Bone mineral density is normal in children with Fanconi anemia

Rose, Susan R.; Rutter, Meilan M.; Mueller, Robin; Harris, M. Jackuelyn; Hamon, Beth; Bulluck, Arin Fletcher; Smith, Franklin O.

doi:10.1002/pbc.22956

Cited by 9 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with FA were shown to have low BMD, more so after hematopoietic stem cell transplantation . Given FA patients’ short stature, some argue that correction for height‐age is required for patients with FA, which eliminates the prevalence of low BMD . Various factors may also contribute to differences between studies with patients affected by FA, including age, treatments, and hypogonadism; as such, using mouse models with identical genetic background would at least eliminate some of these variables.…”

Section: Discussionmentioning

confidence: 99%

“…(7,9) Given FA patients' short stature, some argue that correction for height-age is required for patients with FA, which eliminates the prevalence of low BMD. (6,7) Various factors may also contribute to differences between studies with patients affected by FA, including age, treatments, and hypogonadism; as such, using mouse models with identical genetic background would at least eliminate some of these variables. In our study, we used two different mouse models of FA, FancA -/and FancC -/-, and found growth and mineralization delays in all bones throughout development.…”

Section: Discussionmentioning

confidence: 99%

“…(8)(9)(10)(11) Furthermore, they were shown to have early onset osteopenia or osteoporosis, putting them at higher risk of fractures than the general population and more dramatically so after HSCT. (6,7,12) Several risk factors associated with bone loss are prevalent in patients with FA and include endocrine and pituitary abnormalities, hypogonadism, and prolonged glucocorticoid therapy. (12)(13)(14) However, mechanisms leading to skeletal defects in these patients remain elusive.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Deletion of the Fanconi Anemia C Gene in Mice Leads to Skeletal Anomalies and Defective Bone Mineralization and Microarchitecture

Mazon¹,

Julien²,

Ung³

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Fanconi anemia (FA) is a rare genetic disorder associated with a progressive decline in hematopoietic stem cells leading to bone marrow failure. FA is also characterized by a variety of developmental defects including short stature and skeletal malformations. More than half of children affected with FA have radial-ray abnormalities, and many patients have early onset osteopenia/osteoporosis. Although many Fanconi anemia genes have been identified and a molecular pathway defined, the underlying mechanism leading to bone defects remains elusive. To understand the role of FA genes in skeletal development and bone microarchitecture, we evaluated bone physiology during embryogenesis and in adult FancA- and FancC-deficient mice. We found that both FancA and FancC embryos have abnormal skeletal development shown by skeletal malformations, growth delay, and reduced bone mineralization. FancC adult mice present altered bone morphology and microarchitecture with a significant decrease in cortical bone mineral density in a sex-specific manner. Mechanical testing revealed that male but not female FancC mice show reduced bone strength compared with their wild-type littermates. Ex vivo cultures showed that FancA and FancC bone marrow-derived mesenchymal stem cells ( MSC) have impaired differentiation capabilities together with altered gene expression profiles. Our results suggest that defective bone physiology in FA occurs in utero and possibly results from altered MSC function. These results provide valuable insights into the mechanism involved in FA skeletal defects. © 2018 American Society for Bone and Mineral Research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deletion of the Fanconi Anemia C Gene in Mice Leads to Skeletal Anomalies and Defective Bone Mineralization and Microarchitecture

Mazon¹,

Julien²,

Ung³

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…The only other study reported in the literature that focused on BMD exclusively in FA patients was a cross-sectional analysis of LBMD (but not TBMD) in 37 FA patients (aged 4-23 years, 19 without HCT and 18 post-HCT) [12]. While about 50% of these FA children had LBMD Z-scores for chronological age below −1 SD, most patients had normal BMD when adjusted for height.…”

Section: Discussionmentioning

confidence: 99%

“…Although many of these risk factors are prevalent in FA patients [3, 4, 10, 11], bone health in the FA population is poorly understood. Only two published studies have addressed BMD in children with FA [9, 12], both using DXA. However, it remains unclear to what extent children with FA manifest BMD deficits after HCT, to what degree DXA results are impacted by short stature in this patient population, and which skeletal sites are most informative.…”

Section: Introductionmentioning

confidence: 99%

Bone Mineral Density in Children with Fanconi Anemia after Hematopoietic Cell Transplantation

Petryk

Polgreen

Barnum

et al. 2015

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Fanconi anemia (FA) is an inherited DNA repair disorder associated with short stature and bone marrow failure usually requiring hematopoietic cell transplant (HCT). While low bone mineral density (BMD) has been reported in leukemia patients after HCT, little is known about BMD in FA children after HCT (FA HCT). This study's goals were to compare BMD in FA HCT to BMD in healthy controls, and in children who received HCT for hematologic malignancy (Cancer HCT), and to test for associations between BMD and risk factors for bone loss. This cross-sectional study included 20 FA HCT, 13 Cancer HCT, and 90 healthy controls, age-matched and <18 years old at evaluation. BMD Z-scores for total body (TBMD) and lumbar spine (LBMD) were measured by dual energy x-ray absorptiometry and adjusted for height-forage Z-score (HAZ). FA HCT had lower mean TBMDHAZ Z-score (by 0.8 SD) and higher fraction with Z-score ≤ −1 than healthy controls (42% vs. 11%). No LBMD deficits were detected. FA HCT and Cancer HCT groups did not differ significantly in TBMD or LBMD Z-scores. In FA HCT patients, lower BMI and lower percent fat were associated with lower BMD. This study highlights the importance of monitoring BMD to optimize bone health in FA patients.

show abstract