Endothelin-1 Levels in Patients with Paget's Disease of Bone

Abstract

A locally accelerated bone turnover is the pathophysiological basis of Paget's disease of bone (PD) and may result in severe bone deformations and pain. Affected bone sites are hypervascularized. Secreted endothelial products such as endothelin-1 (ET-1), influence bone metabolism. We investigated a possible correlation between ET-1 plasma concentrations and bone metabolism in patients with PD and whether ET-1 plasma levels are regulated by i. v. bisphosphonate treatment. Plasma ET-1 levels were determined in 22 patients with PD and found to be significantly (p = 0.006) elevated (0.75 +/- 0.48 fmol/ml) compared to 19 healthy controls (0.20 +/- 0.24 fmol/ml). In a group of five patients with PD, plasma ET-1 levels were determined before and after treatment with i. v. pamidronate. On the average, ET-1 levels decreased by 21 % after pamidronate infusions (p = 0.045). The results suggest that bone metabolism in pagetic bone affects endothelial cell metabolism and may also be modulated by endothelial cell products. ET-1 plasma levels may indicate PD activity.

Dynamic contrast-enhanced MRI in Paget’s disease of bone–correlation of regional microcirculation and bone turnover

“…Two studies have found elevated plasma levels of endothelin-1 (ET-1) in PD compared to controls using ET-1 as a marker for angiogenesis [26,27]. In conclusion, our study could demonstrate regional microcirculation in Paget's disease of bone by using dynamic contrastenhanced MRI.…”

Pagetʼs disease of bone: thereʼs more than the affected skeletal – a clinical review and suggestions for the clinical practice

“…Higher level of endothelin-1 (ET-1) has been reported in PDB patients, suggesting both its phyisopathological role in the disease and the fact that metabolism in the pagetic bone affects endothelial cell metabolism, and maybe also modulated by endothelial cell products [69,70]. Larger studies replicating these findings are needed before considering ET-1 as a possible new useful marker of PDB-related activity.…”

“…Arterial calcification in the aorta, iliac, femoral, gluteal and pelvic arteries [70] (cause unknown). (3) Calcification of the aortic valve [88] and the interventricular septum.…”

Effect of endothelin-1 on osteoblastic differentiation is modified by the level of connexin43: comparative study on calvarial osteoblastic cells isolated from Cx43+/−and Cx43+/+ mice

“…ET-1 induces not only a mitogenic effect, but also an inhibition of OB differentiation (Takuwa et al 1990;Hiruma et al 1998;Kitten et al 1997). Other lines of evidence indicate a physiopathological role of ET-1 in several diseases of human bones, such as Paget's disease (Tarquini et al 1998;Pirzer et al 2005) and prostate-cancerinduced OB metastases (Jimeno and Carducci 2004). Moreover, we have demonstrated, in a human cell line, that the Cx43 level alters the ET-1 effects on OB differentiation (Niger et al 2008), as shown for other modulators such as PTH (Donahue et al 1995;Chung et al 2006).…”