Fosamax Renal Protection or Renal Risk: What Clinicians Need to Know

Does alendronate protect the kidneys?

The label describes no kidney-related benefit. Its indications are treatment and prevention of osteoporosis in postmenopausal women, increasing bone mass in men with osteoporosis, glucocorticoid-induced osteoporosis, and Paget's disease of bone [1]. The renal instruction attached to the drug is a restriction on use, not a therapeutic claim [1].

The fracture trial described below reported fracture and adverse-experience outcomes [2]. The benefit that is documented is on fractures, and the kidney statement on the label is the creatinine clearance cutoff.

What the Fosamax label says about kidney function

The label states that Fosamax is not recommended for patients with creatinine clearance less than 35 mL/min, and that no dosage adjustment is necessary in patients with creatinine clearance between 35 and 60 mL/min [1]. Two details matter.

First, this is not listed as a formal contraindication. The label's Contraindications section lists abnormalities of the esophagus that delay emptying such as stricture or achalasia, inability to stand or sit upright for at least 30 minutes, hypocalcemia, hypersensitivity to any component, and, for the oral solution, increased risk of aspiration [1].

Second, the measure named is creatinine clearance, not estimated glomerular filtration rate [1]. They are related but not the same number.

How alendronate is handled by the body

Oral bioavailability is about 0.64% in women and 0.59% in men after an overnight fast, when the dose is taken 2 hours before a standardized breakfast [1]. Alendronate is not metabolized [1]. About 50% of an intravenous dose appears in urine within 72 hours [1]. The estimated terminal half-life in humans exceeds 10 years, reflecting slow release from the skeleton [1]. Bone turnover markers return toward baseline within months of stopping [1].

Adverse reactions in the label's trial tables

In the two 3-year US and multinational studies, drug-related abdominal pain occurred in 6.6% of patients on 10 mg daily versus 4.8% on placebo, musculoskeletal pain in 4.1% versus 2.5%, and esophageal ulcer in 1.5% versus 0% [1].

Oral and intravenous bisphosphonates are not the same exposure

A case series describes kidney injury after intravenous zoledronate, a different drug and route from oral alendronate [3]. In it, six patients (four men, two women, mean age 69.2 years) received zoledronate 4 mg intravenously each month for a mean of 4.7 months; five had multiple myeloma and one had Paget's disease [3]. All six developed renal failure, with mean serum creatinine rising from 1.4 mg/dL to 3.4 mg/dL. Biopsy showed toxic acute tubular necrosis. After the drug was stopped, kidney function improved to a mean final creatinine of 2.3 mg/dL over 1 to 4 months [3].

That is intravenous zoledronate, not a study of oral alendronate, and its numbers should not be applied to the alendronate label's 35 mL/min threshold.

What the fracture trial measured

The Fracture Intervention Trial enrolled 2,027 postmenopausal women aged 55 to 81 with low femoral-neck bone mineral density and at least one vertebral fracture, randomizing 1,022 to alendronate and 1,005 to placebo for 36 months, with the dose starting at 5 mg daily and increasing to 10 mg daily at 24 months [2]. New morphometric vertebral fractures occurred in 78 women (8.0%) on alendronate and 145 (15.0%) on placebo, a relative risk of 0.53 [2]. Clinically apparent vertebral fractures were 2.3% versus 5.0% (relative hazard 0.45), any clinical fracture 13.6% versus 18.2% (relative hazard 0.72), and the relative hazards for hip and wrist fracture were 0.49 and 0.52 [2]. The trial also reported no significant difference between the groups in adverse experiences, including upper gastrointestinal disorders [2].