Bone Health Impairment in Patients with Hemoglobinopathies: From Biological Bases to New Possible Therapeutic Strategies.

Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the ß-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.

Role of Nutraceuticals in Counteracting Inflammation in In Vitro Macrophages Obtained from Childhood Cancer Survivors.

The advancement of anti-cancer therapies has markedly improved the survival rate of children with cancer, making them long-term childhood cancer survivors (CCS). Nevertheless, these treatments cause a low-grade inflammatory state, determining inflamm-aging and, thus, favoring the early onset of chronic diseases normally associated with old age. Identification of novel and safer therapeutic strategies is needed to counteract and prevent inflamm-aging. Macrophages are cells involved in immune and inflammatory responses, with a pivotal role in iron metabolism, which is related to inflammation. We obtained macrophages from CCS patients and evaluated their phenotype markers, inflammatory states, and iron metabolism by Western blotting, ELISA, and iron assays. We observed a strong increase in classically activated phenotype markers (M1) and iron metabolism alteration in CCS, with an increase in intracellular iron concentration and inflammatory markers. These results suggest that the prevalence of M1 macrophages and alteration of iron metabolism could be involved in the worsening of inflammation in CCS. Therefore, we propose macrophages and iron metabolism as novel therapeutic targets to counteract inflamm-aging. To avoid toxic regimens, we tested some nutraceuticals (resveratrol, curcumin, and oil-enriched lycopene), which are already known to exert anti-inflammatory properties. After their administration, we observed a macrophage switch towards the anti-inflammatory phenotype M2, as well as reductions in pro-inflammatory cytokines and the intracellular iron concentration. Therefore, we suggest-for the first time-that nutraceuticals reduce inflammation in CCS macrophages through a novel anti-inflammatory mechanism of action, modulating iron metabolism.