What are the treatment options for osteoporosis?

Osteoporosis Treatment

Bisphosphonates (oral alendronate, risedronate, or IV zoledronic acid) are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with strong evidence for reducing hip, vertebral, and nonvertebral fractures. 1

Treatment Algorithm by Risk Stratification

Standard-Risk Osteoporosis (First-Line)

• Prescribe oral bisphosphonates as initial therapy: alendronate 70 mg once weekly or risedronate 35 mg once weekly, or IV zoledronic acid 5 mg annually 1, 2
• Use generic formulations whenever possible due to significantly lower cost with equivalent efficacy 1, 2
• Treatment duration: Give for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday 1, 2
• Mechanism: Bisphosphonates bind to bone hydroxyapatite and inhibit osteoclast activity, reducing bone resorption without directly affecting bone formation 3

Very High-Risk Patients (Anabolic Agents First)

Start with anabolic agents (teriparatide or romosozumab) BEFORE bisphosphonates, followed by mandatory transition to bisphosphonates or denosumab 1, 4

Very high-risk criteria include: 1, 4

• 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: 1, 2, 5

• Teriparatide 20 mcg subcutaneously daily for up to 24 months: reduces vertebral fractures by 69 per 1000 patients and clinical fractures by 27 per 1000 patients
• Romosozumab: conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect

Critical sequential therapy requirement: After completing anabolic therapy, patients MUST transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss 1, 2

Second-Line Treatment (Bisphosphonate Intolerance)

Denosumab 60 mg subcutaneously every 6 months is reserved for patients with contraindications to bisphosphonates or who experience adverse effects 1, 2

CRITICAL WARNING about denosumab discontinuation: 1, 2, 6

• Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures
• Patients MUST transition to bisphosphonate therapy after stopping denosumab—never simply discontinue
• Do not stop, skip, or delay denosumab without first talking with your doctor, as your risk for breaking bones (especially spine) increases significantly

Essential Adjunctive Measures for ALL Patients

Every patient requires the following regardless of pharmacologic choice: 1, 4

• 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

Agents NOT Recommended

Strongly recommend AGAINST using estrogen therapy, estrogen plus progestogen, or raloxifene for osteoporosis treatment due to unfavorable risk-benefit profiles including cardiovascular events, thromboembolic complications, and stroke 2

Monitoring Strategy

• Do NOT perform bone density monitoring during the 5-year pharmacologic treatment period 1
• Reassess fracture risk at 5 years to determine continuation versus drug holiday 1

Common Pitfalls to Avoid

Bisphosphonate administration errors: 3

• Must be taken in the fasting state with water at least 30 minutes before consuming food or beverages
• Patient must remain upright for at least 30 minutes after taking to reduce risk of esophageal adverse events
• Upper GI adverse events (abdominal pain, nausea, dyspepsia) are the most common side effects, though generally transient

Denosumab discontinuation without transition therapy: 1, 2, 6

• This is the single most dangerous error—causes rebound vertebral fractures
• Always transition to bisphosphonate before stopping denosumab

Dental considerations: 6

• Severe jaw bone problems (osteonecrosis) may occur with denosumab
• Examine mouth before starting treatment and maintain good oral hygiene
• Inform dentist before dental procedures

Stopping anabolic agents without sequential therapy: 1, 2

• Bone gains from teriparatide or romosozumab are rapidly lost without subsequent antiresorptive therapy
• Always follow with bisphosphonate or denosumab