The Clinical Characteristics and Efficacy of Bisphosphonates in Audlt Patients with Osteogenesis Impergecta |
| |
| Institution: | 1. From the Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Beijing, China.;2. Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.;3. *These authors contributed equally to this work and should be considered co–first authors;1. Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada;2. Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan;1. Department of Medical Sciences, Uppsala University, Uppsala, Sweden;2. Science for Life Laboratory, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;3. Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden;4. Department of Dental Medicine, Division of Pediatric Dentistry, Karolinska Institutet, Stockholm, Sweden;5. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;6. Department of Clinical Genetics, Karolinska University Hospital Stockholm, Stockholm, Sweden;7. Neuropediatric unit, Karolinska University Hospital and Department of Women''s and Children''s Health, Karolinska Institutet, Stockholm, Sweden;1. Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China;2. BGI Shenzhen: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China;3. Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China;4. Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China;1. Children''s Hospital, University Hospital Cologne, Cologne, Germany;2. Cologne Centre for Rare Skeletal Dysplasia in Childhood, University Hospital Cologne, Cologne, Germany;3. R&D Department, Medimaps SASU, Merignac, France;4. Center of Prevention and Rehabilitation, University Hospital Cologne, Cologne, Germany;1. Institute of Medical Genetics and Human Genetics, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;2. Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India;3. Pediatric Orthopedics Services, Department of Orthopedics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India;4. Berlin-Brandenburg Center for Regenerative Therapies, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;5. Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain;6. Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain;7. Max Planck Institute for Molecular Genetics, FG Development & Disease, Berlin, Germany |
| |
| Abstract: | Objective: Osteogenesis imperfecta (OI) is characterized by low bone mass and recurrent fractures. Adults with OI are often treated with oral or intravenous bisphosphonates (BPs). We investigated the clinical phenotypes of adult OI patients and prospectively compared the efficacy of oral alendronate (ALN) with intravenous zoledronic acid (ZOL) in OI patients.Methods: This 24-month, observational, randomized clinical study included 60 adult patients with OI. We compared the differences in bone mineral density (BMD) and bone turnover biomarkers between OI adults and healthy subjects. Thereafter, OI patients were randomized at a 2:1 ratio to receive either weekly oral ALN 70 mg or once-yearly infusion of ZOL 5 mg. The efficacy outcomes were changes in BMD, bone turnover biomarkers, and fracture incidence.Results: Adult OI patients had significantly lower BMD and significantly higher cross-linked C-telopeptide of type I collagen (β-CTX) levels than age-/sex-/BMI-matched healthy subjects. A total of 52 patients completed the 24-month clinical study. BMD at lumbar spine, femoral neck, and total hip were equivalently elevated in the ALN (10.5, 13.2, and 14.7%, respectively) and ZOL (11.3, 13.7, and 11.7%, respectively; all P>.05) groups. Serum alkaline phosphatase decreased by 30.3% in the ALN group and 37.3% in the ZOL group (P =.12), and β-CTX decreased by 58.0% in the ALN group and 63.6% in the ZOL group (P =.48). Compared to the prior fracture rates, clinical fracture incidences were decreased in the ALN and ZOL groups (both P<.05).Conclusion: Adults with OI present significantly lower bone mass and higher bone resorption biomarkers than healthy populations. Oral ALN and intravenous ZOL are equally effective at increasing BMD and inhibiting bone turnover in adults with OI. The treatment may reduce fractures in this study, but further efforts are still needed to demonstrate the anti-fracture efficacy of BPs.Abbreviations:25OHD = 25-hydroxyvitamin DALN = alendronateALP = alkaline phosphataseBMD = bone mineral densityBMI = body mass indexBP = bisphosphonateβ-CTX = cross-linked C-telopeptide of type I collagenFN = femoral neckLS = lumbar spineOI = osteogenesis imperfectaRCT = randomized controlled trialTH = total hipZOL = zoledronic acid |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
