Effects of N-containing bisphosphonates on human primary osteoblasts derived from a heterogeneous patient cohort
Abstract
Bisphosphonates (BPs) are prescribed to treat a wide range of skeletal disorders, including osteoporosis, Paget disease, osteogenesis imperfecta and primary or secondary bone cancer. Their pharmacological action is exerted through the accumulation in areas of active bone turnover and the direct inhibition of osteoclast-mediated bone resorption. Indeed, BPs induce osteoclast apoptosis by affecting essential pathways of cell metabolism: either forming non-functional ATP analogues (non-N-containing bisphosphonates) or interfering with mevalonate pathway (N-containing bisphosphonates). However, their role in bone formation and a possible direct effect on osteoblasts (OBs) is controversial and the determination of BP concentrations at different skeletal districts is still an open issue. A serious side effect of the treatment with BPs is the osteonecrosis of jaws (BRONJ), a necrotizing and progressive lesion affecting the mandibular and/or maxillary bone. This drug-related osteonecrosis, whose etiology is not completely unravelled yet, constitutes a severe odontostomatological problem that should not be underestimated. Here, I present the direct effects of two nitrogen containing bisphosphonates, Alendronate (AL) and Zoledronate (ZL), on primary human osteoblast viability, expression and secretion of ECM proteins, functional mediators and bone biomarkers. Osteoblasts, isolated from patients who underwent total hip replacement surgery at IRCCS Galeazzi Orthopaedic Institute, were…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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