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KMID : 1141520210360061211
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Endocrinology and Metabolism
2021 Volume.36 No. 6 p.1211 ~ p.1218
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Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment
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Jang Eun-Hee
Ha Jeong-Hoon
Baek Ki-Hyun
Kang Moo-Il
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Abstract
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Background: Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.
Methods: We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.
Results: After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (-11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).
Conclusion: Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.
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KEYWORD
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Bone density, Hematopoietic stem cell transplantation, DKK1, RANK ligand, Osteoprotegerin
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