Bone mass loss in chronic heart failure is associated with secondary hyperparathyroidism and has prognostic significance

Terrovitis, John; Zotos, Panagiotis; Kaldara, Elisavet; Διάκος, Νικόλαος; Tseliou, Eleni; Vakrou, Stella; Kapelios, Chris J.; Chalazonitis, Athanasios; Nanas, Serafeim; Toumanidis, S.; Kontoyannis, Dimitrios A.; Karga, Eleni; Nanas, John N.

doi:10.1093/eurjhf/hfs002

Cited by 52 publications

(53 citation statements)

References 34 publications

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“…The latter is possible because hyperaldosteronism also has been shown to cause bone loss in rodents (29,30). Osteoporosis also is widely recognized as being associated with heart failure, particularly in elderly patients (31); the proposed pathophysiological mechanisms include secondary hyperparathyroidism, testosterone deficiency, and excessive inflammatory cytokine production (31)(32)(33). Nonetheless, inappropriate AVP secretion is also a hallmark of low-output cardiac failure and in these instances may contribute to bone loss.…”

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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“…3,4, 23 Recent clinical studies have suggested that secondary hyperparathyroidism is associated with HF severity, increased pulmonary capillary wedge pressure, increased BNP, decreased LVEF, and decreased cardiac index in patients with HF and that it develops as a compensatory response to HF. 5,6,9,10, 24 More recent studies have reported that higher PTH in the steady state is associated with higher all-cause and cardiovascular mortality risk 8,10,25-28 and a higher risk of hospitalization for HF. 9, 29 In the present study, approximately 60% of patients had abnormal increase in serum PTH (>65 pg/ml) and impaired renal function.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Serum Parathyroid Hormone Level in Acute Decompensated Heart Failure

Sugimoto

Dohi

Onishi

et al. 2014

Circ J

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“…271 Low vitamin D and elevated parathyroid hormone levels appear to be associated with CHD. [272][273][274] It is well established that adults with advanced heart failure have lower bone mass and vitamin D levels, 244 with approximately half of patients with severe heart failure having osteopenia or osteoporosis, so it is of concern that a significant number of patients with complex CHD at such a young age have demonstrated markers of abnormal bone density/function because this may be a harbinger of osteopenia, osteoporosis, and fracture risk later in life. Patients with Down syndrome are at increased risk for low bone mineral density and fractures.…”

Section: Calcium Hemostasis and Bone Healthmentioning

confidence: 99%

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association

Lui¹,

Saïdi²,

Bhatt³

et al. 2017

Circulation

173

136

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ABSTRACT:Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention.

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Bone mass loss in chronic heart failure is associated with secondary hyperparathyroidism and has prognostic significance

Cited by 52 publications

References 34 publications

Functions of vasopressin and oxytocin in bone mass regulation

Functions of vasopressin and oxytocin in bone mass regulation

Prognostic Value of Serum Parathyroid Hormone Level in Acute Decompensated Heart Failure

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association

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