A Systematic Review of the Effects of Bisphosphonates on Osteoblasts In Vitro

Bisphosphonates (BPs) are widely used to treat bone disorders, prevent skeletal-related events, and manage bone metastasis. These drugs are synthetic analogs of pyrophosphate and primarily function by inhibiting osteoclast activity. However, increasing evidence suggests that they also have an effect on osteoblasts. This systematic review aims to evaluate how bisphosphonates affect osteoblasts by summarizing findings from in vitro studies on the impact of BPs on osteoblast lineage cells, addressing the following question: "Do bisphosphonates affect osteoblast cell lineage function?". For this purpose, the PICO framework was followed, and 36 articles were selected for inclusion in this review. The data suggest that the molecular mechanisms in osteoblasts can vary depending on the specific type of bisphosphonate, as well as the concentration and duration of treatment, leading to either stimulation or inhibition of osteogenesis. Additionally, studies have shown that certain BPs, such as zoledronic acid, can interfere with osteoblast differentiation, proliferation, gene expression, and mineralization capacity, potentially impairing bone healing. On the other hand, other drugs, such as alendronate, demonstrate more positive effects on cell function. Some drugs, such as pamidronate and clodronate, exhibited mixed effects; however, it was observed that high concentrations of these drugs can lead to cytotoxic effects. Despite these adverse effects, it is important to recognize that the clinical benefits of managing bone disorders often outweigh the potential risks highlighted in this review.