Bone turnover and the osteoprotegerin-RANKL pathway in tumor-induced osteomalacia: a longitudinal study of five cases.
Calcif Tissue Int
; 85(4): 293-300, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19763378
ABSTRACT
To evaluate serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-kappaB (RANKL), and their relationship with FGF-23, lumbar bone mineral density (BMD), and bone turnover markers, five patients with tumor-induced osteomalacia (TIO) and 40 healthy controls were studied. TIO patients were followed for 360 days after surgical removal of underlying tumor (n = 2) or beginning of therapy with phosphate and calcitriol when surgical treatment was impossible (n = 3). At diagnosis, TIO patients had higher levels of FGF-23 and bone-specific alkaline phosphatase (bALP) and lower levels of cathepsin K (CathK), RANKL, and RANKL/OPG ratio compared to controls. During the follow-up, FGF-23 decreased significantly only in patients who underwent a surgical excision, while phosphate and BMD increased in all patients. The increases in BMD, phosphate, and renal phosphate reabsorption rate were directly related. In the first 60 days of follow-up, we observed a prolonged inhibition of RANKL, CathK, and bone resorption markers associated with a persistence of TIO symptoms and an increase in bALP. From day 60, levels of bone turnover markers returned progressively within the normal range and a clinical remission was observed. The inhibition of the RANKL/OPG pathway and the uncoupling of bone formation and resorption observed in patients with active TIO may be a compensatory mechanism, attempting to reduce worsening of osteomalacia. The BMD increase during TIO treatment is related to the improvement of phosphate rather than FGF-23 levels. A "hungry bone"-like syndrome was observed after surgical or pharmacological treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteomalacia
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Osso e Ossos
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Transdução de Sinais
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Ligante RANK
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Osteoprotegerina
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Neoplasias
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Calcif Tissue Int
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Itália