Serum osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in bone loss?
OBJECTIVE
Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-kappaB ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss.


METHODS
Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex steroids--with or without pamidronate--prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy controls.


RESULTS
Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls; in the two patient groups it increased by 26-27% at 6 months post-SCT (p=0.002-0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations were clearly elevated (p<0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients.


CONCLUSIONS
Serum sRANKL concentrations may be modulated by bisphosphonates.
Kananen
K
K
Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, 00290, Helsinki, Finland.
Volin
L
L
Laitinen
K
K
Ruutu
T
T
Välimäki
M J
MJ
D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001862:Bone Resorption / Q000097:blood*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006615:Hip / Q000000981:diagnostic imaging; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000209:etiology; D053244:Osteoprotegerin / Q000097:blood*; D000077268:Pamidronate; D053245:RANK Ligand / Q000097:blood* / Q000187:drug effects; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053244:Osteoprotegerin; D053245:RANK Ligand; D000077268:Pamidronate