Impairment of Bone Health in Pediatric Patients with Hemolytic Anemia

Abstract

IntroductionSickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health.Study DesignTo assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients). Biochemical, radiographic and anamnestic parameters of bone health were assessed.ResultsVitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5%) in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG) and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007). Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001). Multiple stepwise regression analysis revealed a significant (P<0.025) influence of LDH (partial r2 = 0.29), diagnosis of hemolytic anemia (partial r2 = 0.05) and age (partial r2 = 0.03) on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis.ConclusionBone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment.

Prevalence of Osteopathologies in Children and Adolescents After Diagnosis of Acute Lymphoblastic Leukemia

“…Clinical and anamnestic parameters were assessed as previously described in detail ( 24 ). Briefly, a physical examination, including determination of weight, height, and pubertal status was performed.…”

“…Briefly, a physical examination, including determination of weight, height, and pubertal status was performed. Patients were also asked to complete a standardized questionnaire regarding vitamin D, calcium and nutritional supplement intake, screen hours and hours of physical activity per day ( 24 ). In addition, the patients were asked for presence of bone pain in the form of regularly occurring (on more than half of the days in the last month), spontaneous, back pain or exercise related knee pain.…”

Age-related changes in biochemical bone profile in thalassemic children

“…In a heterogeneous group of children with mixed hemolytic anemia diagnoses, the degree of hemolytic disease activity was found to influence bone metabolism, mainly promoting the imbalance in the receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system resulting in higher serum RANKL/OPG (sRANKL/OPG) ratio and lowering the bone formation marker, osteocalcin (OC). 11 Lower OC levels were also associated with evidence of hypoparathyroidism in another group of thalassemic children. 12e14 However, this finding was not supported in other studies, 11,15 in which thalassemic children showed significantly higher OC levels compared to controls.…”

“…11 Lower OC levels were also associated with evidence of hypoparathyroidism in another group of thalassemic children. 12e14 However, this finding was not supported in other studies, 11,15 in which thalassemic children showed significantly higher OC levels compared to controls.…”

The dynamics of adult haematopoiesis in the bone and bone marrow environment

“…Several haematological disorders and diseases display an associated osteoporosis phenotype or low bone mineral density. They include patients suffering from beta‐thalassaemia major (Mahachoklertwattana et al , ; Yacobovich & Tamary, ), chronic haemolytic and pernicious anaemia (Gurevitch et al , ; Schundeln et al , ), haemophilia (Barnes et al , ; Iorio et al , ), sickle cell anaemia (Sanner & Ramin, ; Yacobovich & Tamary, ) and bone marrow failure (Townsley et al , ). One could argue that, where a chronic erythropoiesis exists (e.g.…”