Clodronic acid or clodronate disodium is a first generation bisphosphonate indicated in the prevention and treatment of postmenopausal osteoporosis. Clodronic acid is also used for the treatment of hypercalcemia due to malignancy and osteolysis due to malignancy.
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 BRAND NAMES
- International: Bonefos
- Australia: Bonefos PI
- Canada: Bonefos PI, Clasteon PI
- France: Clastoban, Lytos
- Italy: Clasteon, Clodron, Clody, Difosfonal, Niklod, Osteonorm, Osteostab
- UK: Loron
 MECHANISM OF ACTION
Osteoporosis happens when not enough new bone grows to replace the bone that is naturally broken down. Gradually, the bones become thin and fragile, and more likely to break. Osteoporosis is more common in women after the menopause, when the levels of the female hormone estrogen fall, since estrogen helps to keep bones healthy.
Osteoblasts make bone, while osteoclasts resorb or take away bone. Clodronic acid is a first generation (non-nitrogenous) Bisphosphonate, it has no direct effect on bone formation, but it stops the action of the osteoclasts, the cells that are involved in breaking down the bone tissue.
Clodronic acid is internalized by osteoclasts, causing disruption of osteoclast cytoskeleton, loss of the ruffled border, and the subsequent loss of ability to resorb bone.
The gastrointestinal absorption of oral sodium clodronate is low, at around 2%. Due to strong affinity of sodium clodronate to calcium and other divalent cations of food, the intestinal absorption of sodium clodronate is negligible when given with meals.
- Prevention and treatment of postmenopausal osteoporosis
- Management of hypercalcemia caused by a tumour that has spread to the bone; Infact, Calcium can be lost from the damaged bone and seep into the bloodstream. A raised level of calcium in the blood can cause symptoms such as feeling or being sick (nausea or vomiting), tiredness, irritability and sometimes confusion.
- Adjunct therapy in the management of osteolysis resulting from bone metastases of malignant tumors.
Clodronate is mainly eliminated via the kidneys. Therefore, adequate fluid intake must be maintained during clodronate treatment.
- Adult patients with normal renal function
- Treatment of hypercalcemia due to malignancy: Intravenous clodronate treatment is recommended for the treatment of hypercalcemia due to malignancy. However, if oral therapy is used, a high starting dose of 2400 or 3200 mg daily should be used and, depending on the individual response, this can be reduced gradually to 1600 mg daily in order to maintain normocalcemia.
- Treatment of osteolysis due to malignancy: When oral therapy is used to treat increased bone resorption without hypercalcemia the dosage is individual. Recommended starting dose is 1600 mg daily. If clinically necessary, the dose may be increased, but is not recommended to exceed 3200 mg daily.
- Reduction of occurrence of bone metastases in primary breast cancer: The recommended dose is 1600 mg daily.
- treatment of postmenopausal osteoporosis: the usual dosage is 400 or 800 mg/day
- Adult patients with normal renal function
- Intravenous Infusion
- treatment of postmenopausal osteoporosis: intramuscular injection of 100 mg once weekly or 200 mg every 2 weeks, for 1 year or more depending on the patient's condition.
- Hypersensitivity to Clodronate
- Severe inflammation of the gastrointestinal tract.
- Concomitant use of other bisphosphonates.
- Renal functional impairment (serum creatinine exceeding 440 µmol/L (5.0 mg/dL).
 WARNINGS AND PRECAUTIONS
- Bisphosphonates may cause osteonecrosis of the jaw. Potential predisposing factors are tooth extractions, poor oral hygiene, corticosteroids use, alcohol abuse, chemotherapy and radiotherapy.
- Atypical Femur Fractures have been reported with bisphosphonate therapy. Patients should be advised to report any thigh or groin pain to rule out an incomplete femur fracture.
- Clodronate disodium) should NOT be given as a bolus injection since severe local reactions and thrombophlebitis may occur as the result of high local concentrations. The rapid bolus injection may also precipitate acute renal failure. Therefore, appropriate monitoring of renal function during and after intravenous infusion is required.
- Infusion of clodronate disodium may present a risk of hypocalcemia (The drug may chelate blood calcium).
- Sodium clodronate forms poorly soluble complexes with divalent cations. Therefore, it should not be taken with food or drugs containing divalent cations (e.g. antacids or iron preparations).
- Concomitant use with other bisphosphonates is contraindicated.
- Sodium clodronate has been reported to be associated with renal dysfunction when used simultaneously with non steroidal anti inflammatory drugs (NSAIDs), most often diclofenac.
 PREGNANCY AND LACTATION
- Pregnant Women: The safety and efficacy of clodronate in pregnancy has not been established.
- Nursing Women: breast feeding under the treatment with clodronate is not recommended.
 SIDE EFFECTS
Gastrointestinal symptoms such as nausea, vomiting, anorexia and diarrhea are the most frequent adverse events reported during clodronate disodium therapy, particularly with the oral form.