine and Dkk-1 levels were found, respectively, significantly lower and higher in pts with deficient (n=14) and insufficient (n=30) vitamin D status when compared to pts with normal vitamin D status (lumbar spine 0.868±0.151 g/cm<sup>2</sup> vs 1.077±0.165 g/cm<sup>2</sup>; total hip 0.662±0.266 g/cm<sup>2</sup> vs 0.788±0.121 g/cm<sup>2</sup>, and Dkk-1 levels 3,258±672 pg/mL and 3,098+586 pg/ml vs 2,033±697 pg/mL, respectively, all p&lt;0.01). <h3>Conclusions</h3> This study showed a significant increase in serum levels of Dkk-1, associated with osteopenia/osteoporosis in pts affected by SSc and deficient or insufficient vitamin D status, when compared to healthy postmenopausal subjects. Interestingly, since Dkk-1 blocks activation and proliferation of established myofibroblasts <i>in vitro</i> and blocks pericyte proliferation to PDGF, pericyte migration, gene activation, and cytoskeletal reorganization to TGF-β or connective tissue growth factor (all activated in SSc), its increase observed in SSc pts is matter of further investigations<sup>2</sup>. In addition, Dkk-1 should be considered a further marker of disease activity in SSc patients. <h3>References</h3> Cutolo M et al. Autoimmun Rev 2011:12;84-7. Ren S et al. Proc Natl Acad Sci U S A.2013;110:1440-5. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4246