Strongly enhanced levels of sclerostin during human fracture healing

Department of Traumatology, Medical University of Vienna, Vienna, Austria.
Journal of Orthopaedic Research (Impact Factor: 2.99). 10/2012; 30(10):1549-55. DOI: 10.1002/jor.22129
Source: PubMed


Sclerostin (SOST), an antagonist of Wnt signaling, is an important negative regulator of bone formation. However, no data on the role of SOST in the human fracture healing have been published so far. This study addressed this issue. Seventy-five patients with long bone fractures were included into the study and divided in two groups. The first group contained 69 patients with normal fracture healing. Six patients with impaired fracture healing formed the second group. Thirty-four volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SOST levels were measured in fracture hematoma and serum of 16 patients with bone fractures. Fracture hematoma contained significantly higher SOST concentrations compared to patient's serum. SOST levels in fracture hematoma and in patient's serum were both significantly higher than in the serum of controls. Highly elevated SOST serum concentrations were found in patients with physiological fracture healing. SOST levels were decreased in patients with impaired fracture healing. However, this difference was not statistically significant. This is the first study to provide evidence of strongly enhanced SOST levels in patients with bone fracture. The results indicate local and systemic involvement of SOST in humans during fracture healing.

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    • "At the conclusion of this stage, high levels of NF-κB are expected to subside and a bone reparative phase and angiogenesis govern the site. In support of this notion, it has been suggested that bone formation is often repressed in patients suffering from rheumatoid arthritis and that DKK1 and sclerostin (inhibitors of bone formation) were detected in serum of these patients and other inflammatory conditions [18], [19], [50], [56], [57]. Similarly, bacterially contaminated bone fractures fail to heal [58], suggesting that bacteria-derived lipopolysaccharides activate NF-κB in various cells, including osteoclasts and osteoblasts, and impede repair. "
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