Next Article in Journal
Combined Transcutaneous Electrical Spinal Cord Stimulation and Task-Specific Rehabilitation Improves Trunk and Sitting Functions in People with Chronic Tetraplegia
Previous Article in Journal
Tumor Biology and Microenvironment of Vestibular Schwannoma-Relation to Tumor Growth and Hearing Loss
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomedicines
Volume 11
Issue 1
10.3390/biomedicines11010033
biomedicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

The Role of Sympathetic Nerves in Osteoporosis: A Narrative Review

by
Weifei Zhang
1,†,
Yuheng Liu
1,†,
Jixuan Xu
2,
Chen Fan
2,
Bin Zhang
3,
Pin Feng
3,
Yu Wang
1 and
Qingquan Kong
1,3,*
1
Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
2
Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region (Hospital C. T.), Sichuan University, Chengdu 610041, China
3
Department of Orthopedics, Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region (Hospital C. T.), Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2023, 11(1), 33; https://doi.org/10.3390/biomedicines11010033
Submission received: 21 November 2022 / Revised: 9 December 2022 / Accepted: 14 December 2022 / Published: 23 December 2022
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
Browse Figure
Versions Notes

Abstract

:
Osteoporosis, a systemic bone disease, is characterized by decreased bone density due to various reasons, destructed bone microstructure, and increased bone fragility. The incidence of osteoporosis is very high among the elderly, and patients with osteoporosis are prone to suffer from spine fractures and hip fractures, which cause great harm to patients. Meanwhile, osteoporosis is mainly treated with anti-osteoporosis drugs that have side effects. Therefore, the development of new treatment modalities has a significant clinical impact. Sympathetic nerves play an important role in various physiological activities and the regulation of osteoporosis as well. Therefore, the role of sympathetic nerves in osteoporosis was reviewed, aiming to provide information for future targeting of sympathetic nerves in osteoporosis.

1. Introduction

Osteoporosis, a systemic bone disease, is characterized by decreased bone density due to various reasons, destructed bone microstructure, and increased bone fragility [1], and it is defined as the density of the femoral neck or lumbar spine that is less than −2.5 measured by QCT (quantitative computed tomography) or dual energy X-ray. If the bone density is between −2.5 and −1.5, it is called low bone mass [2,3,4]. The incidence of osteoporosis is high, and about 9% of Americans over the age of 50 and 200 million women worldwide develop osteoporosis [5]. The most serious common complication of osteoporosis is fracture. In western societies, one in three women and one in five men suffer osteoporotic fractures for the rest of their lives after the age of 50, especially spine and hip fractures that increase the mortality of osteoporotic patients [6]. The current treatment of osteoporosis is mainly through drug therapy, including antiresorptive agents and drugs that promote bone formation, for example: bisphosphonates estrogen modulators, teriparatide, denosumab, etc. A Rankl inhibitor, denosumab, is a drug recently approved by the FDA to treat osteoporosis. The usage is to inject under the skin every 6 months, which has good anti-osteoporosis curative effects. While these treatments are accompanied with serious adverse events such as thromboembolism, increased risk of stroke, and hypocalcemia, some drugs, such as zoledronic acid, require hospitalization to check renal function, which is inconvenient for clinical use [7,8,9,10,11,12,13,14], and thus it is necessary to develop new treatment methods.
Sympathetic and parasympathetic nerves make up the autonomic nerves, and the autonomic nerve controls vital physiological functions such as heart beat, respiration, digestion, blood pressure, metabolism, etc. [15,16,17,18,19]. The activities of the sympathetic nervous system are relatively extensive; stimulating the sympathetic nerves can cause vasoconstriction of abdominal viscera and skin peripheral blood vessels, strengthening and acceleration of the heartbeat, mydriasis, decreased secretion of digestive glands, increased working ability of tired muscles, etc., The activity of sympathetic nerves is to mainly guarantee the physiological needs of the human body in states of stress [20,21,22,23,24]. Sympathetic nerves also play a regulatory role in osteoporosis [25]. The occurrence of osteoporosis is mainly caused by the decrease of osteogenesis and osteoclastosis [26,27,28,29,30,31]. We mainly discuss five aspects: the structural basis of sympathetic regulation of osteoporosis, the phenomenon of sympathetic nerve regulation of osteoporosis, sympathetic nerve regulation of osteogenesis, sympathetic nerve regulation of osteoclastogenesis, and drugs for treating osteoporosis through regulating sympathetic nerve activity, aiming to provide information for the treatment of osteoporosis.

