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• Small molecules have been proposed as alternatives to regenerate bone tissue. • Small molecule drug dose can often be reduced while still achieving effective therapeutic. • The potential to improve bone repair by making it safer, easier, and more cost-effective with the use of a small molecule delivered in the short-term. Osteogenic small molecules have been adapted as one of the encouraging approaches to regenerate bone tissue. Small molecules used long term will usually result in adverse effects. A novel approach is short-term treatment with osteogenic small molecules. Demonstrating effectiveness for regenerating bone with a short-term treatment or a single-dose administration of osteogenic small molecules could enhance safety by reducing adverse effects. Over the past few years, many small molecules with the potential of regenerating bone tissue have been reported when used for short-term or single-dose administration. Here, I review the relevant literature, paying particular attention to prospects for small molecule-mediated bone regeneration with short-term exposure. [ABSTRACT FROM AUTHOR]