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Research Review: Influence of Iron on Bone Homeostasis – by Balogh, Paragh and Jenny (2018)

January 21, 2019

A summary of the review article:

 

  • ‘Bone is a metabolically active tissue that is continuously being remodelled’
  • ‘The major cell types involved in bone remodelling are osteoclasts and osteoblasts’
  • ‘Osteclasts are involved in bone resorption,¬†Osteoblasts are involved in bone formation’
  • ‘Iron is a Janus face element, being both essential for life and dangerous’
  • ‘Most of the body iron present in red blood cells associated with hemoglobin is in a form of heme’
  • ‘The second largest pool of iron is stored within ferritin’
  • ‘Determination of iron status relies on the measurement of serum indicators, mostly transferrin saturation, soluble transferring receptor and serum ferritin’
  • ‘Because of other influencing factors such as inflammation, determination of iron status is often based on the combination of several indicators’
  • Haemochromatosis, characterised by increased dietary iron uptake and subsequent tissue iron overload, is caused by mutations in diverse genes involved in iron metabolism’
  • ‘Other iron condition include thalassaemia, sickle cell disease and acquired refractory anemias
  • ‘Accumulating evidence suggest that iron overload conditions are associated with bone weakening, which is represented by osteoporosis osteopenia, altered bone microarchitecture and biomechanics, as well as frequent bone fractures’
  • ‘Weak bone phenotype observed in patients with iron overload is a consequence of increased bone resorption by osteoclasts and decreased bone formation by osteoblasts’
  • ‘The incidence of osteoporosis in hereditary haemachromatosis patients is about 25-34% and 40-80% of the patients suffer from osteopaenia’
  • ‘Iron deficiency is a common disease which affects almost 1.2 billion people worldwide’
  • ‘Regarding bone physiology, iron is critically involved in 2 processes i.e., collagen production and metabolism of vitamin D and therefore iron deficiency is considered to have a detrimental impact on bone homeostasis’
  • ‘Bone tissue is rich in collagen type 1, the synthesis of which involves hydroxylation of pro-collagen on proline and lysine residues. The reactions of hydroxylation are catalysed by prolyl-4-hydroxylase and lysyl-hydroxylase, the enzymes of which require ferrous iron for their catalytic activieis’
  • ‘Active vitamin D plays an important role in bone homeostasis through regulating intestinal uptake and tubular reabsorption of calcium and phosphate, the major inorganic components of bones. Vitamin D activiation is regulated by enzymes of the cytochrome P450 family which enzymes contain heme as a prosthetic groups, therefore their activities are dependent on availability of iron’
  • ‘The effect of iron deficiency on bone health is less clear than iron overload’
  • ‘Osteocytes, the third cell types in bone tissue have an emerging role in bone homeostasis and remodelling but we lack complete information about whether iron excess or deficiency influences their activity and function’
  • ‘Iron overload as well as iron deficiency are associated with weakened bones, suggesting that balanced bone homeostasis requires optimal iron levels’
  • ‘Accumulating evidence suggests high iron and low iron influence the differentiation and activity of osteoclasts and osteoblasts in a way that it promotes bone loss’

 

This article was published in the Journal: Pharmaceuticals and can be accessed here.

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