The ANKH and osteoprotegerin mutations suggest two pathogenic pathways, Dr. Rosenthal said, one beginning with increased pyrophosphate production by cartilage, such as one may see with ANKH mutations, hypophosphatasia and hypomagnemesia. The second possible pathway involves disordered bone remodeling caused by osteoprotegerin mutations, hyperparathyroidism, hemochromatosis, injury, OA and age.
Treatment Opportunities
Dr. Rosenthal concluded the session with a brief discussion of CPDD treatment. She reviewed the many current options for managing acute CPP arthritis and lamented the lack of studies showing a role for drugs currently used for chronic CPDD. She hopes improved understanding of CPP arthritis pathophysiology will lead to new potential therapies.
“ANKH is a druggable target and probably belongs to the category of organic anion transporters,” Dr. Rosenthal said. She notes many drugs are organic anion inhibitors, such as probenecid, which, in large quantities, decreases the amount of extracellular ATP secreted by chondrocytes. The RANK-ligand pathway is also “eminently targetable,” she says, noting denosumab mimics the effects of functional osteoprotegerin.
Dr. Rosenthal concluded with enthusiasm that there is much to look forward to in the world of CPP deposition, including the new set of classification criteria coming shortly, very exciting diagnostic modalities on the horizon and an improved mechanistic understanding of the pathogenesis.
“I’m hoping that all of this leads to better management of our patients, which is our ultimate goal,” she said.
Carina Stanton is a freelance science journalist based in Denver.
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- Andrés M, Vela P, Vega Jovaní V, et al. Most needle-shaped calcium pyrophosphate crystals lack birefringence. Rheumatology (Oxford). 2019 Jun 1;58(6):1095–1098.
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