ESPE Abstracts (2015) 84 P-2-205

Mechanism of Bone Disease in Prader-Willi Syndrome

Maria Felicia Faienzaa, Giacomina Brunettib, Graziano Grugnic, Antonino Crinòd, Sarah Bocchinid, Angela Orangerb, Isabella Giganteb, Laura Piacentea, Annamaria Venturaa, Silvia Coluccib, Maria Granob, Luciano Cavalloa & Maurizio Delvecchioa


aSection of Pediatrics, Department of Biomedical Sciences and Human Oncology, University ‘A. Moro’, Bari, Italy; bSection of Human Anatomy and Histology, Department of Basic and Medical Sciences, Neurosciences and Sense Organs, University ‘A. Moro’, Bari, Italy; cDivision of Auxology, Italian Auxological Institute, Research Institute, Verbania, Italy; dAutoimmune Endocrine Diseases Unit, Research Institute – Palidoro, Bambino Gesù Hospital, Roma, Italy


Background: Low bone mineral density (BMD) is found in up to 50% of adolescents and adults with Prader-Willi syndrome (PWS). High fracture risk has been described in adult PWS patients. This bone fragility could be due to inadequate gonadal hormones levels during pubertal development, and to relative growth hormone insufficiency during childhood and adolescence. However, the mechanism/s of low BMD in PWS have not been clarified.

Objective and hypotheses: i) to study the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of PWS subjects and controls; ii) to evaluate the alteration of RANKL/OPG axis.

Method: PBMCs of 26 PWS patients and 26 age and sex-matched controls were cultured in presence/absence of M-CSF and RANKL. Mature multinucleated osteoclasts (OCs) were identified as TRAP+ cells. RANKL and OPG levels were measured in the sera. RANKL expression was also evaluated by flow cytometry. Bone status was assessed by DXA.

Results: A high number of multinucleated TRAP+ OCs were identified in the unstimulated PBMC cultures of PWS patients, while few OCs appeared in cultures of controls (OC number/well 60±5 vs 10±4, P<0.01). In the stimulated cultures the same OC number developed in cultures of patients and controls. Flow cytometry on lymphomonocyte circulating fraction of PWS patients showed higher levels of RANKL than controls (32%±5 vs 5%±2, P<0.01), Significant higher RANKL and lower OPG levels were found in PWS patients than controls. The RANKL/OPG ratio resulted significantly elevated in patients compared with controls (P<0.001). BMD z-score was between <−1 and <−2 in 30% of PWS patients, and < −2.5 in 20% of them.

Conclusion: We demonstrated a high osteoclastogenic potential of PBMCs of PWS patients, which could be due to increased RANKL/OPG ratio. This condition could contribute to bone disease affecting PWS patients.