What alternative medication can an elderly patient with osteoporosis and a history of gastrointestinal (GI) upset and pain while taking Fosamax (alendronate) be prescribed?

Alternative Osteoporosis Medications for Patients Intolerant to Alendronate

First-Line Alternatives

For elderly patients who cannot tolerate oral alendronate due to GI upset, switch to either intravenous zoledronic acid or oral risedronate as first-line alternatives, with intravenous options being particularly valuable for those with oral bisphosphonate intolerance. 1

Intravenous Zoledronic Acid (Preferred for GI Intolerance)

• Zoledronic acid 5 mg IV once yearly eliminates daily GI exposure and is equally effective at reducing hip, vertebral, and nonvertebral fractures 1
• The American College of Physicians strongly recommends zoledronic acid alongside alendronate, risedronate, and denosumab for reducing hip and vertebral fractures in women with known osteoporosis 1
• IV administration bypasses the upper GI tract entirely, making it ideal for patients with esophageal disorders, GERD, or previous bisphosphonate-related GI symptoms 2
• Intravenous pamidronate 60 mg every 3 months produces comparable BMD increases (4.0% spine, 2.9% hip) to oral alendronate and serves as a proven alternative for GI-intolerant patients 2

Key adverse effects of zoledronic acid include: influenza-like symptoms (common after first infusion), arthritis and arthralgias, headaches, hypocalcemia, and uveitis 1

Oral Risedronate (Alternative Oral Bisphosphonate)

• Risedronate 35 mg once weekly or 5 mg daily reduces hip, vertebral, and nonvertebral fractures with a similar efficacy profile to alendronate 1
• The American College of Physicians includes risedronate in its strong recommendation for first-line osteoporosis treatment 1
• GI tolerability: Risedronate causes upper GI irritation but may be better tolerated than alendronate in some patients 1, 3
• Risedronate is not recommended if creatinine clearance is <30 mL/min 3

Subcutaneous Denosumab (Non-Bisphosphonate Option)

• Denosumab 60 mg subcutaneously every 6 months reduces hip, vertebral, and nonvertebral fractures without GI exposure 1
• The American College of Physicians strongly recommends denosumab as a first-line agent for osteoporosis treatment 1
• Adverse effects include mild upper GI symptoms (despite subcutaneous route), rash/eczema, and increased infection risk 1
• Critical warning: Abrupt discontinuation causes rebound vertebral fractures at 6-7 months; requires sequential alendronate therapy if stopping 4

Second-Line Alternatives (Less Preferred)

Oral Ibandronate

• Ibandronate 150 mg once monthly reduces vertebral fractures but does NOT reduce hip or nonvertebral fractures 1, 5
• The American College of Physicians notes ibandronate's limited efficacy compared to other bisphosphonates 1
• Adverse effects include myalgias, cramps, limb pain, and grade 3-4 GI pain in 2.2% of patients 1
• Ibandronate had the highest treatment discontinuation rate (17.2%) due to toxicity in head-to-head trials 1
• Consider only when first-line agents are contraindicated or unavailable 6, 5

Teriparatide (Anabolic Agent)

• Teriparatide 20 mcg subcutaneously daily reduces vertebral and nonvertebral fractures but is reserved for very high-risk patients 1, 7
• Contraindicated in patients at increased risk of bone metastases or hypercalcemia due to osteosarcoma development in animal models 1, 7
• Adverse effects include upper GI symptoms, headaches, hypercalcemia, hypercalciuria, dizziness, and leg cramps 1, 7
• Reserved for patients with prior fracture, very high fracture risk, or those who have failed bisphosphonates 6

Agents NOT Recommended

Raloxifene (Selective Estrogen Receptor Modulator)

• The American College of Physicians strongly recommends AGAINST raloxifene for osteoporosis treatment 1
• Raloxifene reduces only vertebral fractures, not hip or nonvertebral fractures 1
• Serious adverse effects include cardiovascular events, thromboembolic events, pulmonary embolism, cerebrovascular death, and hot flashes 1

Estrogen Therapy

• The American College of Physicians strongly recommends AGAINST menopausal estrogen therapy (with or without progestin) for osteoporosis treatment 1
• Life-threatening risks include coronary heart disease, stroke, pulmonary embolism, and breast cancer 1

Essential Concurrent Therapy (All Patients)

All patients starting any osteoporosis medication must receive:

• Calcium 1,000-1,200 mg daily 6, 4
• Vitamin D 600-800 IU daily (some guidelines recommend 800-1,000 IU), with target serum 25(OH)D level ≥30 ng/mL 6, 4
• Check and correct vitamin D deficiency before starting bisphosphonates to prevent hypocalcemia 4

Pre-Treatment Requirements

Before initiating alternative therapy:

• Verify creatinine clearance ≥30 mL/min for oral bisphosphonates; IV bisphosphonates generally not recommended if CrCl <30 mL/min 6, 3
• Perform dental examination and complete necessary invasive dental procedures before starting therapy to reduce osteonecrosis of the jaw risk 6
• Ensure adequate calcium and vitamin D status 6, 4

Treatment Duration and Monitoring

• Treat for 5 years initially, then reassess fracture risk to determine need for continued therapy 1, 6
• Monitor BMD every 1-2 years during and after treatment 6
• The American College of Physicians recommends against BMD monitoring during the initial 5-year treatment period 1

Common Pitfalls to Avoid

• Do not switch to another oral bisphosphonate if the patient has true esophageal disease or cannot comply with upright positioning requirements—choose IV or subcutaneous options instead 6, 2
• Do not discontinue denosumab without planning sequential bisphosphonate therapy due to rebound fracture risk 4
• Do not forget calcium and vitamin D supplementation—these are mandatory, not optional 6, 4
• Do not use teriparatide as first-line therapy; reserve for very high-risk patients 1, 6