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Letters to the Editor  |   March 2009
Prevention, Diagnosis, and Management of Osteoporosis-Related Fracture
Author Affiliations
  • Mona Fakih, DO, RPh
    Department of Obstetrics and Gynecology, Garden City (Mich) Hospital, Michigan State University College of Osteopathic Medicine, East Lansing
Article Information
Emergency Medicine / Neuromusculoskeletal Disorders / Preventive Medicine
Letters to the Editor   |   March 2009
Prevention, Diagnosis, and Management of Osteoporosis-Related Fracture
The Journal of the American Osteopathic Association, March 2009, Vol. 109, 191-193. doi:10.7556/jaoa.2009.109.3.191
The Journal of the American Osteopathic Association, March 2009, Vol. 109, 191-193. doi:10.7556/jaoa.2009.109.3.191
Web of Science® Times Cited: 17
To the Editor:  
Quality of life is an important consideration when evaluating treatment options to prevent osteoporosis-related fractures in postmenopausal women. The benefit-risk ratio of treatment varies for women, depending on age and severity of menopause-related symptoms. 
The October 2008 review article by M. Jill Gronholz, DO,1 provides valuable information on the use of a multifactoral approach in the management of osteoporosis-related fractures. 
Unfortunately, Dr Gronholz1 seems to dismiss the role of hormone replacement therapy (HRT) as a viable mode of treatment for this population. The following single reference was made in regard to HRT: “Although hormone replacement therapy has long been an option for osteoporosis prevention, recent findings from the Women's Health Initiative [WHI]2,3 resulted in new recommendations to limit its prophylactic use.”1 
It is true that the WHI results indicated significantly increased risks of cardiovascular events and breast cancer for women taking estrogen and progestin therapy. However, level 1a evidence continues to support the use of HRT for risk reduction of osteoporosis-related fractures based on an individual's history, risk factors, and need for treatment of vasomotor symptoms.4 
Results of the WHI showed that the use of conjugated equine estrogen (CEE, 0.625 mg daily) together with medroxyprogesterone acetate (MPA, 2.5 mg daily) reduced the risk of hip and clinical vertebral fractures by 34%, and the overall risk of fractures by 24%, compared with placebo.5 (These percentages are calculated from the associated hazard ratios reported in the study.5) This risk reduction amounted to five fewer hip fractures per 10,000 women per year.5 
In regard to cardiovascular risk, recent data have revealed an important therapeutic window of opportunity for HRT implementation. In the WHI estrogen-plus-progestin arm,6 coronary heart disease (CHD) relative risk results—in terms of hazard ratio (HR) and according to time since menopause—were the following (P for interaction=.33): 
  • <10 years since menopause, HR=0.89
  • 10-19 years since menopause, HR=1.22
  • <20 years since menopause, HR=1.71
In the WHI estrogen-only arm,7 the relative risks of CHD death—according to age at randomization—were the following: 
  • age 50-59 years, HR=0.63
  • age 60-69 years, HR=0.94
  • age 70-79 years, HR=1.11
Thus, recent WHI results5-7 suggest that HRT may decrease coronary disease in younger women (ie, those near the age of menopause), but it may increase the risk of a coronary event in older women. 
Differences in age at HRT initiation and duration of therapy are relevant factors in treatment outcomes. These WHI results5-7 should modify the benefit-risk perception of HRT and support an individualized approach to management. 
In another recent update, WHI investigators reported outcomes in patients 3 years after study medication (ie, estrogen-plus-progestin or placebo) was halted.8 No increased risk for thrombosis, CHD, or stroke was observed during these subsequent 3 years in women who had received HRT. Moreover, a statistically significant increased risk for invasive breast cancer, associated with HRT, did not persist at 3-year follow-up.8 It is also important to note that in the estrogen-only arm of the WHI study,2,7 no increased absolute risk of breast cancer was observed during 6.8-year follow-up. 
