Sodium alendronate

MECHANISM OF ACTION

Sodium alendronate is a nitrogen-containing bisphosphonate that works by inhibiting osteoclast-mediated bone resorption. It binds strongly to hydroxyapatite in bone, and when osteoclasts attach to the bone surface to resorb it, alendronate is internalized by these cells. Inside osteoclasts, it inhibits farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway, which is essential for the prenylation of small GTP-binding proteins required for osteoclast function and survival. This leads to reduced osteoclast activity, apoptosis of osteoclasts, and decreased bone resorption, ultimately increasing bone mineral density and reducing fracture risk.

PHARMACOKINETICS

Absorption

Sodium alendronate has very poor oral absorption (low bioavailability), averaging less than 1% when taken correctly on an empty stomach. Its absorption is dramatically reduced, even to negligible levels, by food, beverages other than plain water, and other medications or supplements. 

Distribution

Alendronate has a low volume of distribution (~0.7 L/kg), as it binds strongly to bone and distributes minimally to soft tissues, contributing to its long skeletal retention.

Metabolism

Sodium alendronate is not metabolized in the body. After absorption, it remains unchanged and is either bound to bone or excreted unchanged by the kidneys. Its lack of metabolism contributes to predictable pharmacokinetics and a long duration of action in bone tissue.

Excretion

Sodium alendronate is excreted unchanged primarily via the kidneys through renal filtration and tubular secretion. A small portion is retained in bone, where it can remain for years, contributing to its long-term antiresorptive effect. Renal function significantly influences its clearance, so dose adjustments may be needed in patients with impaired kidney function.

PHARMACODYNAMICS

Sodium alendronate is a bisphosphonate that inhibits osteoclast-mediated bone resorption, leading to increased bone mineral density and reduced risk of fractures. By binding to hydroxyapatite in bone, it is incorporated into the bone matrix, where it induces osteoclast apoptosis and decreases bone turnover. The result is stronger, denser bones and improved skeletal stability, particularly in conditions like osteoporosis and Paget’s disease. Its effects are long-lasting due to prolonged skeletal retention.

ADMINISTRATION

Sodium alendronate must be taken in the morning immediately after getting out of bed, on an empty stomach, and with specific instructions regarding posture, liquid, food, and with other medications to maximize absorption and reduce the risk of esophageal irritation.

DOSAGE AND STRENGTH

Sodium alendronate is available in tablet form for oral administration, with common strengths of 5 mg, 10 mg, 35 mg, and 70 mg.

Dosage (typical):

• Postmenopausal osteoporosis (treatment): 10 mg once daily or 70 mg once weekly.

• Postmenopausal osteoporosis (prevention): 5 mg once daily or 35 mg once weekly.

• Paget’s disease of bone: 40 mg once daily for 6 months.

• Glucocorticoid-induced osteoporosis: 5–10 mg once daily depending on age and risk factors.

Tablets should be taken on an empty stomach with a full glass of water, at least 30 minutes before food, drink, or other medications, while remaining upright to reduce the risk of esophageal irritation.

DRUG INTERACTIONS

Sodium alendronate’s absorption can be reduced by calcium, magnesium, aluminum, iron supplements, and antacids, so it should be taken at least 30–60 minutes before these agents. Concurrent use with NSAIDs, aspirin, or corticosteroids may increase the risk of gastrointestinal irritation. Medications that slow gastric emptying can also reduce its effectiveness.

FOOD INTERACTIONS

Sodium alendronate should be taken on an empty stomach, at least 30 minutes before eating or drinking anything other than water, because food and beverages (other than plain water) can significantly reduce its absorption. To ensure maximum effectiveness, patients should avoid eating, drinking, or taking other medications immediately after the dose.

CONTRAINDICATIONS

Sodium alendronate is contraindicated in patients with esophageal abnormalities that delay swallowing, inability to remain upright for at least 30 minutes after dosing, hypocalcemia, severe kidney impairment, or known hypersensitivity to alendronate. Caution is also advised in individuals with pre-existing gastrointestinal disorders, as the drug may increase the risk of irritation or ulceration.

SIDE EFFECTS

• Stomach pain or upset stomach

• Heartburn (new or worsening)

• Nausea, gas, or diarrhea

• Constipation

• Headache

• Bone, muscle, or joint pain.

• Jawbone problems (osteonecrosis).

• Unusual thigh bone fractures.

• Low calcium levels (hypocalcemia).

• Eye problems.

• Allergic reactions.

OVERDOSE

• Symptoms of a sodium alendronate overdose may include: 

• Heartburn (new or worsening)

• Nausea

• Stomach or abdominal pain

• Difficulty or pain when swallowing (dysphagia)

• Chest pain

• Vomiting blood or vomitus resembling coffee grounds.

• Bloody, black, or tarry stools (melena)

• Muscle spasms, twitches, or cramps (due to low calcium levels)

• Tingling, numbness, or a burning sensation in the arms, feet, or face.

• Seizures (in severe cases of hypocalcemia)

• Dizziness or lightheadedness

• Clammy skin

• CNS (central nervous system) depression

• Respiratory depression

• Wheezing 

TOXICITY

Toxicity from sodium alendronate is uncommon but can occur, mainly affecting the gastrointestinal tract, bones, and electrolytes. Patients may experience esophagitis, esophageal ulcers, abdominal pain, or nausea, as well as bone, joint, or muscle pain. Rare but serious effects include atypical femoral fractures, hypocalcemia, and osteonecrosis of the jaw, especially with long-term use or high doses. Prompt medical attention is required if severe symptoms develop.