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

Current Osteoporosis Reports

Volumn 5, Issue 4, 2007, Pages 153-159

  Jackson, Rebecca D ^a   Shidham, Shubhangi ^b  

^a OHIO STATE UNIVERSITY   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM; COLECALCIFEROL; ESTROGEN; GESTAGEN; MEDROXYPROGESTERONE ACETATE; PLACEBO; VITAMIN D;

BONE DENSITY; CARDIOVASCULAR RISK; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFICACY; DRUG TOLERABILITY; ETHNICITY; FRAGILITY FRACTURE; HIP FRACTURE; HORMONAL THERAPY; HUMAN; OSTEOLYSIS; POSTMENOPAUSE; REVIEW; RISK FACTOR; TREATMENT OUTCOME; VITAMIN SUPPLEMENTATION; WOMEN'S HEALTH;

EID: 38049021024     PISSN: 15441873     EISSN: 15442241     Source Type: Journal    
DOI: 10.1007/s11914-007-0010-4     Document Type: Review

References (50)

1. Department of Health and Human Services: Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: Office of the Surgeon General; 2004.
2. Cummings SR, Melton LJ III: Epidemiology and outcomes of osteoporosis fractures. Lancet 2002, 359:1761-1767.
3. • Burge 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. This article has the most current data examining the burden of this major public health problem. It includes projections for disease magnitude over the next two decades.
4. Healthy People 2010: http://www.healthypeople.gov/publications. Accessed October 15, 2007.
5. Women's Health Initiative Study Group: Design of the Women's Health Initiative clinical trial and observational study. Control Clin Trials 1998, 19:61-109.
6. Cummings 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.
7. van 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.
8. Wells 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.
9. The Writing Group for the PEPI: Effects of hormone therapy on bone mineral density - results from the post-menopausal estrogcn/progestin interventions (PEPI) trial. JAMA 1996, 276:1389-1396.
10. Lindsay 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.
11. Cauley 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.
12. Weiss 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, 303:11.95-1198.
13. Pasco JA, Kotowicz MA, Henry MJ, et al.: Hormone therapy and risk of non-vertebral fracture: Geelong osteoporosis study. Osteoporosis Int 2004, 15:434-438.
14. Banks 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.
15. Nelson HD, Humphrey LL, Nygren P, et al.: Postmenopausal hormone replacement therapy. JAMA 2002, 288:872-881.
16. Torgerson DL, Bell-Syer SEM: Hormone replacement therapy and prevention of nonvertebral fractures. JAMA 2001, 285:2891- 2897.
17. Komulainen 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.
18. Torgerson DL, Bell-Syer SEM: Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomized trials. BMC Musculoskeletal Disord 2001, 2:7.
19. Stefanick 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.
20. Rossouw JE, Anderson GL, Prentice RL, et al.: Risks and benefits of estrogen plus progestin in healthy post-menopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002, 288:321-333.
21. Anderson 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.
22. Cauley 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.
23. •• Jackson 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. This study examines whether the benefit of estrogen alone for fracture reduction varies based on osteoporosis-related risk factors. The effect of estrogen alone is similar to estrogen plus progestin on skeletal outcomes.
24. Cushman M, Kuller LH, Prentice R, et al.: Estrogen plus progestin and risk of venous thrombosis. JAMA 2004, 292:2947-2958.
25. Chlebowski 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.
26. Wassertheil-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.
27. Manson 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.
28. Shumaker 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.
29. Rapp 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.
30. • Hsia 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. Secondary analyses from the WHI estrogen-alone trial that demonstrate no increase in coronary heart disease risk in young postmenopausal women.
31. Stefanick 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.
32. Hendrix 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.
33. Curb 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.
34. Shumaker 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.
35. Prentice 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 Heath Initiative clinical trial. Am J Epidemiol 2005, 162:404-414.
36. • Rossouw 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. This study examines the hypothesis that younger women or women who start HT closer to menopause are at lesser risk for adverse coronary heart disease outcomes. Although no benefit is noted with younger age, there appears to be greater risk with a longer period of time since menopause.
37. • Manson JE, Allison MA, Rossouw JE, et al.: Estrogen therapy and coronary artery calcification. N Engl J Med 2007, 356:2592-2602. This cross-sectional study examines the effect of prior randomization to estrogen alone or placebo on coronary artery calcification. It suggests that estrogen alone in younger women may reduce a marker of coronary heart disease risk.
38. Jackson 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.
39. Food 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.
40. Cumming RG: Calcium intake and bone mass: a quantitative review of the evidence. Calcif Tissue Int 1990, 47:1194-1201.
41. Shea 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.
42. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al.: Effect of vitamin D on falls: a meta-analysis. JAMA 2004, 291:1999-2006.
43. Bischoff-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.
44. Chapuy 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.
45. The 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.
46. Porthouse 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.
47. •• Cranney 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. Critical analysis of the evidence that vitamin D supplementation, with or without calcium, has musculoskeletal benefits on prevention of bone loss and reduction of fractures; it also preserves muscle strength and reduces falls. Detailed information is included on vitamin D responses across the lifespan and gaps in current knowledge.
48. Gillespie 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.
49. Jackson 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.
50. •• Jackson 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. This study demonstrates that calcium plus vitamin D supplementation reduces risk of hip fracture in women over 60 and for those adherent to study medication. But, it has no effect on reducing risk at other fracture sites. Its use is associated with a 17% increase in risk for kidney stones. The effect of calcium plus vitamin D did not vary by baseline 25(OH) vitamin D levels.