The effectiveness of low-dose HRT (CEE, 0.3 or 0.45 mg daily, combined with MPA, 1.5 or 2.5 mg daily) has been demonstrated for the treatment of patients with vasomotor symptoms or genital atrophy, as well as for the prevention of bone loss, with fewer adverse effects than standard-dose HRT.9,10 These initial results were confirmed by the HOPE (Women's Health, Osteoporosis, Progestin, Estrogen) study.11 Further research, however, is needed to determine the clinical effects of low-dose HRT on fracture, cardiovascular disease, and breast cancer. 
The review article by Dr Gronholz1 mentions only briefly the use of selective estrogen receptor modulators as a treatment or prevention option. Yet, when compared with placebo, raloxifene hydrochloride—approved by the US Food and Drug Administration for the prevention of osteoporosis12—has been shown to decrease bone resorption, increase bone mineral density, and reduce fracture risk by 35% to 50% in women with osteoporosis (P<.001).13 
The North American Menopause Society's position statement14 concludes that recent data support the initiation of HRT at menopause to manage vasomotor symptoms and to reduce the risk of osteoporosis in select postmenopausal women. As noted in the WHI results,5-7 the benefit-risk ratio for HRT is favorable when treatment begins close to menopause, but this benefit-risk ratio decreases with age and with time since menopause. 
These findings should have been emphasized in the review article by Dr Gronholz.1 Furthermore, we, as osteopathic physicians, should consider these findings when making informed treatment recommendations to our patients—especially because our profession emphasizes a holistic approach to patient care. 
In summary, recent data argue for the need to balance the benefits of HRT against its potential risks. Recommendations for individualized regimens and dosing of HRT need to be based on severity of symptoms—choosing the lowest appropriate dose for the shortest duration of time—as well as time since menopause. 
 Dr Gronholz was shown this letter and declined to comment at this time.
 
Gronholz MJ. Prevention, diagnosis, and management of osteoporosis-related fracture: a multifactoral osteopathic approach. J Am Osteopath Assoc. 2008;108:575-585. Available at: http://www.jaoa.org/cgi/content/full/108/10/575. Accessed March 3, 2009.
Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712.
Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al; Women's Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA. 2003;290:1729-1738.
American College of Obstetricians and Gynecologists, Women's Health Care Physicians. ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 50, January 2003. Obstet Gynecol. 2004;103:203-216.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principle results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.
Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Laser NL, et al; Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003; 349:523-534. Available at: http://content.nejm.org/cgi/reprint/349/6/523.pdf. Accessed March 3, 2009.
Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause [published correction appears in JAMA. 2008;299:1426]. JAMA. 2007;297:1465-1477.
Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, et al; WHI Investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299:1036-1045.
Notelovitz M, Lenihan JP, McDermott M, Kerber IJ, Nanavati N, Arce J. Initial 17beta-estradiol dose for treating vasomotor symptoms. Obstet Gynecol. 2000;95:726-731.
De Aloysio D, Rovati LC, Giacovelli G, Setnikar I, Bottiglioni F. Efficacy on climacteric symptoms and safety of low dose estradiol transdermal matrix patches. A randomized, double-blind placebo-controlled study. Arzneimittelforschung. 2000;50:293-300.
Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA. 2002;287:2668-2676.
Neff MJ; American College of Obstetricians and Gynecologists. ACOG releases guidelines for clinical management of osteoporosis. Am Fam Physician. 2004;69:1558,1560. Available at: http://www.aafp.org/afp/20040315/practice.html. Accessed January 28, 2009.
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized controlled trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators [published correction appears in JAMA. 1999;282:2124]. JAMA. 1999;282:637-645.
Utian WH, Archer DF, Bachmann GA, Gallagher C, Grodstein F, Heiman JR, et al; North American Menopause Society. Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause. 2008;15:584-602. Available at: http://www.menopause.org/PSHT08.pdf. Accessed January 28, 2009.