title: Loss of RAGE defense: a cause of Charcot neuroarthropathy?
abstract: OBJECTIVE
  This study investigated the relationship between circulating soluble receptor for advanced glycation end products (sRAGE) and parameters of bone health in patients with Charcot neuroarthropathy (CNA).
  
  
  METHODS
  Eighty men (aged 55.3±9.0 years), including 30 healthy control subjects, 30 type 2 diabetic patients without Charcot, and 20 type 2 diabetic patients with stage 2 (nonacute) CNA, underwent evaluations of peripheral and autonomic neuropathy, nerve conduction, markers of bone turnover, bone mineral density, and bone stiffness of the calcaneus.
  
  
  RESULTS
  CNA patients had worse peripheral and autonomic neuropathy and a lower bone stiffness index than diabetic or control individuals (77.1, 103.3, and 105.1, respectively; P<0.05), but no difference in bone mineral density (P>0.05). CNA subjects also had lower sRAGE levels than control (162 vs. 1,140 pg/mL; P<0.01) and diabetic (162 vs. 522 pg/mL; P<0.05) subjects, and higher circulating osteocalcin levels.
  
  
  CONCLUSIONS
  CNA patients had significantly lower circulating sRAGE, with an accompanying increase in serum markers of bone turnover, and reduced bone stiffness in the calcaneus not accompanied by reductions in bone mineral density. These data suggest a failure of RAGE defense mechanisms against oxidative stress in diabetes. Future studies should determine if medications that increase sRAGE activity could be useful in mitigating progression to CNA.
authors: Department of Kinesiology, California State University San Marcos, San Marcos, California, USA. vinikai@evms.edu
authors: Kara A
authors: KA
authors: Witzke
authors: Aaron I
authors: AI
authors: Vinik
authors: Lisa M
authors: LM
authors: Grant
authors: William P
authors: WP
authors: Grant
authors: Henri K
authors: HK
authors: Parson
authors: Gary L
authors: GL
authors: Pittenger
authors: Niculina
authors: N
authors: Burcus
references: Clin Podiatr Med Surg. 2008 Jan;25(1):29-42, vi
references: 18165109
references: BMC Cell Biol. 2001;2:16
references: 11518540
references: Circ Res. 2010 Mar 19;106(5):842-53
references: 20299674
references: Arthritis Rheum. 1994 Jul;37(7):983-91
references: 8024625
references: J Diabetes. 2009 Dec;1(4):246-54
references: 20923525
references: IBMS Bonekey. 2009 Aug;6(8):268-278
references: 27158323
references: J Foot Ankle Surg. 1997 Jul-Aug;36(4):272-8; discussion 330
references: 9298442
references: J Bone Miner Res. 1996 Jul;11(7):931-7
references: 8797113
references: J Diabetes Complications. 1998 May-Jun;12(3):147-53
references: 9618070
references: Acta Neurol Scand. 2007 Feb;115(2):115-21
references: 17212615
references: Medicine (Baltimore). 1972 May;51(3):191-210
references: 5021769
references: Circulation. 2007 Jan 23;115(3):387-97
references: 17242296
references: Bone. 2007 Feb;40(2):345-53
references: 17064973
references: J Musculoskelet Neuronal Interact. 2010 Mar;10(1):84-91
references: 20190384
references: Arch Physiol Biochem. 2007 Jun;113(3):154-61
references: 17922311
references: Bone. 2006 Nov;39(5):1073-1079
references: 16829221
references: N Engl J Med. 1976 Jan 29;294(5):241-5
references: 1244549
references: Diabetes Care. 2000 Jun;23(6):796-800
references: 10840999
references: Diabetes Technol Ther. 2001 Spring;3(1):29-50
references: 11469707
references: J Bone Miner Res. 2005 Sep;20(9):1647-58
references: 16059636
references: Diabetologia. 2008 Jun;51(6):1035-40
references: 18389210
references: Muscle Nerve. 1995 Jun;18(6):574-84
references: 7753119
references: Osteoporos Int. 2010 Feb;21(2):195-214
references: 19760059
references: Rev Endocr Metab Disord. 2005 May;6(2):117-27
references: 15843883