Endocrinol Metab.  2021 Dec;36(6):1211-1218. 10.3803/EnM.2021.1248.

Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment

Affiliations
  • 1Division of Endocrinology, Department of Internal Medicine, Mizmedi Hospital, Seoul, Korea
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

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.

Keyword

Bone density; Hematopoietic stem cell transplantation; DKK1; RANK ligand; Osteoprotegerin

Figure

  • Fig. 1. Changes in the serum levels of (A) dickkopf-1 (DKK1), (B) serum receptor activator of nuclear factor-κB ligand (sRANKL), (C) osteoprotegerin (OPG), and (D) the receptor activator of nuclear factor-κB ligand (RANKL)/OPG ratio before and after allogeneic stem cell transplantation treatment. Data are presented as the mean±standard deviation. Solid line, all subjects; blue dotted line, male subjects; red dotted line, female subjects.

  • Fig. 2. Changes in bone mineral density at each measurement site relative to baseline. (A) Lumbar spine, (B) femoral neck, (C) total hip. aP<0.05 relative to baseline.


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