Long-term dalteparin in pregnancy decrease in bone mineral density: controlled trial not associated with a substudy of a randomized

Background: The risk of decreased bone mineral density (BMD) with prophylactic dose long-term low-molecular-weight heparin (LMWH) is unknown. Objectives: We sought to determine whether long-term prophylactic dalteparin in pregnancy leads to loss of BMD. Patients/methods: Patients in a substudy of an ongoing multicenter randomized trial investigating the effect of antepartum dalteparin prophylaxis on pregnancy outcomes in thrombophilic pregnant women were randomized to either dalteparin 5000 U s.c. daily until 20 weeks and then 5,000 U s.c. q12 h until > 37 weeks or to the control group. The primary outcome was absolute spine BMD at six weeks postpartum. Results: Of 77 patients eligible for the BMD substudy, 62 were analyzed. 33 patients received a mean of 212 days of dalteparin in the intervention group. 29 patients received a mean of 38 days of postpartum dalteparin in the control group. There was no difference in mean BMD between the intervention (1.11 g cm(-2)) and the control groups (1.14 g cm(-2)). Similarly, there was no difference in T-scores; the difference of -0.34 (95% confidence interval -0.93 to +0.25) in favor of the control group excludes a clinically important increase in fracture risk. Conclusions: Our results suggest that the use of long-term prophylactic dalteparin in pregnancy is not associated with a significant decrease in BMD. Clinical trial registration: ISRCTN87441504 at http:// www.controlled-trials.com.