In Switzerland Amgen, supplier of the RANKL antagonist licensed for the treatment and prevention of osteoporosis known as denosumab (PROLIA; a-t 2010; 41: 60-2), is warning against atypical fractures of the femur which were observed during use of the antibody in the study programme (1). Atypical femur fractures, hence transverse or oblique and occasionally bilateral fractures localised below the trochanter or in the shaft area of the thigh bone, occurring after minimal or no trauma, have so far been described as a complication of bisphosphonate treatment. An association with the strong anti-resorptive action of bisphosphonates and hence their inhibiting effect on bone remodelling is under discussion (a-t 2005; 36: 59-60 and 2010; 41: 117-8). Denosumab, with its anti-resorptive action, also strongly inhibits bone remodelling and since its launch the US product information has therefore contained a note that adverse effects such as atypical fractures are possible (2). Such fractures having since been reported, the product information was suitably adapted in September (3). According to a dear doctor letter in Switzerland, the frequency is expected to be below 1 in 10,000 users.1 During treatment with denosumab, patients should report any emerging or unusual pain in the thigh, hip or groin area. If such pain occur, an atypical femur fracture must be excluded, even on the contralateral side (1,3). In the German summary of product characteristics a suitable warning is missing. The European regulatory authority is currently debating this issue (4).

1

Amgen, Schweiz: Dear doctor letter dated 30. Oct. 2012

2

Amgen: Summary of Product Characteristics (USA) PROLIA, as at June 2010

3

Amgen: Summary of Product Characteristics (USA) PROLIA, as at Sept. 2012

4

Paul-Ehrlich-Institut: letter dated 2. Nov. 2012