Role of Alendronate and Risedronate in Preventing and Treating Osteoporosis

Alendronate and risedronate have similar mechanisms of action, pharmacokinetics, drug interaction profiles, and administration guidelines. Additionally, evaluation of individual drug studies indicates comparable efficacy between the two agents.

The decision as to which bisphosphonate to prescribe for osteoporosis will be influenced by differences in their adverse event profiles (which are being assessed in ongoing trials) and dosing regimens (once-a-week vs once-a-day).

Range of Treatments

A variety of nonpharmacologic and pharmacologic interventions are available for preventing and treating osteoporosis. Adequate intake of calcium and vitamin D, regular exercise, smoking cessation, and limiting alcohol intake are recommended initially. Drug treatment options include estrogen replacement, raloxifene, calcitonin, calcitriol, and bisphosphonates (currently only alendronate and risedronate).

Indications for Bisphosphonates

Risedronate is approved by the US Food and Drug Administration (FDA) for preventing and treating postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and for treating Paget disease of the bone.

Alendronate is also FDA-approved for treating Paget disease, for preventing and treating postmenopausal osteoporosis, and for treating glucocorticoid-induced osteoporosis -but not for preventing glucocorticoidinduced osteoporosis.

Mechanism of Action

The mechanism of action of bisphosphonates is not fully understood. Experimental and clinical studies show that at the tissue level they inhibit bone resorption and bone turnover without directly suppressing bone formation, resulting in increased bone mass and mineralization.

Some experts suggest that bisphosphonates work by inhibiting osteoclast formation, recruitment, and activity, or by reducing the life span of osteoclasts by inducing apoptosis.

Bisphosphonates may also act intracellularly, by inhibiting enzymes in the cholesterol metabolism pathway, protein-tyrosine phosphatases, or osteoclast vacuolar H+,K+-transporting adenosine triphosphatase. To date, however, we have no evidence of receptormediated bisphosphonate action.(1)

Pharmacokinetics: Low Absorption, No Metabolism, Renal Excretion

The mean oral bioavailability of both alendronate and risedronate is very low and is reduced even further when taken with food, requiring that patients take these drugs at least 30 minutes before the first food, beverage (other than water), or medication of the day.

Upon absorption, the bisphosphonates are distributed into the bone. We have no evidence of systemic metabolism of alendronate or risedronate. About 50% of both drugs is excreted unchanged in the urine within 24 to 72 hours.

Peters ML, Leonard M, Licata AA. Role of Alendronate and Risedronate in Preventing and Treating Osteoporosis. Cleve Clin J Med 2001;68:945-951.