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Height-corrected low bone density associates with severe outcomes in sickle cell disease: SCCRIP cohort study results

Oyebimpe O. Adesina, James G. Gurney, Guolian Kang, Martha Villavicencio, Jason R. Hodges, Wassim Chemaitilly, Sue C. Kaste, Babette S. Zemel and Jane S. Hankins

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Sex differences in height-for-age and TBLH aBMD-for-age curves in the SCCRIP pediatric cohort. Stature-for-age curves for female subjects (A) and male subjects (B) in the SCCRIP pediatric cohort, compared with reference data from healthy children and adolescents from the US National Center for Health Statistics. TBLH aBMD vs chronological age for female subjects (C) and male subjects (D) in the SCCRIP pediatric cohort. The TBLH aBMD reference curves were obtained from healthy African American control subjects, ages 6 to 18 years, enrolled in the BMDCS. The 50th percentile (green line) represents the mean value-for-age (z score = 0) of the reference populations.

  • Figure 2.

    TBLH aBMD-for-age z scores vs Ht-aBMD z scores in the SCCRIP pediatric cohort.

Tables

  • Table 1.

    Baseline demographic characteristics and DXA results for the SCCRIP BMD Cohort

    VariableAll (N = 306)Female (n = 153)Male (n = 153)
    School-age (n = 96 [31.4%])Adolescent (n = 210 [68.6%])School-age (n = 46 [30.1%])Adolescent (n = 107 [69.9%])School-age (n = 50 [32.7%)Adolescent (n = 103 [67.3%])
    SCD genotype
     HbSS/Sβ0-thalassemia61 (63.5)136 (64.8)27 (58.7)67 (62.6)34 (68.0)69 (67.0)
     HbSC28 (29.2)52 (24.8)16 (34.8)30 (28.0)12 (24.0)22 (21.4)
     HbSβ+-thalassemia7 (7.3)22 (10.5)3 (6.5)10 (9.4)4 (8.0)12 (11.6)
    Age at DXA, y7.2 ± 1.13*14.8 ± 2.16*7.0 ± 0.78*14.9 ± 2.16*7.4 ± 1.37*14.7 ± 2.17*
    Race/ethnicity
     African American94 (97.9)210 (100.0)44 (95.6)107 (100)50 (100)103(100)
     Other2 (2.1)0 (0)2 (4.4)0 (0)0 (0)0 (0)
    Hydroxyurea use
     No42 (43.8)83 (39.5)21 (45.6)44 (41.1)21 (42.0)39 (37.9)
     Yes54 (56.2)127 (60.5)25 (54.4)63 (58.9)29 (58.0)64 (62.1)
    Chronic RBC transfusions
     No95 (99.0)202 (96.2)46 (100)101 (94.4)49 (98.0)101 (98.1)
     Yes1 (1.0)8 (3.8)0 (0)6 (5.6)1 (2.0)2 (1.9)
    Height, cm122.2 ± 9.74*160.0 ± 11.53*120.7 ± 7.97*158.1 ± 8.51*123.5 ± 11.03*161.9 ± 13.77*
    Height-for-age z scores−0.12 ± 1.07−0.21 ± 1.11−0.19 ± 0.96−0.14 ± 1.09−0.05 ± 1.17−0.29 ± 1.13
    TBLH aBMD, g/cm20.58 ± 0.07*0.86 ± 0.11*0.57 ± 0.06*0.85 ± 0.09*0.59 ± 0.08*0.86 ± 0.14*
    TBLH aBMD z score
     Normal73 (76.0)137 (65.2)35 (76.1)73 (68.2)38 (76.0)64 (62.1)
     Low23 (24.0)73 (34.8)11 (23.9)34 (31.8)12 (24.0)39 (37.9)
    TBLH aBMD z score−1.14 ± 1.03*−1.60 ± 1.25*−1.07 ± 1.06*−1.54 ± 1.20*−1.20 ± 1.01*−1.65 ± 1.30*
    TBLH Ht-aBMD z score
     Normal92 (95.8)*158 (75.2)*44 (95.6)*84 (78.5)*48 (96.0)*74 (71.8)*
     Low4 (4.2)*52 (24.8)*2 (4.4)*23 (21.5)*2 (4.0)*29 (28.2)*
    TBLH Ht-aBMD z score−0.80 ± 0.69*−1.36 ± 1.05*−0.81 ± 0.72*−1.34 ± 1.02*−0.80 ± 0.67*−1.37 ± 1.08*
    • Data are presented as n (%) or mean ± standard deviation.

