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Imbalance of the osteoprotegerin/RANKL ratio in bone marrow microenvironment after allogeneic hemopoietic stem cell transplantation.
Transplantation 2006; 82(11):1449-56T

Abstract

BACKGROUND

Bone loss is a common complication after allogeneic stem cell transplantation. Osteoprotegerin (OPG) plays a critical role in bone remodeling by neutralizing the effect of receptor activator of nuclear factor-kappaB ligand (RANKL) on differentiation and activation of osteoclasts. We investigated OPG and RANKL in serum and marrow plasma in transplanted patients.

MATERIALS AND METHODS

In 36 patients and 36 controls, the relationships among bone mineral density, circulating OPG, RANKL, interferon-gamma, and interleukin-6 levels were investigated; in addition, OPG and RANKL were measured in marrow plasma and in conditioned medium of long-term cultures of marrow mesenchymal-derived osteogenic cells.

RESULTS

Lumbar and femoral bone mineral density were lower in patients than in controls (P<0.01). Serum OPG (sOPG) and interferon-gamma were significantly higher in patients than in controls (P<0.05). Patients' interferon-gamma correlated with sOPG levels (r=0.4; P=0.03). Interleukin-6 did not differ between patients and controls. By contrast, OPG levels were lower in patients than in controls in marrow plasma (P<0.001) and in conditioned media after one (P=0.035) and three months (P=0.003) of culture of marrow mesenchymal-derived osteogenic cells. RANKL was similar in patients and controls. The OPG/RANKL ratio "in situ" was significantly lower in patients than in controls (P<0.05). There was no correlation between sOPG and marrow OPG, RANKL levels, densitometric values, and chronic graft-versus-host disease.

CONCLUSION

Our findings suggest that after allogeneic stem cell transplantation: 1) sOPG bear no relationship with OPG in the bone marrow; 2) increased sOPG can be the result of its enhanced production in extra bone tissues triggered by inflammatory cytokines; 3) low bone marrow OPG levels may be partly related to the persistent quantitative and qualitative deficit of osteoblastic precursors; and 4) reduced OPG/RANKL ratio in bone microenvironment may increase bone remodeling by promoting bone resorption.

Authors+Show Affiliations

Department of Biochemistry and Medical Biotechnology, Hematology Branch, Federico II University of Naples, Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17164716

Citation

Ricci, Patrizia, et al. "Imbalance of the osteoprotegerin/RANKL Ratio in Bone Marrow Microenvironment After Allogeneic Hemopoietic Stem Cell Transplantation." Transplantation, vol. 82, no. 11, 2006, pp. 1449-56.
Ricci P, Tauchmanova L, Risitano AM, et al. Imbalance of the osteoprotegerin/RANKL ratio in bone marrow microenvironment after allogeneic hemopoietic stem cell transplantation. Transplantation. 2006;82(11):1449-56.
Ricci, P., Tauchmanova, L., Risitano, A. M., Carella, C., Mazziotti, G., Lombardi, G., ... Selleri, C. (2006). Imbalance of the osteoprotegerin/RANKL ratio in bone marrow microenvironment after allogeneic hemopoietic stem cell transplantation. Transplantation, 82(11), pp. 1449-56.
Ricci P, et al. Imbalance of the osteoprotegerin/RANKL Ratio in Bone Marrow Microenvironment After Allogeneic Hemopoietic Stem Cell Transplantation. Transplantation. 2006 Dec 15;82(11):1449-56. PubMed PMID: 17164716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Imbalance of the osteoprotegerin/RANKL ratio in bone marrow microenvironment after allogeneic hemopoietic stem cell transplantation. AU - Ricci,Patrizia, AU - Tauchmanova,Libuse, AU - Risitano,Antonio Maria, AU - Carella,Carlo, AU - Mazziotti,Gherardo, AU - Lombardi,Gaetano, AU - Colao,Annamaria, AU - Rotoli,Bruno, AU - Selleri,Carmine, PY - 2006/12/14/pubmed PY - 2007/3/9/medline PY - 2006/12/14/entrez SP - 1449 EP - 56 JF - Transplantation JO - Transplantation VL - 82 IS - 11 N2 - BACKGROUND: Bone loss is a common complication after allogeneic stem cell transplantation. Osteoprotegerin (OPG) plays a critical role in bone remodeling by neutralizing the effect of receptor activator of nuclear factor-kappaB ligand (RANKL) on differentiation and activation of osteoclasts. We investigated OPG and RANKL in serum and marrow plasma in transplanted patients. MATERIALS AND METHODS: In 36 patients and 36 controls, the relationships among bone mineral density, circulating OPG, RANKL, interferon-gamma, and interleukin-6 levels were investigated; in addition, OPG and RANKL were measured in marrow plasma and in conditioned medium of long-term cultures of marrow mesenchymal-derived osteogenic cells. RESULTS: Lumbar and femoral bone mineral density were lower in patients than in controls (P<0.01). Serum OPG (sOPG) and interferon-gamma were significantly higher in patients than in controls (P<0.05). Patients' interferon-gamma correlated with sOPG levels (r=0.4; P=0.03). Interleukin-6 did not differ between patients and controls. By contrast, OPG levels were lower in patients than in controls in marrow plasma (P<0.001) and in conditioned media after one (P=0.035) and three months (P=0.003) of culture of marrow mesenchymal-derived osteogenic cells. RANKL was similar in patients and controls. The OPG/RANKL ratio "in situ" was significantly lower in patients than in controls (P<0.05). There was no correlation between sOPG and marrow OPG, RANKL levels, densitometric values, and chronic graft-versus-host disease. CONCLUSION: Our findings suggest that after allogeneic stem cell transplantation: 1) sOPG bear no relationship with OPG in the bone marrow; 2) increased sOPG can be the result of its enhanced production in extra bone tissues triggered by inflammatory cytokines; 3) low bone marrow OPG levels may be partly related to the persistent quantitative and qualitative deficit of osteoblastic precursors; and 4) reduced OPG/RANKL ratio in bone microenvironment may increase bone remodeling by promoting bone resorption. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/17164716/Imbalance_of_the_osteoprotegerin/RANKL_ratio_in_bone_marrow_microenvironment_after_allogeneic_hemopoietic_stem_cell_transplantation_ L2 - http://dx.doi.org/10.1097/01.tp.0000244588.42519.72 DB - PRIME DP - Unbound Medicine ER -