Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: correlation with the Trabecular Bone Score (TBS)

Ruaro, Barbara; Casabella, Andrea; Paolino, Sabrina; Pizzorni, Carmen; Ghio, Massimo; Seriolo, C.; Molfetta, Luigi; Odetti, Patrizio; Smith, Vanessa; Cutolo, Maurizio

doi:10.1007/s10067-018-4322-9

Cited by 53 publications

(68 citation statements)

References 38 publications

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“…The lumbar spine TBS, a texture analysis parameter correlated to the bone micro-architecture parameters (9,12), was derived for each spine DXA examination by the TBS index (TBS iNsight Medimaps). The lumbar spine L1-L4 TBS was calculated on each spine DXA examination with the operator blinded to clinical parameters and outcomes (6,7,12).…”

Section: Trabecular Bone Scorementioning

confidence: 99%

“…Recent studies demonstrate a higher incidence of osteoporosis (OP) and fractures in SLE patients than in healthy subjects (HS) (3)(4)(5). There is a multifactorial etiology of bone loss in SLE, which includes systemic inflammation; serological, metabolic, and hormonal factors; and maybe also genetic factors and medication (5)(6)(7)(8). Moreover, a high prevalence of morphometric vertebral fractures was observed in SLE patients, although 1/3 had normal bone density, in line with the multifactorial etiology of fractures in SLE (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies demonstrate that patients with rheumatic inflammatory diseases have low vitamin D and an increased risk of low bone mass (3,(6)(7)(8). Currently, the clinical practice gold standard for OP diagnosis, including secondary causes, is a bone mineral density (BMD) analysis by dual-energy X-ray absorptiometry (DXA) (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…It has recently been reported that the trabecular bone score (TBS), an index extracted by DXA that provides an indirect measurement of bone axial microarchitecture, provides vital information on bone quality in several rheumatic diseases (6,7,12).…”

Section: Introductionmentioning

confidence: 99%

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Trabecular Bone Score and Bone Quality in Systemic Lupus Erythematosus Patients

et al. 2020

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Background: Systemic lupus erythematosus (SLE) patients run a higher risk of having low bone mass due to multifactorial events that include physical inactivity, persistent inflammation, low vitamin D levels, and glucocorticoid treatment. This study aimed at obtaining a comparison between bone involvement in SLE patients and healthy matched subjects (HS). Methods: A total of 40 SLE females (average age 54.1 ± 16.3 years) and 40 age-gender matched HS (average age 54.2 ± 15.9 years) were enrolled after having obtained informed written consent. Bone mineral density (BMD, g/cm 2) of the lumbar spine (L1-L4) was analyzed by a dual-energy X-ray absorptiometry (DXA) scan (GE, Lunar Prodigy). The lumbar spine trabecular bone score (TBS) was derived for each spine DXA examination by the TBS index (TBS iNsight Medimaps). Results: The lumbar spine TBS score was statistically significantly lower in SLE patients than in HS (0.797 ± 0.825 vs. 1.398 ± 0.207, p < 0.001, as was BMD (p < 0.001) in all areas examined. Conclusions: SLE is associated with significant low bone mass as evidenced by DXA and TBS. This study emphasizes the importance of using DXA and TBS in the evaluation of the different aspects of bone architecture.

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Section: Trabecular Bone Scorementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trabecular Bone Score and Bone Quality in Systemic Lupus Erythematosus Patients

et al. 2020

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“…Being a secretory Wnt inhibitor, Dkk1 can serve as an ideal serological marker of bone mass. For instance, serum Dkk1 level closely associates with bone mineral density in humans (Butler et al, 2011; Gatti et al, 2012) and is correlated with the trabecular bone score in patients with systemic sclerosis (Ruaro et al, 2018). Serum Dkk1 is also significantly elevated in patients with osteolytic bone metastasis and osteosarcoma (Lee et al, 2007; Voorzanger‐Rousselot et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells

Dong

Yuan

et al. 2020

Cell Biology International

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Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder characterized by progressive ectopic bone formation in the PLL of the spine. Dickkopf‐1 (Dkk1) is a secreted inhibitor of the Wnt pathway that negatively regulates bone formation during skeletal development. However, whether Dkk1 impacts the pathogenesis of OPLL has not been reported. This study is to investigate the role of Dkk1 in the development of OPLL. Our results show that the serum levels of Dkk1 are decreased in OPLL patients compared with non‐OPLL controls. The expression of Dkk1 is also reduced in OPLL ligament cells. Downregulation of Dkk1 in ligament cells is associated with activation of the Wnt/β‐catenin signaling, as indicated by stabilized β‐catenin and increased T‐cell factor‐dependent transcriptional activity. Functionally, Dkk1 exerts a growth‐inhibitory effect by repressing proliferation but promoting apoptosis of ligament cells. Dkk1 also suppresses bone morphogenetic protein 2‐induced entire osteogenic differentiation of ligament cells, and this suppression is mediated via its inhibition of the Wnt pathway. Our results demonstrate for the first time that Dkk1 acts as an important negative regulator in the ossification of the PLL. Targeting the Wnt pathway using Dkk1 may represent a potential therapeutic strategy for the treatment of OPLL.

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