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Bone Turnover and the Osteoprotegerin–RANKL Pathway in Tumor-Induced Osteomalacia: A Longitudinal Study of Five Cases

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Abstract

To evaluate serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-κB (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.

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Acknowledgement

The authors are grateful to Pasquale and Italiacornelia Rendina for their statistical advice.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Federico II University, via Sergio Pansini, 5, 80131, Naples, Italy

    Domenico Rendina, Riccardo Muscariello, Pasquale Strazzullo & Giuseppe Mossetti

  2. Pediatric Endocrinology Unit, Gaetano Rummo Hospital, Benevento, Italy

    Gianpaolo De Filippo

  3. Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy

    Libuse Tauchmanovà & Annamaria Colao

  4. Department of Functional and Morphological Sciences—Section of Pathology, Federico II University, Naples, Italy

    Luigi Insabato

  5. Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, Italian National Research Council, Naples, Italy

    Fernando Gianfrancesco & Teresa Esposito

  6. Department of Clinical Pathology, Second University of Naples, Naples, Italy

    Michele Cioffi

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  1. Domenico Rendina
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  2. Gianpaolo De Filippo
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  10. Pasquale Strazzullo
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  11. Giuseppe Mossetti
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Correspondence to Giuseppe Mossetti.

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Rendina, D., De Filippo, G., Tauchmanovà, L. et al. Bone Turnover and the Osteoprotegerin–RANKL Pathway in Tumor-Induced Osteomalacia: A Longitudinal Study of Five Cases. Calcif Tissue Int 85, 293–300 (2009). https://doi.org/10.1007/s00223-009-9275-1

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  • DOI: https://doi.org/10.1007/s00223-009-9275-1

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