Impact of Bisphosphonates on the Osteoclast Cells of Osteogenesis Imperfecta Patients

Vandana Dhiman¹, Anshita Aggarwal², Sanjay Kumar Bhadada², Naresh Sachdeva², Nirmal Raj Gopinathan³ and D. K. Dhawan¹

¹Department of Biophysics, Panjab University, Chandigarh, India,

²Departments of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

³Departments of Orthopedics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Corresponding Author E-mail: bhadadask@rediffmail.com

Abstract: 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 and 5 received > 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.

Keywords: Apoptosis; Bisphosphonates; Bone Mass;  Fracture; Osteogenesis Imperfecta; Precursor Osteoclast Cells;  Zebra Lines

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