2. Methods

We used “sympathetic nerve” and “osteoporosis”, “sympathetic nerve” and “osteoblast “, “sympathetic nerve” and “osteoclast“ as keywords, and searched all the articles from 1953 to 2022 in PUBMED and MEDLINE. We included only publications published in English and selected those findings that were, in our opinion, the most important. We further analyzed these articles; we mainly selected papers from the past 5 years but also included well-respected older publications (Figure 1). The registration number is: INPLASY2022120079.

3. Results and Discussion

3.1. Structural Basis of Sympathetic Regulation of Osteoporosis

Sympathetic neurons are located in the lateral horn of the thoracolumbar segment of the spinal cord, and their fibers originate from the corresponding spinal segment and terminate in the paravertebral ganglia or prevertebral ganglia, called preganglionic fibers [32,33,34]. After leaving the spinal cord, preganglionic fibers may ascend or descend for several segments in the sympathetic chain and then terminate in ganglia. A preganglionic fiber often has many branches that are connected with different postganglionic neurons, thus resulting in a “scattered” excitation effect [35,36,37].
There are two types of neurotransmitters released by sympathetic nerves: the neurotransmitter released by all sympathetic preganglionic nerve endings is acetylcholine, and all sympathetic postganglionic nerve endings release norepinephrine [38,39,40].
The receptors of the sympathetic nerve are adrenergic receptors, which are divided into two categories, namely α and β [41,42]. α receptors are divided into α1 and α2: α1 is distributed on the presynaptic membrane and vascular smooth muscle, which mainly causes vasoconstriction when excited; α2 is mainly distributed on the presynaptic membrane of noradrenergic nerves and produces negative feedback regulation and inhibition on the secretion of NE when excited [43,44,45]. β receptors are divided into β1, β2, and β3; β1 is mainly distributed on cardiomyocytes. After the activation of β1 receptors, it has positive effects on the myocardium, thus resulting in a series of reactions of myocardial excitation; β2 receptors are mainly distributed on smooth muscles, such as blood vessels, smooth muscle, alimentary canal smooth muscle, bronchial smooth muscle, etc., and this receptor can cause smooth muscle relaxation after activation; β3 receptors are mainly distributed in white and brown adipose tissue to regulate energy metabolism [46,47,48,49].
In fact, many studies have confirmed the presence of sympathetic receptors on the cell membranes of osteoblasts and osteoclasts, which provides a structural basis for sympathetic regulation of the progression of osteoporosis [50,51,52,53,54,55].

3.2. The Phenomenon of Sympathetic Nerve Regulation of Osteoporosis

The discovery of many phenomena indicates that the dysregulation of sympathetic nerves is related to the occurrence of osteoporosis. Interestingly, the regulation of sympathetic nerves in osteoporosis is complex, and sympathetic nerve dysfunction leads to osteoporosis. Inhibition of sympathetic nerves can also treat osteoporosis, which seems contradictory. The specific mechanism is currently unclear, and it requires more and more systematic research.
Many scholars have observed that sympathetic nerve dysfunction leads to osteoporosis: Iris A Enríquez-Pérez et al. found that diabetes-induced reduction in sympathetic nerve fiber density was associated with femoral neck bone loss in mice [56]; Sharareh Roshanzamir et al. discovered that sympathetic nerve disorder caused by electrical burn was associated with osteoporosis [57]; C J Stephens et al. reported a case of reflex sympathetic dystrophy in a patient with severe osteoporosis [58]. The findings of these studies proved that sympathetic nerve disorders indeed lead to the occurrence of osteoporosis, but there is no relevant report on the mechanism at present.
However, according to other scholars, inhibiting sympathetic nerve activity can increase bone mass and prevent osteoporosis from progressing. Based on T Sato et al. the selective β2-adrenergic antagonist butoxamine reduces bone loss in sympathetically hyperactive osteoporotic rats [59]. Wenping Zhang et al. revealed that the beta-blocker propranolol could improve bone mass and inhibit osteoporosis progression in osteoporotic rats [60].

