indication

For the treatment of Paget's disease of the bone (osteitis deformans), postmenopausal and glucocorticoid-induced osteoporosis

pharmacology

Risedronate is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism and is indicated for the treatment and prevention of osteoporosis in postmenopausal women.

mechanism of action

The action of risedronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Risedronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

toxicity

Side effects include abdominal pain, anxiety, back pain, belching, bladder irritation, bone disorders and pain, bronchitis, bursitis, cataracts, chest pain, colitis, constipation, depression, diarrhea, difficulty breathing, dizziness, dry eyes, eye infection, flu-like symptoms, gas, headache, high blood pressure, infection, insomnia, itching, joint disorders and pain, leg cramps, muscle pain, muscle weakness, nausea, neck pain, nerve pain, pain, pneumonia, rash, ringing in ears, sinus problems, sore throat, stomach bleeding, stuffy or runny nose, swelling, tendon problems, tumor, ulcers, urinary tract infection, vertigo, vision problems, and weakness.

biotransformation

No evidence found for metabolization of risedronate in humans or mammals

absorption

Rapid absorption (~1 hr) after an oral dose, occurs throughout the upper gastrointestinal tract

half life

1.5 hours

route of elimination

Risedronate is excreted unchanged primarily via the kidney. Insignificant amounts (<0.1% of intravenous dose) of drug are excreted in the bile in rats.

drug interactions

Calcium: Formation of non-absorbable complexes

Calcium Acetate: Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as risedronate. Avoid administration of oral calcium supplements within or 30 minutes after risedronate.

Calcium Chloride: Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 30 minutes after alendronate/risedronate.

Iron Dextran: Formation of non-absorbable complexes

Magnesium: Formation of non-absorbable complexes