Systematic review of the effects of bisphosphonates on bone density and fracture incidence in childhood acute lymphoblastic leukaemia

Skeletal fragility is a common complication of childhood acute lymphoblastic leukaemia (ALL) but the impact of bisphosphonate therapy on bone mass and fracture is unclear. We aim to conduct a systematic review to evaluate the effects of bisphosphonates on bone mineral density (BMD) and fracture incidence in children with ALL. EMBASE, Medline and the Cochrane Library were thoroughly searched by two researchers. Inclusion criteria was any child under the age of 18 years with a diagnosis of ALL, who had received any bisphosphonate treatment and had serial measurements of bone density performed thereafter. All primary research studies of any study design, excluding case reports, were included. Ten full text papers were identified with two exclusively meeting the inclusion criteria. Both studies administered bisphosphonates to children receiving maintenance chemotherapy for varying durations. Bone density was assessed at regular intervals by dual x-ray absorptiometry (DXA). The majority of participants had an improvement in bone density at the end of each study. However, no size adjustment of DXA data was performed. Limited information on fracture occurrence was provided by one study but did not include routine screening for vertebral fractures. This systematic review identified that there is insufficient evidence to support routine use of prophylactic bisphosphonate therapy in childhood ALL for prevention of fracture and improvement of bone mass. Future well-designed clinical trials in those at highest risk of fractures in ALL are now needed