Reciprocal regulation of calcium-/phosphate-regulating hormones in cyclists during the Giro d’Italia 3-week stage race G. Lombardi 1 , R. Corsetti 2 , P. Lanteri 1 , D. Grasso 1 , E. Vianello 3 , M. G. Marazzi 3 , R. Graziani 4 , A. Colombini 1 , E. Galliera 1,5 , M. M. Corsi Romanelli 3,6 , G. Banfi 1,3 1 Experimental Biochemistry and Molecular Biology Laboratory, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italy, 2 Liquigas Cannondale Pro Cycling Team, Medical board, Sesto al Reghena, Italy, 3 Department of Biomedical Sciences for Health, University of Milano, Milano, Italy, 4 Centro Diagnostico Alto Lombardo – CEDAL, Gallarate, Italy, 5 Department of Biomedical, Surgical and Oral Science, University of Milano, Milano, Italy, 6 Clinical Pathology Operative Unit, Department of Healthcare, Diagnosis and Treatment, Laboratory Medicine, I.R.C.C.S. Policlinico San Donato, San Donato, Italy Corresponding author: Giovanni Lombardi, PhD, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milano, Italy. Tel: +390266214068, Fax: +390266214060, E-mail: giovanni.lombardi@grupposandonato.it Accepted for publication 20 October 2012 Calcium and phosphate are essential for cell functions, and their serum concentrations result from the balance between intestinal absorption, bony storage, and urinary excretion. Fibroblast growth factor 23 (FGF23), expressed by osteocytes and osteoblasts, acts in the kidney, leading to hypophosphatemia and low 1,25- dihydroxycholecalciferol synthesis, but suppresses par- athyroid function. The aim of this study was to explore the effects of a high-energy demanding cycling race on this bone–kidney–parathyroid axis. We studied nine cyclists during the 2011 Giro d’Italia stage race. Pre- analytical and analytical phases followed academic and anti-doping recommendations. Serum parathyroid hormone (PTH), 25(OH)D, total calcium, inorganic phos- phorus, and plasma FGF23 were measured on days -1, 12, and 22 and corrected for changes in plasma volume. Dietary calcium and phosphorus, anthropometric param- eters (height, weight, and body mass index) and indexes of metabolic effort (net energy expenditure, power output) were recorded. Dietary calcium and phosphorus intakes were kept at the same levels throughout the race. Twenty- five (OH)D, PTH, and calcium concentrations remained stable. FGF23 increased 50% with a positive correlation with the indexes of metabolic effort and, consequently, phosphorous decreased, although only in the first half. The strong metabolic effort acts on the bone–kidney– parathyroid system, and the rise in FGF23 plasma con- centration might be aimed at maintaining calcium and phosphorus homeostasis. At least 20 different minerals are required in adequate amounts to sustain the normal function of tissues and cells. A balanced diet, adequate to meet the person’s energy needs, will normally supply the right amounts of all the nutrients required (Maughan, 1999). Phosphate is essential for a number of cellular func- tions and is taken up by the cells from the circulation through sodium-phosphate co-transporters (NaP i -II/III). The serum phosphorus concentration is determined by the balance between intestinal absorption of phosphate from the diet (16 mg/kg/day), bone storage (3 mg/kg/ day), and urinary excretion (13 mg/kg/day; Berndt & Kumar, 2009). About 30% of intestinal phosphate is absorbed in a regulated, 1,25-dihydroxycholecalciferol [1,25(OH) 2 D]-dependent manner (Wilz et al., 1979). Reabsorption from the urine, in the proximal tubules of the kidney, via NaP i -II/III, is fundamental for maintain- ing serum phosphate homeostasis (Murer et al., 2004), and it underlies tight hormonal control by the parathy- roid hormone (PTH) and fibroblast growth factor 23 (FGF23; Bergwitz & Juppner, 2010). In the proximal renal tubule, PTH, through its receptor PTHR1, leads to internalization of the sodium-phosphate co-transporters NaPi-IIa and NaPi-IIc, resulting in renal phosphate wasting and hypophosphatemia (Forster et al., 2006). Because parathyroid glands are “cal- ciostats,” the extracellular calcium concentration [(Ca 2+ ) e ] firmly regulates PTH production, acting at transcriptional and post-transcriptional levels (Kemper et al., 1974). PTH, in turn, regulates the calcium metabo- lism and serum P i , acting at several sites, and high P i concentrations induce PTH production, presumably by lowering (Ca 2+ ) e and increasing the stability of PTH mRNA (Moallem et al., 1998). PTH gene expression is negatively regulated by 1,25(OH) 2 D (Silver et al., 1985) and by FGF23, which suppresses PTH mRNA synthesis and protein secretion in vitro and in vivo in an a-klotho (KL)-dependent way (Ben-Dov et al., 2007). In the parathyroids, 1,25(OH) 2 D inhibits PTH synthe- sis and secretion both directly (Demay et al., 1992) and by inducing the expression of the calcium-sensing recep- Scand J Med Sci Sports 2014: 24: 779–787 doi: 10.1111/sms.12080 © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 779