|BISPHOSPHONATES IN CHILDREN|
Bisphosphonates are synthetic analogues of pyrophosphate. Bisphosphonates were initially used in children nearly 30 years ago. Bisphosphonates reduce osteoclast activity and life span in the body leading to decreased bone resorption. They also inhibit macrophage activity and thus are useful in treating hypercalcemia associated with systemic disorders such as malignancy, immobilization, familial hypocalciuric hypercalcemia. They are also used in osteopathies such as osteogenesis imperfecta, juvenile osteoporosis, Gaucher's disease, hyperphosphatasia, Juvenile chronic arthritis and glucocorticoid-induced osteoporosis to increase bone density. They have also been tried for treatment of calcinosis associated with myositis, fibrodysplasia ossificans, dermatomyositis and scleroderma.
Bisphosphonates are classified into 3 generations
Etidronate and pamidronate have been used maximally in children usually intravenously. Third generation drugs are more potent.
The precise mechanism of their antiresorptive action is unclear. They get incorporated into the skeletal matrix by avidly binding to the hydroxyapatite lattice and finally target the osteoclast, reducing their recruitment, activity and life span. Once therapy is initiated, there is a rapid gain in the bone mass that plateaus to smaller rate of increase after 4 to 6 months. Mineralization of the new bone improves its density by 6 months and leads to relief of pain.
The Gl absorption of bisphosphonates is <10%. Hence most bisphosphonates except alendronate are given IV. This Gl absorption is further reduced by foods containing mild or iron. Hence, oral bisphosphonates are recommended to be taken on an empty stomach with no food intake for half an hour after ingestion of the drug. Since they are Gl irritant and cause nausea, diarrhea and gastritis, they should be taken in an upright position with ingestion of lot of water. Once absorbed, 20 to 50% of the drug is taken up by the bone, remainder is excreted in the urine with a circulating half life of <60 minutes.
Adverse effects of bisphosphonates are uncommon. Defective mineralization has been described in children. Intravenous therapy is associated with hypocalcemia, transient fever, rash, leukopenia and myalgia. Iritis and hearing loss has been also reported with pamidronate. Oral therapy may cause nausea and gastritis.
Dosage - For Osteopathy
Oral Alendronate - 5 mcg/kg/d OD on empty stomach with lot of water.
IV Pamidronate - 1 mg/kg IV every 2 weekly. Monitor for hypocalcemia and leukopenia
Last updated on 1-07-2003
Pediatric Oncall Journal
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