Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. How to diagnose and manage difficult problems of calcium metabolism in sarcoidosis: an evidence-based review Violeta Vucinic a,b , Vesna Skodric-Trifunovic a,b and Svetlana Ignjatovic ´ c,d Introduction Calcium metabolism impairments have long been recog- nized as complication of sarcoidosis. On searching PubMed (the search terms: calcium metab- olism in sarcoidosis), as many as 440 published articles appear to be relevant to the topic. The most recent one was published in January 2011 in the American Journal of Kidney Diseases by a group of French authors – a case of a 29-year-old man with membranous nephropathy associ- ated with sarcoidosis granulomatous tubulointerstitial nephritis, but without an apparent calcium metabolism disorder [1]. The first article published on this topic was in the Journal of Clinical Investigation in January 1948. The kidneys may be affected primarily by sarcoid gran- ulomas or secondarily from hypercalcemia, hypercal- ciuria, and nephrocalcinosis. Hypercalcemia and hyper- calciuria appear to be important clinical features of sarcoidosis, resulting from overproduction of 1,25-dihy- droxyvitamin D3 (calcitriol) by activated macrophages and sarcoidosis granulomas [2]. Calcium homeostasis is primary controlled by levels of vitamin D, parathyroid hormone (PTH) and calcitonin, but it is also influenced by the thyroid gland and sex hormones. In sarcoidosis there is deregulation of these mechanisms, leading to clinically manifested problems. In this article we will shed light on the most recent facts published about calcium metabolism abnormalities in sarcoidosis. Vitamin D and calcium metabolism Vitamin D was classified as a vitamin in the early 20th century and later on as a prohormone (‘conditional’ vitamin) [3]. There are two forms of vitamin D: vitamin D3 (cholecalciferol), which is produced from the conver- sion of 7-dehydrocholesterol in the epidermis and dermis in humans, and vitamin D2 (ergocalciferol), which is produced in mushrooms and yeast. The major source of vitamin D for humans is exposure to sunlight. The efficiency of the conversion of 7-dehydrocholesterol to vitamin D3 is dependent on time of day, season of the year, latitude, skin color and age. There is little vitamin D a Clinic of Pulmonology, Clinical Center Serbia, b Medical School, University of Belgrade, c Department of Medical Biochemistry, School of Pharmacy and d University of Belgrade and Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia Correspondence to Violeta Vucinic, MD, PhD, Professor of Internal Medicine and Pulmonology, Head of Vth Clinical Department (Department of Sarcoidosis), Clinic of Pulmonology, Clinical Center Serbia, Visegradska 26/20, 11000 Belgrade, Serbia Tel: +381 113663460; e-mail: violetavucinic@gmail.com Current Opinion in Pulmonary Medicine 2011, 17:297–302 Purpose of review Calcium metabolism impairments have long been recognized as a complication of sarcoidosis. For more than six decades physicians and investigators have been trying to elucidate this severe problem; nevertheless it seems puzzlingly new for both readers and researchers. Recent findings This review highlights the problems of calcium metabolism in sarcoidosis in relation to vitamin D synthesis, which is definitely altered by granulomatous inflammation. Increasing evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. As calcium homeostasis is primary controlled by levels of vitamin D, parathyroid hormone (PTH) and calcitonin, this literature review emphasizes the role of general immunomodulating properties of vitamin D and the correlation with calcium metabolism impairments, with the special accent on already known interactions with sarcoidosis. Summary Granuloma formation has been related to a failure of the innate immune system. One of the possible explanations is a vitamin D deficiency. The evidence-based findings on calcium metabolism impairments and the interactions with vitamin D might help both clinicians and researchers in developing new strategies. Keywords calcium metabolism, sarcoidosis, vitamin D Curr Opin Pulm Med 17:297–302 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins 1070-5287 1070-5287 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MCP.0b013e328348b3cb