Bone mass loss in chronic heart failure is associated with sympathetic nerve activation

Guan, Zhiyuan<sup>1</sup>; Yuan, Wanqiong<sup>1</sup>; Jia, Jialin<sup>1</sup>; Zhang, Chenggui<sup>1</sup>; Zhu, Junxiong<sup>1</sup>; Huang, Jie<sup>1</sup>; Zhang, Wang<sup>1</sup>; Fan, Dongwei<sup>1,2</sup>; Leng, Huijie<sup>1,2</sup>; Li, Zijian<sup>3</sup>; Xu, Yingsheng<sup>4</sup>; Song, Chunli<sup>1,2</sup>

Affiliations

¹Department of Orthopedics, Peking University Third Hospital, Beijing, China

²Beijing Key Laboratory of Spinal Diseases, Beijing, China

³Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China

⁴Department of Neurology, Peking University Third Hospital, Beijing 100191, China

Abstract and keywords

Purpose: Chronic heart failure causes osteoporosis, but the mechanism remains unclear. The sympathetic nerve plays an important role in both bone metabolism and cardiovascular function.

Methods: Thirty-six adult male SD rats were randomly divided into the following four groups: sham surgery (Sham) group, guanethidine (GD) group, abdominal transverse aorta coarctation-induced heart failure + normal saline (TAC) group, and TAC + guanethidine (TAC + GD) group. Normal saline (0.9 % NaCl) or guanethidine (40 mg/kg/ml) was intraperitoneally injected daily for 5 weeks. Then, DXA, micro-CT, ELISA and RT–PCR analyses were performed 12 weeks after treatment.

Results: The bone loss in rats subjected to TAC-induced chronic heart failure and chemical sympathectomy with guanethidine was increased. Serum norepinephrine levels were increased in rats with TAC-induced heart failure but were decreased in TAC-induced heart failure rats treated with guanethidine. The expression of α2A adrenergic receptor, α2C adrenergic receptor, osteoprotegerin (OPG), and osteocalcin in the tibia decreased in the TAC-induced heart failure group, and the expression of β1 adrenergic receptor, β2 adrenergic receptor, receptor activator of nuclear factor-κ B ligand (RANKL), and RANKL/OPG in the tibia increased in the heart failure group. In addition, these changes in gene expression levels were rescued by chemical sympathectomy with guanethidine.

Conclusions: TAC-induced chronic heart failure is associated with bone mass loss, and the sympathetic nerve plays a significant role in heart failure-related bone mass loss.

Mini abstract: The present study supports the hypothesis that heart failure is related to bone loss, and the excessive activation of sympathetic nerves participates in this pathophysiological process. The present study suggests a potential pathological mechanism of osteoporosis associated with heart failure and new perspectives for developing strategies for heart failure-related bone loss.

Keywords: Heart failure; Sympathetic nerve; Osteoporosis; β Adrenergic receptor; Guanethidine

Links

DOI: 10.1016/j.bone.2022.116596

PubMed: 36307018

WoS: 000884850500003

History

Received: 2022-07-30

Revised: 2022-10-2

Accepted: 2022-10-18

Online: 2022-10-25

Cited Works (2)

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