Alendronate sodium

Alendronate sodium
INN
Drug class
Routes of administration	Oral
Pregnancy category
Bioavailability	0.6–1.8%
Metabolism	Nil
Elimination half-life	10 years (in bone)
Excretion	Renal
Legal status
CAS Number	121268-17-5
PubChem	2089
DrugBank	DB00630
ChemSpider	2006
KEGG	D07482

Alendronate sodium, commonly known as alendronate, is a bisphosphonate medication primarily used to prevent and treat osteoporosis in postmenopausal women and other individuals at high risk of fractures. Additionally, it is employed in managing Paget's disease of bone, a condition characterized by abnormal bone remodeling.

This medication works by inhibiting the activity of osteoclasts, the cells responsible for bone resorption, thereby helping to strengthen bones and reduce the risk of fractures. It is marketed under various brand names, including Fosamax.

History

Alendronate sodium was first approved by the United States Food and Drug Administration (FDA) in 1995. Developed by Merck & Co., it became one of the most prescribed medications for osteoporosis due to its effectiveness and relatively favorable side effect profile.

Chemical Composition

Alendronate sodium is a salt form of alendronic acid. Its chemical formula is C4H13NO7P2Na, and it is a white, crystalline powder that is highly soluble in water. Alendronate belongs to the bisphosphonate class of drugs, which are synthetic analogs of pyrophosphate.

Alendronate sf

AlendronateSodium costs (DrugStats)

Alendronate

Bone Comparison of Healthy and Osteoporotic Vertibrae

Uses

The primary indications for alendronate sodium include:

• Treatment of Osteoporosis: Used to increase bone density and reduce fracture risk in postmenopausal women, men, and individuals receiving long-term glucocorticoid therapy.
• Prevention of Osteoporosis: Recommended for individuals at high risk of developing osteoporosis.
• Paget's disease of none: Administered to regulate abnormal bone turnover and improve bone structure.

Mechanism of Action

Alendronate sodium inhibits the enzyme farnesyl pyrophosphate synthase in osteoclasts. This inhibition prevents the resorption of bone, leading to a net gain in bone mineral density (BMD) over time. By slowing the natural bone breakdown process, alendronate helps maintain stronger bones and reduces the likelihood of fractures, particularly in the spine and hip.

Alendronate-3D-balls

Pharmacokinetics

The pharmacokinetics of alendronate sodium involve its absorption, distribution, metabolism, and excretion. These parameters influence its efficacy and dosing requirements.

Absorption

• Alendronate sodium is poorly absorbed when taken orally, with an approximate bioavailability of only 0.6–0.8%.
• Food, beverages (other than plain water), and certain medications significantly reduce its absorption. It is recommended to take alendronate with plain water on an empty stomach to maximize absorption.

Distribution

• Once absorbed, alendronate binds strongly to hydroxyapatite crystals in bones, where it exerts its therapeutic effects.
• It does not accumulate in other tissues, and its systemic circulation is relatively limited.

Metabolism

• Alendronate sodium is not metabolized by the liver or other organs. It is chemically stable and remains unchanged in the body.

Excretion

• The drug is primarily excreted via the kidneys. Unabsorbed alendronate is eliminated through feces.
• Individuals with renal impairment may experience reduced clearance of the drug, necessitating dose adjustments or alternative therapies.

Administration

To ensure optimal efficacy and minimize side effects, alendronate sodium should be administered with specific instructions:

Dosage

• Osteoporosis treatment: 10 mg once daily or 70 mg once weekly.
• Osteoporosis prevention: 5 mg once daily or 35 mg once weekly.
• Paget's disease: 40 mg once daily for six months.

Instructions for Use

1. . Take the tablet first thing in the morning, at least 30 minutes before eating, drinking, or taking other medications.
2. . Swallow the tablet with a full glass of water (not less than 240 mL or 8 oz).
3. . Avoid lying down for at least 30 minutes after taking the tablet to reduce the risk of esophageal irritation.

Special Considerations

• Patients with gastrointestinal disorders such as esophageal stricture or achalasia should avoid alendronate due to the risk of esophageal irritation or ulceration.
• Those with severe renal impairment (creatinine clearance <35 mL/min) should not use alendronate.

Clinical Uses

Alendronate sodium is widely used in the prevention and treatment of various bone-related conditions. Its effectiveness stems from its ability to inhibit bone resorption mediated by osteoclasts.

