What are the first line treatments for osteoporosis?

First-Line Treatment for Osteoporosis

Bisphosphonates are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with oral alendronate or risedronate preferred due to high-certainty evidence for fracture reduction and significantly lower cost with generic formulations. 1, 2, 3

Treatment Algorithm by Risk Stratification

Standard Risk Osteoporosis (Most Patients)

Start with oral bisphosphonates as initial therapy:

• Alendronate or risedronate are the preferred agents, available as once-weekly formulations (alendronate 70 mg or risedronate 35 mg) for improved convenience and adherence 1, 2, 3
• Zoledronic acid (intravenous, once yearly) is an alternative for patients who cannot tolerate oral formulations 2, 3
• This is a strong recommendation with high-certainty evidence for postmenopausal women, reducing hip fractures by 6 per 1000 patients, clinical vertebral fractures by 18 per 1000, and radiographic vertebral fractures by 56 per 1000 1
• For men, this is a conditional recommendation with low-certainty evidence, primarily extrapolated from studies in women 1, 2
• Generic formulations should be prescribed whenever possible due to equivalent efficacy at significantly lower cost 2, 3

Note: Ibandronate should be avoided as there is no evidence it reduces hip fractures 1

Very High-Risk Osteoporosis (Anabolic Agents First)

Initiate anabolic agents BEFORE bisphosphonates if patient meets very high-risk criteria:

Very high-risk is defined as patients with: 4, 3

• Age >74 years
• Recent fracture within 12 months
• Multiple prior osteoporotic fractures
• T-score ≤-3.0
• Fractures despite ongoing bisphosphonate therapy
• High FRAX scores (≥20% for major osteoporotic fracture or ≥3% for hip fracture)

Anabolic agent options: 4, 3

• Teriparatide reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients
• Romosozumab is conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect

Critical caveat: After completing anabolic therapy, patients MUST transition to bisphosphonates or denosumab to maintain bone gains—this is mandatory, not optional 4, 3

Second-Line Treatment

Denosumab 60 mg subcutaneously every 6 months is reserved for: 1, 2, 3

• Patients with contraindications to bisphosphonates
• Patients who experience adverse effects from bisphosphonates
• This is a conditional recommendation with moderate-certainty evidence for postmenopausal women and low-certainty evidence for men

Major warning about denosumab: Discontinuation causes rebound bone loss and multiple vertebral fractures—patients must transition to bisphosphonate therapy after stopping denosumab 3, 5

Essential Adjunctive Measures for ALL Patients

Every patient requires the following regardless of pharmacologic choice: 2, 3

• Calcium: 1000-1200 mg daily
• Vitamin D: 800-1000 IU daily (target serum level ≥20 ng/mL)
• Weight-bearing and muscle resistance exercises
• Balance exercises and fall prevention counseling
• Smoking cessation
• Alcohol reduction

Treatment Duration and Monitoring

• Initial treatment duration: 5 years with bisphosphonates 2, 3
• Reassess fracture risk at 5 years to determine whether to continue therapy or take a drug holiday 2, 3
• Do not perform bone density monitoring during the 5-year treatment period 3

Important Safety Considerations

Bisphosphonate-associated risks (uncommon but serious): 1

• Osteonecrosis of the jaw (0.01% to 0.3% incidence)
• Atypical femoral or subtrochanteric fractures
• These risks emerge after 2-3 years of treatment but observed events remain uncommon
• Esophageal irritation with oral formulations 2

Administration requirements for oral bisphosphonates: 2

• Must be taken in the fasting state with water
• At least 30 minutes before consuming food or beverages
• Patient must remain upright for 30 minutes after administration

Denosumab-specific warnings: 3, 5

• Severe hypocalcemia risk, especially in patients with advanced chronic kidney disease
• Mandatory transition to bisphosphonates upon discontinuation to prevent rebound vertebral fractures

Common Pitfalls to Avoid

• Do not use ibandronate as it lacks evidence for hip fracture reduction 1
• Do not stop denosumab without transitioning to bisphosphonates—this causes dangerous rebound bone loss 3
• Do not continue anabolic agents indefinitely—they must be followed by antiresorptive therapy 4, 3
• Do not skip calcium and vitamin D supplementation—these are essential adjuncts, not optional 2, 3