The example of sodium fluoride (NaF) clearly demonstrates an instance where increasing bone mass while altering maturation can negatively affect drug efficacy. NaF was a promising osteoporosis treatment because it increased BMD.5 However, it became evident that the treated patients were at increased risk of fracture,6, 7 which was later attributed to NaF-induced aberrant mineralization.8 Had there been a preclinical model to assess the effect of NaF on maturation, it is likely that these fractures could have been avoided.
5. , , , et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Eng J Med. 1990;322(12):802–9.
6. , , , . Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. Clin Orthop Relat Res. 1990;261:268–75.
7. , . Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. J Bone Miner Res. 1989;4(2):223–5.
8. , , , , . Abnormal bone mineralization after fluoride treatment in osteoporosis: a small-angle x-ray-scattering study. J Bone Miner Res. 1994;9(10):1541–9.
*Full study online at https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbm4.10344