Endocrine Abstracts

Bisphosphonates (BPs) are synthetic analogues of pyrophosphate that inhibit osteoclast-mediated bone resorption and reduce bone turnover. Of proven therapeutic benefit, licensed indications for clinical use of BPs include, 1) prevention of osteoporotc fractures, 2) management of bone pain (Paget’s disease, metastatic breast cancer & myeloma) and 3) treatment of hypercalcaemia of malignancy. The perceived safety of BPs has, however, resulted in growth of ‘off-label’ use, not just in adults, but also in children in whom they are currently used to treat osteogenesis imperfecta, juvenile osteoporosis & fibrous dysplasia. ‘Off-label’ use in adults is most widespread in Oncological practice, where high dose parenteral BPs are used to prevent skeletal complications of myeloma & metastatic cancers.

New safety concerns have arisen in association with more liberal use of high dose BPs. Osteonecrosis of the Jaw (ONJ) is rare in osteoporosis practice (1:10 000–1:100 000) but is 1000 times commoner with the high dose parenteral regimens used in patients with cancer. Acquired osteopetrosis with fractures has also been attributed to use of high dose parenteral BP in a child. Recently, atypical subtrochanteric femoral fractures have also been linked to BP treatment for osteoporosis, although certainty that these are truly a complication of BPs is lacking.

BPs are uniquely effective in the treatment of skeletal disease and carry recognised risks when used with caution (e.g. Cr Cl should be >30–35 ml/min). Deviation from licensed indications and dosage regimens carries increasingly recognised, tangible risks; these risks may be acceptable in the context of potential benefits but only if administered after appropriate exposition of the risks & benefits that may result.