Figure 3.

NSAIDs interfere with somatic growth and growth plate development in vivo in mice, and ex vivo in human tissue. Male (A) and female (D) C57/B6 mice were treated once daily from P7 to P13 (underlined days) by ip injection with 15-μg/g·d ibuprofen (IBU) in DMSO, or DMSO only. Maximum volume received was 10 μL per 5 g body weight. Nose-to-rump length was measured daily. Male (B) and female (E) mice were treated with 10-μg/g·d celecoxib (CEL) or vehicle for the same period of time. Male (C) and female (F) mice were treated with IBU, CEL, or vehicle for 7 days starting at P14. Repeated measures ANOVA was used to determine significance between curves, and t tests within each day used to determine the day at which the difference became significant. G–L, Male mice treated with IBU and CEL at the same doses from P14 to P20 were killed on P21 4 hours after receiving a single ip dose of BrdU, and 1 tibia from each mouse was excised, fixed in paraformaldehyde, and decalcified in EDTA. Panels G (vehicle treated), H (IBU treated), and I (CEL treated) are tibial sections stained for ColX and counterstained with H&E. Brackets are included to indicate the size of the hypertrophic zone. Panels J (vehicle treated), K (IBU treated), and L (CEL treated) were stained for BrdU for assessment of cell proliferation. M, Human metatarsal sections cultured in BJGb for 24 hours; sections received either no treatment, or IGF-I alone or with increasing concentrations of either IBU or CEL. BrdU was added for 4 hours before fixation and cell proliferation visualized by staining with anti-BrdU antisera.