Sickle Cell Disease, Sickle Cell Anemia, Low Bone Density, Osteoporosis, Osteopenia, Vertebral Fracture, Vertebral Compression, Osteonecrosis, Ischemic Necrosis, Avascular Necrosis
Conditions
Keywords
sickle cell disease, sickle cell anemia, low bone density, osteoporosis, osteopenia, low bone mass
Brief summary
A prospective study to determine how low bone mineral density and/or vertebral compression fractures associate with pain in adults with sickle cell disease
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.
Interventions
Measure bone mineral density at the lumbar spine, left total hip, left forearm, and whole body
OTHERVertebral fracture analysis
Obtain thoracolumbar morphometry in DXA scan, then determine presence and severity of vertebral compression fractures by VFA
OTHERAdult 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
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Doris Duke Charitable Foundation
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Prospective cohort study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact T-scores | Baseline | 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) |
| Total Hip Bone Mineral Density (BMD) | Baseline | Areal bone mineral density of the total hip measured by dual-energy X-ray absorptiometry (DXA) scan and reported in grams per square centimeter. |
| Lumbar Spine Bone Mineral Density | Baseline | Areal bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) scan and reported in grams per square centimeter. |
| Lumbar Spine Bone Mineral Density-Z-scores | Baseline | 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. |
| Total Hip Bone Mineral Density-Z-scores | At enrollment | 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. |
| Femoral Neck Bone Mineral Density (BMD) | Baseline | Areal bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry (DXA) scan and reported in grams per square centimeter. |
| Femoral Neck Bone Mineral Density Z-scores | Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spinal Deformity Index | Baseline | 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. |
Countries
United States
Participant flow
Recruitment details
One hundred and twenty-eight unique adults (age 18 years and older) with SCD of any genotype seen in the Adult Sickle Cell clinic at UCD's Comprehensive Cancer Center between 2022-2023 were eligible to participate in the SCD Bone Pain study.
Pre-assignment details
From this convenience sample of 128 SCD adults, 72 were approached to participate in the study, and 53 participants eventually enrolled in the SCD Bone Pain study
Participants by arm
| Arm | Count |
|---|---|
| SCD Bone Pain Study Cohort Prospective cohort of 53 adults with sickle cell disease (SCD) to assess the following:
1. Bone mineral density (BMD) at the lumbar spine, left total hip, left forearm, and whole body, using a dual-energy X-ray absorptiometry (DXA) scan
2. Spinal deformity index (measure of presence and severity of vertebral fractures) using thoracolumbar morphometry obtained from the DXA scanner
3. Patient-reported pain impact score obtained from the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain impact questionnaire | 53 |
| Total | 53 |
Baseline characteristics
| Characteristic | SCD Bone Pain Study Cohort |
|---|---|
| Age, Continuous | 36 Years |
| Body mass index (BMI) | 24.6 kg/m2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 172 cm |
| Osteonecrosis No | 31 Participants |
| Osteonecrosis Yes | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 53 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 19 Participants |
| Sickle cell disease (SCD) genotype Hb SB+ | 2 Participants |
| Sickle cell disease (SCD) genotype Hb SB0 | 5 Participants |
| Sickle cell disease (SCD) genotype Hb SC | 15 Participants |
| Sickle cell disease (SCD) genotype Hb SD | 1 Participants |
| Sickle cell disease (SCD) genotype Hb SS | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 53 |
| other Total, other adverse events | 0 / 53 |
| serious Total, serious adverse events | 0 / 53 |
Outcome results
Primary
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)
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact T-scores | 47.1 T-score |
| Group B | Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact T-scores | 52.4 T-score |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median (interquartile range) for each group, based on the ASCQ-Me Pain Impact instrument (lower scores indicate worse pain impact). Welch two-sample t-test (two-sided) was used to account for unequal variances. A p-value \< 0.05 was considered statistically significant.p-value: 0.23Welch two sample t-test (two sided)
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Femoral Neck Bone Mineral Density (BMD) | 0.77 g/cm2 |
| Group B | Femoral Neck Bone Mineral Density (BMD) | 0.94 g/cm2 |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median (full range) for each group, measured by DXA at the femoral neck. Distribution was non-normal, so a Wilcoxon rank-sum test (two-sided) was used. A p-value \< 0.05 was considered statistically significant.p-value: 0.013Wilcoxon rank-sum test (two-sided)
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Femoral Neck Bone Mineral Density Z-scores | -0.95 Z-score |
| Group B | Femoral Neck Bone Mineral Density Z-scores | -0.60 Z-score |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median ± full range for each group, derived from DXA femoral neck scans. Welch two-sample t-test (two-sided) was used to account for unequal variances. A p-value \< 0.05 was considered statistically significant.p-value: 0.166Welch two sample t-test
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Lumbar Spine Bone Mineral Density | 0.97 g/cm2 |
| Group B | Lumbar Spine Bone Mineral Density | 1.0 g/cm2 |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median (full range) for each group, measured by DXA at the lumbar spine. Distribution was non-normal, so a Wilcoxon rank-sum test (two-sided) was used. A p-value \< 0.05 was considered statistically significant.p-value: 0.321Wilcoxon rank-sum test (two-sided)
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Lumbar Spine Bone Mineral Density-Z-scores | -1.35 Z-score |
| Group B | Lumbar Spine Bone Mineral Density-Z-scores | -1.60 Z-score |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median ± full range for each group, derived from DXA lumbar spine scans. Welch two-sample t-test (two-sided) was used to account for unequal variances. A p-value \< 0.05 was considered statistically significant.p-value: 0.714Welch two sample t-test
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Total Hip Bone Mineral Density (BMD) | 0.90 g/cm2 |
| Group B | Total Hip Bone Mineral Density (BMD) | 1.03 g/cm2 |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median (full range) for each group, measured by DXA at the total hip. Distribution was non-normal, so a Wilcoxon rank-sum test (two-sided) was used. A p-value \< 0.05 was considered statistically significant.p-value: 0.09Wilcoxon rank-sum test (two-sided)
Primary
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.
Time frame: At enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Total Hip Bone Mineral Density-Z-scores | -0.75 Z-score |
| Group B | Total Hip Bone Mineral Density-Z-scores | -0.5 Z-score |
Comparison: Comparison between Group A and Group B as defined above. Values are reported as median ± full range for each group, derived from DXA total hip scans. Welch two-sample t-test (two-sided) was used to account for unequal variances. A p-value \< 0.05 was considered statistically significant.p-value: 0.604Welch two sample t-test (two sided)
Secondary
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.
Time frame: Baseline
Population: Statistical analysis of spinal deformity index is ongoing. Complete results will be provided by February 2026.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Spinal Deformity Index | 2.00 score on a scale | Standard Deviation 2.71 |
| Group B | Spinal Deformity Index | 3.13 score on a scale | Standard Deviation 3.98 |