endothelin-1 and Osteitis-Deformans

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.

Topics: Aged; Biomarkers; Endothelin-1; Female; Humans; Male; Middle Aged; Osteitis Deformans

The abundance of endothelial cells in bone marrow and the proximity of these cells to osteoclasts and osteoblasts suggest a role for endothelin-1 (ET-1) on bone metabolism. In vitro, the direct contact with bone endothelial cells induces osteoclastic progenitors to differentiate into mature elements. Recently it has been reported that ET-1 inhibits osteoclastic bone resorption and cell mobility through a specific receptor on osteoclasts; other authors demonstrated that ET-1 exerts a mitogenic activity on osteoblast-like cells (MC3T3) by stimulating tyrosin phosphorylation. We measured ET-1 circulating levels in patients with active Paget's bone disease, a condition with accelerated bone turnover. For the study we recruited 11 patients with Paget's bone disease (5F, 6M; mean age 68.2 +/- 3.6) in the acute stage of the disease; 10 healthy subjects (7F, 3M; mean age 66.5 +/- 3.9) were also enrolled as controls. Plasma ET-1 levels were measured with RIA kits provided by Nichols Institute. Patients showed significantly (P < 0.01) higher ET-1 circulating levels than controls (6.35 +/- 1.9 versus 3.4 +/- 1.2 pg/ml) with a positive correlation (r = 0.63; P = 0.038) with serum alkaline phosphatase (ALP), but not with urinary hydroxyproline. The higher levels of ET-1 in our patients suggest a physiopathological role for this peptide in the disease and, could perhaps represent a new useful marker of Paget's bone disease activity.

Topics: Acute Disease; Aged; Alkaline Phosphatase; Biomarkers; Endothelin-1; Female; Humans; Hydroxyproline; Male; Osteitis Deformans