3.3. Sympathetic Regulation of Osteogenesis

The main reason for the occurrence of osteoporosis is the decrease in osteogenesis and osteoclastosis [61,62,63,64,65,66,67,68]. Osteoblast differentiation is a central step in bone formation [26,27,28,29,30,31]. Many studies have illustrated that the sympathetic nerve affects bone formation and the progression of osteoporosis by regulating osteoblast differentiation (Table 1).
At present, most scholars hold the view that sympathetic nerve activation inhibits osteoblast differentiation and osteogenesis. In addition, it promotes the formation of osteoporosis. Ziyan Wang et al. indicated that long-term use of adrenergic drugs increases the odds of fracture, and the β2-adrenergic receptor agonist terbutaline directly inhibits osteogenesis by impairing osteogenic differentiation and mineralization [69]. Yupeng Wu et al. confirmed that the inhibition of sympathetic nerve activity can promote the osteogenic differentiation capacity of osteoblasts and mesenchymal stem cells [70]. Takayuki Yamada et al., discovered that the activation of the sympathetic nerve inhibits osteoblast differentiation [71]. Yoon Jung Choi et al. revealed that the α-blocker doxazosin activates ERK1/2 in stem cells to promote osteogenic differentiation [72]. The view that the sympathetic nerve inhibits osteogenesis is also supported by other researchers [52,73].
However, some scholars agree that the activation of sympathetic nerves promotes osteogenesis and inhibits the progression of osteoporosis. On the basis of Yun Ma et al. a reduction in norepinephrine leads to a reduction in osteogenesis [74]. Ji-Ye He et al. revealed that sympathetic neurons can promote osteoblast differentiation through the BMP signaling pathway [75]. Takuya Uemura et al. found that epinephrine accelerates osteoblastic differentiation by enhancing bone morphogenetic protein signaling through a cAMP/protein kinase A signaling pathway [76].
All in all, there is a certain degree of controversy about the role of sympathetic nerves in osteogenesis. At present, most researchers argue that sympathetic nerve activation promotes osteogenesis, and some scholars hold the opposite view, which requires additional systematic research in the future.

3.4. Sympathetic Nerve Regulation of Osteoclastogenesis

The process of bone resorption is as follows: monocytes differentiate into osteoclasts that attach to the old bone area, secrete acidic substances to dissolve minerals, and secrete protease substances to digest old bones [77,78,79,80,81,82]. It is well known that an important cause of osteoporosis is increased osteoclastic activity [83,84,85,86]. The opinion of most scholars is that increased sympathetic nerve activity promotes the process of osteoclastic bone formation (Table 2).
Florent Elefteriou et al. found that leptin activates sympathetic nerves to increase osteoclast differentiation, leading to increased bone resorption and eventually leading to the progression of osteoporosis [87]; H Cao et al. found that the sympathetic nervous system increases the RANKL/OPG ratio of peripheral blood mononuclear cells through β-2 adrenergic receptors, promotes their differentiation into osteoclasts, and increases bone resorption [88]; Sarah J Aitken et al. found that the activation of sympathetic nerves promotes osteoclastogenesis and bone resorption [89]; U Frediani et al. found that catecholamines stimulate osteoclast differentiation by binding to β2 adrenergic receptors, thus promoting the progression of osteoporosis [90]. Most importantly, other researchers have made similar findings [54,91].
In general, the role of sympathetic nerves in osteoclasts is relatively well established, and sympathetic nerve activation promotes the process of osteoclast differentiation.

