Decreased bone density and bone strength in a mouse model of severe factor <scp>VIII</scp> deficiency

Liel, Meghan S.; Greenberg, Daniel; Recht, Michael; Vanek, Chaim; Klein, Robert F.; Taylor, Jason

doi:10.1111/j.1365-2141.2012.09101.x

Cited by 42 publications

(47 citation statements)

References 11 publications

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“…Our previous work demonstrated that FVIII KO male mice exhibited lower BMD and cortical bone mass that resulted in femora less resistant to fractures compared with their WT littermates independent of haemarthroses, differences in physical activity and medical comorbidities, confirming clinical studies showing decreased BMD in patients with haemophilia. This work suggested that the mechanism may be directly due to FVIII deficiency . This study expands on these findings.…”

Section: Discussionsupporting

confidence: 73%

“…In recently reported experiments in genetically engineered factor VIII (FVIII) knockout (KO) mice, we assessed the skeletal phenotype of 23 male FVIII‐deficient and 20 male wild‐type (WT) mice at 18–20 weeks of age, when skeletal maturity had been achieved. In summary, we demonstrated a biologically significant decrease in femur BMD, cortical thickness, ultimate force to fracture and stiffness in the FVIII KO mice compared with WT controls, despite the fact that the FVIII KO mice had no bleeding episodes and no difference in locomotor activity . Here, we report that the impaired skeletal health seen in FVIII KO mice is due to increased bone resorption resulting from increased osteoclastic activity.…”

Section: Introductionmentioning

confidence: 54%

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The bone disease associated with factor VIII deficiency in mice is secondary to increased bone resorption

et al. 2013

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Osteopenia and osteoporosis have increasingly become a recognized morbidity of factor VIII (FVIII) deficiency. Recently, we demonstrated that FVIII knockout (KO) mice had significantly decreased bone mass and bone strength despite the fact that they did not have haemarthroses. The aim of this study was to explore the mechanism of bone disease associated with FVIII deficiency. We compared biochemical markers of bone formation and osteoclastogenesis, inflammatory cytokines, as well as static and dynamic histomorphometry of genetically engineered FVIII KO male mice to those of wild-type (WT) controls. At 20 weeks of age, FVIII KO mice, as well as WT controls, were sacrificed. Serum and bones were obtained at the time of sacrifice to study biochemical markers of bone formation (osteocalcin) and osteoclastogenesis (receptor activator of nuclear factor kappa-β and osteoprotegerin), levels of inflammatory cytokines (interleukin-1α and interferon-β) and to perform static and dynamic histomorphometry of tibia cancellous bone. There was no difference in the biochemical markers of bone formation or osteoclastogenesis. However, there were differences in the two bone-associated cytokines studied. In addition, histomorphometric examination revealed cancellous osteopenia in FVIII KO mice as evidenced by decreased bone area and trabecular number and increased trabecular separation. Bone formation parameters were normal in FVIII KO mice. In contrast, osteoclast-lined bone perimeter was increased. These data demonstrate that bone disease in FVIII KO mice is due to an increased rate of bone resorption.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 54%

The bone disease associated with factor VIII deficiency in mice is secondary to increased bone resorption

et al. 2013

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“…This is also supported by data from recent experimental studies, showing that factor VIII knockout mice demonstrate significantly decreased bone mass and bone strength, without the presence of haemarthroses . The mechanism leading to this skeletal impairment is increased rate of bone resorption .…”

Section: Introductionsupporting

confidence: 70%

Haemophilia and low bone mass. Ok, but what about fracture risk?

et al. 2016

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“…Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are other causes of low BMD [6][7][8]. Vitamin D deficiency and low levels of clotting factor [9] may, also, play a role. Each factor can lead to low BMD through a different pathway and to a variable degree [10].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D deficiency and osteoporosis in hemophilic children

Eldash

Atwa²,

Saad³

2017

Blood Coagulation &Amp; Fibrinolysis

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The aim of this study is to investigate bone state and factors affecting it in children with hemophilia. This is a case-control study that included 37 children with hemophilia and 37 healthy controls. The patients were selected from the outpatient pediatric hematology clinic of Fayoum University Hospital, Egypt. Bone mineral density, serum vitamin D, parathormone, calcium, phosphorus, and calcium creatinine ratio levels were evaluated. Vitamin D level and bone mineral density were significantly lower in hemophiliacs than in control group (P < 0.0001). About 43.2% of cases had moderate vitamin D deficiency, whereas 35.1% had mild deficiency. Vitamin D positively correlated with bone mineral density Z-score, whereas it negatively correlated with total joint score. Positive correlation between bone mineral density and age was also found. Serum levels of urea, urinary calcium creatinine ratio, and parathormone were found to be higher in cases than in control. Also, serum calcium level was found to be lower in patients than in controls. We concluded that vitamin D deficiency is an essential cause of decreased bone mineral density in hemophilic children. Hemophilic arthropathy with consecutive immobilization plays an important role in vitamin D deficiency and decreased bone mineral density.

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Decreased bone density and bone strength in a mouse model of severe factor VIII deficiency

Cited by 42 publications

References 11 publications

The bone disease associated with factor VIII deficiency in mice is secondary to increased bone resorption

The bone disease associated with factor VIII deficiency in mice is secondary to increased bone resorption

Haemophilia and low bone mass. Ok, but what about fracture risk?

Vitamin D deficiency and osteoporosis in hemophilic children

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