{"paper_id":"31bd5981-e8b3-4966-8378-1f786c577b6a","body_text":"Abstract\nOsteoporosis, a major public health problem, is characterized by increased risk for fracture. To reduce the morbidity and excess loss of life associated with this common disease, we need to understand the efficacy of treatment strategies for fracture reduction. The Women’s Health Initiative Clinical Trials have extended our understanding of the effect of hormone therapy and calcium plus vitamin D supplements on risk for hip and total fractures. Although estrogen, with or without progestin, significantly decreases fracture risk at all skeletal sites—almost irrespective of underlying risk for osteoporosis—its risks outweigh its benefits, negating its general use for fracture reduction. For calcium-replete women, calcium plus vitamin D supplementation has a non-significant effect, hence the case for universal supplementation loses merit. But, that argument gains credibility for women over age 60—as a 21% reduction in hip fractures attests—showing that calcium plus vitamin D has a positive effect on bone health in older postmenopausal women.\nSimilar content being viewed by others\nReferences and Recommended Reading\nDepartment of Health and Human Services: Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: Office of the Surgeon General; 2004.\nCummings SR, Melton LJ III: Epidemiology and outcomes of osteoporosis fractures. Lancet 2002, 359:1761–1767.\nBurge R, Dawson-Hughes B, Solomon DH, et al.: Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 2006, 21:465–475.\nHealthy People 2010: http://www.healthypeople.gov/publications. Accessed October 15, 2007.\nWomen’s Health Initiative Study Group: Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 1998, 19:61–109.\nCummings SR, Browner WS, Bauer D, et al.: Endogenous and calciotropic hormones and the risk of hip and vertebral fractures in older women: the Study of Osteoporotic Fractures. N Engl J Med 1998, 339:733–738.\nvan Barrett-Connor E, Mueller JE, von Muhlen DG, et al.: Low levels of estradiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study. J Clin Endocrinol Metab 2000, 85:219–223.\nWells G, Tugwell P, Shea B, et al.: Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocrine Rev 2002, 23:529–539.\nThe Writing Group for the PEPI: Effects of hormone therapy on bone mineral density—results from the post-menopausal estrogen/progestin interventions (PEPI) trial. JAMA 1996, 276:1389–1396.\nLindsay R, Gallagher JC, Kleerekoper M, et al.: Effect of lower doses of conjugated estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002, 287:2668–2676.\nCauley JA, Seeley DG, Ensrud K, et al.: Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med 1995, 122:9–16.\nWeiss NS, Ure CL, Ballard JH, et al.: Decreased risk of fractures of hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980, 303:1195–1198.\nPasco JA, Kotowicz MA, Henry MJ, et al.: Hormone therapy and risk of non-vertebral fracture: Geelong osteoporosis study. Osteoporosis Int 2004, 15:434–438.\nBanks E, Beral V, Reeves G, et al.: Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women. JAMA 2004, 291:2212–2220.\nNelson HD, Humphrey LL, Nygren P, et al.: Postmenopausal hormone replacement therapy. JAMA 2002, 288:872–881.\nTorgerson DL, Bell-Syer SEM: Hormone replacement therapy and prevention of nonvertebral fractures. JAMA 2001, 285:2891–2897.\nKomulainen MH, Kruger H, Tuppurainen MT, et al.: HRT and vitamin D in prevention of non-vertebral fractures in post-menopausal women: a 5-year randomized trial. Maturitas 1998, 31:45–54.\nTorgerson DL, Bell-Syer SEM: Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomized trials. BMC Musculoskeletal Disord 2001, 2:7.\nStefanick ML, Cochrane BB, Hsia J, et al.: The Women’s Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. Ann Epidemiol 2003, 13:S78–S86.\nRossouw JE, Anderson GL, Prentice RL, et al.: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002, 288:321–333.\nAnderson GL, Limacher MC, Assaf AR, et al.: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004, 291:1701–1712.\nCauley JA, Robbins J, Chen Z, et al.: Effects of estrogen plus progestin on risk for fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 2003, 290:1729–1738.\nJackson RD, Wactawski-Wende J, LaCroix AZ, et al.: Effects of conjugated equine estrogen on risk for fractures and BMD in postmenopausal women with hysterectomy: results from the Women’s Health Initiative randomized trial. J Bone Miner Res 2006, 21:817–828.