Background

The bisphosphonates (previously referred to as biphosphonates or diphosphonates) are a group of agents which are analogues of pyrophosphate. When administered either orally or parenterally they are adsorbed onto hydroxyapatite crystals in bone mineral and, because their structure renders them resistant to enzyme degradation, they act principally by inhibiting bone resorption, although some effect on bone formation probably also occurs.1 The net effect is to promote bone mineral accretion while at the same time considerably reducing bone turnover. Because of this latter effect, there have been concerns about the use of bisphosphonates in children in whom bone turnover is normally much greater than in adults. As a result, there have been fears that interference with the rapid remodelling process, which is necessary in growing bones, might result in bone deformity or serious disruption of the normal mineralisation process. The limited experience of their use has, so far, largely proved these fears to be groundless.

Wide experience of the use of bisphosphonates has been gained in adults, principally for the treatment of involutional osteoporosis, Paget’s osteitis deformans, and the hypercalcaemia and bone pain of malignancy. Several hundred papers have been published on these topics, many of them as a result of properly controlled trials. In contrast, very few studies in children have been published.2-25These are all anecdotal and only one study included any control subjects.15 Nevertheless, the limited experience of the use of bisphosphonates in children and adolescents which has so far been gained does suggest that, for some conditions such as osteogenesis imperfecta and perhaps juvenile osteoporosis, wider use is indicated and may provide a useful additional therapeutic measure.

Pharmacology

The bisphosphonates are pharmacologically simple compounds that all have a phosphorus-carbon-phosphorus structure (compare with the phosphorus-oxygen-phosphorus structure of pyrophosphate). The presence of carbon rather than oxygen allows …