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Cathepsin K ist eine Cysteinproteinase und somit ein essentielles Enzym in der Degradation von Kollagen Typ I. Es wird fast ausschlieslich in Osteoklasten exprimiert. Aufgrund des physiologischen Mechanismus stellt diese Protease einen pharmakologischen Angriffspunkt fur die Entwicklung neuer Medikamente in der Osteologie dar. In den letzten Jahrzehnten wurde intensiv daran geforscht, hochwirksame, selektive und oral einnehmbare Cathepsin K-Inhibitoren zu entwickeln. Im Gegensatz zu Balicatib und Relacatib, deren Weiterentwicklung wegen kutaner Nebenwirkungen bei relativ geringer Spezifitat eingestellt wurde, wendete sich die Forschung den spezifischeren Cathepsin K-Inhibitoren Odanacatib (ODN) und ONO-5334 zu. So hebt Odanacatib bei postmenopausalen Frauen sehr deutlich die Knochenmineraldichte und hemmt die Knochenresorption. Als Voraussetzung fur die Weiterentwicklung konnte in einer Langzeituntersuchung die Sicherheit und Wirksamkeit des Medikaments bestatigt werden. Jedoch nehmen nach dessen Absetzen Knochenresorption und Knochenmasseverlust wieder zu. Eine Phase III Frakturpraventionsstudie an postmenopausalen Frauen mit Osteoporose befindet sich derzeit in der Endphase.

A 79-year-old woman presented with hematemesis. As upper gastrointestinal tract bleeding was suspected, acute gastroduodenoscopy was performed. This showed reflux esophagitis with multiple ulcerations (Los Angeles classification grade D) and oozing hemorrhage (Forrest Ib) in the lower third of the esophagus (●" Fig.1a). The bleeding was originating from a large area of ulceration, so clipping or injection of epinephrine would have been associated with a risk of causing further bleeding. We therefore decided to place an Ella Danis stent (flare diameters, 30mm; body diameter, 25mm; length, 135mm; EllaCS, Hradec Kralove, Czech Republic). After the stent had been expanded, the hemorrhage stopped immediately (●" Fig.1b). The stent stayed in place as a result of its expansion forces; no anchor or clipping was needed. Hemostasis was maintained during the following days. After 5 days, the stent was carefully removed with a forceps without using an overtube. There was considerable improvement in the esophageal appearance with no signs of active bleeding. The vascular stump that had previously bled could still be seen (●" Fig.1c). Two days later the patient was discharged without any further complications. The use of stents for esophageal bleeding was originally reported for acute variceal hemorrhage when endoscopic band ligation could not be performed or was unsuccessful [1,2]. More recently it has been used to treat bleeding from an esophageal ulcer after endoscopic band ligation [3]. Other publications have reported the successful off-label use of the Ella Danis stent in bleeding due to complications after mucosectomy or sphincterotomy, necrotizing esophagitis, as well as in anastomotic leakage [3–5]. So far, there are no data available concerning the safe application of an Ella Danis stent in acute hemorrhage due to severe reflux esophagitis. As there is not sufficient data on efficacy, safety, and complications, further investigation is needed; however, the Ella Danis stent appears to be a promising tool in the endoscopic treatment of a broad spectrum of causes of acute nonvariceal esophageal bleeding.

Cathepsin K, a cysteine protease, is an essential enzyme in degradation of collagen type I. Since cathepsin K is relatively specific to osteoclasts, it represents a promising candidate for drug development. In the past decades, efforts have been made in developing highly potent, selective and orally applicable cathepsin K inhibitors. In contrast to balicatib and relacatib, whose drug development programmes were stopped due to cutaneous side-effects related to limited drug specificity, the more specific cathepsin K inhibitors odanacatib (ODN) and ONO-5334 have entered clinical trials. Odanacatib progressively increases bone mineral density (BMD) and decreases bone resorption markers in postmenopausal women with low BMD. Its clinical efficacy and safety was confirmed by several clinical studies but indicates that odanacatib is characterized by a resolution-of-effect with increases in bone resorption and rapid decreases in BMD following treatment discontinuation. A phase III fracture prevention study in postmenopausal women with osteoporosis is currently in the final phase.