Should a postmenopausal woman in her 70s with osteoporosis continue taking estradiol (estrogen replacement therapy) as treatment for osteoporosis?

Should a Postmenopausal Woman with Osteoporosis Continue Estradiol?

No, a postmenopausal woman in her 70s with osteoporosis should discontinue estradiol and transition to first-line bisphosphonate therapy (alendronate, risedronate, or zoledronic acid) or denosumab. 1

Why Estrogen Should Be Discontinued

Strong Recommendation Against Estrogen for Osteoporosis Treatment

• The American College of Physicians strongly recommends against using estrogen therapy or estrogen plus progestogen therapy for the treatment of osteoporosis in women (strong recommendation; moderate-quality evidence). 1

• Hormone replacement therapy increases the risk of breast cancer (RH 1.26,95% CI 1.00-1.59), stroke (RH 1.41,95% CI 1.07-1.85), coronary heart disease, and venous thromboembolism. 1

• The USPSTF recommends against the routine use of HRT for the primary prevention of chronic disease in women. 1

Critical Context: Estrogen Is Only FDA-Approved for Prevention, Not Treatment

• The FDA label for estradiol indicates it is approved for "prevention of osteoporosis," not treatment of established osteoporosis. 2

• When prescribing solely for prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk where non-estrogen medications are not appropriate. 2

• This patient already has osteoporosis (not just at risk), making estrogen inappropriate by FDA indication. 2

What Should Be Prescribed Instead

First-Line Therapy Recommendations

• The American College of Physicians strongly recommends offering pharmacologic therapy with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women with osteoporosis (T-score ≤ -2.5 or those who have experienced a fragility fracture). 1

• Bisphosphonates (alendronate, risedronate, zoledronic acid) and denosumab reduce radiographic vertebral fractures as well as clinical, nonvertebral, and hip fractures. 1

Specific Treatment Algorithm

Step 1: Confirm osteoporosis diagnosis

• DXA scan showing T-score ≤ -2.5, or history of fragility fracture. 1

Step 2: Select first-line agent

• Alendronate (oral, weekly), risedronate (oral, weekly or monthly), zoledronic acid (IV, yearly), or denosumab (subcutaneous, every 6 months). 1
• Choose generic drugs when possible to reduce costs. 1

Step 3: Counsel on adherence

• Bisphosphonates require specific instructions: taken on an empty stomach, remaining upright for 30 minutes. 1
• Discuss side effects: mild gastrointestinal symptoms, rare osteonecrosis of the jaw or atypical subtrochanteric fracture. 1

Step 4: Treatment duration

• Continue therapy for 5 years, then reevaluate the risk and benefits to continue. 1
• Do not perform bone density monitoring during the initial 5-year treatment period. 1

Common Pitfalls to Avoid

The "Estrogen Has Been Working" Fallacy

• While estrogen does increase bone mineral density and can reduce fracture risk 3, the harm-benefit ratio is unfavorable when used specifically for osteoporosis treatment in older postmenopausal women. 1

• The Women's Health Initiative found that adverse effects outweighed potential bone benefits, leading to the recommendation against HRT for osteoporosis. 4

Misunderstanding FDA Indications

• Estradiol is FDA-approved for osteoporosis prevention in women at significant risk when non-estrogen medications are not appropriate. 2

• It is not indicated as treatment for established osteoporosis, which this patient has. 2

Ignoring Age-Related Risk

• A woman in her 70s faces substantially higher cardiovascular and thromboembolic risks from estrogen therapy compared to younger postmenopausal women. 1

• The risk-benefit calculation that might favor estrogen in a 55-year-old for menopausal symptoms does not apply to a 70-year-old with osteoporosis. 1

Nuance: When Estrogen Might Continue

The only scenario where continuing estrogen would be reasonable is if this patient is taking it primarily for moderate to severe vasomotor symptoms (hot flashes) that significantly impair quality of life, and the osteoporosis benefit is secondary. 2

• Even in this case, the FDA recommends using the lowest effective dose for the shortest duration consistent with treatment goals. 2

• The patient should be reevaluated periodically (every 3-6 months) to determine if treatment is still necessary. 2

• However, bisphosphonate therapy should still be added for the osteoporosis itself. 1