https://orcid.org/0000-0002-2292-4816
Key Points
Anemia, indirect bilirubinemia, leukocytosis, and crizanlizumab use directly associate with low bone density in sickle cell disease
Adults with sickle cell-related low bone density and osteonecrosis reported worse pain impact than those with either complication alone
Low bone mineral density (BMD) is prevalent skeletal finding in people with sickle cell disease (SCD), but its clinical consequences are poorly understood. We hypothesized that low BMD, independent of osteonecrosis (ON), would associate with worse pain in SCD adults. In the SCD Bone Pain study, 53 ambulatory adults (64% females, mean age 38±11years, 66% Hb SS/Sβ0 thalassemia) underwent dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine, hip, forearm, and whole body. They also completed the Adult Sickle Cell Quality of Life Measurement Information System pain impact questionnaire. Twenty-three participants (43%) had low bone mass, defined as lumbar spine, total hip, or femoral neck BMD Z-scores ≤ -2. In multivariate linear regression, lumbar spine BMD Z-scores significantly changed by +0.31, -0.29, -0.14, and -1.3 for every unit increase in hemoglobin, indirect bilirubin, and white blood cell count, and with Crizanlizumab use, respectively. Pain impact T-scores significantly decreased (worsened) by 6.0 and 6.5 with reduced estimated glomerular filtration rate and chronic opioid therapy, respectively, but increased (improved) by 3.8 for every unit increase in serum phosphate. Median [interquartile range] pain impact T-scores were significantly lower in participants with low BMD and ON (38.3 [37.4, 40.1]), compared to those with either low BMD (49.5 [43.6, 54.4), p=3x10-5 or ON (52.7 [45.3, 57]), p=2x10-4 alone. Whether sickle cell-related low BMD results from impaired bone formation and/or accelerated bone loss remains unclear. Understanding how low bone density, with or without osteonecrosis, mediates SCD pain warrants further investigation. NCT05283148
