Bone Abstracts

Objectives: As the receptor activator of the nuclear factor κB (RANK)/receptor activator of the nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) cytokine system is essential for osteoclastogenesis and Wnt signaling pathway for osteoblastogenesis, we decided to assess these two main bone regulatory pathways in patients with malignant bone tumors on the completion of anticancer therapy.

Methods: The study included 35 patients (median age 15.0 years) with diagnosed malignant bone tumors (25 patients with osteosarcoma, ten patients with Ewing sarcoma) treated at the Department of Surgical Oncology for Children and Youth at the Institute of Mother and Child in Warsaw. All patients were treated with preoperative chemotherapy, after which surgery was performed and then they were administrated postoperative chemotherapy. After completion of treatment (about 2 months after last course of postoperative chemotherapy) densitometry scans were performed and biochemical bone metabolism parameters were determined. Total bone mineral density (BMD) and lumbar spine BMD measurement was performed by dual energy-ray absorptiometry (DXA). Bone metabolism markers (RANKL, OPG, sclerostin, Dickkopf-related protein 1 – Dkk-1) were determined by immunoenzymatic assays. The obtained results were compared with the control group consisting of 30 healthy children (median age 14.5 years) without diseases that may influence bone metabolism. This study was approved by the Ethics Committee of the Institute of Mother and Child.

Results: In patients with bone tumors, we determined comparable to controls concentration of sclerostin (0.40 vs 0.43 ng/ml) and lower by about 15% concentration of Dkk-1 (1.66 vs 1.95 ng/ml). Additionally, we observed higher median value (P<0.05) of RANKL in the patient group and similar concentration of osteoprotegerin in both studied groups. The ratios of RANKL/OPG and sclerostin/Dkk-1 were slightly higher in patients than in the controls (0.34 vs 0.30 and 0.24 vs 0.22 respectively). We observed also reduced z-score total BMD (−1.15 vs 0.21; P<0.01) and z-score BMDL1-L4 (−1.03 vs −0.02; P<0.01) in patients after anticancer treatment compared with the control group.

Conclusion: We found alterations in both bone regulatory pathways in patients with bone tumors after anticancer treatment. These changes may be related to lower bone mineral density in these patients.

Disclosure: The authors declared no competing interests.