Cellular and Molecular Life Sciences

, Volume 76, Issue 19, pp 3723–3744 | Cite as

Deregulated miRNAs in osteoporosis: effects in bone metastasis

  • Daniele BellaviaEmail author
  • F. Salamanna
  • L. Raimondi
  • A. De Luca
  • V. Carina
  • V. Costa
  • R. Alessandro
  • M. Fini
  • G. Giavaresi


Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have been considered and described to clarify the evidence of this link. The main goal of this review is to underline as deregulated miRNAs in osteoporosis may have specific roles in the development of bone metastases. The review showed that several circulating osteoporotic miRNAs could facilitate tumor progression and bone-metastasis formation in several tumor types, i.e., breast cancer, prostate cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, and multiple myeloma. In detail, serum up-regulation of pro-osteoporotic miRNAs, as well as serum down-regulation of anti-osteoporotic miRNAs are common features of all these tumors and are able to promote bone metastasis. These results are of key importance and could help researcher and clinicians to establish new therapeutic strategies connected with deregulation of circulating miRNAs and able to interfere with pathogenic processes of osteoporosis, tumor progressions, and bone-metastasis formation.


miRNA Osteoporosis Osteolysis Bone metastasis 



3′ Untranslated region


Argonaut 2


Breast cancer


Bone-marrow mesenchymal stem cells


Bone morphogenetic proteins


Ciliary neurotrophic factor


Di George syndrome critical region gene 8


Esophageal squamous cell carcinoma


Glypican 3




Multiple myeloma


Matrix metalloproteinase


Metastasis suppressor protein 1




Non-small-cell lung cancer








Prostate cancer


Parathyroid hormone


Peripheral blood mononuclear cells


Quantitative real-time polymerase chain reaction


Receptor activator of nuclear factor kappa-B ligand


Skeletal-related events


Transforming growth factor-beta


Tumor necrosis factor alpha


Wingless-type MMTV integration site family



Dr. Daniele Bellavia, Dr. Angela De Luca, Dr. Valeria Carina, Dr. Viviana Costa, and Dr. Lavinia Raimondi contributed to the manuscript by working at the Technology Platform of Tissue Engineering, Theranostics and Oncology (Lab.Manager Dr. Gianluca Giavaresi), a laboratory started-up by the Rizzoli Orthopedic Institute in Palermo (Italy) with the grants also of National Operative Program projects (PON, MIUR).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests. No benefits in any form were received or will be received from a commercial party related directly or indirectly to the subject of this article.


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Authors and Affiliations

  1. 1.IRCCS Istituto Ortopedico RizzoliBolognaItaly
  2. 2.Laboratory of Preclinical and Surgical StudiesIRCCS Istituto Ortopedico RizzoliBolognaItaly
  3. 3.Section of Biology and Genetics, Department of BioMedicine, Neuroscience and Advanced Diagnostics (Bi.N.D)University of PalermoPalermoItaly
  4. 4.Institute of Biomedicine and Molecular Immunology (IBIM)National Research CouncilPalermoItaly

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