The Use of Bisphosphonates in Pediatrics

Abstract

Bisphosphonates are widely used for the prevention and treatment of osteoporosis in adulthood. In the last years, bisphosphonates have been increasingly used in pediatric patients for the treatment of a growing number of disorders associated with osteoporosis, resistant hypercalcemia or heterotopic calcifications. The use of bisphosphonates in pediatric patients has been proven safe; however, the risk of potential severe consequences into adulthood should be kept in mind. Well-defined criteria for bisphosphonates treatment in pediatric patients are not specified, therefore an accurate selection of patients who could benefit from bisphosphonates is mandatory. A strict follow-up of pediatric patients receiving long-term bisphosphonate therapy is strongly recommended. The purpose of this mini review is to provide a summary of current knowledge on some main general aspects of the structure, mechanisms of action, pharmacokinetics, and bioavailability of bisphosphonates, and to focus on the latest advances of bisphosphonate treatment in pediatric patients. Particular attention has been paid to the common and potential adverse effects of bisphosphonate treatment, and some suggestions concerning the clinical approach and general measures for bisphosphonate treatment in pediatric patients are reported.

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“…A recent review discussed the beneficial effects of bisphosphonates in pediatric disorders, such as, idiopathic juvenile osteoporosis, secondary osteoporosis from glucocorticoid use, hypercalcemic disorders, and heterotopic calcification [12]. As analogs of pyrophosphate, bisphosphonates are absorbed into hydroxyapatite crystals, which make them resistant to enzymatic degradation [8].…”

“…Drug-induced osteopetrosis is related to cumulative overdose of bisphosphonate. Known side effects, such as atypical femur fracture, osteonecrosis of the jaws, and orbital inflammation have been reported only in adult, not in pediatric patients [12]. Potential adverse effects of bisphosphonate therapy are a marked decrease in cancellous bone remodeling and an increase in the amount of residual calcified cartilage within secondary spongiosa.…”

“…Urinary excretion of pamidronate after cessation of longterm treatment has continued for up to 8 years [20]. Because of insufficient evidence supporting routine use of bisphosphonates in clinical practice, bisphosphonate-based therapy should be restricted to specialist with experience in the management of pediatric bone disease [12].…”

Bisphosphonates in pediatric rheumatology: A review

“…Other bisphosphonate preparations with their doses and routes of administration [5,6] are listed in Table 1.…”

“…The main mechanism of elimination of bisphosphonates is by renal excretion [6]. Pamidronate urinary excretion after the cessation of long-term treatment with daily oral administration has been shown to be detectable up to 8 years after the cessation of treatment.…”