3.5. Drugs for Treating Osteoporosis through Regulating Sympathetic Nerve Activity

The most common treatment for osteoporosis is anti-osteoporosis drugs, such as bisphosphonates, raloxifene, estrogens, parathyroid hormone, etc. These drugs can achieve certain clinical effects, but there are also clinical limitations and side effects [92,93,94,95,96,97]. For example, zoledronic acid requires testing of renal function before being infused during an outpatient clinic visit, and the use of zoledronic acid may have side effects on the jaw [98,99,100,101]; raloxifene may cause venous thromboembolism [102,103,104]; estrogen therapy for osteoporosis leads to an increased risk of gynecological tumors [105,106,107]; the parathyroid hormone analog teriparatide may cause lower blood pressure in osteoporosis patients [108,109,110]. Therefore, it is of clinical significance to develop new drugs for the treatment of osteoporosis. Given our previous discussion, sympathetic nerves play an important role in the progression of osteoporosis, and many potential drugs have been found to inhibit osteoporosis through sympathetic nerves (Table 3).
Hao Chen et al. found that the β2-adrenergic antagonist propranolol has a therapeutic effect on osteoporosis [111]; T Sato et al., discovered that the selective beta2-adrenergic antagonist butoxamine ameliorates osteoporosis with an overactive sympathetic nervous system [59]; Hideo Shimizu et al. proved that cilnidipine inhibits the progression of osteoporosis in ovariectomized hypertensive rats by inhibiting sympathetic nerve activity [112]; Wenping Zhang et al. revealed that the beta-blocker propranolol increases bone mass in osteoporotic mice [60].
In general, scholars agree that drugs that inhibit sympathetic nerve activity have potential effects on the treatment of osteoporosis. For example, propranolol is a potential drug for osteoporosis treatmen;, propranolol is a drug mainly used to treat isocardial arrhythmias of atrial and ventricular premature beats and is also effective for hypertension. If a patient with arrhythmia or high blood pressure happens to suffer from osteoporosis, then propranolol may be a very suitable drug, which requires comprehensive clinical research; certainly, propranolol should not be used in patients with bronchospasm and cardiogenic shock [113].

4. Conclusions

Osteoporosis is a common disease, and the resulting spine and hip fractures are detrimental to the life quality and safety of the elderly. The current treatment for osteoporosis usually involves anti-osteoporosis drugs, but these drugs have side effects. It is of clinical importance to find new anti-osteoporosis drugs.
Sympathetic nerves are part of the autonomic nervous system and have a wide range of regulatory effects. Osteoporosis is mainly caused by decreased osteogenesis and increased osteoclasts. There are sympathetic receptors on their cell membranes, and sympathetic neuromodulation of osteoporosis provides a structural basis. Sympathetic inactivation may lead to osteoporosis, and the inhibition of sympathetic activity also inhibits osteoporosis progression, which seems paradoxical and requires more research. Many scholars argue that sympathetic nerves can inhibit osteogenesis, but some scholars hold the opposite view. Sympathetic nerve-promoting osteoclasts are recognized by many researchers. Furthermore, some drugs can inhibit the progression of osteoporosis by regulating sympathetic nerve activity, such as propranolol, which may become a therapeutic drug for patients with arrhythmia or high blood pressure who happen to suffer from osteoporosis in the future.

Author Contributions

Y.W. and Q.K. designed the manuscript; C.F., B.Z. and P.F. checked related literature; W.Z., Y.L. and J.X. wrote the manuscript and participated in the revision. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by China, the Sichuan Science and Technology Program (2020YFS0080, 2020YFQ0007, 2021JDRC0159), the Science and Technology Project of the Tibet Autonomous Region (XZ201901-GB-08), the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21026, ZYJC21077), the Natural Science Fund of the Tibet Autonomous Region (XZ202101ZR0112G), the Science and Technology Major Project of Tibetan Autonomous Region of China (XZ202201ZD0001G), and the Project of the Hospital of Chengdu Office of the People’s Government of the Tibet Autonomous Region (2020-YJYB-1).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no competing interest.

