Alterations in bone turnover markers in patients with noncardio-embolic ischemic stroke.

BACKGROUND: The major cause of ischemic stroke is unstable or thrombogenic atherosclerotic plaques. Vascular calcification, a process that appears crucial for plaque stability, shares common features with bone formation. Many bone turnover proteins exhibit metabolic properties, but the evidence is conflicting regarding their possible involvement in vascular disease. Antibodies against sclerostin and dickkopf-1 are currently being evaluated as potential therapy for treating bone disorders. It is important to carefully assess the cardiovascular and metabolic effects of these proteins. The aim of the present study was to explore serum levels of bone turnover markers in patients with acute noncardio-embolic ischemic stroke in comparison with healthy controls. METHODS: In a cross-sectional study, we compared 48 patients aged ≥75 years with noncardio-embolic ischemic stroke and 46 healthy controls. Serum levels of dickkopf-1, sclerostin, osteoprotegerin, osteopontin and osteocalcin were determined by Luminex technique. RESULTS: We found clearly increased serum levels of osteoprotegerin, sclerostin, dickkopf-1 and osteopontin in patients with stroke compared with healthy controls. No difference was seen in serum levels of osteocalcin between the two groups. CONCLUSION: Our findings strengthen the hypothesis of bone turnover markers being involved in vascular disease. Whether these proteins can be used as candidate markers for increased stroke risk or prognostic biomarkers remains to be further elucidated.

Serum levels of the bone turnover markers dickkopf-1, sclerostin, osteoprotegerin, osteopontin, osteocalcin and 25-hydroxyvitamin D in Swedish geriatric patients aged 75 years or older with a fresh hip fracture and in healthy controls.

BACKGROUND: Bone turnover markers have a potential clinical use in describing bone remodeling and in predicting fractures. AIMS: In an elderly population ≥75 years with a fresh hip fracture, and in healthy controls, investigate bone turnover markers and their relation to each other, to vitamin D status and to bone mineral density (BMD). METHODS: In a cross-sectional study serum levels of dickkopf-1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, 25-hydroxyvitamin D (25(OH)D) were analyzed in 89 Swedish patients with a fresh hip fracture and in 82 healthy volunteers. Serum levels of bone markers were determined by Luminex technique. RESULTS: S-25-hydroxyvitamin D (S-25(OH)D) was decreased in patients compared to controls (48 ± 21 vs. 76 ± 25 nmol/L, p < 0.001). SOST, but none of the other bone turnover markers correlated with BMD (r = 0.50, p < 0.001). Compared with controls, higher levels of OPG (488 ± 1.4 vs. 191 ± 1.4 ng/L, p < 0.001), OPN (69 ± 1.7 vs. 19 ± 1.4 µg/L, p < 0.001), DKK-1 (273 ± 1.7 vs. 168 ± 1.7 ng/L, p < 0.001), and lower levels of osteocalcin (5.8 ± 3.5 vs. 9.5 ± 3.6 µg/L, p < 0.001), were found in the fracture group. Levels of OPG, DKK-1 and SOST in both groups were positively associated. S-25(OH)D concentration was not found to be strongly associated with any of the bone markers. CONCLUSIONS: In contrast to findings in other studies, we found no strong correlation between 25(OH)D and the investigated bone markers. Both in patients with a fresh hip fracture and in healthy elderly, DKK-1, SOST and OPG appear to be associated. This suggests a relevance in these relationships meriting further investigation.