title: Age-associated iron accumulation in bone: implications for postmenopausal osteoporosis and a new target for prevention and treatment by chelation.
abstract: Iron accumulation in tissues is believed to be a characteristic of aged humans and a risk factor for some chronic diseases. However, it is not known whether age-associated iron accumulation is part of the pathogenesis of postmenopausal osteoporosis that affects approximately one out three women worldwide. Here, we confirmed that this accumulation of iron was associated with osteopenia in ovariectomized (OVX) rats (a model of peri- and postmenopausal osteoporosis due to estrogen deficiency). To further investigate whether the increased iron level plays a causal role in the onset of bone loss, we treated OVX rats with an orally active and bone targeted chelator that prevented iron accumulation in their skeletal tissues. The results showed that this treatment mitigated the loss of bone mass and the deterioration of bone micro-architecture. We also found that one possible mechanism of the protective action of iron chelation was to significantly reduce bone resorption. Thus, these findings provide a novel target and a potentially useful therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis and perhaps other age-related diseases.
authors.affiliation: Radiobiology Division, Department of Radiology, School of Medicine, University of Utah, 729 Arapeen Dr. Suite 2334, Salt Lake City, UT 84108, USA. gang.liu@m.cc.utah.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Men
authors.forename: Gerry H
authors.initials: GH
authors.lastname: Kenner
authors.forename: Scott C
authors.initials: SC
authors.lastname: Miller
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D015913:Chelation Therapy; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014266:Trientine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000085:Acetates; D007502:Iron Chelating Agents; C076893:docosyl-triethylenetetraminepentaacetic acid; D007501:Iron; D014266:Trientine