Low Vitamin D Levels Lead to Pain Problems for Sickle Cell Patients

December 14, 2021
Kenny Walter

Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.

High dose vitamin D supplementation has been linked to fewer pain days and higher physical activity scores for patients with chronic pain.

New data from the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition shows vitamin D deficiencies cause more pain problems for patients with sickle cell disease (SCD).

A team, led by Latika Puri, MD, MBBS, Department of Pediatrics, Division of Pediatric Hematology/ Oncology, Loma Linda University, evaluated the relationship between vitamin D levels, acute health care utilization and self-reported pain among children with SCD.

The Problem

Patients with sickle cell disease often also suffer from vitamin D deficiencies, often due to their dark skin color, limited physical activity, poor nutrition, and renal dysfunction.

In the past investigators have found vitamin D deficiencies were linked to increased frequency of acute pain events and higher opioid use in this patient population. However, this research has only been conducted in smaller retrospective studies and he impact of vitamin D deficiency on pain related patient reported outcomes has not been examined.

In addition, high dose vitamin D supplementation has been linked to fewer pain days and higher physical activity scores for patients with chronic pain.

The Solution

The investigators hypothesized that vitamin D deficiency is associated with increase health care utilization for pain and patient-reported outcomes for pain.

In the study, the investigators examined 799 pediatric patients with sickle cell disease from the Sickle Cell Clinical Research and Intervention Program (SCCRIP), at St. Jude Children’s Research Hospital

The team extracted democrapgic, clinical, and laboratory data from the SCCRIP database and analyzed prospective pain events leading to hospital visits for patients.

They also analyzed pain-related hospitalizations by the number of pain-related hospitalizations within 2 years prior to and after vitamin D measurement in a cross-sectional design and longitudinally.

In addition, the team analyzed associations between vitamin D and cross-sectional pain events with adjusting for hydroxyurea use using a generalized linear regression model and assessed the associations between vitamin D and longitudinal pain events, with adjusting for SCD genotype, sex, age, hydroxyurea use and interaction between age and hydroxyurea use using a generalized linear mixed effect model.

To measure pain and pain interference the investigators used Pain and Hurt and Pain Impact scales from the Pediatric Quality of Life Inventory™ Sickle Cell Disease Module (PedsQL™ SCD).

Assessments include a Likert response scale and items are reverse -scored and transformed to a 0-100 scale where higher scores indicate better health related quality of life in that scale.

Mean scores between the 2 groups were compared using 2 sample t-test or Wilcoxon rank sum test .


The range at time of first vitamin D measurement for entire cohort was 8.7 (4.7), (0.8-18 years) and mean (SD) initial vitamin D level for entire cohort was 19.0 (9.4) ng/dl.

The mean number of pain-related hospitalizations within two years of first vitamin D measurement was higher in the vitamin D deficient group as compared to non-deficient group [0.81(1.97) vs 0.66 (1.2), (P = 0.0034)].

Longitudinal data analyses showed vitamin D deficiency was associated with increased number of pain related hospitalizations (p=0.0091), after adjusting for covariates.

Mean scores for Pain and Hurt in vitamin D deficient compared to non deficient group were [74.5.7(18.2) versus 83.5(15.6), P < 0.001], while mean scores for Pain Impact in vitamin D deficient group as compared to non deficient group were [(66.7 (22.7) versus 75.5 (22.3), P <0.001].

“Results indicated that low vitamin D levels predicted higher frequency of painful events leading to a hospital visit and were associated with higher prevalence of self-reported pain and pain interference,” the authors wrote. “Further studies evaluating mechanisms by which vitamin D influences sickle cell pain are warranted and larger controlled trials can help evaluate the therapeutic efficacy of vitamin D for sickle cell pain.”

The study, “Vitamin D Levels: Associations with Acute Pain Events and Self-Reported Pain in Children with Sickle Cell Disease,” was published online by ASH.