Abstract
Objective: To evaluate serum levels of bone metabolism biomarkers in patients with Paget's disease of bone (PDB).Methods: Serum levels of osteopontin, sclerostin, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin, Dickkopf-related protein 1 (DKK-1), and soluble frizzled-related protein 1 (sFRP-1) were measured in 57 patients with Paget’s disease of bone and 24 controls with primary osteoarthritis. Subgroup analysis was employed to identify any differences in bone metabolism biomarker levels according to disease activity or current treatment.Results: Patients with PDB presented higher levels of osteopontin and RANKL. When compared with patients with inactive disease, patients with active disease presented higher levels of bone-specific alkaline phosphatase (BAP) and osteopontin. There was a significant correlation between serum levels of BAP and osteopontin. There was no significant correlation between levels of BAP and other bone metabolism biomarkers. Current disease extension on bone scintigraphy had a significant correlation with serum levels of osteopontin and BAP. There was no significant correlation between current disease extension and other bone metabolism biomarkers. Serum levels of osteopontin and RANKL were correlated to serum levels of BAP and disease extension.Conclusion: Patients with PDB presented higher levels of osteopontin and RANKL. Osteopontin could be a useful biomarker for activity and extension of PDB.
Highlights
Paget’s disease of bone (PDB) is a common osteometabolic disease characterized by increased and disorganized bone turnover
The difference had not reached statistical significance, levels of serum receptor activator of nuclear factor kappa-Β ligand (RANKL) were higher in patients in comparison to controls (110.27±214.40 pg/mL vs 24.69±8.00 pg/mL, p = 0.061), as were the relations between serum levels of RANKL and osteoprotegerin (4.92 ±14.10 vs 0.97±2.14, p = 0.195)
There was a significant correlation between serum levels of bone-specific alkaline phosphatase (BAP) and osteopontin (r 0.549 p
Summary
Paget’s disease of bone (PDB) is a common osteometabolic disease characterized by increased and disorganized bone turnover. It is usually asymptomatic, but some patients may present with bone pain, fractures, deformities, secondary osteoarthritis, neurologic and cardiac complications and, in rare cases, neoplasm. Osteoblasts regulate osteoclasts secreting mediators as RANKL and osteoprotegerin; osteoclasts on the other hand, stimulate osteoblasts' differentiation and activation by secretion of cytokines, the liberation of growth factors previously embedded in the bone matrix and by cell to cell contact. Osteocytes are key sensors that regulate both osteoclasts and osteoblasts, secreting, among other mediators, prostaglandins, RANKL, and sclerostin [3, 4]
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