title: Effects of intermittent intravenous ibandronate injections on bone quality and micro-architecture in women with postmenopausal osteoporosis: the DIVA study.
abstract: In the Dosing IntraVenous Administration (DIVA) study, IV ibandronate injections (15-30 s duration) provided significantly greater gains in bone mineral density than daily oral ibandronate (P<0.001). Single transiliac bone biopsy was performed in a subgroup of women (n=109/1395) from DIVA to assess the impact of ibandronate on newly formed bone and bone remodeling. Patients received ibandronate IV injections 2 mg every 2 months, 3 mg every 3 months or oral ibandronate 2.5 mg daily, plus oral or IV placebo, as appropriate to maintain blinding. Of the 1395 participants from the DIVA study, 122 were enrolled in the substudy. Qualitative histological analysis was performed on all biopsy cores and 89 cores were considered to be evaluable for quantitative histomorphometry. Following 2 years of ibandronate treatment, trabecular bone maintained its normal lamellar structure with no evidence of woven bone, marrow fibrosis, cellular toxicity, or other qualitative abnormalities. Primary mineralization of new bone remained normal, as indicated by the slightly lower osteoid thickness and osteoid volume, with normal mineral apposition rate compared to healthy, postmenopausal women. Mineralizing surface, osteoid surface, activation frequency and bone formation rate were decreased in all ibandronate-treated groups compared with values from healthy, postmenopausal women. Specifically, the bone formation rate (BFR/BV and BFR/BS) was approximately 5 times lower in the ibandronate-treated (3 mg) group than in healthy, postmenopausal women. Histomorphometric analysis of transiliac bone biopsies demonstrated normal micro-structure of newly formed bone with normal mineralization and reduced remodeling after oral or IV ibandronate.
authors.affiliation: Creighton University School of Medicine, Creighton University, Omaha, Nebraska, USA. rrecker@creighton.edu
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Louis-George
authors.initials: LG
authors.lastname: Ste-Marie
authors.forename: Bente
authors.initials: B
authors.lastname: Langdahl
authors.forename: Edward
authors.initials: E
authors.lastname: Czerwinski
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonvoisin
authors.forename: Daiva
authors.initials: D
authors.lastname: Masanauskaite
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowell
authors.forename: Dieter
authors.initials: D
authors.lastname: Felsenberg
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D004164:Diphosphonates / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology
chemical_list: D004164:Diphosphonates; D000077557:Ibandronic Acid