Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia

Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

“…Thus, low bone density and bone density loss seem to be influenced by the occurrence of ON, as well as previously identified factors such as age and weight at diagnosis, B-cell-immunophenotype, use of corticosteroids, folate antagonists or irradiation, physical inactivity, and nutritional deficiencies. 17,[21][22][23][24][25] Bone density loss in patients with ON is most likely affected by a combination of avoidance of weight-bearing activities and sports activities 37 and by ON itself. 38 Previous studies in healthy volunteers and astronauts have shown that "skeletal unloading" induces osteopenia, [39][40][41] with a 3% loss of BMD after 12 weeks.…”

“…7 As previously described, 17,22 only pediatric ALL patients who were 4 years of age and older at T3 were included for dual energy X-ray absorptiometry measurements (DXA; by Lunar DPX-L scanner, Madison, WI, USA or Hologic scanner, Waltham, MA, USA), as control BMD values are only available for this age group. BMD of the lumbar spine (BMD LS ) was measured with a Hologic or Lunar DXA scanner.…”

“…In addition, in a subset of the cohort, BMD of the total body (BMD TB ) was measured with a Lunar DXA scanner in one treatment center. 17,22 DXA results of the Hologic scanner were compared with the manufacturer's own reference data and DXA results of the Lunar scanner were compared with data from healthy Dutch children, measured on the same scanner. 27 Analyses were performed with age-and sex-matched standard deviation scores (SDS) of BMD, and BMD was categorized into BMD < -1 SDS and BMD < -2 SDS, as previously described.…”

“…20 We and others have shown that BMD is already low when ALL is diagnosed, and that the final BMD loss at cessation of ALL treatment is mainly determined by BMD values at the start of treatment. 17,21,22 This suggests that the disease itself and genetic variation in genes that influence bone density may be important risk factors for BMD loss. The final BMD loss is also determined by treatment with certain drugs, e.g.…”

Risk factors for symptomatic osteonecrosis in childhood ALL: A retrospective study of a Slovenian pediatric ALL population between 1970 and 2004

“…ESR1 plays an important role in the regulation of skeletal growth and maintenance of bone mass (37). We investigated a common polymorphism in the ESR1 gene (XbaI), which has already been extensively studied (15,(38)(39)(40)42). A meta-analysis of association studies involving 5,834 subjects showed a correlation of G allele with higher BMD and decreased risk of fracture (38), while in another large-scale genome-wide study a correlation with fracture that was independent of BMD was observed (15).…”