Vitamin D and Bisphosphonates in the Treatment of Sickle Cell Disease

Vitamin D Supplementation and Anti-resorptive Therapy (Bisphosphonates) Treatment of Young Adult Patients With 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.

Study Overview

Status

Completed

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

Study Type

Observational

Enrollment (Actual)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Genova, Italy, 16128
        • Ospedali Galliera - S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro
      • Genova, Italy, 16128
        • Ospedali Galliera - S.S.D. Ortogeriatria per intensità di cure
      • Verona, Italy, 37129
        • Universita Degli Studi Di Verona

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of vertebral fracture
Time Frame: 5 years follow up
5 years follow up

Secondary Outcome Measures

Outcome Measure
Time Frame
severity of vertebral fracture
Time Frame: 5 years follow up
5 years follow up
Incidence of non-vertebral fracture
Time Frame: 5 years follow up
5 years follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Luca G Dalle Carbonare, MD, Universita Degli Studi Di Verona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

September 1, 2017

Study Registration Dates

First Submitted

October 28, 2016

First Submitted That Met QC Criteria

November 21, 2016

First Posted (ESTIMATE)

November 23, 2016

Study Record Updates

Last Update Posted (ACTUAL)

October 6, 2017

Last Update Submitted That Met QC Criteria

October 5, 2017

Last Verified

December 1, 2015

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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