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Thromb Haemost 1996; 75(02): 254-257
DOI: 10.1055/s-0038-1650255
Original Article
Schattauer GmbH Stuttgart

The Effects of Long-term Heparin Therapy During Pregnancy on Bone Density

A Prospective Matched Cohort Study
James D Douketis
1   The Department of Medicine, Chedoke-McMaster Hospitals and McMaster University, Hamilton, Ontario, Canada
,
Jeffrey S Ginsberg
1   The Department of Medicine, Chedoke-McMaster Hospitals and McMaster University, Hamilton, Ontario, Canada
,
Robert F Burrows
2   The Departments of Obstetrics and Gynecology, Chedoke-McMaster Hospitals and McMaster University, Hamilton, Ontario, Canada
,
Eric K Duku
3   The Departments of Clinical Epidemiology and Biostatistics, Chedoke-McMaster Hospitals and McMaster University, Hamilton, Ontario, Canada
,
Colin E Webber
4   The Department of Nuclear Medicine, Chedoke-McMaster Hospitals and McMaster University, Hamilton, Ontario, Canada
,
Patrick Brill-Edwards
1   The Department of Medicine, Chedoke-McMaster Hospitals and McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Received: 29 April 1995

Accepted after resubmission20 October 1995

Publication Date:
26 July 2018 (online)

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Summary

We performed a prospective matched cohort study to investigate the effects of long-term (>1 month) heparin therapy on lumbar spine bone density. Twenty-five women who received heparin during pregnancy, and 25 matched controls underwent dual photon absorptiometry of the lumbar spine in the post-partum period. Zero of 25 heparin-treated patients developed fractures. Heparin-treated patients had a 0.082 g/cm2 lower bone density compared to untreated controls, which is clinically and statistically significant (p = 0.0077). There were 6 matched pairs in which only the heparin-treated patient had a bone density below 1.0 g/ cm2, compared to only one pair in which only the control patient had a bone density below this level (p = 0.089). The correlation coefficients of the difference .in bone density in each matched pair, and the duration of heparin therapy, the mean daily dose, and the total dose of heparin were 0.042, -0.015, and 0.021, respectively; none of these values is statistically significant. We conclude: 1) long-term heparin therapy was associated with a significant reduction in bone density, although fractures are uncommon, 2) there was no significant correlation between lumbar bone density and the dose or duration of heparin.

 

