Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties

Dioxins are known to decrease bone strength, architecture and density. However, their detailed effects on bone material properties are unknown. Here we used nanoindentation methods to characterize the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on nanomechanical behaviour of bone matrix. Pregnant rats were treated with a single intragastric dose of TCDD (1 microg/kg) or vehicle on gestational day 11. Tibias of female offspring were sampled on postnatal day (PND) 35 or 70, scanned at mid-diaphysis with pQCT, and evaluated by three-point bending and nanoindentation. TCDD treatment decreased bone mineralization (p<0.05), tibial length (p<0.01), cross-sectional geometry (p<0.05) and bending strength (p<0.05). Controls showed normal maturation pattern between PND 35 and 70 with decreased plasticity by 5.3% and increased dynamic hardness, storage and complex moduli by 26%, 13% and 12% respectively (p<0.05), while similar maturation was not observed in TCDD-exposed pups. In conclusion, for the first time, we demonstrate retardation of bone matrix maturation process in TCDD-exposed animals. In addition, the study confirms that developmental TCDD exposure has adverse effects on bone size, strength and mineralization. The current results in conjunction with macromechanical behaviour suggest that reduced bone strength caused by TCDD is more associated with the mineralization and altered geometry of bones than with changes at the bone matrix level.