Vitamin D and Bisphosphonates in the Treatment of Sickle Cell Disease
Vitamin D and Bisphosphonates in the Treatment of Sickle Cell Disease
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
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