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Bone in heart failure

Loncar G1,2,3, Cvetinovic N4, Lainscak M5,6, Isaković A2, von Haehling S3,7.

J Cachexia Sarcopenia Muscle. 2020 Feb 22. doi: 10.1002/jcsm.12516. [Epub ahead of print]

Abstract
There is an increasing interest in osteoporosis and reduced bone mineral density affecting not only post-menopausal women but also men, particularly with coexisting chronic diseases. Bone status in patients with stable chronic heart failure (HF) has been rarely studied so far. HF and osteoporosis are highly prevalent aging-related syndromes that exact a huge impact on society. Both disorders are common causes of loss of function and independence, and of prolonged hospitalizations, presenting a heavy burden on the health care system. The most devastating complication of osteoporosis is hip fracture, which is associated with high mortality risk and among those who survive, leads to a loss of function and independence often necessitating admission to long-term care. Current HF guidelines do not suggest screening methods or patient education in terms of osteoporosis or osteoporotic fracture. This review may serve as a solid base to discuss the need for bone health evaluation in HF patients.

Gaps in evidence and future

perspective

1. Major HF guidelines do not cover the screening method or patient education in terms of osteoporosis or osteoporotic fracture, even though HF represents a substantially increased risk of fracture. Future HF guidelines should consider this issue.

2. New data are required to prove that testosterone deficiency may be the mechanistic explanation for bone loss in men with HF. A desirable methodological approach here would be an assessment of whether correction of testosterone deficiency could improve bone mass in these patients.

3. Further research is needed to confirm the potential of adiponectin and other adipokines in the crosstalk between musculoskeletal system and energy metabolism in HF. Interventional studies using the application of adiponectin or its mimicking agent osmotin may provide new insight into whether there is a causal relationship between adiponectin and musculoskeletal depletion.

4. It would be interesting to assess the potential biochemical crosstalk between skeletal muscle and bone metabolism, via biohumoral markers produced by muscles called myokines, in both healthy subjects and patients with HF. The role of myokines may be of importance for beneficial influence of physical training in healthy subjects.130 However, there are no data evaluating if beneficial effect of physical training may be regulated by myokines in patients with HF.

5. The mechanism underlies OPG/RANKL, and bone status in HF warrants further randomized prospective, outcome study in larger population and bench works.

6. Secondary hyperparathyroidism is a potential cause for bone loss in the context of HF, which may be treated with cinacalcet. No study to date has evaluated the prognostic effect of adjustment of serum PTH by cinacalcet in HF patients. Cinacalcet prevents hyperparathyroidism and its consequences.131 Treatment with the drug significantly lowers the rates of cardiovascular death and major cardiovascular events in patients on haemodialysis.132 If future studies prove the beneficial prognostic effect of PTH adjustment, PTH may transform from risk marker to modifiable risk factor in the context of HF with establishment of new treatment target in this severe disease.

7. It would be of interest to assess efficacy/safety profile of anti-osteoporotic drugs in the context of HF including bisphosphonates, vitamin D supplementation, selective oestrogen receptor modulator (raloxifene), and biologicals (denosumab).

Conclusions

Heart failure and osteoporosis are highly prevalent agingrelated diseases that exact a huge impact on society. Published studies show that HF is related with reduced BMD and increased risk of osteoporotic fractures, especially in those with more severe HF. Both disorders are common causes of loss of function and independence, and of prolonged hospitalizations, presenting a heavy burden on the health care system

When HF and osteoporosis are both present in a patient, subsequent mortality is more than additive. On the other hand, current HF guidelines do not suggest screening methods or patient education for osteoporosis or osteoporotic fractures. Thus, this review and as well as other studies may serve as a base to discuss the necessities of bone health evaluation in HF patients.