Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis

Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Ionescu, Claudio; Dartizio, Carmela; Troplini, Sonila; Kunnathully, Vidya Satheesn; Adami, Silvano; Rossini, Maurizio

doi:10.1016/j.bone.2014.06.037

Cited by 22 publications

(14 citation statements)

References 17 publications

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“…On the other hand, the current study has not found a clear effect of bisphosphonates on sclerostin levels as observed in other studies reporting that sclerostin is increased after treatment with these agents . The relatively low number of patients taking bisphosphonates, the liver disease, and other confounding factors may explain these results as well.…”

Section: Discussioncontrasting

confidence: 77%

Sclerostin Expression in Bile Ducts of Patients With Chronic Cholestasis May Influence the Bone Disease in Primary Biliary Cirrhosis

Guañabens

Ruiz-Gaspà

Gifre

et al. 2016

Journal of Bone and Mineral Research

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Sclerostin is involved in the regulation of osteoblastogenesis and little is known about its role in the development of bone disease in primary biliary cirrhosis (PBC), characterized by low bone formation. Therefore, we have assessed the circulating levels and the liver expression of sclerostin in this cholestatic disease. Serum sclerostin levels were measured in 79 women with PBC (mean age 60.6 AE 1.2 years) and in 80 control women. Lumbar and femoral bone mineral density (BMD), as well as parameters of mineral metabolism and bone remodeling, were measured. Moreover, sclerostin gene (SOST) expression in the liver was assessed by real-time PCR in samples of liver tissue taken by biopsy in 11 PBC patients and in 5 normal liver specimens. Presence and distribution of sclerostin was evaluated in liver slices from 11 patients by immunohistochemistry. The severity of histologic lesions was assessed semiquantitatively in the same liver samples. PBC patients had higher sclerostin levels than controls (75.6 AE 3.9 versus 31.7 AE 1.6 pmol/L, p < 0.001). Serum sclerostin correlated inversely with markers of bone formation and resorption. Sclerostin mRNA in the liver was overexpressed compared with control samples (2.7-fold versus healthy liver). Sclerostin was detected by immunohistochemistry in 7 of the 11 liver samples, mainly located in the bile ducts. Liver sclerostin was associated with the severity of cholangitis (p ¼ 0.02) and indirectly with the degree of lobular inflammation (p ¼ 0.03). Sclerostin mRNA expression was higher in samples that tested positive by immunohistochemistry and particularly in those with lobular granuloma (p ¼ 0.02). The increased expression of sclerostin in the liver and the association with histologic cholangitis may explain the high serum levels of this protein in patients with PBC, thus suggesting that sclerostin may influence the decreased bone formation in this cholestatic disease.

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Section: Discussioncontrasting

confidence: 77%

Sclerostin Expression in Bile Ducts of Patients With Chronic Cholestasis May Influence the Bone Disease in Primary Biliary Cirrhosis

Guañabens

Ruiz-Gaspà

Gifre

et al. 2016

Journal of Bone and Mineral Research

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“…Zoledronic acid is known to reduce both Scl and DKK-1 in postmenopausal osteoporosis, but this effect was not shown for diverse oral BP, suggesting different potencies or affinities to bone responsible for these differing results [15,24]. However, when Scl and DKK-1 were used in a comparable study population, levels increased during yearly zoledronic acid treatment, while in patients treated weekly with intramuscular clodronate, only Scl increased and DKK-1 remained stable [25].…”

Section: Discussionmentioning

confidence: 88%

Ibandronate Increases Sclerostin Levels and Bone Strength in Male Patients with Idiopathic Osteoporosis

et al. 2015

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The pathomechanism of male idiopathic osteoporosis (MIO) differs from postmenopausal osteoporosis with regard to alterations in osteoblast activity. We evaluated intravenous ibandronate (IBN) in 25 MIO patients with fragility fractures in a prospective, monocentric, single-arm, and open-label study for 24 months. The impact and changes of sclerostin (Scl), Dickkopf-1 (DKK-1), CTX, and PINP were examined. Additionally, volumetric cortical, trabecular and areal bone mineral density (BMD), trabecular bone score (TBS), and finite element analyses (FEA) were evaluated. Compared to baseline, median Scl levels were increased after 1 month (Δ 121%, p < 0.0001) and remained elevated for 12 months. DKK-1 decreased (p < 0.001) to a lesser extent until month 9 with values comparable to baseline at study endpoint. Early changes (baseline-month 1) of Scl negatively correlated with early changes of DKK-1 (-0.72), CTX (-0.82), and PINP (-0.55; p < 0.005 for all). The overall changes over the 24 months study period of Scl negatively correlated with decreased CTX (-0.32) and DKK-1 levels (-0.57, p < 0.0001 for both); CTX and PINP changes positively correlated at each time point (p < 0.001). Volumetric hip BMD increased by 12 and 18%, respectively (p < 0.0001 for both). Cross-sectional moment of inertia and section modulus for total hip significantly improved (p < 0.05 for all). Areal BMD at total hip, spine, and TBS increased. FEA displayed an increase in bone strength both in the hip (17%) and vertebrae (13%, all p < 0.0001) at anatomical sites susceptible for fragility fracture. IBN increases Scl and improves cortical and trabecular bone strength with early and ongoing vigorous suppression of bone resorption.

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“…However, the peripheral concentrations of these markers under different clinical situations and treatment conditions do not always reflect the expected data. The relationship to the really observed bone mass and other circulating bone turnover markers has often been found contrary to their assumed regulative effect on osteoblasts [43][44][45][46]. Thus, the influence of biological factors (age, menopausal and hormonal status, renal function) on the concentration of both analytes in serum/plasma [47,48], the still not fully understood molecular processes in the bone [49,50], but also simply unresolved analytical problems [51] may currently be reasons for these substantial interpretation difficulties of the two analytes in serum/plasma.…”

Section: Sclerostin and Dickkopf-1 As Negative Regulatorsmentioning

confidence: 90%

Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis

Jung

Lein

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis

Cited by 22 publications

References 17 publications

Sclerostin Expression in Bile Ducts of Patients With Chronic Cholestasis May Influence the Bone Disease in Primary Biliary Cirrhosis

Sclerostin Expression in Bile Ducts of Patients With Chronic Cholestasis May Influence the Bone Disease in Primary Biliary Cirrhosis

Ibandronate Increases Sclerostin Levels and Bone Strength in Male Patients with Idiopathic Osteoporosis

Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis

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