title: Neridronate improves bone mineral density and reduces back pain in β-thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel-arm, open-label study.
abstract: Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open-label study, 118 adults with β-thalassaemia and bone mineral density (BMD) Z scores ≤-2·0 were randomized 1:1-500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P < 0·001), and values were significantly higher than the control group at both time intervals. Neridronate also significantly decreased serum bone alkaline phosphatase and C-telopeptide of collagen type 1 levels from as early as 3 months (P = 0·04 and P < 0·001, respectively), reaching significantly lower values at 12 months compared with the control group (P < 0·05). Reductions in back pain and analgesic use were also evident, starting 3 months from commencing treatment. Treatment was well tolerated by all patients. In this largest randomized trial in thalassaemia-induced osteoporosis to date, neridronate was safe and effective in reducing bone resorption and increasing BMD. The associated reduction in back pain and improved quality of life will encourage adherence to therapy. (Clinicaltrials.gov identifier NCT01140321.).
authors.affiliation: Centro della Microcitemia e delle Anemia Congenite - Ematologia, Ospedale Galliera, Genoa, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.affiliation: Department of Paediatrics and Orthopaedics, Second University of Naples, Naples, Italy.
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
authors.affiliation: Department of Gerontology and Muscloskeletal Sciences, Ospedale Galliera, Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giusti
authors.affiliation: Division of Haematology, Presidio Ospedaliero A. Perrino, Brindisi, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.affiliation: UO Ematologia con Talassemia, Ospedali Villa Sofia-V.Cervello, Palermo, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Pitrolo
authors.affiliation: Fondazione IRCCS 'Ca Granda', Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.affiliation: Centro Microcitemia, Ospedale 'Bianchi Melacrino Morelli', Reggio Calabria, Italy.
authors.forename: Domenico Giuseppe
authors.initials: DG
authors.lastname: D'Ascola
authors.affiliation: Department of Clinical and Experimental Medicine, University of Ferrara, Arcispedale Sant'Anna, Ferrara, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Borgna Pignatti
authors.affiliation: UO Ematologia con Talassemia, Ospedali Villa Sofia-V.Cervello, Palermo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigano
authors.affiliation: UOS Talassemia Pediatrica ed Emoglobinopatie Pediatriche, Azienda Ospedaliera 'Antonio Cardarelli', Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Filosa
authors.affiliation: Department of Paediatrics and Orthopaedics, Second University of Naples, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Iolascon
authors.affiliation: Department of Paediatrics and Orthopaedics, Second University of Naples, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Nobili
authors.affiliation: Fondazione IRCCS 'Ca Granda', Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Baldini
authors.affiliation: Centro della Microcitemia e delle Anemia Congenite - Ematologia, Ospedale Galliera, Genoa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosa
authors.affiliation: Centro della Microcitemia e delle Anemia Congenite - Ematologia, Ospedale Galliera, Genoa, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pinto
authors.affiliation: Department of Gerontology and Muscloskeletal Sciences, Ospedale Galliera, Genoa, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Palummeri
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001416:Back Pain / Q000209:etiology / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010455:Peptides / Q000097:blood; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; D000469:Alkaline Phosphatase