Effect of Caffeine on the Skeletal System—A Review of Experimental Studies

Background: Caffeine is one of the most widely consumed bioactive compounds worldwide. The available data regarding its effects on bone metabolism and skeletal health remain inconsistent. The aim of this study was to review experimental studies on the effects of caffeine on the skeletal system. Methods: A literature search was conducted using PubMed to identify original experimental studies investigating the effects of caffeine on the skeletal system published up to December 2025. The reviewed studies included in vivo studies on different animal models and in vitro studies on bone-related cells. Due to data heterogeneity, a narrative analysis was performed. Results: Fifty-three studies on caffeine effects were included in the review. The findings indicate that the effects of caffeine are dose-dependent and bidirectional. Low-to-moderate doses in vivo generally exerted neutral or sometimes beneficial effects on the skeletal system, whereas higher doses were associated with impaired bone development, reduced mineralization, and increased bone loss. In estrogen-deficient animals, moderate doses showed potential protective effects, while high doses exacerbated bone loss. In vitro studies demonstrated concentration-dependent effects, with high concentrations often reducing cell viability and osteogenic activity. Conclusions: The effects of caffeine on the skeletal system are complex and context-dependent. While high exposure may adversely affect bone, low-to-moderate intake appears to be safe and may exert beneficial effects under specific conditions.