Osteoporosis

• Postmenopausal osteoporosis: Alendronate is a first-line treatment for postmenopausal women with osteoporosis. It significantly reduces the risk of vertebral, non-vertebral, and hip fractures.
• Glucocorticoid-induced osteoporosis: Long-term use of glucocorticoids can lead to bone loss. Alendronate is effective in preventing and treating osteoporosis in patients receiving chronic glucocorticoid therapy.
• Osteoporosis in Men: Alendronate is approved for the treatment of osteoporosis in men, reducing the risk of fractures.

Paget's Disease of Bone

• Alendronate is effective in managing Paget's disease, a condition characterized by abnormal bone remodeling. It helps normalize alkaline phosphatase levels and reduce bone pain.

Prevention of Bone Loss

• Alendronate is used to prevent bone loss in individuals at high risk of developing osteoporosis, particularly in postmenopausal women or those undergoing treatments that affect bone density, such as aromatase inhibitors or androgen deprivation therapy.

Efficacy

Numerous clinical trials have demonstrated the efficacy of alendronate sodium in improving bone mineral density (BMD) and reducing fracture risks.

Bone Mineral Density (BMD)

• Studies have shown that alendronate increases BMD in the spine, hip, and other sites prone to fractures.
• Long-term use of the drug (up to 10 years) maintains or improves BMD in treated individuals.

Fracture Risk Reduction

• Alendronate significantly reduces the risk of vertebral fractures by up to 50%.
• It decreases the risk of non-vertebral and hip fractures in individuals with osteoporosis.

Comparative Effectiveness

• Alendronate has been compared to other bisphosphonates, such as risedronate and zoledronic acid. While all bisphosphonates are effective, alendronate remains a commonly prescribed option due to its well-established safety and efficacy profile.

Combination Therapy

• In certain cases, alendronate is combined with calcium and vitamin D supplements to enhance bone health. This combination is particularly useful in individuals with deficiencies in these nutrients.

Safety Profile

Alendronate sodium has a well-documented safety profile when used as directed. However, like all medications, it may cause side effects or interact with other conditions and medications.

Common Side Effects

The most frequently reported side effects include:

• Gastrointestinal discomfort:
  • Abdominal pain
  • Dyspepsia (indigestion)
  • Esophagitis or esophageal irritation
• Musculoskeletal pain:
  • Bone, joint, or muscle pain
• Mild hypocalcemia:
  • Typically transient and manageable with calcium and vitamin D supplementation.

Serious Side Effects

Though rare, more serious adverse effects have been reported:

• Esophageal ulcers or erosions: Can occur if the medication is not taken with adequate water or if the patient lies down immediately after taking it.
• Osteonecrosis of the Jaw (ONJ): More common in individuals undergoing invasive dental procedures or those with cancer receiving high-dose bisphosphonates.
• Atypical femur fractures: Rare fractures of the femur have been observed, particularly with long-term use.

Precautions and Monitoring

Patients taking alendronate should adhere to specific precautions:

• Administration instructions:
  • Take the medication with a full glass of water.
  • Remain upright for at least 30 minutes post-administration to prevent esophageal irritation.
• Routine monitoring:
  • Periodic assessments of bone mineral density (BMD).
  • Monitoring calcium and vitamin D levels to prevent deficiencies.
  • Evaluating kidney function in patients with renal impairment.

Contraindications

The use of alendronate sodium is contraindicated in the following conditions:

• Hypocalcemia: Must be corrected prior to initiating therapy.
• Esophageal abnormalities: Conditions such as strictures or achalasia that delay esophageal emptying.
• Inability to Remain Upright: Patients who cannot sit or stand upright for at least 30 minutes.
• Allergic Reactions: Known hypersensitivity to alendronate or its components.
• Severe renal impairment: Alendronate is not recommended for patients with a creatinine clearance below 35 mL/min.

Special Populations

Pregnancy and Lactation

• Pregnancy: Alendronate is classified as a Category C drug in the FDA pregnancy category system. Its use is not recommended unless the benefits outweigh potential risks.
• Lactation: It is unknown if alendronate is excreted in human breast milk; caution is advised when administering to nursing mothers.

Pediatric and Geriatric Use

• Pediatrics: Safety and efficacy in children have not been fully established, except in specific conditions such as osteogenesis imperfecta.
• Geriatrics: Older adults tolerate alendronate well, but they may require monitoring for renal function and calcium levels.

Drug Interactions

Alendronate may interact with other medications or substances:

• Calcium and Antacids: These can reduce the absorption of alendronate if taken simultaneously.
• NSAIDs: Concurrent use may increase the risk of gastrointestinal irritation.
• Other Bisphosphonates: Should not be used together due to the risk of cumulative side effects.

Also see

• Bisphosphonates
• Osteoporosis
• Paget's disease of bone
• Bone mineral density