3. Discussion
calcification, PXE, gastrointestinal intolerance
DISEASE, OSTEOPOROTIC FRACTURE, PATHOGENESIS, MINERALIZATION
Our trial shows that administration of lansoprazole 30 mg increased PPi levels in patients with PXE compared with the placebo in a short period of 8 weeks. Because PPi is recognized as a molecule directly involved in the pathogenesis of calcification in these patients, lansoprazole might be considered for new clinical trials with clinical outcomes.Of note, PPi levels were similar at visits one and three (The rationale for our trial relies on the fact that TNAP activity is higher and PPi is lower in PXE patients compared with non-PXE subjects [Another interesting point concerning lansoprazole and PXE is the effect of the drug on PHOSPHO1, a cytosolic phosphatase highly expressed in osteoblasts and essential for bone mineralization [There were very few adverse side effects, with six in the placebo phase and three in the lansoprazole phase, mainly gastrointestinal intolerance, and in only one case causing the patient to drop out of the study (in the placebo phase). Putting this into perspective, we should take into account the long-term side effects of lansoprazole: on the one hand, it has been shown to increase the risk of osteoporotic fractures under long-term use and a high dose [In our study, lansoprazole elevated PPi more than the placebo by an average of 18%, partially compensating for the 30% deficit the patients with PXE had relative to the controls, but without normalizing levels [We do not know if the observed 18% increase might provide a clinical benefit to patients, such as delaying the progression of the disease. Only a long-term trial with clinical end points might answer this question, or a mid-term trial with the deposition of Na18F in the neck skin as the end point [Our trial has several limitations that should be taken into account: the low number of participants, the short-term follow-up (only 8 weeks of therapy), the fact we do not know how many days it took for PPi to be increased after lansoprazole was taken, the absence of clinical values as end points, as well the heterogeneous response in some patients.In conclusion, our trial supports the establishment of a new clinical trial with lansoprazole in PXE patients, with clinical outcomes as the major end points. It might be considered as monotherapy or as an adjuvant with a second medication, such as oral PPi ingestion.