J Bone Metab.  2019 Aug;26(3):169-177. 10.11005/jbm.2019.26.3.169.

Effects of Di(2-ethylhexyl)phthalate on Bone Metabolism in Ovariectomized Mice

  • 1Department of Obstetrics and Gynecology, Soonchunhyang University College of Medicine, Bucheon, Korea.
  • 2Department of Obstetrics and Gynecology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. drrabbit@catholic.ac.kr


The molecular pathways of how endocrine disruptors affect bone mineral density (BMD) and bone remodeling are still unclear. The purpose of this experimental study is to determine the effects of di(2-ethylhexyl)phthalate (DEHP) on bone metabolism in ovariectomized mice.
Twenty-six-month-old female CD-1 mice were divided into 4 groups: control, low-dose DEHP, high-dose DEHP, and estrogen groups (n=5, each group). All mice were subjected to ovariectomy for the induction of artificial menopause and then exposed to corn oil, DEHP, and estrogen for 2 months. Micro-computed tomography (Micro-CT) of the bone and analysis of blood samples for bone markers were performed to observe the changes in bone metabolism.
Osteocalcin level was decreased in the control, low-dose and high-dose DEHP group, the reduction width was greater in the high-dose DEHP group (−0.219 ng/mL) than control group (−0.077 ng/mL, P<0.05). C-terminal telopeptide of type I collagen level was increased in the control, low-dose and high-dose DEHP group, the increase range of low-dose DEHP group (0.329 ng/mL) showed greater than control group (0.093 ng/mL, P<0.05). Micro-CT analysis revealed that the BMD was significantly lower in the high-dose DEHP group (19.8×10⁻² g/cm³) than control group (27.2×10⁻² g/cm³, P<0.05). The structure model index was significantly higher in the high-dose DEHP group (2.737) than low-dose DEHP group (2.648) and estrogen group (2.63, P<0.05). It means the progression of osteoporosis in the high-dose DEHP group.
These results confirm the negative effects of DEHP on bone health in ovariectomized mice. Further continuous studies on genetic pathways and other endocrine disruptors will be necessary to validate these findings.


Diethylhexyl phthalate; Osteoporosis; Ovariectomy; X-ray microtomography
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