Osteopetrosis rescue upon RANKL administration to Rankl-/- mice: A new therapy for human RANKL-dependent ARO

Nadia Lo Iacono, Harry C. Blair, Pietro L. Poliani, Veronica Marrella, Francesca Ficara, Barbara Cassani, Fabio Facchetti, Elena Fontana, Matteo M. Guerrini, Elisabetta Traggiai, Francesca Schena, Marianna Paulis, Stefano Mantero, Antonio Inforzato, Serenella Valaperta, Alessandra Pangrazio, Laura Crisafulli, Virginia Maina, Paul Kostenuik, Paolo VezzoniAnna Villa, Cristina Sobacchi

Research output: Contribution to journalArticlepeer-review


In the last decades the molecular basis of monogenic diseases has been largely unraveled, although their treatment has often remained unsatisfactory. Autosomal recessive osteopetrosis (ARO) belongs to the small group of genetic diseases that are usually treated with hematopoietic stem cell transplantation (HSCT). However, this approach is not effective in the recently identified form carrying mutations in the receptor activator of NF-κB ligand (RANKL) gene. In this subset, therapy replacement approach based on RANKL delivery has a strong rationale. Here we demonstrate that the systematic administration of RANKL for 1 month to Rankl-/- mice, which closely resemble the human disease, significantly improves the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated. Overall, we provide evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial. © 2012 American Society for Bone and Mineral Research.

Original languageEnglish
Pages (from-to)2501-2510
Number of pages10
JournalJournal of Bone and Mineral Research
Issue number12
Publication statusPublished - Dec 2012


  • BONE

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism


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