Sickle Cell Disease (SCD) Bone Pain Study

Association Between Low Bone Density, Vertebral Fractures, and Pain in Sickle Cell Disease

A prospective study to determine how low bone mineral density and/or vertebral compression fractures associate with pain in adults with sickle cell disease

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoporosis; Osteonecrosis; Avascular Necrosis; Sickle Cell Disease; Sickle Cell Anemia; Osteopenia; Vertebral Fracture; Vertebral Compression; Low Bone Density; Ischemic Necrosis
• Intervention / Treatment: Other: Dual-energy X-ray absorptiometry; Other: Vertebral fracture analysis; Other: Adult Sickle Cell Quality of Life Measurement System pain impact questionnaire

Detailed Description

The investigators hypothesize that adults with sickle cell disease (SCD) and low bone density and/or vertebral compression fractures on a dual X-ray absorptiometry (DXA) scan (adjusted for age, sex, SCD genotype, relevant labs, presence of osteonecrosis, and SCD-modifying therapies) will report more severe pain than those with normal bone density or no vertebral fractures. The Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) is a validated patient-reported outcome measure of physical, mental, and social health in adults with SCD. This cross-sectional observational study involves obtaining a baseline DXA scan, vertebral fracture analysis (VFA) and pain assessment using ASCQ-Me pain impact scores. The investigators plan to recruit 50 adults with SCD followed at University of California Davis Medical Center between Nov 2022- Dec 2023 and anticipate enrolling up to 4 adults with SCD per month. The study endpoints are listed below:

• To determine the association between bone density Z-scores and ASCQ-Me pain impact scores in a prospective cohort of adults with SCD
• To study the association between Spine Deformity Index scores (SDI, a proxy for vertebral fracture analysis) and ASCQ-Me pain impact scores in a prospective cohort of adults with SCD
• To assess the correlation between baseline hematological and biochemical laboratory parameters (including bone biomarkers), bone density, and/or vertebral fractures in a prospective cohort of adults with SCD

The investigators' goal is to complete primary data analysis by Mar 2024. As an exploratory endpoint, 1cc of serum and 5cc of urine will be collected from each study participant once (at baseline), after an overnight fast, for bone biomarker analyses.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Adults with sickle cell disease (any genotype) followed at the University of California Davis Medical Center

Description

Inclusion Criteria:

• Age 18-80 years with SCD (any genotype, confirmed by hemoglobin electrophoresis or high performance liquid chromatography)
• Ability to provide written informed consent
• Ability to lay on a DXA scanner
• Negative urine pregnancy test for women of childbearing potential at study entry

Exclusion Criteria:

• Pregnant women
• Adults unable to consent
• Individuals who are not yet adults (infants, children, teenagers)
• Prisoners
• Hospitalizations (any cause) within 2 weeks of study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: SCD Bone Pain Study Cohort; Prospective cohort of 50 adults with sickle cell disease (SCD) undergoing research DXA scan to assess bone mineral density and thoracolumbar morphometry for vertebral fracture analysis

Other: Dual-energy X-ray absorptiometry; Measure bone mineral density at the lumbar spine, left total hip, left forearm, and whole body; Other Names: DXA scan; Other: Vertebral fracture analysis; Obtain thoracolumbar morphometry in DXA scan, then determine presence and severity of vertebral compression fractures by VFA; Other Names: VFA; Other: Adult Sickle Cell Quality of Life Measurement System pain impact questionnaire; Calculate patient-reported total pain scores to determine the pain phenotype of each study participant; Other Names: ASCQ-Me Pain scores

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lumbar Spine Bone Mineral Density	Areal bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) scan and reported in grams per square centimeter.	Baseline
Lumbar Spine Bone Mineral Density-Z-scores	Number of standard deviations between measured lumbar spine bone mineral density (g/cm2) for each participant and mean lumbar spine bone mineral density (g/cm2) of the reference population. A Z-score of 0 represents the mean of the reference population. A negative Z-score means the measured bone mineral density values are lower (worse) the reference mean, while positive Z-scores mean they are above/higher. Bone mineral density Z-scores ≤ -2 indicates low bone density.	Baseline
Total Hip Bone Mineral Density (BMD)	Areal bone mineral density of the total hip measured by dual-energy X-ray absorptiometry (DXA) scan and reported in grams per square centimeter.	Baseline
Total Hip Bone Mineral Density-Z-scores	Number of standard deviations between measured total hip bone mineral density (g/cm2) for each participant and mean total hip bone mineral density (g/cm2) of the reference population. A Z-score of 0 represents the mean of the reference population. A negative Z-score means the measured bone mineral density values are lower (worse) the reference mean, while positive Z-scores mean they are above/higher. Bone mineral density Z-scores ≤ -2 indicates low bone density.	At enrollment
Femoral Neck Bone Mineral Density (BMD)	Areal bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry (DXA) scan and reported in grams per square centimeter.	Baseline
Femoral Neck Bone Mineral Density Z-scores	Number of standard deviations between measured lumbar spine bone mineral density (g/cm2) for each participant and mean lumbar spine bone mineral density (g/cm2) of the reference population. A Z-score of 0 represents the mean of the reference population. A negative Z-score means the measured bone mineral density values are lower (worse) the reference mean, while positive Z-scores mean they are above/higher. Bone mineral density Z-scores ≤ -2 indicates low bone density.	Baseline
Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact T-scores	Patient-reported outcome measure of pain impact in the preceding 7 days before bone density measurements. The Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) pain impact T-scores range from about 30-100. The ASCQ-Me pain impact T-score has standardized mean T-score of 50 and standard deviation of 10, which were derived from a reference population of ambulatory adult with sickle cell disease across the United States. ASCQ-Me pain impact T-scores less than 50 are lower/worse than the reference mean (more severe pain impact), while pain impact T-scores greater than 50 are above/better than the reference mean (less severe pain impact)	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spinal Deformity Index	The spinal deformity index (SDI) is a semi-quantitative measure of number and severity of vertebral fractures observed on lateral spine X-rays of the thoracolumbar spine. To calculate the SDI, vertebrae are assigned a score as follows: 0 (no fracture), 1 (mild fracture), 2 (moderate fracture), and 3 (severe fracture). The total SDI is the summation of all T12-L4 vertebrae measured on the lateral spine X-rays. Minimum SDI =0 and Maximum SDI=15. Higher scores mean increased (worse) fracture burden, lower scores mean decreased (less) fracture burden.	Baseline

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Doris Duke Charitable Foundation
• Investigators: Principal Investigator: Oyebimpe O Adesina, MD, MS, UC Davis School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2022
• Primary Completion (Actual): April 30, 2024
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: osteoporosis; sickle cell disease; osteopenia; sickle cell anemia; low bone mass; low bone density
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Wounds and Injuries; Pathologic Processes; Genetic Diseases, Inborn; Metabolic Diseases; Hematologic Diseases; Fractures, Bone; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Back Injuries; Spinal Injuries; Necrosis; Osteoporosis; Anemia, Sickle Cell; Bone Diseases, Metabolic; Osteonecrosis; Spinal Fractures
• Other Study ID Numbers: 1782537; K23HL148310 (U.S. NIH Grant/Contract); 2020095 (Other Grant/Funding Number: Doris Duke Charitable Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No