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

General Treatment for Osteoporosis

First-Line Pharmacologic Treatment

Bisphosphonates are the mandatory first-line therapy for osteoporosis in postmenopausal women and older adults, based on high-certainty evidence showing they reduce hip fractures by 50% and vertebral fractures by 47-56% over 3 years. 1

Specific Bisphosphonate Regimens

• Alendronate 70 mg once weekly (oral) 2, 1
• Risedronate 35 mg once weekly (oral) 2, 1
• Zoledronic acid 5 mg IV annually (for patients unable to tolerate oral formulations) 3, 1

Bisphosphonates offer the most favorable balance of efficacy, safety, patient preferences, and cost compared to all other drug classes, with generic formulations making them significantly more cost-effective than alternatives like denosumab. 1

Essential Supplementation (Non-Negotiable)

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. 3, 1 Target serum vitamin D level ≥20 ng/mL. 3

Treatment Duration and Monitoring Strategy

• Initial treatment duration is 5 years with bisphosphonates 3, 1
• Do not monitor bone density during the initial 5-year treatment period—this provides no clinical benefit 3, 1
• After 5 years, reassess fracture risk to determine if continued therapy is warranted 3, 1
• Patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years of use 2

Mandatory Lifestyle Modifications

Implement the following for all patients: 1, 4

• Weight-bearing exercise and resistance training
• Smoking cessation
• Limit alcohol intake
• Fall prevention strategies
• Maintain healthy body weight

Safety Profile and 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, be aware of: 1

• Rare but serious: Osteonecrosis of the jaw (0.01% to 0.3% incidence) and atypical femoral fractures
• Common but mild: Upper GI symptoms, influenza-like symptoms, myalgias, arthralgias, and headaches 3
• Risk of severe adverse effects increases with prolonged use beyond 5 years 3

Second-Line Pharmacologic Option

Denosumab 60 mg subcutaneously every 6 months is the recommended alternative for patients with contraindications to or intolerance of bisphosphonates. 1, 5

Critical Denosumab Warning

Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients. 2, 3

Very High-Risk Patients (Anabolic Agents)

For postmenopausal women at very high risk of fracture (history of osteoporotic fracture or multiple risk factors), consider anabolic agents as initial therapy instead of bisphosphonates: 2, 1

• Teriparatide
• Abaloparatide
• Romosozumab

These agents must be followed by transition to an antiresorptive agent after discontinuation. 1 Teriparatide reduces vertebral fractures by 65% and non-vertebral fractures by 53%. 6

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. 3

Evaluate Secondary Causes

All patients require workup for secondary causes of bone loss: 3

• Vitamin D deficiency
• Hypogonadism
• Glucocorticoid exposure
• Malabsorption disorders
• Hyperparathyroidism
• Hyperthyroidism
• Alcohol abuse

Special Population: Males with Primary Osteoporosis

Bisphosphonates are first-line treatment for males with primary osteoporosis, with denosumab as second-line for those with contraindications or adverse effects from bisphosphonates. 2, 1 Bisphosphonates probably reduce radiographic vertebral fractures at 12-36 months (moderate certainty evidence), though no RCTs have evaluated hip fractures in males. 2

Cost Considerations

Prescribe generic bisphosphonates whenever possible rather than expensive brand-name medications or newer agents, as they are significantly more cost-effective while maintaining equivalent efficacy. 1