Bone biomarkers are chemical substances produced during the bone remodelling pro-cess that can provide beneficial information concerning bone metabolism. Recently, some studies highlighted the importance of Wnt signalling, a crucial pathway for osteo-blast differentiation and a master bone mass regulator. In fact, serum levels of Dkk1 and SOST, which are negative regulators of Wnt signalling, increase with age and are associ-ated with bone mass loss. Previous studies from the CEDOC group showed that, in fra-gility fracture patients, osteoblast terminal differentiation is impaired, which is associated with bone mechanical fragility. Therefore, it was hypothesized that serum Wnt regulators are associated to bone fragility and can constitute new markers for osteoporosis treatment decision.
In this dissertation, the association between bone gene expression of markers of osteoblast and osteoclast differentiation and of Wnt pathway regulators (Dkk1, Dkk2, SOST, WIF1 and sFRP1) with bone mineral density was analysed. Furthermore, the association between serum levels of bone biomarkers and Wnt regulators and bone mineral density was analysed as well. A set of 128 patients submitted to hip arthroplasty, aged above 40 years old, were evaluated from a clinical database. Linear regression analysis was performed to assess the above-mentioned associations. Associations within estimators were conducted to compute missing values. Stepwise regression was used with the Backward elimination process and bootstrapping was used to externally validate the models. Besides the bone biomarkers, four variables were included to the models, namely sex, rheumatoid arthritis, corticoid use and secondary osteoporosis.
Positive correlations were found between serum levels of Wnt regulators (P1NP, SOST and Dkk1) and BMD. With respect to the genetic expression of bone biomarkers, Dkk2 and sFRP1 were negatively associated with BMD, whereas Lrp6 and WIF1 were positively correlated. These results demonstrate that an upregulation of bone gene expression of Wnt regulators, namely some of the Wnt inhibitors, is associated with low bone mass. The low number of patients is a limitation and further studies need to be conducted in larger populations and with the inclusion of more bone biomarkers. This dissertation was conducted under the project ARIBOS, funded by the Portuguese Society of Rheumatology