References

  1. Cotts, K.G.; Cifu, A.S. Treatment of Osteoporosis. Jama 2018, 319, 1040–1041. [Google Scholar] [CrossRef]
  2. Simon, A.; Schäfer, H.S.; Schmidt, F.N.; Stürznickel, J.; Amling, M.; Rolvien, T. Compartment-specific effects of muscle strength on bone microarchitecture in women at high risk of osteoporosis. J. Cachexia Sarcopenia Muscle 2022, 13, 2310–2321. [Google Scholar] [CrossRef]
  3. Yu, J.S.; Krishna, N.G.; Fox, M.G.; Blankenbaker, D.G.; Frick, M.A.; Jawetz, S.T.; Li, G.; Reitman, C.; Said, N.; Stensby, J.D.; et al. ACR Appropriateness Criteria® Osteoporosis and Bone Mineral Density: 2022 Update. J. Am. Coll. Radiol. JACR 2022, 19, S417–S432. [Google Scholar] [CrossRef]
  4. Rondanelli, M.; Guido, D.; Opizzi, A.; Faliva, M.A.; Perna, S.; Grassi, M. A path model of sarcopenia on bone mass loss in elderly subjects. J. Nutr. Health Aging 2014, 18, 15–21. [Google Scholar] [CrossRef]
  5. Dong, Q.; Luo, G.; Lane, N.E.; Lui, L.Y.; Marshall, L.M.; Kado, D.M.; Cawthon, P.; Perry, J.; Johnston, S.K.; Haynor, D.; et al. Deep Learning Classification of Spinal Osteoporotic Compression Fractures on Radiographs using an Adaptation of the Genant Semiquantitative Criteria. Acad. Radiol. 2022, 29, 1819–1832. [Google Scholar] [CrossRef]
  6. Lorentzon, M.; Johansson, H.; Harvey, N.C.; Liu, E.; Vandenput, L.; McCloskey, E.V.; Kanis, J.A. Osteoporosis and fractures in women: The burden of disease. Climacteric J. Int. Menopause Soc. 2022, 25, 4–10. [Google Scholar] [CrossRef]
  7. Patel, D.; Wairkar, S. Bone regeneration in osteoporosis: Opportunities and challenges. Drug Deliv. Transl. Res. 2022. [Google Scholar] [CrossRef]
  8. Trivedi, T.; Guise, T.A. Systemic effects of abnormal bone resorption on muscle, metabolism, and cognition. Bone 2022, 154, 116245. [Google Scholar] [CrossRef]
  9. Lu, J.; Hu, D.; Ma, C.; Shuai, B. Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis. Front. Pharmacol. 2022, 13, 938447. [Google Scholar] [CrossRef]
  10. Kalinkovich, A.; Livshits, G. Biased and allosteric modulation of bone cell-expressing G protein-coupled receptors as a novel approach to osteoporosis therapy. Pharmacol. Res. 2021, 171, 105794. [Google Scholar] [CrossRef]
  11. Singh, S.; Dutta, S.; Khasbage, S.; Kumar, T.; Sachin, J.; Sharma, J.; Varthya, S.B. A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis. Osteoporos. Int. 2022, 33, 1–12. [Google Scholar] [CrossRef]
  12. Charopoulos, I.; Orme, S.; Giannoudis, P.V. The role and efficacy of denosumab in the treatment of osteoporosis: An update. Expert Opin. Drug Saf. 2011, 10, 205–217. [Google Scholar] [CrossRef]
  13. LeBoff, M.S.; Greenspan, S.L.; Insogna, K.L.; Lewiecki, E.M.; Saag, K.G.; Singer, A.J.; Siris, E.S. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporos. Int. 2022, 33, 2049–2102. [Google Scholar] [CrossRef]
  14. Yamasaki, M.; Yuasa, T.; Uehara, S.; Fujii, Y.; Yamamoto, S.; Masuda, H.; Fukui, I.; Yonese, J. Improvement of renal function by changing the bone-modifying agent from zoledronic acid to denosumab. Int. J. Clin. Oncol. 2016, 21, 1191–1195. [Google Scholar] [CrossRef] [Green Version]
  15. Hyun, U.; Sohn, J.W. Autonomic control of energy balance and glucose homeostasis. Exp. Mol. Med. 2022, 54, 370–376. [Google Scholar] [CrossRef]
