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• W2954967633 abstract "To the Editor: We read with great interest Rose et al's1Rose S. On S.J. Fuchs W. et al.Magnesium supplementation in the treatment of pseudoxanthoma elasticum: a randomized trial.J Am Acad Dermatol. 2019; 81: 263-265Abstract Full Text Full Text PDF Scopus (9) Google Scholar report on their randomized controlled trial on magnesium supplementation to treat pseudoxanthoma elasticum (PXE). Indeed, magnesium is effective against elastic tissue calcification in PXE mouse models.1Rose S. On S.J. Fuchs W. et al.Magnesium supplementation in the treatment of pseudoxanthoma elasticum: a randomized trial.J Am Acad Dermatol. 2019; 81: 263-265Abstract Full Text Full Text PDF Scopus (9) Google Scholar However, in this study, we regret that magnesium treatment results in only a trend toward improvement.1Rose S. On S.J. Fuchs W. et al.Magnesium supplementation in the treatment of pseudoxanthoma elasticum: a randomized trial.J Am Acad Dermatol. 2019; 81: 263-265Abstract Full Text Full Text PDF Scopus (9) Google Scholar So, various factors might account for lack of statistical effect beyond a small sample size. Magnesium supplements and magnesium salt are combinations of magnesium and other minerals and come in 4 different forms: insoluble inorganic salts (oxide carbonate hydroxide), soluble inorganic salts (chloride sulfate), soluble organic salts (citrate lactate gluconate), and soluble organic complexes (glycinate bisglycinate).2Coudray C. Rambeau M. Feillet-Coudray C. et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.Magnes Res. 2005; 18: 215-223PubMed Google Scholar Importantly, the amount of magnesium absorbed by the patient depends on its form.2Coudray C. Rambeau M. Feillet-Coudray C. et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.Magnes Res. 2005; 18: 215-223PubMed Google Scholar Magnesium bioavailability, or the quantity absorbed, is the most relevant pharmacologic parameter in magnesium salt selection.2Coudray C. Rambeau M. Feillet-Coudray C. et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.Magnes Res. 2005; 18: 215-223PubMed Google Scholar The authors used magnesium oxide, one of the cheapest available salts, which has a relatively high magnesium content but low bioavailability.2Coudray C. Rambeau M. Feillet-Coudray C. et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.Magnes Res. 2005; 18: 215-223PubMed Google Scholar Indeed, excessively high magnesium content might have a laxative effect. Hence, the necessity for dose splitting.2Coudray C. Rambeau M. Feillet-Coudray C. et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.Magnes Res. 2005; 18: 215-223PubMed Google Scholar Magnesium citrate has the highest bioavailability of all magnesium salts, compared with chelated forms and magnesium oxide.2Coudray C. Rambeau M. Feillet-Coudray C. et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.Magnes Res. 2005; 18: 215-223PubMed Google Scholar In a randomized, placebo-controlled study, 46 healthy participants received daily 300-mg doses of magnesium citrate or magnesium oxide.3Walker A.F. Marakis G. Christie S. Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study.Magnes Res. 2003; 16: 183-191PubMed Google Scholar Saliva, blood, and 24-hour urine samples were taken at baseline, 24 hours, and 60 days. The magnesium content in the 60-day urine sample was higher in the patients taking magnesium citrate than the patients taking magnesium oxide.3Walker A.F. Marakis G. Christie S. Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study.Magnes Res. 2003; 16: 183-191PubMed Google Scholar Magnesium citrate treatment induced higher mean serum magnesium concentrations than magnesium oxide treatment after 24-hour (P = .026) and 60-day (P = .006) supplementation.3Walker A.F. Marakis G. Christie S. Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study.Magnes Res. 2003; 16: 183-191PubMed Google Scholar Magnesium citrate is more soluble than magnesium oxide; hence, its higher absorption rate as demonstrated by higher plasma concentration and urinary excretion outcomes than magnesium oxide at various time points after administration.3Walker A.F. Marakis G. Christie S. Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study.Magnes Res. 2003; 16: 183-191PubMed Google Scholar Thus, available data suggest that magnesium citrate is better suited to therapeutic and supplementary use.3Walker A.F. Marakis G. Christie S. Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study.Magnes Res. 2003; 16: 183-191PubMed Google Scholar Citric acid, a low-molecular-weight organic acid, promotes magnesium absorption by increasing its solubility,3Walker A.F. Marakis G. Christie S. Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study.Magnes Res. 2003; 16: 183-191PubMed Google Scholar, 4Ou Y. Liu Z. Li S. et al.Citrate attenuates vascular calcification in chronic renal failure rats.APMIS. 2017; 125: 452-458Google Scholar and citrate is a major substrate in cellular energy metabolism and other cellular processes that can bind calcium and inhibit nucleation and calcium crystal growth,4Ou Y. Liu Z. Li S. et al.Citrate attenuates vascular calcification in chronic renal failure rats.APMIS. 2017; 125: 452-458Google Scholar which is a desired outcome for PXE. In a recent study, citrate was found to inhibit calcification in the urine of a chronic kidney disease patient.4Ou Y. Liu Z. Li S. et al.Citrate attenuates vascular calcification in chronic renal failure rats.APMIS. 2017; 125: 452-458Google Scholar Also, potassium magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis,4Ou Y. Liu Z. Li S. et al.Citrate attenuates vascular calcification in chronic renal failure rats.APMIS. 2017; 125: 452-458Google Scholar a complication frequently observed in PXE patients. Furthermore, magnesium citrate has been shown to protect against vascular calcification in the adenine-induced chronic renal failure rat model.4Ou Y. Liu Z. Li S. et al.Citrate attenuates vascular calcification in chronic renal failure rats.APMIS. 2017; 125: 452-458Google Scholar Magnesium should remain a new treatment option for PXE calcification, yet larger studies are required. We suggest considering magnesium citrate, the highest bioavailable magnesium salt for treatment of PXE calcification, in future clinical trials. Because vascular calcification is a well-known predictive risk factor of subsequent cardiovascular mortality,5de Baaij J.H.F. Hoenderop J.G.J. Bindels R.J.M. Magnesium in man: implications for health and disease.Physiol Rev. 2015; 95: 1-46Crossref PubMed Scopus (695) Google Scholar changes in vascular calcification could constitute a trial endpoint. Magnesium balance in PXE patients should additionally constitute a secondary endpoint. Therefore, serum magnesium concentration, red blood cell magnesium concentration, and 24-hour urinary magnesium excretion are potentially useful biomarkers of magnesium status.5de Baaij J.H.F. Hoenderop J.G.J. Bindels R.J.M. Magnesium in man: implications for health and disease.Physiol Rev. 2015; 95: 1-46Crossref PubMed Scopus (695) Google Scholar Given the rarity of PXE and the few patients involved, it is time to combine efforts for a cure, and we call for international multicenter trials encompassing all PXE patient associations. The authors wish to thank the Patients' Association PXE France, the Fondation Groupama, and the Centre Hospitalier Universitaire de Rennes – Corect for their support for our work. The authors wish to thank Ms Hazel Chaouch for formatting this article and English language corrections. Magnesium supplementation in the treatment of pseudoxanthoma elasticum: A randomized trialJournal of the American Academy of DermatologyVol. 81Issue 1PreviewTo the Editor: Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive connective tissue disorder with significant systemic morbidity due to progressive elastic fiber mineralization; treatment is lacking.1-5 Research in humans and mouse models of PXE has linked increased magnesium levels to decreased calcification. Specifically, in an animal PXE model, magnesium prevented elastic tissue calcification, and in a prior study by LaRusso et al, there was a reduction in elastic fiber calcification in the magnesium-containing placebo arm. Full-Text PDF Reply to: “Comment on ‘Magnesium supplementation in the treatment of pseudoxanthoma elasticum: Is magnesium oxide the best choice?'”Journal of the American Academy of DermatologyVol. 81Issue 5PreviewTo the Editor: We thank Dr Omarjee for his thought-provoking letter.1 The reason that we used magnesium oxide in our studies was because that form of magnesium was indeed the form studied by Kupetsky-Rincon et al to reduce carotid intima-media thickness in a mouse model of pseudoxanthoma elasticum (PXE).2 We are, however, intrigued by Dr Omarjee's points about magnesium citrate and agree that clinical trials with alternative forms of magnesium might be worthwhile. There are, however, newer candidates that interfere with calcification that are likely to be studied sooner, and because of PXE's rarity, multiple studies of different compounds will be challenging. Full-Text PDF" @default.
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