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Aims: Osteogenesis imperfecta (OI) is a rare inherited disorder causing low bone density and increased fragility. Bisphosphonates (BP) are a treatment of choice for OI. Few studies have investigated the long-term effects of BP in OI patients. Thus, aim of our study was to follow up adults affected by OI to evaluate changes in metabolic, clinical situation and safety of long-term neridronic acid therapy, BP authorized for OI treatment. Study design: Longitudinal observational study. Place and duration of the Study: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition. Year: 2004 - October 2010. Methodology: 68 patients underwent clinical examination, laboratory endocrine/ metabolic, pro-inflammatory cytokines screening, ECG at baseline and every 3 months and bone mineral density evaluation, by DEXA, once a year. Results: Skeletal evaluation showed a significant increase of BMD through follow up. Patients were evaluated for metabolic and cardiovascular risk factors, which were unmodified by long-term therapy. Conclusion: Long-term neridronic acid treatment increases bone density, does not alter metabolic parameters indicating that this therapy can be considered safe and a valid therapeutic option for OI patients.