1. Translational Research on Renal and Cardiovascular Diseases (TRECARD), Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain.
2. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
3. Molecular Medicine Unit, Department of Medicine, University of Salamanca and Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, Salamanca, Spain.
4. Internal Medicine Service, Virgen de la Luz Hospital, Cuenca, Spain.
5. Research Unit, Primary Care Centre of La Alamedilla, Salamanca, Spain.
6. Metabolic Bone Unit, University Hospital of Salamanca, Spain.
7. Institute of Health Sciences Studies of Castilla y Leon (IECSCYL), Research Unit, University Hospital of Salamanca, Salamanca, Spain
*These authors contributed equally to this work
Paget´s disease of bone (PDB) is characterized by increased bone resorption followed by an excessive compensatory bone formation, with an abnormal bone structure with altered mechanical properties. Pagetic bone also has a higher vascularization and marrow fibrosis. Despite of pagetic bone being a highly vascularized tissue, there are no studies on the plasma levels of angiogenic mediators in the different states of the disease; moreover, the effect of PDB treatment on plasma levels of these angiogenic mediators is not very well known. The aim of this study was to analyse plasma levels of cytokines implicated in the increased bone turnover (OPG, RANKL, sclerostin) and hypervascularization (VEGF, PGF, ENG) observed in PDB and their evolution and response to zoledronic acid treatment in 70 PDB patients, 29 with an active disease measured by plasma alkaline phosphatase (ALP). Plasma ALP concentration was higher in active PDB than in inactive PDB patients, whereas there were no differences in OPG, RANKL, sclerostin, VEGF, PGF and ENG plasma levels between active and inactive PDB patients. ALP decreased at 3 and 12 months after zoledronic acid treatment. RANKL levels were reduced and sclerostin levels were increased after 12 months of treatment. PGF levels were lower 12 months after zoledronic acid treatment, whereas there were no differences in plasma VEGF and ENG after zoledronic acid treatment. Summarizing, zoledronic acid treatment is associated to decreases in plasma levels of ALP, RANKL, sclerostin and P1GF in active PDB patients. This treatment may reduce bone turnover and might reduce the pathological vascularisation typical of pagetic bone.
Keywords: Paget´s disease of bone, zoledronic acid, RANKL, sclerostin, PGF