Hyponatremia and bone disease

Abstract

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.

Hyponatremia, bone mineral density and falls in the elderly; Results from AHAP study

“…Nearly, one third of body sodium is stored in the bone [25]. The association of HN with balance impairment, falls and bone fractures in the elderly can be justified by different mechanisms including increase unsteady gait related to cognitive impairment; bone resorption and its fragility [1,7,8,25], furthermore, another research presented that the sustained low extracellular sodium ion concentrations could directly stimulate osteoclastogenesis and that hyponatremia-induced oxidative stress might be involved in the mechanism [26].…”

“…Chronic diseases [3,4] and concurrent use of certain medications such as diuretics [5] and antidepressants [6] put older people at greater risk of HN. Recent studies demonstrate that HN can be associated with osteoporosis, falls and fractures [1,[7][8][9][10][11]. The association of HN with falls and fractures might be independent of osteoporosis [12].…”

Increased levels of sodium chloride directly increase osteoclastic differentiation and resorption in mice and men

“…However, there is inconclusive evidence on the effect of hyponatremia on the development of osteoporosis in human patients [ 36 ]. Hyponatremia seems to directly contribute to increased bone resorption through decreased cellular uptake of ascorbic acid and the induction of oxidative stress [ 37 ]. Furthermore, it has been investigated that hyponatremic patients have elevated circulating levels of arginine vasopressin (AVP) and that this is at least in part responsible for the phenotype [ 38 ].…”

Nephroendocrinology: When endocrinology meets nephrology

“…Disturbances in sodium and water balance including hyponatremia, hypernatremia, dehydration, and age-related kidney changes are then reviewed by Koch and Fulop [16], followed by an excellent review on hyponatremia and bone disease by Negri and Ayus [17], pointing out the importance to consider a bone density scan in patients with hyponatremia and to check a serum sodium concentration in (elderly) patients presenting with an orthopedic injury/fracture.…”

“…The third set of articles is related to bone in patients with chronic kidney disease, starting out with an overview of secondary hyperparathyroidism, including tools for its possible prevention [18]. With the increasing number of kidney transplantations in diabetic and other patients, it becomes important to understand pathophysiological processes posttransplantation such as osteoporosis which is reviewed by the nephroendocrinology team Gosmanova and Gosmanov [19].…”