Hyponatremia and bone disease.
Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients, especially in those receiving medications that can cause hyponatremia. Furthermore, elderly patients with an unsteady gait and/or confusion should be evaluated for the presence of mild hyponatremia, and if present, treatment should be initiated. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and hyponatremia corrected, if present.
Instituto de Investigaciones Metabólicas, Universidad del Salvador, Buenos Aires, Argentina.
Armando Luis
AL
Negri
Renal Consultants of Houston, 2412 Westgate Street, Houston, TX, 77019, USA. carlosayus@yahoo.com.|Hospital Italiano, Buenos Aires, Argentina. carlosayus@yahoo.com.|Hospital Universitario Austral, Buenos Aires, Argentina. carlosayus@yahoo.com.
Juan Carlos
JC
Ayus
D000375:Aging / Q000378:metabolism*; D050723:Fractures, Bone / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007010:Hyponatremia / Q000150:complications / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism
Arginine vasopressin; Falls; Fractures; Gait disturbances; Hyponatremia; Osteoporosis
J Bone Miner Res. 2011 Aug;26(8):1822-8
21381111
Am J Public Health. 1994 Aug;84(8):1287-91
8059887
QJM. 2008 Jul;101(7):583-8
18477645
CNS Spectr. 2006 Jun;11(6):429-32
16816780
Clin J Am Soc Nephrol. 2010 Feb;5(2):275-80
20056759
Ann Intern Med. 2010 Mar 16;152(6):380-90
20231569
J Biol Chem. 2011 Mar 25;286(12):10864-75
21135109
Nephrol Dial Transplant. 2003 Dec;18(12):2486-91
14605269
J Clin Endocrinol Metab. 2014 Oct;99(10):3527-30
24971663
Age Ageing. 2014 Nov;43(6):821-6
24908106
J Nephrol. 2012 Sep-Oct;25(5):789-93
22135036
JAMA. 1999 Jun 23-30;281(24):2299-304
10386554
J Am Geriatr Soc. 2006 Feb;54(2):345-53
16460390
J Clin Endocrinol Metab. 2011 Apr;96(4):1046-52
21289257
Brain Res. 1991 Dec 20;567(2):274-82
1817731
N Engl J Med. 2009 Nov 26;361(22):2153-64
19940300
Chest. 1995 Feb;107(2):517-21
7842787
Ann Intern Med. 2011 Dec 6;155(11):ITC6-1-ITC6-15; quiz ITC6-16
22147729
Scott Med J. 2002 Oct;47(5):115-6
12469566
Nephrol Dial Transplant. 2016 Oct;31(10 ):1662-9
27190372
Am J Med. 2006 Jan;119(1):71.e1-8
16431193
Am J Med. 2013 Dec;126(12):1127-37.e1
24262726
Osteoporos Int. 2015 Mar;26(3):1005-16
25466529
J Clin Endocrinol Metab. 2015 Aug;100(8):3021-31
26083821
Nat Clin Pract Nephrol. 2006 May;2(5):283-8, quiz 289
16932441
J Am Soc Nephrol. 2016 Mar;27(3):766-80
26376860
Nutrition. 2016 Oct;32(10 ):1097-102
27222345
J Clin Invest. 1955 Jul;34(7, Part 1):997-1004
14392215
J Endocrinol. 2010 Jul;206(1):105-11
20392812
Ann Intern Med. 2000 May 2;132(9):711-4
10787364
J Am Geriatr Soc. 1995 Dec;43(12):1410-3
7490395
N Engl J Med. 1994 Mar 3;330(9):613-22
7905600
Am J Physiol Renal Physiol. 2008 Sep;295(3):F619-24
18448591
Am J Kidney Dis. 2016 Jun;67(6):893-901
26874645
Osteoporos Int. 2016 Mar;27(3):989-1001
26496739
J Bone Miner Res. 2015 Jun;30(6):970-5
25294595
Int Urol Nephrol. 2009;41(3):733-7
19472069
J Clin Invest. 1991 Jul;88(1):303-9
2056123
Lancet. 2011 Apr 9;377(9773):1276-87
21450337
Therapie. 2000 Sep-Oct;55(5):597-604
11201974
J Am Geriatr Soc. 2006 Feb;54(2):255-61
16460376
Trends Endocrinol Metab. 2008 Mar;19(2):43-9
18291667
Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18644-9
24167258
Ann Intern Med. 2003 Sep 16;139(6):476-82
13679324
Osteoporos Int. 2015 Sep;26(9):2291-8
25807914
Eur J Endocrinol. 2014 Feb 25;170(3):G1-47
24569125
J Clin Psychiatry. 2012 Nov;73(11):e1379-83
23218167
J Bone Miner Res. 2010 Mar;25(3):554-63
19751154
Rev Med Interne. 2007 Sep;28(9):642-4
17499890
Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):164-9
26699482
Ann Intern Med. 1992 Dec 1;117(11):891-7
1443949
J Clin Invest. 1954 Jun;33(6):867-73
13163179
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14075-9
19666502
N Engl J Med. 2006 Nov 16;355(20):2099-112
17105757