For nearly 30 years, bisphosphonate therapy has been used in the paediatric population, but there is little high quality evidence to support its use in most bone health conditions of childhood. However, there are often few, if any, alternative therapeutic options, and therefore it is used in a wide range of clinical scenarios. The most common indication remains skeletal fragility, caused by a primary or secondary bone disorder. Osteogenesis imperfecta is the best studied of the primary bone disorders, but even in this condition there are many observational studies, but few randomized trials. Secondary bone health problems have a wide variety of antecedents, including neuromuscular disorders, malnutrition/malabsorption, and glucocorticoid therapy. In this diverse group, the evidence base is even patchier. However, for both the primary and secondary groups, bisphosphonates remain the first line therapeutic option for many patients, with the data suggesting improved bone mineral density, reduced fracture risk and reduction in bone pain.
Indications beyond skeletal fragility remain largely experimental, with observational data of its effectiveness in treating bone cysts, avascular necrosis, chronic recurrent multifocal osteomyeltitis, fibrous dysplasia, generalized arterial calcification of infancy, and hypercalcaemia.
Bisphosphonates are generally well tolerated aside from an acute phase response accompanied by hypocalcaemia with the first dose. Longer term side effects seem to be few with no strong evidence of increased risk of atypical femoral fractures, and no reported cases of osteonecrosis of the jaw in children. However, bone turnover is substantially reduced, and the long term effect of this on the developing skeleton remains unclear.
Overall, bisphosphonates remain the mainstay of treatment for skeletal fragility in children, with use also in some other bony conditions. Newer agents may lead to improved outcomes but this remains under investigation.