Florenzano P, et al. - In this investigation, researchers described the natural history of fibrous dysplasia (FD), a mosaic disease in which bone is replaced with fibro-osseous tissue, disease activity and its association with pain, the effect of bisphosphonates on the natural history of bone turnover markers (BTMs) and the effect of bisphosphonates on the progression of FD burden during childhood. Findings suggested an association of FD with an age-dependent decline in bone turnover and other markers of disease activity. In contrast, pain in adults with FD is more common and severe and does not relate to bone turnover. The treatment with bisphosphonate does not significantly affect the age-dependent reduction in bone turnover and does not prevent the progression of FD disease burden in children. These findings should be taken into account in the evaluation of use and response to bisphosphonates in patients treated for FD and in any study using BTMs as surrogate endpoints in combination with the established adverse effects of antiresorptives.