Diverticulitis with denosumab (PROLIA): A 64 year old female, who was operated several years previously for breast cancer and had received adjuvant radiotherapy, was diagnosed with osteoporosis with thoracic vertebral body-sintering fracture in the context of an upper-ankle fracture. Initially, she was treated for two years with bisphosphonates, calcium and vitamin D. After switching to denosumab (PROLIA), there were multiple severe inflammatory episodes of a known diverticulosis, which eventually required surgery. Shortly thereafter, diverticulitis reoccurred (NETZWERK report 16,685). Diverticulitis is one of the serious infections, which occurred more frequently with denosumab than with placebo in the approval studies for the treatment of females with postmenopausal osteoporosis and, in particular, in males with bone loss due to hormone ablation (1-3). An increased risk of infection with the monoclonal antibody appears plausible: The denosumab-inhibited RANK*-ligand, which belongs to the tumour necrosis factor superfamily, is not only involved in bone metabolism, but also has important functions in the immune system, such as in the maturation of dendritic (antigen-presenting) cells (cf. a-t 2010; 41: 60-2 (2). The European Medicines Agency (EMA) documented, in the context of spontaneous reporting, 71 communications of diverticulitis with denosumab. Predominantly affected are females who use PROLIA (4).

1

ROTHSTEIN, A.: Slides for the FDA presentation for the August 13, 2009 Advisory Committee Meeting; http://www.a-turl.de/?k=erza

2

FDA: Briefing Document Advisory Committee Meeting, August 13, 2009; http://www.a-turl.de/?k=alje

3

Amgen: Summary of Product Characteristics PROLIA, as at July 2014

4

EMA: European database of suspected adverse drug reaction reports on diverticulitis with denosumab, as at Oct. 2014, accessed Dec. 2014

RANK = Receptor Activator of Nuclear Factor Kappa B