  • References

  • 1 Ginsberg JS, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 1992; 102: 385s-390s
    CrossrefPubMedSearch in Google Scholar
  • 2 Ginsberg JS, Hirsh J, Turner C, Burrows R, Levine MN. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 1989; 149: 2233-2236
    PubMedSearch in Google Scholar
  • 3 Levine MN. Non-hemorrhagic complications of anticoagulant therapy. Semin Thromb Haemost 1986; 12: 63-66
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Griffith GC, Nichols Jr G, Asher JD, Flanagan B. Heparin osteoporosis. JAMA 1965; 193: 91-94
    CrossrefPubMedSearch in Google Scholar
  • 5 Dahlman TC. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin. Am J Obstet Gynecol 1993; 168: 1265-1270
    CrossrefPubMedSearch in Google Scholar
  • 6 Hellgren M, Nygards E-B. Long-term therapy with subcutaneous heparin during pregnancy. Gynecol Obstet Invest 1982; 13: 76-89
    CrossrefPubMedSearch in Google Scholar
  • 7 Dahlman T, Lindvall N, Hellgren M. Osteopenia in pregnancy during long-term heparin treatment: A radiological study post partum. Br J Obstet Gynecol 1990; 97: 221-228
    CrossrefPubMedSearch in Google Scholar
  • 8 Johnston Jr CC, Epstein S. Clinical, biochemical, radiographic, epidemiology, and economic features of osteoporosis. Ortho Clin North Am 1981; 12: 559-569
    PubMedSearch in Google Scholar
  • 9 Smith DM, Khairi MRA, Johnston Jr CC. The loss of bone mineral and its relationship to the risk of fracture. J Clin Invest 1975; 56: 311-318
    CrossrefPubMedSearch in Google Scholar
  • 10 Hiu SL, Slemenda CS, Jonston Jr CC. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 1988; 81: 1804-1809
    CrossrefPubMedSearch in Google Scholar
  • 11 Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott JC, Vogt TM. Bone density at various sites for prediction of hip fractures. Lancet 1993; 341: 72-75
    CrossrefPubMedSearch in Google Scholar
  • 12 Wasnich RD, Ross PD, Heillbrun LK, Vogel JM. Selection of the optimal site for fracture site prediction. Clin Orthop 1987; 81: 262-268
    PubMedSearch in Google Scholar
  • 13 Briney WG. Is measurement of bone density useful. Rheum Dis Clin North Am 1993; 19: 95-106
    PubMedSearch in Google Scholar
  • 14 Heuck AF, Block J, Glueer C-C, Steiger P, Genant HK. Mild versus definite osteoporosis: Comparison of bone densitometry techniques using different statistical models. J Bone Min Res 1989; 4: 891-900
    PubMedSearch in Google Scholar
  • 15 Barbour LA, Kick SD, Steiner JF, LoVerde ME, Heddleston LN, Lear JL, Baron AE, Barton PL. A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 1994; 170: 862-869
    CrossrefPubMedSearch in Google Scholar
  • 16 Dahlman TC, Sjoberg HE, Ringertz H. Bone mineral density during longterm prophylaxis with heparin in pregnancy. Am J Obstet Gynecol 1994; 170: 1315-1320
    CrossrefPubMedSearch in Google Scholar
  • 17 Jaffe MD, Willis PW III. Multiple fractures associated with long-term sodium heparin therapy. JAMA 1965; 193: 158-160
    PubMedSearch in Google Scholar
  • 18 Silber M, Olund A. Successful outcome of pregnancy complicated by giant myoma and severe heparin-induced osteopenia. Gynecol Obstet Invest 1989; 28: 51-52
    CrossrefPubMedSearch in Google Scholar
  • 19 Squires JW, Pinch LW. Heparin-induced spinal fractures. JAMA 1979; 241: 2417-2418
    CrossrefPubMedSearch in Google Scholar
  • 20 Sackler JP, Liu L. Heparin-induced osteoporosis. Br J Radiol 1973; 46: 548-550
    CrossrefPubMedSearch in Google Scholar
  • 21 Griffiths HT, Liu DTY. Severe heparin osteoporosis in pregnancy. Postgrad Med J 1984; 60: 424-425
    CrossrefPubMedSearch in Google Scholar
  • 22 Wise PH, Hall AJ. Heparin-induced osteoporosis in pregnancy. Br Med J 1980; 2: 110-111
    PubMedSearch in Google Scholar
  • 23 De Swiet M, Ward PD, Fidler J, Horsman A, Katz D, Letsky E, Peacock M, Wise PH. Prolonged heparin therapy in pregnancy causes bone demineralization. Br J Obstet Gynecol 1983; 90: 1129-1134
    CrossrefPubMedSearch in Google Scholar
  • 24 Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R, Coates G, Webber C. Heparin effect on bone density. Thromb Haemost 1990; 64: 286-289