\nCushman M, Kuller LH, Prentice R, et al.: Estrogen plus progestin and risk of venous thrombosis. JAMA 2004, 292:2947–2958.\nChlebowski RT, Hendrix SL, Langer RD, et al.: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative randomized trial. JAMA 2003, 289:3243–3253.\nWassertheil-Smoller S, Hendrix SL, Limacher M, et al.: Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 2003, 289:2673–2684.\nManson JE, Hsia J, Johnson KC, et al.: Estrogen plus progestin and the risk for coronary heart disease. N Engl J Med 2003, 349:523–534.\nShumaker SA, Legault C, Rapp SR, et al.: Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003, 289:2651–2662.\nRapp SR, Espeland MA, Shumaker SA, et al.: Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003, 289:2663–2672.\nHsia J, Langer RD, Manson JE, et al.: Conjugated equine estrogens and coronary heart disease: the Women’s Health Initiative. Arch Intern Med 2006, 166:357–365.\nStefanick ML, Anderson GL, Margolis KL, et al.: Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006, 295:1647–1657.\nHendrix SL, Wassertheil-Smoller S, Johnson KC, et al.: Effects of conjugated equine estrogens on stroke in the Women’s Health Initiative. Circulation 2006, 113:2425–2434.\nCurb JD, Prentice RL, Bray PF, et al.: Venous thromboembolism and conjugated equine estrogen in women without a uterus. Arch Intern Med 2006, 166:772–780.\nShumaker SA, Legault C, Kuller L, et al.: Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study. JAMA 2004, 291:1366–1376.\nPrentice RL, Langer RD, Stefanick ML, et al.: Combined postmenopausal hormone therapy and cardiovascular disease: toward resolving the discrepancy between observational studies and the Women’s Health Initiative clinical trial. Am J Epidemiol 2005, 162:404–414.\nRossouw JE, Prentice RL, Manson JE, et al.: Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007, 297:1465–1477.\nManson JE, Allison MA, Rossouw JE, et al.: Estrogen therapy and coronary artery calcification. N Engl J Med 2007, 356:2592–2602.\nJackson RD, Watts NL Caralis PD, et al.: Fracture risk after estrogen plus progestin discontinuation: the Women’s Health Initiative [abstract]. Presented at the American Society of Bone and Mineral Research 24th Annual Meeting. San Antonio, TX; September 20–24, 2002.\nFood and Nutrition Board, Institute of Medicine: Vitamin D: Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, DC: National Academic Press; 1999:25–287.\nCumming RG: Calcium intake and bone mass: a quantitative review of the evidence. Calcif Tissue Int 1990, 47:1194–1201.\nShea B, Wells G, Cranney A, et al.: Osteoporosis Methodology Group and the Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Endocr Rev 2002, 23:552–559.\nBischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al.: Effect of vitamin D on falls: a meta-analysis. JAMA 2004, 291:1999–2006.\nBischoff-Ferrari HA, Willett WC, Wong JB, et al.: Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005, 293:2257–2264.\nChapuy MC, Arlot ME, Duboeuf F, et al.: Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992, 327:1637–1642.\nThe RECORD Trial Group: Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people: a randomized placebo-controlled trial. Lancet 2005, 365:1599–1600.\nPorthouse J, Cockayne S, King C, et al.: Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 2005, 330:1003.\nCranney A, Horsley T, O’Donnell S, et al.: Effectiveness and Safety of Vitamin D. Evidence Report/Technology Assessment. AHRQ publication number 0X-EO. Rockville, MD: Agency for Health Care Research and Quality; 2007.\nGillespie WJ, Avenell A, Henry DA, et al.: Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2001, CD000227.\nJackson RD, LaCroix A, Cauley JA, et al.: The Women’s Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Ann Epidemiol 2003, 13S:98–106.\nJackson RD, LaCroix AZ, Gass M, et al.: Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006, 354:669–683.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nJackson, R.D., Shidham, S. The role of hormone therapy and calcium plus vitamin D for reduction of bone loss and risk for fractures: Lessons learned from the women’s health initiative. Curr Osteoporos Rep 5, 153–159 (2007). https://doi.org/10.1007/s11914-007-0010-4\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s11914-007-0010-4","source_license":"CC0","license_restricted":false}