Introduction
Risedronate is a bisphosphonate medication primarily used for the prevention and treatment of osteoporosis in postmenopausal women and glucocorticoid-induced osteoporosis. It belongs to the nitrogen-containing bisphosphonate class and works by inhibiting bone resorption, thereby increasing bone mineral density and reducing fracture risk.
Mechanism of Action
Risedronate exerts its pharmacological effects by binding to hydroxyapatite crystals in bone tissue. As a nitrogen-containing bisphosphonate, it inhibits farnesyl pyrophosphate synthase in the mevalonate pathway, disrupting the formation of isoprenoid lipids essential for osteoclast function. This inhibition leads to reduced osteoclast-mediated bone resorption, decreased bone turnover, and ultimately increased bone mineral density.
Indications
- Treatment of osteoporosis in postmenopausal women
- Prevention of osteoporosis in postmenopausal women
- Treatment and prevention of glucocorticoid-induced osteoporosis in men and women
- Treatment of Paget's disease of bone
- Treatment of osteoporosis in men
Dosage and Administration
Osteoporosis treatment/prevention:- 5 mg orally daily or 35 mg orally once weekly
- 150 mg orally once monthly
- 5 mg orally daily
- 30 mg orally daily for 2 months
- Take on an empty stomach with 6-8 ounces of plain water
- Remain upright for at least 30 minutes after administration
- Avoid food, beverages, and other medications for at least 30 minutes
- Renal impairment: Not recommended if CrCl <30 mL/min
- Hepatic impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Bioavailability is approximately 0.63% when administered after an overnight fast. Food and beverages significantly reduce absorption. Distribution: Approximately 60% of absorbed dose distributes to bone, with the remainder excreted unchanged in urine. Metabolism: Not metabolized; no cytochrome P450 interactions Elimination: Renal excretion of unchanged drug with half-life of approximately 220 hours in bone tissue Protein binding: Approximately 24%Contraindications
- Hypersensitivity to risedronate or any component of the formulation
- Hypocalcemia
- Esophageal abnormalities that delay esophageal emptying
- Inability to stand or sit upright for at least 30 minutes
- Severe renal impairment (CrCl <30 mL/min)
Warnings and Precautions
Osteonecrosis of the jaw: Risk increases with duration of therapy, dental procedures, and concomitant risk factors Atypical femoral fractures: Low-energy subtrochanteric and diaphyseal fractures reported Esophageal irritation: May cause esophageal ulcers, erosions, and strictures Hypocalcemia: Must be corrected before initiating therapy Renal impairment: Use with caution in moderate renal impairment Pregnancy: Category C - use only if potential benefit justifies potential risk Breastfeeding: Not recommended due to potential for serious adverse reactionsDrug Interactions
Calcium supplements/antacids: Significantly reduce absorption (administer at different time of day) Iron preparations: Reduce absorption (separate administration by at least 2 hours) Aspirin/NSAIDs: May increase risk of gastrointestinal irritation Aminoglycosides: May have additive effect on lowering serum calciumAdverse Effects
Common (>10%):- Arthralgia
- Back pain
- Constipation
- Dyspepsia
- Headache
- Abdominal pain
- Diarrhea
- Nausea
- Rash
- Dizziness
- Osteonecrosis of the jaw
- Atypical femoral fractures
- Severe hypocalcemia
- Esophageal ulceration
- Uveitis and scleritis
- Severe skin reactions
Monitoring Parameters
- Bone mineral density (baseline and every 1-2 years)
- Serum calcium levels (baseline and periodically)
- Renal function (baseline and periodically)
- Dental examinations (regularly during therapy)
- Signs/symptoms of esophageal disorders
- Vitamin D status (baseline and as needed)
- Alkaline phosphatase (for Paget's disease monitoring)
Patient Education
- Take medication first thing in the morning with plain water only
- Remain upright for at least 30 minutes after taking medication
- Do not eat, drink, or take other medications for at least 30 minutes
- Ensure adequate calcium and vitamin D intake through diet or supplements
- Report any new thigh or groin pain immediately
- Maintain good oral hygiene and regular dental check-ups
- Notify all healthcare providers about risedronate use before any dental procedures
- Do not stop or start any new medications without consulting healthcare provider
- Report difficulty swallowing, chest pain, or heartburn
References
1. Watts NB, et al. Osteoporos Int. 2010;21(5):723-732. 2. Harris ST, et al. JAMA. 1999;282(14):1344-1352. 3. Risedronate prescribing information. FDA-approved labeling. 4. McClung MR, et al. N Engl J Med. 2001;344(5):333-340. 5. Adler RA, et al. Endocr Pract. 2016;22(Suppl 4):1-42. 6. Khan AA, et al. J Bone Miner Res. 2015;30(1):3-23. 7. Miller PD, et al. Bone. 2005;36(1):22-28. 8. Reginster JY, et al. Osteoporos Int. 2000;11(1):83-91.