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EFFECT OF SICKLE CELL DISEASE AND SICKLE CELL TRAIT ON PARAMETERS OF BONE METABOLISM
Author(s): ,
Biree Andemariam
Affiliations:
Hematology/Oncology,University of Connecticut,Farmington,United States
,
Sasia Jones
Affiliations:
Hematology/Oncology,University of Connecticut,Farmington,United States
,
Liping Xiao
Affiliations:
Endocrinology,University of Connecticut,Farmington,United States
,
William Zempsky
Affiliations:
Pediatrics,Connecticut Childrens Medical Center,Hartford,United States
,
Douglas Adams
Affiliations:
Orthopedic Surgery,University of Connecticut,Farmington,United States
,
Marja Hurley
Affiliations:
Endocrinology,University of Connecticut,Farmington,United States
Pamela Taxel
Affiliations:
Endocrinology,University of Connecticut,Farmington,United States
(Abstract release date: 05/19/16) EHA Library. Andemariam B. 06/09/16; 135048; PB2148
Dr. Biree Andemariam
Dr. Biree Andemariam
Contributions
Abstract
Abstract: PB2148

Type: Publication Only

Background
Sickle cell disease (SCD) has sequelae for bone health including infarcts, low BMD and osteomyelitis. Sickle cell trait (SCT) is clinically silent but common in individuals of African descent (AD), many of whom are unaware of their status. Although SCD poses increased risk for low BMD and vitamin D, there are no data on the relationship between SCT status and BMD, vitamin D level, and serum markers of bone metabolism.  We hypothesized that premenopausal AD women with SCT have a significantly lower BMD and higher serum bone turnover markers than race- and age-matched control AD women and are intermediate between healthy controls and subjects with SCD.

Aims
To compare BMD, vitamin D level, and serum bone turnover markers in pre-menopausal AD women with and without SCT and SCD.

Methods
To assess the effect of sickle cell disorders on bone homeostasis in pre-menopausal AD women, we recruited AD subjects with SCT and SCD following informed consent and compared serum and radiographic bone parameters to control ADs. We compared vitamin D level, hemoglobin (g/dL), body mass index (BMI), daily calcium intake, BMD of lumbar spine (L-spine), femoral neck (FN) and total hip (TH), as well as serum bone turnover biomarkers between control, SCT and SCD premenopausal AD women.  Serum bone turnover markers included CTX, P1NP, osteocalcin, sclersostin, vitamin D binding protein, IGF-1 and iPTH. Subjects were 35-45 years old with regular menstrual periods, not taking oral contraceptives or medications that influence bone metabolism, and without known metabolic bone disorders. Statistical analysis included a one-way ANOVA test and two-group t-tests for comparing group means using SPSS statistical software.

Results
A preliminary data analysis was performed on 21 subjects including 9 controls, 5 with SCT, and 7 with SCD.  The mean age of the cohort was 40.8 ± 4.8 years, and mean BMI was 29.8 ± 7.6 kg/m2. BMI was lower in the SCD group compared with SCT (24.5 vs. 34.1 kg/m2, p = 0.01). Mean hemoglobin levels were lower in SCD (8.7 ± 2.8 g/dL) versus control (12.7 ± 0.9 g/dL) and SCT (12.3 ± 2.8 g/dL) subjects (p=0.001).  Daily calcium intake did not differ between groups. Mean vitamin D level for the entire cohort was 21 ± 6 ng/dl and there was no difference between groups. BMD T-scores were normal for all groups at all anatomic sites; however, compared to controls, mean L-spine and FN BMD was significantly lower in the SCD group (1.4 ± 0.2 g/cm2 vs. 1.1 ± 0.2 g/cm2, p=0.04; 1.1 ± 0.2 g/cm2 vs. 0.9 ± 0.1 g/cm2, p= 0.03, respectively). FN BMD in the SCD group was lower than SCT (p= 0.046). Overall, BMI correlated with mean TH BMD (r=0.666, p=0.001); and serum IGF-1 correlated with mean FN (r= 0.633, p=0.003) and mean TH BMD (r= 0.513, p=0.021). Mean serum sclerostin levels were significantly decreased in both SCT and SCD subjects (Control 2975 ± 786, SCT 2141 ± 402, SCD 1613 ± 598, p=0.002). The groups did not demonstrate a difference in serum CTX, P1NP, osteocalcin, vitamin D binding protein or iPTH.

