Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density

Abstract

Introduction: In contrast to unfractionated heparin (UFH), use of low-molecular weight heparin (LMWH) during pregnancy has not been reported to be associated with a significant decrease in bone mineral density (BMD). The aim of this study was to investigate whether long-term use of LMWH during pregnancy is associated with subsequent decrease in BMD or with increased number of osteoporotic fractures.

Materials and methods: In this observational cohort study BMD was measured by dual energy X-ray absorptiometry (DEXA) 4-7years after the last delivery in 152 women. Ninety-two women had prolonged LMWH-exposure during pregnancy - 75 as prophylaxis and 17 as treatment for venous thromboembolic event (VTE). Dalteparin and enoxaparin were the LMWH-preparations used. Sixty women without LMWH-exposure served as controls. A questionnaire about lifestyle factors and medical history was filled out by the subjects.

Results: Lumbar spine BMD in the LMWH users was lower than that in the controls both in the prophylactic group (1.22g/cm(2) vs. 1.27g/cm(2); p=0.03), and in the treatment group (1.20g/cm(2) vs. 1.27g/cm(2); p=0.07). BMD in femoral neck did not differ between the LMWH-users and controls. However, after adjusting for potential confounding factors, LMWH-exposure did not remain associated with decreased BMD in lumbar spine. Use of contraceptive pills was positively associated with BMD in lumbar spine. Incidence of osteopenia was 13% in the LMWH-group and 8% in the control-group, (p=0.4). No osteoporosis or osteoporotic fractures were found.

Conclusions: Prolonged use of LMWH during pregnancy was not associated with subsequent decrease in BMD, osteopenia, osteoporosis, or osteoporotic fractures.

Keywords: Bone mineral density; Low-molecular-weight heparin; Osteopenia; Osteoporosis; Pregnancy; Risk factors.