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Melton LJ III, Eddy DM, Johnston Jr CC. Screening for osteoporosis. Ann Intern Med 1990; 112: 516-528
    CrossrefPubMedSearch in Google Scholar
  • 26 Pocock N, Eisman J, Gwinn T, Sambrook P, Kelly P, Freund J, Yeates M. Muscle strength, physical fitness, and weight but not age predict femoral neck bone mass. J Bone Min Res 1989; 4: 441-446
    PubMedSearch in Google Scholar
  • 27 Pocock NA, Eisman JA, Yeates MG, Sambrook PN, Eberl S. Physical fitness is a major determinant of femoral neck and lumbar spine bone mineral density. J Clin Invest 1986; 78: 618-621
    CrossrefPubMedSearch in Google Scholar
  • 28 Stevenson JC, Lees B, Devenport M, Cust MP, Ganger KF. Determinants of bone density in normal women: risk factors for future osteoporosis. Br Med J 1989; 298: 924-928
    CrossrefPubMedSearch in Google Scholar
  • 29 Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med 1994; 330: 387-392
    CrossrefPubMedSearch in Google Scholar
  • 30 Webber CE. Some factors which influence the evaluation of a dual photon measurement of lumbar spine bone mineral mass. J Can Radiol Assoc 1989; 40: 87-91
    PubMedSearch in Google Scholar
  • 31 Matzsch T, Bergqvist D, Hedner U, Nilsson B, Ostergaard P. Heparin-induced osteoporosis in rats. Thromb Haemost 1986; 56: 293-294
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Monreal M, Vinas L, Monreal L, Lavin S, Lafoz E, Angles AM. Heparin-related osteoporosis in rats. A comparative study between unfractionated heparin and a low molecular weight heparin. Haemostasis 1990; 20: 204-207
    PubMedSearch in Google Scholar
  • 33 Matzsch T, Bergqvist D, Hedner U, Nilsson B, Ostergaard P. Effects of low molecular weight heparin and unfractionated heparin on induction of osteoporosis in rats. Thromb Haemost 1990; 65: 505-509
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Riggs BL, Wahner HW, Dunn WL, Mazess RB, Offord KP, Melton LJ III. Differential changes in bone density of the appendicular and axial skeleton with ageing: relationship to spinal osteoporosis. J Clin Invest 1981; 67: 328-335
    CrossrefPubMedSearch in Google Scholar
  • 35 Melton LJ, Wahner HW, Richelson LS, O’Fallon WM, Riggs BL. Osteoporosis and the risks of hip fracture. Am J Epidemiol 1986; 124: 254-261
    CrossrefPubMedSearch in Google Scholar
  • 36 Gardner SB, Winter PD, Gardner MJ. Confidence Interval Analysis, British Medical Journal. copyright 1991, version 1.1
    PubMed
  • 37 Christiansen C, Riis BJ. Five years with continuous combined estrogen progesterone therapy. Br J Obstet Gynecol 1990; 97: 1087-1092
    CrossrefPubMedSearch in Google Scholar
  • 38 Riggs BL, Melton LJ III. Involutional osteoporosis. N Engl J Med 1986; 314: 1676-1686
    CrossrefPubMedSearch in Google Scholar
  • 39 Chan GM, Slater P, Roberts CC, Thomas MR, Folland D, Jackson R. Bone mineral status of lactating mothers of different ages. Am J Obstet Gynecol 1982; 144: 438-441
    CrossrefPubMedSearch in Google Scholar
  • 40 Hayslip CC, Klein TA, Wray HL, Duncan WE. The effect of lactation on bone mineral content in healthy postpartum women. Obstet Gynecol 1989; 73: 588-592
    PubMedSearch in Google Scholar
  • 41 Anonymous. Extended lactation and loss of bone. Nutr Rev 1994 52. 25-28
    PubMedSearch in Google Scholar
  • 42 Sowers M, Corton G, Shapiro B, Jannausch ML, Crutchfield M, Smith ML, Randolph JF, Hollis B. Changes in bone density with lactation. JAMA 1993; 269: 3130-3135
    CrossrefPubMedSearch in Google Scholar
  • 43 Omri A, Delaloye JF, Bachmann F. Low molecular weight heparin novo (LHN-1) does not cross the placenta during the second trimester of pregnancy. Thromb Haemost 1989; 61: 55-56
    Thieme ConnectPubMedSearch in Google Scholar
  • 44 Monreal M, Olive A, Lafoz E, del Rrio L. Heparins, coumarin, and bone density. Lancet 1991; 338: 706
    PubMedSearch in Google Scholar
  • 45 Melissari E, Murray WJG, Das S, Wilson NV, Philip M, Kakkar VV. Does low molecular weight heparin have a role in the development of osteoporosis. Thromb Haemost 1993; 69: 646
    PubMedSearch in Google Scholar