Tags

Type your tag names separated by a space and hit enter

Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle.
J Bone Miner Res 2004; 19(5):722-7JB

Abstract

Osteoporosis represents an important cause of morbidity in adult thalassemic patients, and its pathogenesis has not, as yet, been completely clarified. In our study, we observed that thalassemic patients showed a significantly lower OPG/RANKL ratio than normal subjects. These data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis.

INTRODUCTION

Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and RANKL, have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss.

MATERIALS AND METHODS

We measured, in 30 thalassemic patients and in 20 healthy control subjects, serum OPG and RANKL levels, and determined their correlations with bone turnover markers, BMD, sex steroid levels, erythropoietin, and hemoglobin.

RESULTS

Thalassemic patients had an unbalanced bone turnover with an increased resorption phase (shown by high levels of pyridinium cross-links) and a decreased neoformation phase (shown by the slightly low levels of osteocalcin). Moreover, they displayed lower BMD values than controls both at the lumbar and femoral level. As far as the OPG/RANKL system is concerned, thalassemic patients showed no differences in plasma levels of OPG compared with controls, and significantly higher plasma levels of RANKL, with a consequent significantly lower OPG/RANKL ratio.

CONCLUSIONS

Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients.

Authors+Show Affiliations

Department of Internal Medicine, University of Messina, Messina, Italy. nancynat@libero.itNo affiliation info availableNo 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

Language

eng

PubMed ID

15068494

Citation

Morabito, Nunziata, et al. "Osteoprotegerin and RANKL in the Pathogenesis of Thalassemia-induced Osteoporosis: New Pieces of the Puzzle." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 19, no. 5, 2004, pp. 722-7.
Morabito N, Gaudio A, Lasco A, et al. Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle. J Bone Miner Res. 2004;19(5):722-7.
Morabito, N., Gaudio, A., Lasco, A., Atteritano, M., Pizzoleo, M. A., Cincotta, M., ... Frisina, N. (2004). Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 19(5), pp. 722-7.
Morabito N, et al. Osteoprotegerin and RANKL in the Pathogenesis of Thalassemia-induced Osteoporosis: New Pieces of the Puzzle. J Bone Miner Res. 2004;19(5):722-7. PubMed PMID: 15068494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle. AU - Morabito,Nunziata, AU - Gaudio,Agostino, AU - Lasco,Antonino, AU - Atteritano,Marco, AU - Pizzoleo,Maria Antonia, AU - Cincotta,Maria, AU - La Rosa,Mariangela, AU - Guarino,Roberta, AU - Meo,Anna, AU - Frisina,Nicola, Y1 - 2004/01/12/ PY - 2003/05/06/received PY - 2003/11/11/revised PY - 2004/01/09/accepted PY - 2004/4/8/pubmed PY - 2004/8/4/medline PY - 2004/4/8/entrez SP - 722 EP - 7 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 19 IS - 5 N2 - UNLABELLED: Osteoporosis represents an important cause of morbidity in adult thalassemic patients, and its pathogenesis has not, as yet, been completely clarified. In our study, we observed that thalassemic patients showed a significantly lower OPG/RANKL ratio than normal subjects. These data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis. INTRODUCTION: Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and RANKL, have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. MATERIALS AND METHODS: We measured, in 30 thalassemic patients and in 20 healthy control subjects, serum OPG and RANKL levels, and determined their correlations with bone turnover markers, BMD, sex steroid levels, erythropoietin, and hemoglobin. RESULTS: Thalassemic patients had an unbalanced bone turnover with an increased resorption phase (shown by high levels of pyridinium cross-links) and a decreased neoformation phase (shown by the slightly low levels of osteocalcin). Moreover, they displayed lower BMD values than controls both at the lumbar and femoral level. As far as the OPG/RANKL system is concerned, thalassemic patients showed no differences in plasma levels of OPG compared with controls, and significantly higher plasma levels of RANKL, with a consequent significantly lower OPG/RANKL ratio. CONCLUSIONS: Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/15068494/Osteoprotegerin_and_RANKL_in_the_pathogenesis_of_thalassemia_induced_osteoporosis:_new_pieces_of_the_puzzle_ L2 - https://doi.org/10.1359/JBMR.040113 DB - PRIME DP - Unbound Medicine ER -