What are the treatment options for osteoporosis?

Treatment for Osteoporosis

Oral bisphosphonates (alendronate or risedronate) are the first-line pharmacologic treatment for osteoporosis due to their proven efficacy in reducing fractures, favorable safety profile, and lower cost compared to other medications. 1, 2

Initial Assessment and Risk Stratification

Before initiating treatment, determine fracture risk based on:

• History of fragility fractures (especially vertebral or hip fractures) - this is the strongest predictor of future fracture risk and warrants treatment regardless of bone density 2, 3
• Bone mineral density (BMD) - treatment is indicated for T-score ≤ -2.5 at the spine, hip, or femoral neck 2, 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

Very high-risk patients (prior vertebral/hip fracture, T-score ≤ -2.5, or multiple fractures) should be considered for anabolic agents as initial therapy rather than bisphosphonates 5

Foundational Non-Pharmacologic Interventions

All patients require these measures regardless of medication choice:

• Calcium supplementation: 1,000 mg/day for ages 19-50; 1,200 mg/day for ages 51+ 2, 5
• Vitamin D supplementation: 600 IU/day for ages 19-70; 800 IU/day for ages 71+ 2, 5
• Target serum vitamin D level: ≥20 ng/mL (50 nmol/L) 2
• Weight-bearing and resistance training exercises to reduce fracture risk 2, 5
• Smoking cessation and limiting alcohol to 1-2 drinks/day 1, 2
• Fall prevention strategies: vision/hearing assessment, medication review, home safety evaluation 2

First-Line Pharmacologic Treatment

Oral bisphosphonates are the preferred initial therapy for the vast majority of patients:

• Alendronate (weekly or daily dosing) or risedronate (weekly, daily, or monthly dosing) 1, 2
• These agents inhibit osteoclast activity, reduce bone resorption, and have proven efficacy in reducing vertebral and nonvertebral fractures 6, 7
• Contraindications to oral bisphosphonates: esophageal abnormalities, inability to remain upright for 30 minutes after dosing, hypocalcemia, severe renal impairment (CrCl <35 mL/min) 2, 5, 6
• Administration requirements: Take on empty stomach with full glass of water, remain upright for at least 30 minutes, wait 30 minutes before eating or taking other medications 6

Second-Line Treatment Options

When oral bisphosphonates are contraindicated, not tolerated, or ineffective:

• IV bisphosphonates (zoledronic acid) - preferred when oral formulations cannot be used due to GI issues or concerns about adherence 1, 2
• Denosumab (subcutaneous injection every 6 months) - RANKL inhibitor that reduces bone resorption 1, 2, 8
  • Critical warning: After stopping denosumab, patients must transition to an antiresorptive agent (bisphosphonate) to prevent rapid bone loss and rebound vertebral fractures 1, 2, 8
• Raloxifene (selective estrogen receptor modulator) - option for younger postmenopausal women, but generally avoided in patients with hormone-responsive cancers 2, 5

Anabolic Agents for High-Risk Patients

Teriparatide (daily subcutaneous injection) or other anabolic agents should be considered for:

• Patients with severe osteoporosis (T-score ≤ -3.0) 9
• Those who have sustained fractures despite bisphosphonate therapy 9, 7
• Very high-risk patients as initial therapy 5

Critical requirement: After completing anabolic therapy, patients must transition to an antiresorptive agent (bisphosphonate or denosumab) to maintain bone gains and prevent rebound fractures 1, 2, 5

Contraindications to teriparatide: Open epiphyses, Paget's disease, prior skeletal radiation, bone metastases, hereditary disorders predisposing to osteosarcoma 5, 9

Treatment Duration and Monitoring

• Bisphosphonate duration: Reassess after 5 years of therapy 1, 2
• Consider drug holiday after 5 years for patients at lower fracture risk, but continue treatment for those at high risk (prior fracture, T-score still ≤ -2.5) 1, 2
• Monitor BMD every 1-2 years while on treatment 5
• Long-term bisphosphonate risks (>5 years): Atypical femoral fractures and osteonecrosis of the jaw - though rare, these risks increase with prolonged use 2, 8

Special Populations

Glucocorticoid-induced osteoporosis (≥7.5 mg/day prednisone equivalent for ≥6 months):

• Oral bisphosphonates are first-line for adults ≥40 years at moderate-to-high fracture risk 1, 5
• For adults <40 years: treat with oral bisphosphonates if history of osteoporotic fracture, Z-score <-2.3, or bone loss ≥10%/year 1

Men with osteoporosis:

• Treatment recommendations mirror those for postmenopausal women 2, 5
• Bisphosphonates are first-line for T-score ≤ -2.5 or history of fragility fracture 2

Women of childbearing potential:

• If not planning pregnancy and using effective contraception: oral bisphosphonates preferred 1
• Avoid denosumab due to potential fetal harm 1, 8

Critical Safety Considerations

Before starting bisphosphonates:

• Dental examination recommended - address any needed dental work before initiating therapy 2, 8
• Correct hypocalcemia before starting treatment 5, 6, 8
• Assess renal function 5, 6

Denosumab-specific warnings:

• Serious infections (skin, abdomen, urinary tract, endocarditis) may occur more frequently 8
• Severe hypocalcemia risk, especially in patients with renal impairment 8
• Osteonecrosis of the jaw and atypical femoral fractures can occur 8
• Never abruptly discontinue without transitioning to another antiresorptive agent 1, 8

Cost Considerations

Prescribe generic medications when possible to improve affordability and adherence - generic alendronate and risedronate are significantly less expensive than brand-name or newer agents 1, 2