Chronic hyponatremia: a new risk factor for fragility fractures in the elderly?

ÓRgÃO OfICIAL DA SOCIEDADE PORTUgUESA DE REUMATOLOgIA 308 CARTA AO EDITOR Chronic hyponatremia: a new risk factor for fragility fractures in the elderly? ACTA REUMATOL PORT. 2015;40:308-309 To the Editor, Multiple risk factors for osteoporotic fracture, inclu - ding osteoporosis and falls, are widely known. It is also clear that osteoporotic fractures impose a significant morbidity and mortality in the elderly, with major mone tary costs associated. Recent studies suggest that chronic hyponatremia (serum [Na+] < 135mEq/L), albeit slight (serum [Na+] = 125-134 mEq/L), may be associated with falls, osteoporosis and fractures. PubMed search for “(“osteoporosis” OR “fracture” OR “falls”) AND “hyponatre - mia”“ (March 1st 2014, last five years, english) retrieved three dozen results. Several studies have shown associations between chronic hyponatremia and falls, fractures or osteoporosis: • Falls incidence in elderly people with mild chronic hyponatremia is significant1 • Hyponatremia is not associated with lower bone mineral density1(despite the relation between hyponatremia and osteoporosis suggested by a previous cross-sectional survey2) • Hyponatremia incidence in elderly patients admitted for fracture secondary to accidental fall is considera - ble3 • Hyponatremia is very prevalent in elderly patients with fragility fracture.4 But, can hyponatremia per se cause bone disease? Indeed, several studies have shown that chronic hyponatremia may be an independent risk factor for falls, fractures and osteoporosis due to increased probability of falls1[adjusted odds ratio (aOR) 1.35], osteoporosis2[aOR 2.85 for hip osteoporosis], fracture3[OR 4.16] and osteoporotic fracture5[OR 1.46], and the increased risk of incident nonvertebral fracture1[adjus - ted hazard ratio (aHR) 1.34 95% CI 1.08-1.68, Henriques M1 1. Medical Department, Physical and Rehabilitation Medicine Department, Navy’s Physical Education Centre; North Lisbon Hospital Centre – Saint Mary’s Hospital p=0.009] and vertebral fracture1(combined prevalent and incident) [aOR 1.61, 95% CI 1.00-2.59, p=0.049]. Furthermore, chronic hyponatremia is associated with increased likelihood of in-hospital death after hip fracture (OR 3.64)6and increased all-cause mortality risk (aHR 1.21, 95% CI 1.03-1.43, p=0.022)1. Laboratory studies indicate that hyponatremia stimu lates osteoclastogenesis7and animal model stu - dies associate hyponatremia with decreased thickness of cortical bone and increased number of osteoclasts2. There are already proposals for the mechanism of bone disease induced by chronic hyponatremia in humans (Figure 1)8. This question seems to be problematic considering that chronic hyponatremia is a common disorder in the elderly8and usually asymptomatic (75-80% of cases7): 7.2% of patients attending for the first time in primary care to 49.2% of those observed for the first time in the hospital9, 10% of patients admitted to the emergency room (ER),10 7% of ambulatory elderly up to 53% of institutionalized elderly2. Moreover, the elderly are subject to situations of grea ter propensity for chronic hyponatremia installation, as polypharmacy (e.g. diuretics, antidepressants, antiepileptics, proton pump inhibitors) and diseases (e.g. syndrome of inappropriate secretion of antidiuretic hormone (± 50% of chronic hyponatremia ca - ses), diabetes mellitus, hypothyroidism, hepatic cirrhosis, congestive heart failure, kidney disease)8. Physicians who follow elderly patients should be awa re for the association between bone disease and chro nic hyponatremia. As the measurement of serum sodium is a simple, available and inexpensive procedure, it should be achieved in elderly patients with increased risk of hyponatremia, presenting clinical symptoms consistent with hyponatraemia, or which are observed in the ER for bone injury8. Upon the hyponatremia diagnosis it’s necessary to establish the appropriate treatment. In the asympto - matic cases it’s recommended, at least, the identification ÓRgÃO OfICIAL DA SOCIEDADE PORTUgUESA DE REUMATOLOgIA 309 Henriques M of reversible causes to prevent recurrence and fluid res - triction of 0.5 to 1L/day. Selective vasopressin rece ptor V2 antagonists may be a treatment option in the future. Benefits of prevention, diagnosis and effective treatment of chronic hyponatremia in falls, osteoporosis and fracture risk, as quality of life, are yet to prove8. For this, new prospective studies are needed. Chronic hyponatremia may present itself as a new and important independent risk factor for falls, fractu - res and osteoporosis in the elderly. That said, medical community should be alert to this problem and invest in prevention, diagnosis and treatment! CoRREspondEnCE to Moisés Henriques Estrada da Luz nº199, 6º Dto 1600-155 Lisboa, Portugal E-mail: [email protected] REFEREnCEs 1. Hoorn EJ, Rivadeneira F, van Meurs JB, et al. Mild hyponatremia as a risk factor for fractures: the Rotterdam Study. J Bone Miner Res. 2011;26(8):1822-1828. 2. Verbalis JG, Barsony J, Sugimura Y, et al. Hyponatremia-induced osteoporosis. J Bone Miner Res. 2010;25(3):554-563. 3. Kengne FG, Andres C, Sattar L, et al. Mild hyponatremia and risk of fracture in the ambulatory elderly. Q J Med. 2008; 101:583-588. 4. Cumming K, Hoyle GE, Hutchison JD, Soiza RL. Prevalence, incidence and etiology of hyponatremia in elderly patients with fragility fractures. PLoS One. 2014;9(2):e88272. 5. Arampatzis S, Gaetcke LM, Funk GC, et al. Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department. Maturitas. 2013;75(1):81-86. 6. Hagino T, Ochiai S, Watanabe Y, et al. Hyponatremia at admission is associated with in-hospital death in patients with hip fracture. Arch Orthop Trauma Surg. 2013;133(4):507-511. 7. Barsony J, Sugimura Y, Verbalis JG. Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss. J Biol Chem. 2011;286(12):10864-10875. 8. Ayus JC, Negri AL, Kalantar-Zadeh K, Moritz ML. Is chronic hyponatremia a novel risk factor for hip fracture in the elderly? Nephrol Dial Transplant. 2012;27(10):3725-3731. 9. Hawkins RC. Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta. 2003;337(1-2):169-172. 10. Arampatzis S, Frauchiger B, Fiedler GM, et al. Characteristics, symptoms, and outcome of severe dysnatremias present on hos pital admission. Am J Med. 2012;125(11):1125.e1-1125. e7. Inferior limit of serum [Na+] to impaired gait (134mEq/L) and reduced attention (132mEq/L) 1/3 of total body Na+ is in the bones; 40% of bone [Na+] is exchangeable to blood circulation ↓ gait balance + ↓ attention + mental confusion ↓ bone mineralization + ↑ osteoclasts activity CNS impairment Osteoporosis Falls Bone fragility Chronic Hiponatremia Bone fracture Inferior limit of serum [Na+] to impaired gait (134mEq/L) and reduced attention (132mEq/L) 1/3 of total body Na+ is in the bones; 40% of bone [Na+] is exchangeable to blood circulation ↓ gait balance + ↓ attention + mental confusion ↓ bone mineralization + ↑ osteoclasts activity CNS impairment Osteoporosis Falls Bone fragility Chronic Hiponatremia Bone fracture FIGURE 1. Mechanism of bone disease induced by chronic hyponatremia in humans