Hyponatremia associated with large-bone fracture in elderly patients

Sandhu, Harminder; Gilles, Emmanuelle; Devita, Maria; Panagopoulos, Georgia; Michelis, Michael F.

doi:10.1007/s11255-009-9585-2

Cited by 132 publications

(107 citation statements)

References 19 publications

(23 reference statements)

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“…AVP could indeed be a primary determinant for the osteoporosis that is known to accompany chronic hyponatremic states (22)(23)(24)(25)(26)(27)(28), although high aldosterone levels, for example in SIADH, may contribute also (21). The latter is possible because hyperaldosteronism also has been shown to cause bone loss in rodents (29,30).…”

Section: Discussionmentioning

confidence: 99%

Functions of vasopressin and oxytocin in bone mass regulation

Sun

Tamma

Yuen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr −/− mice have osteopenia, and Avpr1α −/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr −/− :Avpr1α −/− doublemutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avpstimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α −/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling.O ver the past decade, we have described direct actions of anterior and posterior pituitary hormones on the skeleton (1-8). We have shown that these actions are exerted via G protein-coupled receptors resident on both osteoblasts and osteoclasts. We also find that the skeleton is highly sensitive to the action of posterior pituitary hormones; for example, mice haploinsufficient in oxytocin (Oxt) have osteopenic bones, but lactation is normal; lactation is impaired only in Oxt −/− mice (2). Likewise, Tshr haploinsufficient mice are completely euthyroid with normal thyroid follicles but display significant osteopenia (4). The exquisite sensitivity of the skeleton to pituitary hormones comes as no surprise, considering that the pituitary gland and the skeleton are both evolutionarily more primitive than target endocrine organs (7).Apart from the known actions of growth hormone on the skeleton, Tsh, Fsh, Acth, Oxt, and vasopressin (Avp) have all been shown to regulate the formation and/or function of both osteoblasts and osteoclasts and thus to control bone remodeling in vivo (2-4, 6-8). The two neurohypophyseal hormones Oxt and Avp have opposing functions (2, 3). Oxt stimulates and Avp inhibits osteoblast formation. Consequently, the genetic deletion of the Oxt receptor (Oxtr) and Avp receptor 1α (Avpr1α) yields opposing phenotypes, notably osteopenia in Oxtr −/− mice and high bone mass in Avpr1α −/− mice (2, 3). These findings may explain the rapid recovery of bone loss at weaning when plasma Oxt levels are high (9) and also the profound loss of bone noted in chronic hyponatremic states, such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which serum Avp levels are elevated (3).We find high levels of Oxtr expression on ...

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Section: Discussionmentioning

confidence: 99%

Functions of vasopressin and oxytocin in bone mass regulation

Sun

Tamma

Yuen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…49 Hyponatremia, a common and potentially serious adverse event complicating the use of SSRIs in older adults, has been implicated in fractures in a small case-control study. 50 Antidepressants may also directly impair postural control. Increased postural sway was noted in depressed patients in the first week of treatment with sertraline, when compared with nortriptyline and controls.…”

