Background Patients affected by systemic sclerosis (SSc) might present an increased risk of low bone mass as a result of multisystemic disorder such as gut malabsorption or malnutrition and decreased 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 requiare for new bone formattino and is increased in postmenopausal patients.
Objectives In this study, bone mineral density (BMD), 25-hydroxyvitamin D [25(OH) D] status and Dkk-1 levels were evaluated in order to investigate in SSc patients the incidence of osteoporosis and/or osteopenia, in according to their different nailfold videocapillaroscopic (NVC) microangiopathy pattern (namely “Early”, “Active”, and “Late”).
Methods Seventy-four postmenopausal patients (mean age 64±3 years) affected by SSc (“early” n=12; “active” n=21 and “late” pattern n=41) and 63 age-matched healthy controls (mean age 63±5 years) were studied. BMD (g/cm2) of the lumbar spine (L1-L4) and of the proximal femur (femoral neck, 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)D 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) The statistical analysis was performed by non-parametric tests.
Results Out of 74 enrolled patients with SSc, 56 (76%) presented bone loss; in particular 32 (43%) showed osteoporosis and 24 (32%) osteopenia. BMD was found significantly lower in SSc patients than in control group (lumbar spine: 0.890±0.21 g/cm2 vs 1.028±0.26 g/cm2; femoral neck 0.698±0.21 g/cm2 vs 0.855±0.23 g/cm2; total hip 0.801±0.14 g/cm2 vs 0.922±0.19 g/cm2, overall significance p<0.001). DKK-1 levels were significantly higher in SSc patients than in control group (2734±894 pg/mL vs 2044±692 pg/mL, p<0.007). Vitamin D levels were found lower in SSc patients than in controls (18.6+ 31 ng/ml vs 42.8+ 23 ng/ml). Interestingly, BMD (lumbar spine 0.870±0.150 g/cm2 vs 1.077±0.165 g/cm2; total hip 0.660±0.246 g/cm2 vs 0.783±0.113 g/cm2) and 25(OH)D levels (9.3±2.3 ng/ml vs 16.8±3.6 ng/ml) were found lower and Dkk-1 levels (3265±666 pg/mL vs 2033±697 pg/mL) higher in patients with “late” pattern than “early”/“active” NVC patterns.
Conclusions This study showed a significant increase in serum levels of Dkk-1, associated with osteopenia/osteoporosis and deficient Vitamin D status in SSc patients with late NVC pattern 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-Î2 or connective tissue growth factor (all activated in SSc), its increase observed in SSc patients is matter of further investigations2,3.
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Ren S et al. Proc Natl Acad Sci U S A 2013;110:1440-5
Dees C et al. Ann Rheum Dis 2014:6;1232-9
Disclosure of Interest None declared
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