Hyponatremia and bone: an emerging relationship

Abstract

Hyponatremia is the most common electrolyte disorder and is mainly known for its neurological complications. New studies suggest previously unrecognized complications of hyponatremia, including falls, osteoporosis and fractures. Because these novel associations are mainly derived from epidemiological studies, it remains unclear whether hyponatremia has a direct effect on bone or whether it is a surrogate marker of another etiology. However, one animal and one in vitro study now show that hyponatremia can have direct effects on bone, mainly via activation of osteoclasts. The association between hyponatremia and fractures appears to be independent of osteoporosis (defined as low BMD). Also, data suggest that this association cannot be fully explained by the possibility that hyponatremia predisposes to falls. Hyponatremia, therefore, also has an effect on bone quality that is not captured by BMD. Here, the emerging relationship between hyponatremia and bone is reviewed, with special emphasis on possible mechanisms, unanswered questions and clinical implications.

Analysis of hyponatraemia associated post-operative mortality in 3897 hip fracture patients

“…Increasing age is a strong independent risk factor for hyponatraemia [3,5]. In recent years the relationship between hyponatraemia and bone, including an association with falls and fractures, has become more established in the literature [9]. Fracture risk is elevated in osteoporotic bone due to low bone mineral density (BMD) and increased bone fragility [10].…”

Diuretic Use and Risk of Vertebral Fracture in Women

“…51 With raised activity of osteoclasts, bone resorption is increased without concomitant bone formation, impairing local repair of microdamage and decreasing bone quality, thereby increasing fracture risk, all of which is not captured by bone mineral density measurements. 52, 53 Skeletal bone is a rich reservoir of sodium 54 and may play a key role in maintaining sodium homeostasis, 55 but possibly at the expense of the bone’s structural integrity.…”

Hyponatremia and osteoporosis: reappraisal of a novel association

“…Increased osteoclastic activity may be mediated by increased expression level of vasopression receptors AVPr1alpha and AVPr2alpha triggering Erk (kinase) signaling pathway in favor of suppressing bone formation and stimulating bone resorption [27]. Another mechanism for activation of osteoclasts could be via voltage-gated sodium channels which are highly expressed in bone and are sensitive to changes in extracellular tonicity and, therefore, may mediate the activation of osteoclasts in chronic hyponatremia [13, 18, 28–30]. …”