Postmenopausal Osteoporosis: Pharmacologic Options for Prevention

Postmenopausal osteoporosis is a major health problem, primarily because of the severe morbidity and mortality associated with osteoporotic fractures. As it is easier to prevent osteoporosis than to treat it, the primary goal of therapy is to retard menopause-associated bone loss. In women whose risk profile indicates a need for osteoporosis prevention, the first step is to evaluate nutritional status and other health factors. If lifestyle modifications are inadequate in reducing risk, clinicians have several pharmacologic options.

Pharmacologic Options

ERT/HRT. Both estrogen replacement therapy (ERT) and hormone replacement therapy (HRT; estrogen plus progestogen) reduce bone loss by decreasing bone absorption. Many ERT/HRT products have been approved by the Food and Drug Administration (FDA) for the prevention of postmenopausal osteoporosis. In general, ERT/HRT is thought to work best during the first 5 to 10 years after menopause, although it has also been shown to preserve bone when started in women older than 60.¹ Ideally, ERT/HRT requires a commitment to long-term use, because when therapy stops, significant bone loss resumes.²

Despite its advantages, ERT/HRT has a high discontinuation rate--up to 75% after 6 months.³ Frequently cited among reasons for stopping are concerns about the link between estrogen and breast cancer and possible uterine bleeding.

Recommended dosing is 0.625 mg daily of conjugated equine estrogens (or the equivalent), although 0.3 mg daily has been shown to preserve bone while minimizing unwanted effects.^4,5 Estrogen increases the risk for venous thromboembolism (VTE), and is thus contraindicated in women with a history of VTE or in those immobilized for prolonged periods. Breast cancer risk is yet undetermined, although some studies have revealed a slight risk increase.

Bisphosphonates. These nonhormonal drugs inhibit osteoclast activity, thereby reducing bone resorption. They lack some of estrogen's drawbacks--they do not exert adverse effects on the uterus or breast and they are not linked to VTE--but they also lack estrogen's nonskeletal advantages.

Bisphosphonates may cause upper gastrointestinal problems such as dysphagia, esophagitis, and ulcers. As food reduces their absorption, bisphosphonates should be taken on an empty stomach, with water only. Users should then wait at least 30 minutes before eating, drinking other liquids, or taking other medications.

Two oral bisphosphonates have been FDA-approved to prevent postmenopausal osteoporosis: alendronate (Fosamax) and risedronate (Actonel). Both increase bone mineral density (BMD) and decrease vertebral fracture risk.

For women in early postmenopause, alendronate has been shown to increase vertebral and hip BMD.⁶ Recommended dosing for osteoporosis prevention is 5 mg daily. The once-weekly formulation of alendronate seems to be just as effective as the daily-dose formulation. Risedronate 5 mg daily is similar to alendronate in terms of its benefits.⁷

Selective estrogen receptor modulators (SERMs). These estrogen-like compounds have antiresorptive properties. Only one SERM, raloxifene (Evista), has been approved for osteoporosis prevention. Raloxifene increases BMD in the spine, hip, and wrist,⁸ although to a lesser degree than ERT/HRT or the bisphosphonates. Like estrogen, raloxifene has potentially harmful effects in women who are at risk for VTE. Unlike estrogen, raloxifene does not jeopardize endometrial/breast tissue, but it also does not ease menopause symptoms and may exacerbate hot flashes. 

Clinical Implications
Osteoporosis prevention in postmenopausal women begins with risk assessment and, if needed, BMD testing. Clinicians should encourage all postmenopausal women, regardless of their risk factors, to participate in osteoporosis prevention through a combination of nutritional and lifestyle measures. If preventive pharmacotherapy is needed, clinicians have several options. In the author's practice, ERT/HRT is considered a good choice for women who need therapy for other menopause symptoms. These women should be re-evaluated periodically to determine whether the estrogen dose should be lowered or whether they should be switched to a different therapy.

Raloxifene is considered for women who do not have troublesome vasomotor symptoms or who want a medication that improves BMD without the risk for uterine/breast stimulation. Bisphosphonates are an excellent choice for women who need to prevent bone loss only.
Therapy must be tailored to each woman's needs. Also, clinicians should recommend adequate intakes of calcium (1200-1500 mg/d) and vitamin D (400-600 IU/d), as well as resistant-type exercises to augment the drugs' benefits.

Interventions to stave off bone loss can help to improve postmenopausal women's quality of life and avoid the serious consequences of fractures. Osteoporosis is preventable, but clinicians must take the lead in identifying which women are at risk and encouraging both nonmedical and medical prevention strategies that can increase BMD and decrease fracture risk.

References:

References

1. Lindsay R, Tohme JF. Estrogen treatment of patients with established postmenopausal osteoporosis. Obstet Gynecol. 1990;67:290-295.

2. Quigley ME, Martin PL, Burnier AM, Brooks P. Estrogen therapy arrests bone loss in elderly women. Am J Obstet Gynecol. 1987;156:1516-1523.

3. Berman RS, Epstein RS, Lydick EG. Compliance of women in taking estrogen replacement therapy. J Womens Health. 1996;5:213-220.

4. Genant HK, Lucas J, Weiss S, et al, for the Estratab/Osteoporosis Study Group. Low-dose esterified estrogen therapy: effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Arch Intern Med. 1997;157: 2609-2615.

5. Recker RR, Davies KM, Dowd RM, Heaney RP. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women: a randomized controlled trial. Ann Intern Med. 1999;130:897-904.

6. McClung M, Clemmesen B, Daifotis A, et al. Alendronate prevents postmenopausal bone loss in women without osteoporosis: a double-blind, randomized, controlled trial. Ann Intern Med. 1998;128:253-261.

7. Mortensen L, Charles P, Bekker PJ, et al. Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up. J Clin Endocrinol Metab. 1998;83:396-402.

8. Delmas PD, Bjanarson NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337:1641-1647.

JoAnn V. Pinkerton, MD, is an Associate Professor, Department of Obstetrics and Gynecology, and Medical Director, The Woman's Place--Midlife Health Center, University of Virginia, Charlottesville. She is a member of The North American Menopause Society's Professional Education Committee.

Originally published in The Female Patient Patient Handout -- July, 2001

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