Does Fosamax (Alendronate) Affect Bone Quality?
Fosamax (alendronate) improves bone quality by increasing bone mineral density, normalizing bone architecture, and producing structurally normal bone without impairing mineralization. The evidence consistently demonstrates that alendronate enhances bone quality rather than compromising it, as confirmed by both histomorphometric analysis and clinical outcomes.
Bone Quality Improvements with Alendronate
Alendronate produces normal lamellar bone even where preexisting bone was abnormal. In patients with Paget's disease treated with alendronate 40 mg/day for 6 months, normal lamellar bone was produced during treatment, even where preexisting bone was woven and disorganized 1. This demonstrates that alendronate not only prevents further deterioration but actively supports the formation of structurally sound bone.
Histological Evidence of Normal Bone Formation
Bone histology remains normal during alendronate treatment. In 49 patients biopsied after one year of treatment with alendronate at doses up to 10 mg/day, bone histology was completely normal 1.
Alendronate does not impair bone mineralization. Histomorphometric analyses in patients treated for osteoporosis confirmed that alendronate did not impair mineralization, and the expected decrease in the rate of bone turnover was observed 1.
Normal bone is formed on top of alendronate-incorporated matrix. Studies in rats and mice showed that normal bone was formed on top of the alendronate that was incorporated inside the bone matrix 1.
Mechanism Supporting Bone Quality
Alendronate specifically inhibits osteoclast activity without interfering with normal bone formation processes. The drug binds to bone hydroxyapatite and reduces bone resorption with no direct negative effect on bone formation 1.
Osteoclasts lose their resorptive capacity but maintain normal attachment. At the cellular level, osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption, effectively shutting down excessive bone breakdown 1.
Bone formation exceeds bone resorption at remodeling sites. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover, and bone formation exceeds bone resorption at remodeling sites, leading to progressive gains in bone mass 1.
Clinical Evidence of Improved Bone Quality
Alendronate increases bone mineral density at all skeletal sites by 2.3% to 5.1% over 12 months. In a randomized controlled trial of 112 men with prostate cancer, alendronate increased bone mineral density of the hip and spine by 2.3% and 5.1%, respectively, after 12 months 2.
Sustained BMD increases occur across multiple skeletal sites. Women receiving alendronate experienced progressive increases in BMD at all skeletal sites including the spine, femoral neck, trochanter, and total body, with one study showing a 2.5% increase in total body BMD 2.
Alendronate is more effective than other bisphosphonates for increasing bone mass. In patients with primary biliary cirrhosis, alendronate increased lumbar spine BMD by 4.8% compared to 0.587% with cyclical etidronate, demonstrating superior efficacy 2.
Fracture Risk Reduction as Quality Indicator
Alendronate reduces vertebral fractures by 45-48% and hip fractures by 40-53%, confirming improved bone structural integrity. The reduction in fracture risk directly reflects improved bone quality, as stronger, better-organized bone is more resistant to fracture 3, 4.
Vertebral fracture risk decreases by 45% in both primary and secondary prevention. Meta-analysis showed a 45% relative risk reduction for vertebral fractures (RR = 0.55; 95% CI, 0.45 to 0.67) 4.
Hip fracture risk decreases by 53% in secondary prevention. For patients with existing osteoporosis, alendronate reduced hip fractures with a 53% relative risk reduction (RR = 0.47; 95% CI, 0.26 to 0.85) 4.
Important Caveats
Alendronate must be taken correctly to avoid esophageal complications. The drug must be taken in the fasting state with water at least 30 minutes before consuming food or beverages, and patients must remain upright for at least 30 minutes 5, 6.
Absolute contraindications include esophageal abnormalities and inability to remain upright. Patients with esophageal abnormalities, inability to stand or sit upright for at least 30 minutes, hypocalcemia, or hypersensitivity should not receive alendronate 5.
Vitamin D deficiency must be corrected before starting therapy. Correcting vitamin D deficiency before initiating bisphosphonate therapy is essential to avoid hypocalcemia 5.
Dental examination is recommended before starting treatment. This reduces the risk of osteonecrosis of the jaw, a rare but serious complication 5.