Section: Antidepressants and Fallsmentioning

confidence: 99%

The Complex Interplay of Depression and Falls in Older Adults: A Clinical Review

Iaboni

Flint

2013

The American Journal of Geriatric Psychiatry

220

178

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Depression and falls have a significant bidirectional relationship. Excessive fear of falling, which is frequently associated with depression, also increases the risk of falls. Both depression and fear of falling are associated with impairment of gait and balance, an association that is mediated through cognitive, sensory, and motor pathways. The management of depression in fall-prone individuals is challenging, since antidepressant medications can increase the risk of falls, selective serotonin reuptake inhibitors may increase the risk of fragility fractures, and data are lacking about the effect of fall rehabilitation programs on clinically significant depression. Based on the current state of knowledge, exercise (particularly Tai Chi) and cognitive-behavioral therapy should be considered for the first-line treatment of mild depression in older fallers. Antidepressant medications are indicated to treat moderate to severe depression in fall-prone individuals, but with appropriate precautions including low starting dose and slow dose titration, use of psychotropic monotherapy whenever possible, and monitoring for orthostatic hypotension and hyponatremia. To date, there have been no recommendations for osteoporosis monitoring and treatment in individuals prescribed antidepressant medications, beyond the usual clinical guidelines. However, treatment of the older depressed person who is at risk of falls provides the opportunity to inquire about his or her adherence with osteoporosis and fracture-prevention guidelines. KeywordsAntidepressants; depression; falls; fear of falling; fractures One-third of community-dwelling seniors fall each year, with half of these individuals falling more than once. Ten percent of all falls result in a major injury, which can lead to institutionalization and death. 1 Falls often result in a fear of further falls, leading to fearrelated restriction of activities: this activity restriction has been associated with subsequent impairment in balance, mobility, and disability. 2,3 Send correspondence and reprint requests to Alastair

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“…In a longitudinal analysis of data from the Osteoporotic Fractures in Men Study (MrOS), it was reported that after adjusting for age, BMI, study center, and other covariates, hyponatremia was associated with up to a doubling in the risk of hip and morphometric spine fractures, independent of BMD (25). Accordingly, aside from reduction in BMD, chronic hyponatremia has also been associated with increased fracture rates in elderly (4,8,11,(14)(15)(16) and with metabolic bone loss through an uncoupling of bone resorption and formation in rats indicating the effect of hyponatremia on bone quality (10). Cellular and molecular data have confirmed increased osteoclastic bone resorption in response to low extracellular sodium levels (26) which represents attempts of the body to preserve sodium homeostasis at the expense of bone structural integrity leading hyponatremia-induced bone resorption and osteoporosis (13).…”

Section: Discussionmentioning

confidence: 99%

“…Chronic hyponatremia has been associated with increased fracture rate (4,(14)(15)(16) as well as osteoporosis at the femoral neck and total hip (13) in humans and with metabolic bone loss in rats (10).…”

Section: Introductionmentioning

confidence: 99%

Bone Mineral Density and Osteoporosis in Hyponatremic Versus Normonatremic Patients: A Retrospective 12-Month Analysis

Takır¹,

Bakan²,

Tahra³

et al. 2017

Turk Neph Dial Transpl

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OBJECTIVE:To evaluate the change in osteoporosis rate and bone mineral density (BMD) in a cohort hyponatremic versus normonatremic patients under 12-month osteoporosis treatment. MATERIAL and METHODS:A total of 280 patients with osteoporosis who were receiving antiosteoporosis treatment were included in the study. Patients were divided into two groups based on baseline serum sodium levels including hyponatremic (n=45) and normonatremic (n=235) groups. Baseline and follow up data on T scores and rate of osteoporosis were compared in hyponatremic vs. normonatremic groups. RESULTS:Baseline T scores of the femur neck were significantly lower in hyponatremic than in normonatremic (p=0.008) patients, while at the end of 1-year follow up, the two groups had similarly improved T scores of femur neck (p=0.43). Hyponatremic than normonatremic patients had significantly higher rate of osteoporosis (p=0.03) at baseline, whereas two groups had similar osteoporosis rates at the end of 1-year follow up (p=0.25). CONCLUSION:In conclusion, our data suggest a reduced BMD at femur neck and higher rate of osteoporosis in case of mild chronic hyponatremia, whereas similar efficacy of 12-month osteoporosis treatment in improving BMD scores and reducing osteoporosis rate in hyponatremic and normonatremic patients regardless of the natremic status

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Hyponatremia associated with large-bone fracture in elderly patients

Cited by 132 publications

References 19 publications

Functions of vasopressin and oxytocin in bone mass regulation

Functions of vasopressin and oxytocin in bone mass regulation

The Complex Interplay of Depression and Falls in Older Adults: A Clinical Review

Bone Mineral Density and Osteoporosis in Hyponatremic Versus Normonatremic Patients: A Retrospective 12-Month Analysis

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