Does Fosamax (alendronate) rebuild bone?

Does Fosamax Rebuild Bone?

Fosamax (alendronate) does not rebuild bone in the traditional sense—it prevents bone breakdown by inhibiting osteoclasts, which indirectly allows bone formation to exceed resorption, resulting in progressive gains in bone mass. 1

Mechanism of Action

• Alendronate specifically inhibits osteoclast activity (the cells that break down bone) without directly stimulating bone formation 1
• At active bone remodeling sites, alendronate reduces bone turnover, and because bone formation exceeds bone resorption at these sites, this leads to progressive gains in bone mass 1
• Normal bone is formed on top of areas where alendronate has been incorporated into the bone matrix, demonstrating that the drug allows physiologic bone formation to occur while suppressing excessive resorption 1

Clinical Evidence of Bone Mass Improvement

• In postmenopausal women with osteoporosis, alendronate 10 mg daily produces significant increases in bone mineral density (BMD): 8.8% in the spine, 5.9% in the femoral neck, 7.8% in the trochanter, and 2.5% in total body over 3 years 2
• In men with osteoporosis, alendronate increases BMD at all skeletal sites by 2.3% to 5.1% over 12 months 3
• A 2023 meta-analysis demonstrated that alendronate monotherapy improved BMD at the lumbar spine by 5.2%, total hip by 2.34%, and femoral neck by 2.53% in men 4
• These BMD improvements exceed the surrogate threshold effect for fracture reduction (1.83% for any fracture, 1.42% for vertebral fracture) 4

Critical Distinction: Prevention vs. Rebuilding

• Alendronate reduces bone resorption with no direct effect on bone formation, though bone formation is ultimately reduced because resorption and formation are coupled during bone turnover 1
• The drug must be continuously administered to suppress osteoclasts on newly formed resorption surfaces, as it is not pharmacologically active once incorporated into bone matrix 1
• The net effect is a shift in the balance toward bone formation, resulting in progressive gains in bone mass rather than true "rebuilding" of bone architecture 1

Fracture Risk Reduction (The Most Important Outcome)

• Alendronate reduces vertebral fractures by 48% and decreases progression of vertebral deformities by 33% over 3 years 2
• In men treated with zoledronate (another bisphosphonate), vertebral fracture risk was reduced by 67% (relative risk 0.33) after 12 months of treatment 4
• These fracture reductions represent the clinically meaningful outcome that matters for morbidity and mortality, not just BMD changes 4, 2

Recommended Dosing

• For treatment of established osteoporosis: 70 mg once weekly (therapeutically equivalent to 10 mg daily with better convenience and adherence) 5
• For prevention of osteoporosis: 35 mg once weekly 5
• Treatment duration should typically be 5 years 6

Important Safety Considerations

• Alendronate must be taken correctly to avoid esophageal complications: patients must remain upright for at least 30 minutes after taking the drug 3
• Contraindications include esophageal abnormalities, inability to remain upright for 30 minutes, hypocalcemia, and GFR < 35 mL/min/1.73 m² 5, 6
• Vitamin D deficiency must be corrected before starting therapy 3
• Rare but serious adverse events include atypical subtrochanteric fractures and osteonecrosis of the jaw 6
• A dental examination is recommended before starting treatment to reduce the risk of osteonecrosis of the jaw 3