The Impact of Bisphosphonates on the Osteoclast Cells of Osteogenesis Imperfecta Patients

• Published in: Biomedical & pharmacology journal 2018-06, Vol.11 (2), p.645-651
• Main Authors: Dhiman, Vandana, Aggarwal, Anshita, Bhadada, Sanjay Kumar, Sachdeva, Naresh, Gopinathan, Nirmal Raj, Dhawan, D.K
• Format: Article
• Language: English
• Subjects: Bone density; Bone disorder agents; Care and treatment; Children; Fractures (Injuries); Medical research; Osteochondrodysplasias; Osteogenesis imperfecta; Pamidronate; Phosphonates; Zoledronic acid
• ISSN: 0974-6242; 2456-2610
• DOI: 10.13005/bpj/1417

Bisphosphonates (BPs) are widely used for treatment of osteogenesis imperfecta (OI). However, prolonged use may be associated with suppression of bone turnover, the exact molecular mechanism of which is poorly understood. The objective of this study was to evaluate the effect of zoledronic acid (ZOL) on precursor osteoclasts by studying caspase 3 activity. A total of 15 children participated in the study (n = 10 OI patients, n= 5 controls). Out of the 10 OI children, 5 had received a cumulative dose of 30 mg of ZOL. Isolated mononuclear cells were studied for caspase 3 activity from all study participants. The mean age of study participants was 7 ±1.5 years. Six of them had OI type IV, two had type III and one had types I & II each. Radiographs showed “zebra stripe sign” and dense metaphyses; suggestive of acquired osteosclerosis. Bone turnover markers (PINP and CTx) were suppressed in all OI patients compared to controls. Caspase-3 activity was significantly increased in precursor osteoclasts cells at higher doses of BPs (>30 mg). Overzealous use of ZOL in OI suppresses bone turnover markers (P1NP, CTx) causes osteosclerosis and increased expression of caspase 3 activity in precursor osteoclasts which results in adynamic bone.