This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Komulainen, M. Articles by Saarikoski, S. Search for Related Content PubMed PubMed Citation Articles by Komulainen, M. Articles by Saarikoski, S.

Prevention of Femoral and Lumbar Bone Loss with Hormone Replacement Therapy and Vitamin D₃ in Early Postmenopausal Women: A Population-Based 5-Year Randomized Trial¹

Departments of Obstetrics and Gynecology (M.K., M.T.T., A.-M.H., S.S.), Surgery (H.K., E.A.), and Clinical Physiology and Nuclear Medicine, Kuopio University Hospital (J.J.); and the A. I. Virtanen Institute (M.K., H.K., M.T.T., A.-M.H., E.A., S.S.) and the Research Institute of Public Health (R.H.), University of Kuopio, Kuopio, Finland

Address all correspondence and requests for reprints to: M. Komulainen, M.D., Department of Obstetrics and Gynecology, Kuopio University Hospital, 70211 Kuopio, Finland. E-mail: mkomulai{at}uku.fi

The long term effects of hormone replacement therapy (HRT) and vitamin D₃ (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n = 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D₃ (300 and 100 IU/day during the fifth year), 3) HRT and Vit D combined, and 4) placebo. Lumbar (L2–L4) and femoral neck BMD were determined by dual x-ray absorptiometry (DXA) at baseline and after 2.5 and 5 yr of treatment.

Intention to treat analysis (n = 464) showed that after 5 yr, lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [+0.2% (P = 0.658) and +0.9% (P = 0.117), respectively], whereas lumbar BMD decreased by 4.6% in the Vit D group and by 4.5% in the placebo group (P < 0.001 in both). The loss of femoral neck BMD was less in the HRT (-1.4%; P = 0.005) and HRT plus Vit D (-1.3%; P = 0.003) groups than in the Vit D and placebo groups (-4.3%; P < 0.001 in both). Among those 370 women who complied with the 5-yr treatment, the effect was more pronounced: lumbar BMD had increased by 1.5% in the HRT (P = 0.009) and by 1.8% in the HRT plus Vit D group (P = 0.005), with a plateau after 2.5 yr, whereas lumbar BMD had decreased in both the Vit D and placebo groups (4.6% and 4.7%; P < 0.001, respectively). Femoral neck BMD decreased again less in the HRT (-0.4%) and HRT plus Vit D (-0.6%) groups than in the Vit D and placebo groups (-4.4% in both).

This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis. The data suggest that low dose vitamin D₃ supplementation does not prevent bone loss in healthy, nonosteoporotic, early postmenopausal women, and it confers no benefit additional to that of HRT alone.

This article has been cited by other articles:

				K. M Seamans and K. D Cashman Existing and potentially novel functional markers of vitamin D status: a systematic review Am. J. Clinical Nutrition, June 1, 2009; 89(6): 1997S - 2008S. [Abstract] [Full Text] [PDF]

				M. Doren Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis Eur. Heart J., April 1, 2009; 30(7): 866 - 867. [Full Text] [PDF]

				M. Doren and E. M. Greiser RE: "INVITED COMMENTARY: HORMONE THERAPY AND RISK OF CORONARY HEART DISEASE WHY RENEW THE FOCUS ON THE EARLY YEARS OF MENOPAUSE?" Am. J. Epidemiol., December 15, 2007; 166(12): 1479 - 1480. [Full Text] [PDF]

				P. Autier and S. Gandini Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials Arch Intern Med, September 10, 2007; 167(16): 1730 - 1737. [Abstract] [Full Text] [PDF]

				M. Doren, J.-A. Nilsson, and O. Johnell Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis Hum. Reprod., August 1, 2003; 18(8): 1737 - 1746. [Abstract] [Full Text] [PDF]

				B. A. in 't Veld, L. J. Launer, M. M. B. Breteler, A. Hofman, and B. H. Ch. Stricker Pharmacologic Agents Associated with a Preventive Effect on Alzheimer's Disease: A Review of the Epidemiologic Evidence Epidemiol. Rev., December 1, 2002; 24(2): 248 - 268. [Full Text] [PDF]

				E. Papadimitropoulos, G. Wells, B. Shea, W. Gillespie, B. Weaver, N. Zytaruk, A. Cranney, J. Adachi, P. Tugwell, R. Josse, et al. VIII: Meta-Analysis of the Efficacy of Vitamin D Treatment in Preventing Osteoporosis in Postmenopausal Women Endocr. Rev., August 1, 2002; 23(4): 560 - 569. [Full Text] [PDF]