    • Hb, hemoglobin; RBC, red blood cell.

    • * P < .05 between school-age vs adolescent values.

    • Defined as ≥4 RBC transfusions per year.

  • Table 2.

    Clinical correlates of low BMD in the SCCRIP BMD cohort

    VariableAll (N = 306)Female (n = 153)Male (n = 153)
    Normal BMD (n = 250 [81.7%])Low BMD (n = 56 [18.3%])Normal BMD (n = 128 [83.7%])Low BMD (n = 25 [16.3%])Normal BMD (n = 122 [79.7%])Low BMD (n = 31 [20.3%])
    SCD genotype
     HbSS/Sβ0-thalassemia152 (60.8)*45 (80.4)*75 (58.6)*19 (76.0)*77 (63.1)*26 (83.9)*
     HbSC76 (30.4)*4 (7.1)*44 (34.4)*2 (8.0)*32 (26.3)*2(6.4)*
     HbSβ+-thalassemia22 (8.8)*7 (12.5)*9 (7.1)*4 (16.0)*13 (10.7)*3 (9.7)*
    Age at DXA, y11.9 ± 4.09*14.5 ± 2.75*12.2 ± 4.1814.2 ± 2.7711.7 ± 3.98*14.7 ± 2.77*
    Age category
     School-age92 (36.8)*4 (7.1)*44 (33.9)*2 (8.0)*48 (39.3)*2 (6.5)*
     Adolescent158 (63.2)*52 (92.9)*84 (65.6)*23 (92.0)*74 (60.7)*29 (93.6)*
    VOEs per year (total)0.25 ± 0.440.22 ± 0.480.21 ± 0.370.27 ± 0.590.29 ± 0.500.19 ± 0.39
    VOEs per year (2 y to DXA)0.58 ± 2.120.71 ± 1.700.47 ± 1.480.56 ± 1.230.69 ± 2.540.84 ± 2.57
    VOEs total (categorical)
     <5 times141 (56.4)35 (62.567 (52.3)17 (68.0)74 (60.7)18 (58.1)
     5-10 times63 (25.2)11 (19.6)43 (33.6)3 (12.0)20 (16.4)8 (25.8)
     >10 times46 (18.4)10 (17.9)18 (14.1)5 (20.0)28 (22.9)5 (16.1)
    Hydroxyurea use
     No109 (43.6)16 (28.6)57 (44.5)8 (32.0)52 (42.6)8 (25.8)
     Yes141 (56.4)40 (71.4)71 (55.5)17 (68.0)70 (57.4)23 (74.2)
    Hydroxyurea duration
     <5 y187 (74.8)34 (60.7)97 (75.8)16 (64.0)90 (73.6)18 (58.1)
     5-10 y41 (16.4)15 (27.8)22 (17.2)7 (28.0)19 (15.6)8 (25.8)
     >10 y22 (8.8)7 (12.5)9 (7.0)2 (8.0)13 (10.7)5 (16.1)
    Hydroxyurea duration, y2.9 ± 3.95*4.1 ± 4.31*2.8 ± 3.883.6 ± 3.883.1 ± 4.034.4 ± 4.66
    Chronic RBC transfusions
     No245 (98.0)52 (92.9)125 (97.7)22 (88.0)120 (98.4)30 (96.8)
     Yes5 (2.0)4 (7.1)3 (2.3)3 (12.0)2 (1.6)1 (3.2)
    Chronic pain
     No244 (97.6)51 (91.1)125 (97.7)24 (96.0)119 (97.5)27 (87.1)
     Yes6 (2.4)*5 (8.9)*3 (2.3)1 (4.0)3 (2.5)*4 (12.9)*
    Hip osteonecrosis
     No242 (96.8)49 (87.5)126 (98.4)24 (96.0)116 (95.1)25 (80.7)
     Yes8 (3.2)*7 (12.5)*2 (1.6)1 (4.0)6 (4.9)*6 (19.3)*
    Hip osteonecrosis grade
     Less severe3 (1.2)*2 (3.6)*1 (0.8)0 (0)2 (1.6)*2 (6.5)*
     Severe5 (2.0)*5 (8.9)*1 (0.8)1 (4.0)4 (3.3)*4 (12.9)*
     None242 (96.8)49 (87.5)126 (98.4)24 (96.0)116 (95.1)25 (80.6)
    Vitamin D status§
     Normal68 (28.8)9 (17.7)31 (25.4)2 (8.0)37 (32.5)7 (26.9)
     Insufficient91 (38.6)23 (45.1)54 (44.3)10 (40.0)37 (32.5)13 (50.0)
     Deficient77 (32.6)19 (37.3)37 (30.3)13 (52.0)40 (35.1)6 (23.1)
    • Data are presented as n (%) or mean ± standard deviation.

