What are the treatment options for osteoporosis?

Treatment Options for Osteoporosis

Oral bisphosphonates (alendronate or risedronate) should be your first-line pharmacologic treatment for osteoporosis due to their proven efficacy in reducing vertebral and hip fractures, favorable safety profile, and low cost. 1, 2

Initial Assessment and Risk Stratification

Before initiating treatment, determine fracture risk using:

• T-score ≤ -2.5 on DEXA scan indicates osteoporosis and warrants treatment 2, 3
• History of fragility fracture (vertebral or hip) is the strongest predictor of future fracture risk and indicates treatment regardless of DEXA results 2, 3, 4
• FRAX calculator for patients with T-scores between -1.0 and -2.5: treat if 10-year risk of major osteoporotic fracture ≥20% or hip fracture risk ≥3% 2
• Age considerations: Screen all women ≥65 years and postmenopausal women <65 years with risk factors 2, 5

Non-Pharmacologic Interventions (Foundation for All Patients)

Every patient should receive these interventions regardless of pharmacologic treatment:

• Calcium intake: 1,000-1,200 mg daily (dietary plus supplementation) 1, 2
• Vitamin D: 600-800 IU daily, targeting serum 25(OH)D levels ≥30 ng/mL 1, 2
• Weight-bearing and resistance exercises: At least 30 minutes daily to reduce fracture risk and improve balance 1, 2, 3
• Fall prevention: Vision/hearing assessment, medication review for drugs affecting balance, home safety evaluation 1, 2
• Lifestyle modifications: Smoking cessation, limit alcohol to ≤2 servings daily 1, 2

Pharmacologic Treatment Algorithm

First-Line: Oral Bisphosphonates

For women ≥40 years with high or very high fracture risk, strongly recommend oral bisphosphonates (alendronate or risedronate) as initial therapy. 1, 2

• Mechanism: Inhibit osteoclast activity, reducing bone resorption without directly affecting bone formation 6
• Efficacy: Reduce vertebral fractures by approximately 50% and hip fractures by 40-50% over 3-5 years 1
• Dosing options: Daily, weekly, or monthly oral formulations; IV options (zoledronic acid) available 1, 2
• Administration requirements: Take on empty stomach with full glass of water, remain upright for 30 minutes 6
• Contraindications: Esophageal abnormalities, inability to remain upright for 30 minutes, hypocalcemia, severe renal impairment 6

Second-Line: Denosumab

Use denosumab for patients with contraindications to or adverse effects from bisphosphonates. 1, 2

• Mechanism: Monoclonal antibody that inhibits RANKL, reducing osteoclast formation and activity 7
• Dosing: 60 mg subcutaneous injection every 6 months 7
• Efficacy: Reduces vertebral and hip fractures comparably to bisphosphonates 1, 3
• Critical warning: After discontinuation, patients must transition to an antiresorptive agent to prevent rapid bone loss and rebound vertebral fractures 1, 2, 7

Anabolic Agents (Very High-Risk Patients)

For patients with very high fracture risk (recent vertebral fractures, hip fracture with T-score ≤-2.5, or multiple fractures), consider anabolic agents as initial therapy. 1, 2, 3

Teriparatide (PTH 1-34)

• Indications: Postmenopausal women, men with primary or hypogonadal osteoporosis, glucocorticoid-induced osteoporosis at high risk for fracture 8
• Mechanism: Stimulates new bone formation, improving bone architecture and density 8, 4
• Dosing: 20 mcg subcutaneous injection daily 8
• Duration: Typically limited to 2 years 8
• Mandatory follow-up: Must transition to antiresorptive therapy after discontinuation to maintain bone gains and prevent rebound fractures 1, 2

When to Choose Anabolic Over Antiresorptive

For adults ≥40 years with very high fracture risk, conditionally recommend PTH/PTHrP (teriparatide, abaloparatide) over antiresorptives. 1

• Teriparatide increased lumbar and hip BMD more than alendronate and decreased vertebral fractures at 36 months 1
• The anabolic effect is blunted if treatment follows prior antiresorptive therapy, so use anabolic agents first in very high-risk patients 1