Conclusion
In this preliminary analysis we assessed parameters of bone metabolism in SCT and SCD compared with controls. In the overall cohort, IGF-1, a reflection of bone formation, positively correlated with FN and TH BMD. Sclerostin, an inhibitor of Wnt-signaling and bone formation, was decreased among SCT and SCD subjects, although the explanation is unclear.  Further study in an expanded population is needed to verify and further elucidate the pathophysiologic basis of these findings.

Session topic: E-poster

Keyword(s): Bone formation, Bone mineral density, Sickle cell disease
Abstract: PB2148

Type: Publication Only

Background
Sickle cell disease (SCD) has sequelae for bone health including infarcts, low BMD and osteomyelitis. Sickle cell trait (SCT) is clinically silent but common in individuals of African descent (AD), many of whom are unaware of their status. Although SCD poses increased risk for low BMD and vitamin D, there are no data on the relationship between SCT status and BMD, vitamin D level, and serum markers of bone metabolism.  We hypothesized that premenopausal AD women with SCT have a significantly lower BMD and higher serum bone turnover markers than race- and age-matched control AD women and are intermediate between healthy controls and subjects with SCD.

Aims
To compare BMD, vitamin D level, and serum bone turnover markers in pre-menopausal AD women with and without SCT and SCD.

Methods
To assess the effect of sickle cell disorders on bone homeostasis in pre-menopausal AD women, we recruited AD subjects with SCT and SCD following informed consent and compared serum and radiographic bone parameters to control ADs. We compared vitamin D level, hemoglobin (g/dL), body mass index (BMI), daily calcium intake, BMD of lumbar spine (L-spine), femoral neck (FN) and total hip (TH), as well as serum bone turnover biomarkers between control, SCT and SCD premenopausal AD women.  Serum bone turnover markers included CTX, P1NP, osteocalcin, sclersostin, vitamin D binding protein, IGF-1 and iPTH. Subjects were 35-45 years old with regular menstrual periods, not taking oral contraceptives or medications that influence bone metabolism, and without known metabolic bone disorders. Statistical analysis included a one-way ANOVA test and two-group t-tests for comparing group means using SPSS statistical software.

Results
A preliminary data analysis was performed on 21 subjects including 9 controls, 5 with SCT, and 7 with SCD.  The mean age of the cohort was 40.8 ± 4.8 years, and mean BMI was 29.8 ± 7.6 kg/m2. BMI was lower in the SCD group compared with SCT (24.5 vs. 34.1 kg/m2, p = 0.01). Mean hemoglobin levels were lower in SCD (8.7 ± 2.8 g/dL) versus control (12.7 ± 0.9 g/dL) and SCT (12.3 ± 2.8 g/dL) subjects (p=0.001).  Daily calcium intake did not differ between groups. Mean vitamin D level for the entire cohort was 21 ± 6 ng/dl and there was no difference between groups. BMD T-scores were normal for all groups at all anatomic sites; however, compared to controls, mean L-spine and FN BMD was significantly lower in the SCD group (1.4 ± 0.2 g/cm2 vs. 1.1 ± 0.2 g/cm2, p=0.04; 1.1 ± 0.2 g/cm2 vs. 0.9 ± 0.1 g/cm2, p= 0.03, respectively). FN BMD in the SCD group was lower than SCT (p= 0.046). Overall, BMI correlated with mean TH BMD (r=0.666, p=0.001); and serum IGF-1 correlated with mean FN (r= 0.633, p=0.003) and mean TH BMD (r= 0.513, p=0.021). Mean serum sclerostin levels were significantly decreased in both SCT and SCD subjects (Control 2975 ± 786, SCT 2141 ± 402, SCD 1613 ± 598, p=0.002). The groups did not demonstrate a difference in serum CTX, P1NP, osteocalcin, vitamin D binding protein or iPTH.

Conclusion
In this preliminary analysis we assessed parameters of bone metabolism in SCT and SCD compared with controls. In the overall cohort, IGF-1, a reflection of bone formation, positively correlated with FN and TH BMD. Sclerostin, an inhibitor of Wnt-signaling and bone formation, was decreased among SCT and SCD subjects, although the explanation is unclear.  Further study in an expanded population is needed to verify and further elucidate the pathophysiologic basis of these findings.

Session topic: E-poster

Keyword(s): Bone formation, Bone mineral density, Sickle cell disease

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