Klotho, a New Marker for Osteoporosis and Muscle Strength in β-Thalassemia Major

β-thalassemia syndromes are a group of hereditary blood disorders characterized by reduced or absent β-globin synthesis, resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. Growth retardation is observed frequently and fragility fractures are common in these patients. Osteoporosis affects approximately 51% of the patients with another 45% suffering from osteopenia. In recent years, researchers have focused the attention on a gene called α-Klotho (Klotho). The Klotho gene encodes a protein that is expressed in kidney, parathyroid gland and choroid plexus. Klotho protein is present in blood, urine and cerebrospinal fluid and it is involved in calcium homeostasis in the kidney. Re-absorption of calcium in the distal tubule of the kidney. knock-out mutants for the gene. These animals developed an 'aging' phenotype which included, among other conditions, reduced bone density, growth retardation, hypogonadism There are very few clinical studies that link the levels of secreted Klotho in peripheral blood and phenotype in humans and none of them in β-thalassemia subjects. Aim of this study was to analyze possible correlations between plasma level of Klotho protein and osteoporosis, poor muscle strength and fractures in patients with β-thalassemia major. A total of 106 β-thalassemia major patients and 95 healthy blood donors were enrolled. Patients with β-thalassemia major had lower level of Klotho than healthy controls. Klotho was lower in patients with osteopenia/osteoporosis. Moreover, a low level of protein increased the probability of fragility fracture. The muscle strength was found directly correlated to Klotho (up to 580 pg/ml). This analysis suggests that age- or even a disease-related decrease of Klotho may play a key role in the chain of events producing sarcopenia and osteoporosis, components of the dysmobility syndrome. Furthermore, this study identifies Klotho as a potential risk factor for dysmobility syndrome and its clinically relevant complication, namely fragility fractures.