  16. Boyes, N.G.; Marciniuk, D.D.; Haddad, H.; Tomczak, C.R. Autonomic cardiovascular reflex control of hemodynamics during exercise in heart failure with reduced ejection fraction and the effects of exercise training. Rev. Cardiovasc. Med. 2022, 23, 72. [Google Scholar] [CrossRef]
  17. Cuenca-Bermejo, L.; Almela, P.; Navarro-Zaragoza, J.; Fernández Villalba, E.; González-Cuello, A.M.; Laorden, M.L.; Herrero, M.T. Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence. Int. J. Mol. Sci. 2021, 22, 13488. [Google Scholar] [CrossRef]
  18. Fujiu, K.; Manabe, I. Nerve-macrophage interactions in cardiovascular disease. Int. Immunol. 2022, 34, 81–95. [Google Scholar] [CrossRef]
  19. van Weperen, V.Y.H.; Vos, M.A.; Ajijola, O.A. Autonomic modulation of ventricular electrical activity: Recent developments and clinical implications. Clin. Auton. Res. Off. J. Clin. Auton. Res. Soc. 2021, 31, 659–676. [Google Scholar] [CrossRef]
  20. Haas, A.; Borsook, D.; Adler, G.; Freeman, R. Stress, hypoglycemia, and the autonomic nervous system. Auton. Neurosci. Basic Clin. 2022, 240, 102983. [Google Scholar] [CrossRef]
  21. Nakamura, K.; Nakamura, Y.; Kataoka, N. A hypothalamomedullary network for physiological responses to environmental stresses. Nat. Rev. Neurosci. 2022, 23, 35–52. [Google Scholar] [CrossRef]
  22. Barman, S.M.; Yates, B.J. Deciphering the Neural Control of Sympathetic Nerve Activity: Status Report and Directions for Future Research. Front. Neurosci. 2017, 11, 730. [Google Scholar] [CrossRef] [Green Version]
  23. Guzmán-Mejía, F.; Godínez-Victoria, M.; Vega-Bautista, A.; Pacheco-Yépez, J.; Drago-Serrano, M.E. Intestinal Homeostasis under Stress Siege. Int. J. Mol. Sci. 2021, 22, 5095. [Google Scholar] [CrossRef]
  24. Spiesshoefer, J.; Regmi, B.; Ottaviani, M.M.; Kahles, F.; Giannoni, A.; Borrelli, C.; Passino, C.; Macefield, V.; Dreher, M. Sympathetic and Vagal Nerve Activity in COPD: Pathophysiology, Presumed Determinants and Underappreciated Therapeutic Potential. Front. Physiol. 2022, 13, 919422. [Google Scholar] [CrossRef]
  25. He, J.Y.; Jiang, L.S.; Dai, L.Y. The roles of the sympathetic nervous system in osteoporotic diseases: A review of experimental and clinical studies. Ageing Res. Rev. 2011, 10, 253–263. [Google Scholar] [CrossRef]
  26. Cao, L.; Wang, J.; Zhang, Y.; Tian, F.; Wang, C. Osteoprotective effects of flavonoids: Evidence from in vivo and in vitro studies (Review). Mol. Med. Rep. 2022, 25, 200. [Google Scholar] [CrossRef]
  27. Che, Y.; Yang, J.; Tang, F.; Wei, Z.; Chao, Y.; Li, N.; Li, H.; Wu, S.; Dong, X. New Function of Cholesterol Oxidation Products Involved in Osteoporosis Pathogenesis. Int. J. Mol. Sci. 2022, 23, 2020. [Google Scholar] [CrossRef]
  28. Omosule, C.L.; Phillips, C.L. Deciphering Myostatin’s Regulatory, Metabolic, and Developmental Influence in Skeletal Diseases. Front. Genet. 2021, 12, 662908. [Google Scholar] [CrossRef]
  29. Honda, M.; Hariya, R.; Matsumoto, M.; Aizawa, M. Acceleration of Osteogenesis via Stimulation of Angiogenesis by Combination with Scaffold and Connective Tissue Growth Factor. Materials 2019, 12, 2068. [Google Scholar] [CrossRef] [Green Version]
  30. Yi, S.J.; Lee, H.; Lee, J.; Lee, K.; Kim, J.; Kim, Y.; Park, J.I.; Kim, K. Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation. Int. J. Mol. Sci. 2019, 20, 3147. [Google Scholar] [CrossRef]
