vitamin d and bisphosphonates in the treatment of sickle cell disease

Conditions: Sickle Cells Disease

Summary: sickle cell disease (scd) is a worldwide distributed hereditary red cell disorder, which affects approximately 75,000 individuals in the united states and almost 20,000- 25,000 subjects in europe, this latter mainly related to the immigration fluxes from endemic areas such as sub-saharian africa to european countries. studies of global burden disease have pointed out the invalidating impact of scd on patient quality of life. this requires the development of new therapeutic options to treat sickle cell related acute and chronic complications. scd is caused by a point mutation in the β-globin gene resulting in the synthesis of pathological hemoglobin s (hbs). hbs displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density and further acceleration of hbs polymerization. pathophysiological studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of scd, in which intravascular sickling in capillaries and small vessels leads to vaso-occlusion and impaired blood flow with ischemic/reperfusion injury. in microcirculation, vaso-occlusive events (voc) result from a complex and still partially known scenario, involving the interactions between different cell types, including dense red cells, reticulocytes, abnormally activated endothelial cells, leukocytes, platelets and plasma factors. target organs, such as bone or lung, are involved in both acute and chronic clinical manifestations of scd, related to their peculiar anatomic organization mainly characterized by sluggish circulation and relative local hypoxia. vocs combined with marrow hyperplasia and inflammation has been suggested to contribute to the development of sickle bone disease (sbd). recently, it has been proposed a possible role of vitamin d deficiency in sbd, which appears to be subordinated to the primary defect in bone homeostasis. in a humanized mouse model for scd, we recently reported that sbd is due to imbalance between osteoblast/osteoclast activity induced by recurrent vocs. in addition, we show that zoledronic acid prevents bone impairment related to scd, reducing osteoclast activity and improving osteoblast performance.

this is a retrospective study aimed to evaluate sickle bone disease (sbd) in a population of young adult patients with sickle cell disease treated with vitamin d supplementation and anti-resorptive therapy (bisphosphonates). we plan to analyze data from 1 january 2010 to 31 december 2015. in addition to the standard hematological analysis, the following parameters and radiologic exams will be evaluated: * serum levels of ca2+, p, vitamin d, parathormone , creatinine, blood urea nitrogen , na, k, cl * bone turnover markers: c-terminal telopeptide (ctx), n-terminal propeptide of type i procollagen (pinp) * bone densitometry (dxa) at lumbar spine and proximal femur * standard x-ray at dorsal-lumbar spine in ll projection for morphometric analysis

Eligibility criteria:
inclusion criteria: * young adult patients with sickle cell disease (older than 18 years of age) and younger than 50 years of age exclusion criteria: * women with positive pregnant test, patients with history of heart, renal and liver failure, patients taking drugs influencing bone metabolisms within the two years before the beginning of the study (i.e.: glucocorticoids, hormonal replacement) * patients in meonopause, patients with traumatic vertebral fracture * patients with hypo/hyperthyroidism * patients with hyperparathyroidism * patients with osteomalacia, patients with history of paget disease * patients with cushing syndrome * patients with malabsorption diseases (i.e.: caeliac disease) * patients with history of cancer

Keywords: sickle-cells disease bisphosphonates vitamine d