LAUSR

For a long time, phosphate, the anion that incorporates the element phosphorus, has been considered of minor relevance compared to its most studied parent calcium. However, the interest in phosphate metabolism has been remarkably increased in the last two decades. This has been mainly driven, among others, by two factors. The first one relates to the appreciation that hypophosphatemia (as well as hyperphosphatemia), has deleterious effects not only on bone but also on other organs and systems such as skeletal muscle, myocardium, the haematopoietic, respiratory and central nervous systems, in addition to sensory organs [1]. Further impetus has been fuelled by finding molecular mechanisms underlying congenital diseases characterized by hypo and hyperphosphatemia and discovery of drugs reversing the culprit mechanism. It is therefore consequential devoting a special issue of Calcified Tissue International to phosphate metabolism. Dr Munro Peacock elegantly reviewed phosphate metabolism emphasizing differences occurring in different periods of life, addressing old and new systemic actors involved in its homeostasis [2]. There has been a long-standing debate on the putative mechanisms underlying the sensing of changes in phosphorus concentrations in humans. Kritmetapak and Kumar [3], shed lights on this important aspect. Multicellular organisms have developed complex systems of phosphorus sensing. Indeed, there is a strong evidence that type III sodium phosphate cotransporter acts as a cell-surface phosphorus sensor to changes of extracellular concentrations. There is no doubt that inorganic phosphate is fundamental in the process of biomineralization, a complex and lifelong process needed to maintain the structural integrity of the three specialized mineralized tissues, i.e. bone, teeth and ossicles. However, Bhadada and Rao highlight that the exact mechanisms underlying this process are not fully understood [4]. It is a common finding that deviations from normal values of serum phosphate often go unnoticed by general practitioners, but also by doctors working in hospitals of National Health Systems and in Academic centres. However, both reduced and increased values of serum phosphate represent important biochemical clues of silent diseases. Roux’s group [5] offers a detailed overview of diseases and drugs that cause hypo and hyperphosphatemia. Step by step approaches to investigate these biochemical abnormalities, reported in Figs. 1 and 2, are particularly illustrative. The most striking scientific advances concerning pathogenetic mechanism, have been made in understanding congenital diseases causing hypophosphatemia in children [6]. Some of these conditions may go unrecognized and are diagnosed later in life; this situation may pose difficulties concerning type and duration of treatment as outlined by Marcucci and Brandi [7]. Congenital diseases causing hyperphosphatemia, are described by Ito and Fukumoto [8]. Scientific advances in understanding mechanisms underlying these conditions have been made; however, developments in therapy lag behind those reached in hypophosphatemic conditions. Bacchetta and co-workers [9] give a detailed description of deleterious effects of hyperphosphatemia in patients with kidney failure suggesting optimal treatment in the context of complex mineral and bone disorders associated with chronic kidney disease. Tumour induced osteomalacia represents a difficult clinical condition to diagnose and treat [10, 11]. Recently there has been a surge of case descriptions in the literature, hopefully implying a raising awareness of the disease. Collins’s group [12] report the latest advances in the field and propose a new nomenclature under the “umbrella term” of oncogenic osteomalacia, to include all cases of benign or malignant neoplasms associated with FGF23 excess. Until recently, therapy of hypophosphatemic conditions related to fibroblast growth factor 23 excess was * Salvatore Minisola [email protected]