Study of bone metabolism and angiogenesis in patients undergoing high-dose chemotherapy/autologous hematopoietic stem cell transplantation

Eur J Haematol. 2018 Feb;100(2):131-139. doi: 10.1111/ejh.12990. Epub 2017 Dec 4.

Abstract

Objectives: As the interaction between hematopoietic stem cells (HSCs) and endosteal and endothelial niches in HSCs homing is essential, we aimed to study bone turnover and angiogenesis in 29 patients with lymphoma/multiple myeloma undergoing hematopoietic stem cell transplantation (HSCT).

Methods: Serum samples were collected before high-dose chemotherapy (HDT), at the end of HDT, after HSC infusion, at the nadir of myelotoxicity, and at engraftment. Bone metabolism (CTX, TRACP-5b, bALP, OC, DKK1, RANKL, OPG), and angiogenesis (Ang1, Ang2) markers were measured. These markers were also measured in 21 control patients before and after conventional chemotherapy.

Results and conclusions: Bone resorption declined during HSCT (decrease in TRACP-5b [P < .001] and CTX [P = .006]). Bone formation declined as well (decrease in bALP and OC [P < .001 for both]). RANKL/OPG ratio, an indicator of osteoclastic activation, did not change significantly (P = .5). Ang1/Ang2 ratio, a vessel equilibrium marker, decreased significantly (P < .001) suggesting endothelial destabilization. The changes observed in the control group were similar except of bALP and RANKL/OPG ratio. Moreover, Ang1/Ang2 ratio on the day after HSC infusion strongly correlated with time to neutrophil and platelet engraftment (P < .001 for both). Conclusively, bone turnover and vessel destabilization represent important events during HSCT probably reflecting the effect of chemotherapy.

Keywords: angiogenesis; bone metabolism; engraftment; hematopoietic stem cell transplantation.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Bone Remodeling*
  • Bone Resorption / metabolism
  • Bone Resorption / pathology
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology*
  • Female
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Lymphoma / complications
  • Lymphoma / pathology
  • Lymphoma / therapy
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Neovascularization, Pathologic*
  • Osteogenesis
  • Transplantation, Autologous
  • Young Adult

Substances

  • Biomarkers