Background: Decreased BMD is a relatively common serious complication of long-term heparin use, however there have not been adequately powered randomized controlled trials addressing its risk in association with long-term use of LMWH. The TIPPS study is an ongoing multi-center randomized trial designed to compare the effect of LMWH prophylaxis vs. no prophylaxis on pregnancy outcomes in thrombophilic pregnant women. A separate sub-study was planned a priori to assess the effect of LMWH on BMD.

Methods: Pregnant women (<20 weeks) were included if they had history of: pregnancy complications or were at moderate risk of venous thrombosis, and had a confirmed thrombophilia. They were excluded if they had history of underlying bone or thyroid disease, long-term use of corticosteroids, metabolic bone agents or anticonvulsants, or >100 kg wt. Patients (pts) were randomized to either LMWH (dalteparin [dalt] 5,000 U qd until 20 wks and then 10,000 qd until term) or control (ctrl) group. All participants received post-partum dalt 5,000 U qd from postpartum d1 to d42. BMD (hip and lumbar spine) was performed 6 wk post-partum. A sample size of 26 pts per group was calculated to detect a 10% difference in absolute BMD (α=0.05, β=0.10). Primary outcome was absolute spine BMD compared using an unpaired t-test. Results were analyzed as-treated; 31 pts received dalt and 22 did not (4 pts randomized to ctrl group crossed over).

BMD and T-score results in treatement groups

Dalteparin1No dalteparin1p Value
1Mean (SD) 
BMD (spine) 1.12 (0.26) 1.21 (0.14) 0.115 
T-score (spine) −0.32 (1.25) 0.13 (1.15) 0.196 
BMD (hip) 0.97 (0.21) 1.02 (0.12) 0.319 
T-score (hip) 0.17 (0.96) 0.36 (1.01) 0.479 
Dalteparin1No dalteparin1p Value
1Mean (SD) 
BMD (spine) 1.12 (0.26) 1.21 (0.14) 0.115 
T-score (spine) −0.32 (1.25) 0.13 (1.15) 0.196 
BMD (hip) 0.97 (0.21) 1.02 (0.12) 0.319 
T-score (hip) 0.17 (0.96) 0.36 (1.01) 0.479 
View Large

Duration of dalt treatment was 214.5±41.9d for dalt group and 47±38.6d for ctrl (p<0.001). Two cases of osteoporosis (Opo) and 7 cases of osteopenia (Ope) were documented in the dalt group vs 0 of Opo and 3 of Ope in the ctrl group respectively. Results of post-hoc logistic regression analysis examining the odds of obtaining an abnormal (Opo or Ope) spine or hip BMD result in both treatment groups were non significant (Crude OR 2.59; 95%CI 0.61, 10.97; p=0.20; Adjusted OR 6.83; 95%CI 0.17, 272.33; p=0.307) as well as results of post-hoc multiple linear regression to predict changes in BMD and T-scores.

Multiple linear regression analysis predicting BMD and T-score in patients receiving dalteparin

UnadjustedAdjusted
Beta (SE)pBeta (SE)p
BMD (spine) −0.099(0.06) 0.12 −0.226(0.16) 0.16 
BMD (hip) −0.051(0.05) 0.32 −0.190(0.13) 0.15 
T-score (spine) −0.444(0.34) 0.66 −0.641(0.87) 0.47 
T-score (hip) −0.195(0.27) 0.48 −0.661(0.68) 0.34 
UnadjustedAdjusted
Beta (SE)pBeta (SE)p
BMD (spine) −0.099(0.06) 0.12 −0.226(0.16) 0.16 
BMD (hip) −0.051(0.05) 0.32 −0.190(0.13) 0.15 
T-score (spine) −0.444(0.34) 0.66 −0.641(0.87) 0.47 
T-score (hip) −0.195(0.27) 0.48 −0.661(0.68) 0.34 
View Large

Conclusion: Our results suggest that the use of long term prophylactic dalteparin in pregnancy is not associated with a significant decrease in BMD.

Topics:
low-molecular-weight heparin, pregnancy, thrombophilia associated with pregnancy, bone mineral density, dalteparin, brachial plexus neuritis, adrenal corticosteroids, anticonvulsants, glucocorticoids, heparin

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution