Background 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 skin1. 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.
Objectives 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
Methods 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/cm2) of the lumbar spine (L1-L4) 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 (>30 ng/ml), insufficient (<30 and >10 ng/ml), and deficient <10 ng/ml)
Results 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/cm2 vs 1.039±0.18 g/cm2 and total hip 0.809±0.125 g/cm2 vs 0.903±0.11 g/cm2, both p<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<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/cm2 vs 1.077±0.165 g/cm2; total hip 0.662±0.266 g/cm2 vs 0.788±0.121 g/cm2, and Dkk-1 levels 3,258±672 pg/mL and 3,098+586 pg/ml vs 2,033±697 pg/mL, respectively, all p<0.01).
Conclusions 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 in vitro 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 investigations2. In addition, Dkk-1 should be considered a further marker of disease activity in SSc patients.
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.
Disclosure of Interest None declared