Cathepsin K inhibition causes skin hardening
MedWire News: A drug used to treat osteoporosis, balicatib, can cause skin hardening or morphea in those who take it, say researchers.
"This observation emphasizes the importance of intracellular collagen degradation in the skin, a pathway so far vastly underappreciated," said study author Thomas Rünger from Boston University School of Medicine in Massachusetts, USA.
He added that the finding "also sheds new light on our understanding of the mechanisms involved in morphea, or skin hardening. Failed collagen degradation has so far not been thought to cause morphea."
Rünger and team observed that nine out of 709 patients treated for osteoporosis with balicatib, a cathepsin K (catK) inhibitor, developed skin hardening, mostly around the neck, abdomen, and chest. These patients were taking 10, 25, or 50 mg/day of the drug. No patients in the lowest dose group, 5 mg/day, or the placebo group developed morphea-like changes.
As morphea is normally very rare, with a reported incidence rate of 12 cases per 1,000,000 people, the researchers believe the skin-hardening effects seen in patients taking balicatib in this study are likely to be drug-related.
The researchers explain that although catK was originally assumed to be only expressed in osteoclasts, where it regulates bone resorption, recent research has shown expression of this protease in lung and dermal fibroblasts. It is also thought to be involved in the breakdown of the extracellular collagen matrix in the lungs and skin.
"It is therefore plausible that the observed dermal fibrosis in balicatib-treated patients is a result of impaired degradation of extracellular matrix proteins and may represent a class effect of catK inhibitors," write Rünger et al in the Journal of the American Academy of Dermatology.
"Resolution in most patients after discontinuation of balicatib and the fact that these skin changes were most common with the highest dose and not observed with the lowest dose of balicatib suggest that these adverse events were dose-related," they add.
The investigators recommend that further studies of catK inhibitors for the treatment of osteoporosis or cancer should include monitoring for morphea-like adverse effects.
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By Helen Albert