Vitamin D and Bisphosphonates in the Treatment of Sickle Cell Disease
Condition: Sickle Cells Disease
MeSH terms: Anemia, Sickle Cell
Study type: Observational

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.
    

Detailed description: 
      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
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with sickle cell disease older than 18 years of age and younger than 50 years of
        age
      
Keywords: Sickle-cells Disease; bisphosphonates; Vitamine D