    • * P < .05 between low vs normal BMD per variable.

    • Defined as RBC transfusions ≥4 times/year.

    • Less severe, necrotic lesion ≤30% femoral head volume; severe, necrotic lesion >30% femoral head volume.

    • § Normal, 25(OH)D, >30 ng/mL; insufficient, 25(OH)D 20 to 30 ng/mL; and deficient, 25(OH)D <20 ng/mL.

  • Table 3.

    Laboratory parameters in the SCCRIP BMD cohort

    VariableAll (N = 306)Female (n = 153)Male (n = 153)
    Normal BMD (n = 250 [81.7%])Low BMD (n = 56 [18.3%])Normal BMD (n = 128 [83.7%])Low BMD (n = 25 [16.3%])Normal BMD (n = 122 [79.7%])Low BMD (n = 31 [20.3%])
    WBC, ×109/L9.3 ± 4.039.6 ± 3.719.0 ± 3.929.5 ± 4.379.7 ± 4.139.6 ± 3.14
    Hemoglobin, g/dL10.2 ± 1.60*9.5 ± 1.45*10.0 ± 1.459.5 ± 1.3110.3 ± 1.74*9.5 ± 1.58*
    Platelets, ×109/L343.5 ± 174.97383.0 ± 182.02323.4 ± 158.85388.0 ± 196.77363.9 ± 188.42378.8 ± 172.07
    LDH, U/L411.0 ± 177.51420.9 ± 164.17374.8 ± 149.96369.9 ± 143.80449.9 ± 196.30461.6 ± 170.24
    Total bilirubin, mg/dL1.9 ± 1.28*2.6 ± 1.62*1.7 ± 1.092.4 ± 1.722.0 ± 1.44*2.7 ± 1.55*
    Indirect bilirubin, mg/dL2.1 ± 1.21*2.6 ± 1.48*2.0 ± 0.962.6 ± 1.582.1 ± 1.41*2.6 ± 1.44*
    Fetal hemoglobin, %15.3 ± 10.6413.1 ± 7.8215.0 ± 10.8511.7 ± 7.6415.6 ± 10.4614.2 ± 7.95
    Albumin, g/dL4.4 ± 0.274.4 ± 0.314.4 ± 0.274.5 ± 0.254.5 ± 0.284.4 ± 0.35
    ALP, U/L158.4 ± 72.09142.5 ± 59.77140.4 ± 72.30128.1 ± 62.48176.4 ± 67.50154.3 ± 55.81
    AST/SGOT, U/L34.8 ± 15.1734.8 ± 12.2932.1 ± 15.1431.4 ± 11.2237.5 ± 14.7837.6 ± 12.62
    Calcium, mg/dL9.5 ± 0.37*9.4 ± 0.31*9.4 ± 0.389.4 ± 0.289.5 ± 0.35*9.3 ± 0.34*
    Creatinine, mg/dL0.5 ± 0.160.5 ± 0.130.5 ± 0.150.5 ± 0.110.5 ± 0.180.5 ± 0.15
    BUN, mg/dL7.5 ± 2.677.0 ± 2.077.2 ± 2.166.7 ± 2.267.9 ± 3.087.1 ± 1.93
    Vitamin D, ng/mL25.0 ± 11.1322.5 ± 8.3524.8 ± 10.85*19.6 ± 8.17*25.3 ± 11.4625.2 ± 7.70
    • Data are presented as mean ± standard deviation.

    • ALP, alkaline phosphatase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; LDH, lactate dehydrogenase; SGOT, serum glutamic-oxaloacetic transaminase; WBC, white blood cell count.

    • * P < .05 for normal vs low BMD values, per variable.

  • Table 4.

    Multivariate regression of low BMD correlates in the SCCRIP cohort

    VariableTotal cohortHbSS/Sβ0-thalassemia subgroup
    Adjusted OR (95% CI)PAdjusted OR (95% CI)P
    Adolescent category7.7 (1.94-30.20).00374.7 (1.23-18.17).023
    Hip osteonecrosis4.0 (1.02-15.63).0463.7 (0.69-20.11).13
    Chronic pain10.4 (1.51-71.24).0179.3 (0.97-88.70).053
    Hemoglobin0.74 (0.57-0.96).022NANA
    Indirect bilirubinNANA1.4 (0.99-1.90).055
    • CI, confidence interval; NA, variable not selected in final model.