Alternative Agents

Raloxifene (SERM)

• Best for: Younger postmenopausal women concerned about breast cancer risk 2
• Efficacy: Reduces vertebral fractures but not hip or nonvertebral fractures 1
• Avoid in: Patients with hormone-responsive cancers, history of thromboembolic events 1, 2, 7

Romosozumab

• Indication: Very high-risk patients, particularly those with recent vertebral fractures 3, 9, 5
• Mechanism: Sclerostin inhibitor with dual action (increases bone formation, decreases resorption) 3
• Must follow with: Antiresorptive therapy after completion 9

Treatment Duration and Monitoring

Bisphosphonate Duration

Treat with bisphosphonates for 5 years, then reassess for drug holiday. 1, 2

• Consider stopping after 5 years unless patient has strong indication for continuation (T-score remains ≤-2.5, history of fracture during treatment, very high baseline risk) 1, 2
• Continuing beyond 5 years reduces vertebral fractures but increases risk of atypical femoral fractures and osteonecrosis of the jaw 1
• Drug holiday duration should be individualized based on fracture risk and medication half-life 1

Monitoring During Treatment

Do not routinely monitor BMD during the initial 5 years of treatment. 1, 2

• BMD monitoring during treatment does not predict fracture risk reduction 1
• Exception: Cancer patients with elevated fracture risk should have BMD monitored every 24 months (or every 12 months if risk factors change significantly) 1

Special Populations

Men with Osteoporosis

Treat men with osteoporosis using the same first-line approach as women: oral bisphosphonates. 1, 2

• Bisphosphonates reduce vertebral fractures in men 1
• Denosumab is second-line for men with contraindications to bisphosphonates 2

Glucocorticoid-Induced Osteoporosis

For adults ≥40 years on chronic glucocorticoids (≥2.5 mg/day prednisone for >3 months) with high or very high fracture risk, strongly recommend oral bisphosphonates. 1, 2

• For very high-risk patients on very high-dose glucocorticoids (≥30 mg/day for >30 days), conditionally recommend PTH/PTHrP over antiresorptives 1
• All patients on chronic glucocorticoids should optimize calcium (1,000-1,200 mg daily) and vitamin D (maintain 25(OH)D ≥30-50 ng/mL) 1

Cancer Patients

For cancer patients with osteoporosis or high fracture risk, recommend bone-modifying agents (oral bisphosphonates, IV bisphosphonates, or denosumab). 1, 2

• Avoid hormonal therapies in patients with hormone-responsive cancers 1, 2
• Monitor BMD every 24 months in cancer patients with elevated fracture risk 1

Common Pitfalls and How to Avoid Them

Critical Safety Concerns

Long-term bisphosphonate use (>5 years) increases risk of rare but serious adverse events:

• Atypical femoral fractures: Subtrochanteric or diaphyseal fractures with prodromal thigh pain 1, 7
• Osteonecrosis of the jaw: Risk increases with dental procedures; examine mouth before starting treatment and maintain good oral hygiene 1, 7
• Action: Reassess need for continuation after 5 years 1, 2

Denosumab Discontinuation

Never stop denosumab without transitioning to another antiresorptive agent. 1, 2, 7

• Discontinuation causes rapid bone loss and increased risk of multiple vertebral fractures (rebound effect) 1, 7
• Transition to bisphosphonate therapy before stopping denosumab 2

Anabolic Agent Sequencing

Always follow anabolic therapy with antiresorptive therapy. 1, 2

• Bone gains from teriparatide or abaloparatide are lost without subsequent antiresorptive treatment 1, 2
• Starting anabolic agents after bisphosphonates blunts the anabolic response 1
• Optimal sequence: Anabolic first (if very high risk), then transition to antiresorptive 1

Medication Adherence

Prescribe generic medications when possible to improve adherence and reduce costs. 1, 2

• Poor adherence (30-50% of patients don't take medications correctly) is a major barrier to fracture prevention 10
• Offer multiple dosing options (daily, weekly, monthly, IV) to match patient preferences 2