  31. Ghorbaninejad, M.; Khademi-Shirvan, M.; Hosseini, S.; Baghaban Eslaminejad, M. Epidrugs: Novel epigenetic regulators that open a new window for targeting osteoblast differentiation. Stem Cell Res. Ther. 2020, 11, 456. [Google Scholar] [CrossRef]
  32. Veshchitskii, A.A.; Kirik, O.V.; Korzhevskii, D.E.; Merkulyeva, N. Development of neurochemical labeling in the intermediolateral nucleus of cats’ spinal cord. Anat. Rec. 2022. [Google Scholar] [CrossRef]
  33. Farmer, D.G.S.; Pracejus, N.; Dempsey, B.; Turner, A.; Bokiniec, P.; Paton, J.F.R.; Pickering, A.E.; Burguet, J.; Andrey, P.; Goodchild, A.K.; et al. On the presence and functional significance of sympathetic premotor neurons with collateralized spinal axons in the rat. J. Physiol. 2019, 597, 3407–3423. [Google Scholar] [CrossRef]
  34. Clement, P.; Giuliano, F. Physiology and Pharmacology of Ejaculation. Basic Clin. Pharmacol. Toxicol. 2016, 119 (Suppl. 3), 18–25. [Google Scholar] [CrossRef] [Green Version]
  35. Kim, S.W.; Chung, S.J.; Lee, S.; Oh, K.; Yoo, S.K.; Lee, P.H.; Kim, S.M.; Shin, H.Y.; Yun, M. Postganglionic Sudomotor Dysfunction and Brain Glucose Hypometabolism in Patients with Multiple System Atrophy. J. Park. Dis. 2021, 11, 1247–1256. [Google Scholar] [CrossRef]
  36. Wang, Z.M.; Messi, M.L.; Grinevich, V.; Budygin, E.; Delbono, O. Postganglionic sympathetic neurons, but not locus coeruleus optostimulation, activates neuromuscular transmission in the adult mouse in vivo. Mol. Cell. Neurosci. 2020, 109, 103563. [Google Scholar] [CrossRef]
  37. Buchmann, S.J.; Penzlin, A.I.; Kubasch, M.L.; Illigens, B.M.; Siepmann, T. Assessment of sudomotor function. Clin. Auton. Res. Off. J. Clin. Auton. Res. Soc. 2019, 29, 41–53. [Google Scholar] [CrossRef]
  38. Hansen, T.; Tarasova, O.S.; Khammy, M.M.; Ferreira, A.; Kennard, J.A.; Andresen, J.; Staehr, C.; Brain, K.L.; Nilsson, H.; Aalkjaer, C. [Ca(2+) ] changes in sympathetic varicosities and Schwann cells in rat mesenteric arteries-Relation to noradrenaline release and contraction. Acta Physiol. 2019, 226, e13279. [Google Scholar] [CrossRef] [Green Version]
  39. Berg, T. Voltage-Sensitive K(+) Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats. Front. Neurol. 2015, 6, 260. [Google Scholar] [CrossRef] [Green Version]
  40. Chistiakov, D.A.; Ashwell, K.W.; Orekhov, A.N.; Bobryshev, Y.V. Innervation of the arterial wall and its modification in atherosclerosis. Auton. Neurosci. Basic Clin. 2015, 193, 7–11. [Google Scholar] [CrossRef]
  41. Qin, Y.J.; Xiao, K.; Zhong, Z.; Zhao, Y.; Zhang, Y.L.; Sun, X.F. Markers of the sympathetic, parasympathetic and sensory nervous system are altered in the human diabetic choroid. Peptides 2021, 146, 170661. [Google Scholar] [CrossRef]
  42. Bellinger, D.L.; Wood, C.; Wergedal, J.E.; Lorton, D. Driving β(2)- While Suppressing α-Adrenergic Receptor Activity Suppresses Joint Pathology in Inflammatory Arthritis. Front. Immunol. 2021, 12, 628065. [Google Scholar] [CrossRef]
  43. Lee, S.H.; Kwon, S.C.; Ok, S.H.; Ahn, S.H.; Bae, S.I.; Kim, J.Y.; Hwang, Y.; Park, K.E.; Kim, M.; Sohn, J.T. Dexmedetomidine-Induced Aortic Contraction Involves Transactivation of the Epidermal Growth Factor Receptor in Rats. Int. J. Mol. Sci. 2022, 23, 4320. [Google Scholar] [CrossRef]
