Treatment for Osteoporosis in Postmenopausal Women
Start oral bisphosphonates (alendronate 70 mg once weekly or risedronate 35 mg once weekly) as first-line therapy for all postmenopausal women with osteoporosis, combined with calcium 1,200 mg daily and vitamin D 800 IU daily. 1, 2, 3
First-Line Pharmacologic Treatment
Bisphosphonates are the mandatory initial therapy based on high-certainty evidence showing they reduce hip fractures by 50% and vertebral fractures by 47-56% over 3 years. 1, 2, 3
Specific bisphosphonate options include:
Bisphosphonates have the most favorable balance of efficacy, safety, patient preferences, and cost compared to all other drug classes, with generic formulations available making them significantly more cost-effective than alternatives. 1, 3
Essential Concurrent Supplementation
All patients must receive calcium 1,200 mg daily and vitamin D 800 IU daily, as pharmacologic therapy is significantly less effective without adequate supplementation. 2, 3, 4, 5
Target serum vitamin D level ≥20 ng/mL (≥50 nmol/L). 2
Treatment Duration and Monitoring Strategy
Initial treatment duration is 5 years with bisphosphonates, after which fracture risk should be reassessed to determine if continued therapy is warranted. 2, 3, 4
Do not monitor bone mineral density during the initial 5-year treatment period, as this provides no clinical benefit and bisphosphonates reduce fractures even when BMD does not increase. 2, 3
After 5 years, patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. 1, 4
If therapy is discontinued, reassess fracture risk periodically and restart treatment if yearly BMD falls >4%. 1
Safety Profile and Adverse Effects
High-certainty evidence shows no difference in serious adverse events between bisphosphonates and placebo in randomized controlled trials at 2-3 years. 1, 2, 3
Common adverse effects include mild upper GI symptoms (abdominal pain, nausea, dyspepsia), influenza-like symptoms, myalgias, arthralgias, and headaches. 6
Rare but serious adverse effects include osteonecrosis of the jaw (0.01% to 0.3% incidence) and atypical femoral fractures, with risk increasing with longer treatment duration beyond 5 years. 1, 2, 3
Critical Administration Instructions to Prevent Upper GI Adverse Events
Take bisphosphonates first thing in the morning on an empty stomach with a full glass (6-8 oz) of plain water only. 4, 5
Remain upright (sitting or standing) for at least 30 minutes after taking the medication and do not eat or drink anything else during this time. 4, 5
Do not lie down until after eating the first meal of the day. 4, 5
Second-Line Pharmacologic Treatment
Denosumab 60 mg subcutaneously every 6 months is recommended as second-line therapy for patients with contraindications to or intolerance of bisphosphonates. 1, 2, 3
Critical warning: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy, as abrupt discontinuation is associated with multiple vertebral fractures in some patients. 2, 3
Very High-Risk Patients (Anabolic Therapy)
For postmenopausal women at very high risk of fracture (multiple prevalent fractures, very low BMD [T-score < -3.0], or fracture on osteoporosis therapy), consider anabolic agents as initial therapy instead of bisphosphonates:
This is a conditional recommendation based on low to moderate-certainty evidence. 1
After completing anabolic therapy, transition to antiresorptive therapy (bisphosphonate or denosumab) to maintain gains. 3
Teriparatide may increase the risk for serious adverse events and probably increases the risk for withdrawal due to adverse events. 1
Mandatory Lifestyle Modifications
Weight-bearing exercise and resistance training to improve bone density and reduce fall risk. 2, 3, 7
Limit alcohol intake to no more than 2 drinks per day. 2, 3, 7
Fall prevention strategies including home safety assessment, vision correction, medication review, and balance training. 2, 3, 7
Maintain adequate protein intake to support bone health. 7
Agents to Avoid
The American College of Physicians strongly recommends against using menopausal estrogen therapy, estrogen plus progestogen therapy, or raloxifene for osteoporosis treatment due to unfavorable benefit-harm balance. 1
While hormone replacement therapy can prevent bone loss, the increased risk of breast cancer (15-30% after 10 years) and cardiovascular events outweighs benefits for osteoporosis treatment alone. 1
Cost Considerations
- Prescribe generic bisphosphonates whenever possible rather than expensive brand-name medications or newer agents like denosumab, as they are significantly more cost-effective while maintaining equivalent efficacy. 1, 3
Common Pitfalls to Avoid
Failing to ensure adequate calcium and vitamin D supplementation, which significantly reduces bisphosphonate efficacy. 2, 3
Monitoring BMD during the initial 5-year treatment period, which provides no clinical benefit and may lead to unnecessary treatment changes. 2, 3
Continuing bisphosphonates indefinitely without reassessing fracture risk after 5 years, which increases the risk of rare serious adverse effects like atypical femoral fractures. 1, 2, 4
Abruptly discontinuing denosumab without transitioning to bisphosphonate therapy, which can cause rebound vertebral fractures. 2, 3
Improper administration of oral bisphosphonates (not taking on empty stomach, not remaining upright for 30 minutes), which increases risk of esophageal adverse events. 4, 5, 6