What is the first‑line bisphosphonate regimen for an adult with osteoporosis (postmenopausal woman, man >50, or on chronic glucocorticoids) and confirmed low bone density or a prior fragility fracture, including dosing, contraindications, monitoring, and second‑line alternatives?

First-Line Bisphosphonate Regimen for Osteoporosis

Oral bisphosphonates—specifically alendronate 70 mg once weekly or risedronate 35 mg once weekly—are the first-line pharmacologic treatment for adults with osteoporosis, including postmenopausal women, men over 50, and patients on chronic glucocorticoids. 1, 2

Specific Dosing Regimens

Postmenopausal Women and Men >50 Years

• Alendronate 70 mg once weekly (preferred) or 10 mg daily 1, 2
• Risedronate 35 mg once weekly or 5 mg daily 1
• Alternative oral options: Risedronate 75 mg on two consecutive days per month or 150 mg once monthly 1

Glucocorticoid-Induced Osteoporosis

• Alendronate 5 mg daily for premenopausal women and men 1
• Alendronate 10 mg daily for postmenopausal women not on estrogen 1, 2
• Same weekly dosing options (70 mg alendronate or 35 mg risedronate) are acceptable alternatives 1

Critical Pre-Treatment Requirements

Vitamin D Repletion (Mandatory Before Starting)

• Check baseline 25(OH)D level before prescribing any bisphosphonate 3
• Target serum 25(OH)D ≥32 ng/mL before initiating therapy 3
• For levels >15 ng/mL: Vitamin D3 2,000 IU daily for 12 weeks 3
• For levels <15 ng/mL: Vitamin D2 50,000 IU weekly for 8-12 weeks 3
• Failure to correct vitamin D deficiency increases risk of bisphosphonate-related hypocalcemia, particularly with IV formulations 3

Baseline Laboratory Assessment

• Measure serum creatinine to calculate creatinine clearance 3
• Ensure adequate calcium status 1, 2

Administration Instructions (Critical for Efficacy and Safety)

Oral Bisphosphonate Administration

• Take upon arising for the day, at least 30 minutes before first food, beverage, or medication 2
• Swallow with full glass (6-8 ounces) of plain water only—no other beverages, including mineral water 2
• Remain upright (standing or sitting) for at least 30 minutes after taking medication and until after first food 2
• Never take at bedtime or before arising—this increases esophageal adverse event risk 2

Concurrent Supplementation (Mandatory)

• Calcium 1,000-1,200 mg daily 1, 3
• Vitamin D 600-800 IU daily for maintenance after repletion 1, 3
• Higher vitamin D doses needed for patients with malabsorption, chronic kidney disease, or on glucocorticoids 3

Absolute Contraindications

• Creatinine clearance <30-35 mL/min (contraindication to all bisphosphonates) 1, 3
• Esophageal abnormalities that delay esophageal emptying (stricture, achalasia) 1, 3, 2
• Inability to stand or sit upright for at least 30 minutes 1, 2
• Hypocalcemia (must be corrected before starting) 1, 2
• Hypersensitivity to bisphosphonates 1, 2

Second-Line Alternatives When Bisphosphonates Are Contraindicated

For Postmenopausal Women

1. Denosumab 60 mg subcutaneously every 6 months (second-line, moderate-certainty evidence) 1
2. IV bisphosphonates (zoledronic acid 5 mg IV annually or ibandronate 3 mg IV every 3 months) if only oral formulation is contraindicated 1
3. Romosozumab or teriparatide followed by bisphosphonate—reserved for very high fracture risk only 1

For Men

1. Denosumab (second-line, low-certainty evidence) 1
2. IV bisphosphonates if oral contraindicated 1

For Glucocorticoid-Induced Osteoporosis (When Oral Bisphosphonates Inappropriate)

Preference order: 1

1. IV bisphosphonates
2. Teriparatide
3. Denosumab
4. Raloxifene (postmenopausal women only, if no other options available)

Monitoring Strategy

• Bone mineral density (BMD) testing every 2-3 years depending on risk factors 1
• Earlier reassessment for patients on very high-dose glucocorticoids (≥30 mg/day prednisone) or with history of osteoporotic fractures 1
• Periodic serum 25(OH)D monitoring for patients with malabsorption or at high risk of deficiency 3, 2

Rare but Serious Adverse Events

• Osteonecrosis of the jaw (ONJ): Incidence 0.01-0.3% overall, risk increases with longer treatment duration and invasive dental procedures 1, 3
• Atypical femoral fractures: Risk increases with treatment duration beyond 5 years 1, 3
• Esophagitis and upper GI adverse events: Minimized by proper administration technique 1, 2

These risks are low and should not prevent appropriate treatment in patients who need fracture prevention 1, 4

Duration of Therapy Considerations

• Consider drug holiday after 3-5 years in patients at low fracture risk 4
• Continue therapy in patients with ongoing high fracture risk (prior fracture, very low BMD, high-dose glucocorticoids) 1

Special Populations

Women of Childbearing Potential

• Require careful counseling about long-term skeletal retention of bisphosphonates 3
• Must use effective contraception during treatment 1
• Consider alternative agents (teriparatide) if pregnancy planned within treatment period 1

Patients Requiring Dental Work

• Inform dentist of bisphosphonate use due to ONJ risk 3
• Complete necessary invasive dental procedures before starting therapy when possible 3