JoAnn V. Pinkerton, MD

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.

. 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.

 Ideally, ERT/HRT requires a commitment to long-term use, because when therapy stops, significant bone loss resumes.

Despite its advantages, ERT/HRT has a high discontinuation rate--up to 75% after 6 months.

 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.

 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.

. 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.

 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.

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,

 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. 

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.

    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

Articles

Postmenopausal osteoporosis is a major health problem, primarily because of the severe morbidity and mortality associated with osteoporotic fractures.

JoAnn V. Pinkerton, MD

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Postmenopausal Osteoporosis: Pharmacologic Options for Prevention