What is the first line treatment for a postmenopausal woman or older adult with osteoporosis?

First-Line Treatment for Osteoporosis

Bisphosphonates (specifically alendronate, risedronate, or zoledronic acid) are the recommended first-line pharmacologic treatment for osteoporosis in postmenopausal women and older adults, based on their proven efficacy in reducing hip and vertebral fractures, favorable safety profile, and low cost. 1, 2

Treatment Algorithm

Step 1: Confirm Diagnosis and Assess Risk

• Confirm osteoporosis with DEXA scan showing T-score ≤ -2.5 2, 3
• For T-scores between -1.0 and -2.5, calculate 10-year fracture risk using FRAX tool 3
• Initiate treatment if FRAX shows ≥20% risk of major osteoporotic fracture OR ≥3% risk of hip fracture 3
• Consider treatment even without osteoporosis on DEXA if patient has history of low-trauma fracture 3

Step 2: Initiate First-Line Bisphosphonate Therapy

The American College of Physicians strongly recommends bisphosphonates as initial therapy based on high-certainty evidence showing they reduce hip fractures by 50% and vertebral fractures by 47-56% over 3 years. 1, 3

Specific bisphosphonate options (choose one):

• Alendronate 70 mg once weekly (most commonly used oral option) 1, 2, 3, 4
• Risedronate 35 mg once weekly (alternative oral option) 1, 3, 5
• Zoledronic acid 5 mg IV annually (for patients unable to tolerate oral medications) 1

Rationale for bisphosphonates as first-line: Bisphosphonates have the most favorable balance among benefits, harms, patient preferences, and cost compared to all other drug classes, with generic formulations available making them significantly more cost-effective than alternatives like denosumab. 1, 6

Step 3: Essential Supplementation (Required for All Patients)

• Calcium 1,200 mg daily 2, 3
• Vitamin D 800 IU daily (target serum level ≥20 ng/mL) 2, 3
• Pharmacologic therapy is less effective without adequate calcium and vitamin D supplementation 3

Step 4: Proper Administration Technique for Oral Bisphosphonates

Critical administration instructions to minimize gastrointestinal adverse effects and maximize absorption: 1, 3

• Take on empty stomach first thing in morning with full glass of plain water
• Remain upright (sitting or standing) for at least 30 minutes after taking medication 1
• Do not eat, drink, or take other medications for at least 30 minutes after dose 1
• Patients at increased risk of aspiration should not receive alendronate solution 1

Step 5: Treatment Duration and Monitoring

• Initial treatment duration: 5 years 1, 2, 3
• Do NOT monitor bone density during the initial 5-year treatment period 2, 3
• After 5 years, reassess fracture risk to determine if continued therapy is warranted 1, 2, 3
• Consider stopping bisphosphonate treatment after 5 years unless patient has strong indication for continuation, as longer duration increases risk of rare but serious adverse effects 1

Second-Line Treatment: Denosumab

Denosumab 60 mg subcutaneously every 6 months should be reserved as second-line therapy for patients who have contraindications to bisphosphonates or experience adverse effects from bisphosphonate therapy. 1, 2

Critical warning about denosumab: Abrupt discontinuation leads to rebound bone turnover and significantly increased risk of multiple vertebral fractures; if discontinuing denosumab, must transition to a bisphosphonate to prevent rebound bone loss. 2, 3

Contraindications to Bisphosphonates

• Hypocalcemia (must be corrected before initiating therapy) 1
• Creatinine clearance <35 mL/min for zoledronic acid 1
• Inability to stand or sit upright for at least 30 minutes 1
• Hypersensitivity to bisphosphonates 1

Safety Profile and Adverse Effects

Common Short-Term Effects

• Upper gastrointestinal symptoms (heartburn, nausea, abdominal pain) with oral bisphosphonates 3, 7
• Acute phase reactions (fever, myalgia, flu-like symptoms) with IV bisphosphonates, particularly zoledronic acid 7

Rare Long-Term Serious Adverse Effects

High-certainty evidence shows no difference in serious adverse events between bisphosphonates and placebo in randomized controlled trials at 3+ years. 1

However, observational studies show increased risk of rare complications with longer treatment duration: 1

• Osteonecrosis of the jaw: 0.01% to 0.3% incidence in bisphosphonate users, risk increases with longer duration 1
• Atypical femoral fractures: Risk increases with treatment duration beyond 5 years, higher risk in Asian females (595 per 100,000 person-years) compared to non-Hispanic White females (109 per 100,000 person-years) 1

Lifestyle Modifications (Essential Adjuncts)

• Weight-bearing exercise (walking, dancing) 2, 3
• Smoking cessation 2, 3
• Limit alcohol intake 2, 3
• Fall prevention counseling and evaluation 1

Special Populations

Males with Primary Osteoporosis

• Bisphosphonates are first-line treatment (same as postmenopausal women) 1
• Denosumab is second-line for males with contraindications or adverse effects from bisphosphonates 1
• No evidence suggests differences in treatment benefits or harms by sex 1

Very High Fracture Risk Patients

• For postmenopausal females at very high risk of fracture, consider anabolic agents (teriparatide or romosozumab) as initial therapy instead of bisphosphonates 1
• If anabolic agents are used initially, must transition to antiresorptive agent (bisphosphonate or denosumab) after discontinuation to preserve gains and prevent rebound fractures 1

Common Pitfalls to Avoid

• Never skip calcium and vitamin D supplementation - pharmacologic therapy effectiveness is significantly reduced without adequate supplementation 3
• Never monitor bone density during initial 5-year treatment period - this is not recommended and provides no clinical benefit 2, 3
• Never abruptly discontinue denosumab without transitioning to bisphosphonate - this causes dangerous rebound bone loss and multiple vertebral fractures 2, 3
• Ensure proper oral bisphosphonate administration technique - improper technique leads to poor absorption and increased gastrointestinal adverse effects 3
• Do not use combination therapy - combining multiple osteoporosis medications is not recommended 1

Cost Considerations

Generic bisphosphonates should be prescribed 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, 6