Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment maintenance regimens should be considered on a case-by-case basis.