  44. Motiejunaite, J.; Amar, L.; Vidal-Petiot, E. Adrenergic receptors and cardiovascular effects of catecholamines. Ann. D’endocrinologie 2021, 82, 193–197. [Google Scholar] [CrossRef]
  45. Mulcahy, L.; Tudor, E.; Bailey, S.R. Validation of canine uterine and testicular arteries for the functional characterisation of receptor-mediated contraction as a replacement for laboratory animal tissues in teaching. PLoS ONE 2020, 15, e0230516. [Google Scholar] [CrossRef]
  46. Ezeani, M.; Prabhu, S. PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation. Mol. Cell. Biochem. 2022. [Google Scholar] [CrossRef]
  47. Al Katat, A.; Zhao, J.; Calderone, A.; Parent, L. Sympathetic Stimulation Upregulates the Ca(2+) Channel Subunit, Ca(V)α2δ1, via the β1 and ERK 1/2 Pathway in Neonatal Ventricular Cardiomyocytes. Cells 2022, 11, 188. [Google Scholar] [CrossRef]
  48. Bundgaard, H.; Axelsson, A.; Hartvig Thomsen, J.; Sørgaard, M.; Kofoed, K.F.; Hasselbalch, R.; Fry, N.A.; Valeur, N.; Boesgaard, S.; Gustafsson, F.; et al. The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: The BEAT-HF trial. Eur. J. Heart Fail. 2017, 19, 566–575. [Google Scholar] [CrossRef] [Green Version]
  49. Myagmar, B.E.; Flynn, J.M.; Cowley, P.M.; Swigart, P.M.; Montgomery, M.D.; Thai, K.; Nair, D.; Gupta, R.; Deng, D.X.; Hosoda, C.; et al. Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent. Circ. Res. 2017, 120, 1103–1115. [Google Scholar] [CrossRef] [Green Version]
  50. Togari, A.; Arai, M.; Mizutani, S.; Mizutani, S.; Koshihara, Y.; Nagatsu, T. Expression of mRNAs for neuropeptide receptors and beta-adrenergic receptors in human osteoblasts and human osteogenic sarcoma cells. Neurosci. Lett. 1997, 233, 125–128. [Google Scholar] [CrossRef]
  51. Togari, A. Adrenergic regulation of bone metabolism: Possible involvement of sympathetic innervation of osteoblastic and osteoclastic cells. Microsc. Res. Tech. 2002, 58, 77–84. [Google Scholar] [CrossRef]
  52. Ma, Y.; Nyman, J.S.; Tao, H.; Moss, H.H.; Yang, X.; Elefteriou, F. β2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone. Endocrinology 2011, 152, 1412–1422. [Google Scholar] [CrossRef] [Green Version]
  53. Fonseca, T.L.; Jorgetti, V.; Costa, C.C.; Capelo, L.P.; Covarrubias, A.E.; Moulatlet, A.C.; Teixeira, M.B.; Hesse, E.; Morethson, P.; Beber, E.H.; et al. Double disruption of α2A- and α2C-adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype. J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res. 2011, 26, 591–603. [Google Scholar] [CrossRef] [Green Version]
  54. Okada, Y.; Hamada, N.; Kim, Y.; Takahashi, Y.; Sasaguri, K.; Ozono, S.; Sato, S. Blockade of sympathetic b-receptors inhibits Porphyromonas gingivalis-induced alveolar bone loss in an experimental rat periodontitis model. Arch. Oral Biol. 2010, 55, 502–508. [Google Scholar] [CrossRef]
  55. Suga, S.; Goto, S.; Togari, A. Demonstration of direct neurite-osteoclastic cell communication in vitro via the adrenergic receptor. J. Pharmacol. Sci. 2010, 112, 184–191. [Google Scholar] [CrossRef] [Green Version]
  56. Enríquez-Pérez, I.A.; Galindo-Ordoñez, K.E.; Pantoja-Ortíz, C.E.; Martínez-Martínez, A.; Acosta-González, R.I.; Muñoz-Islas, E.; Jiménez-Andrade, J.M. Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck. Neurosci. Lett. 2017, 655, 28–34. [Google Scholar] [CrossRef]
  57. Roshanzamir, S.; Dabbaghmanesh, M.H.; Dabbaghmanesh, A.; Nejati, S. Autonomic dysfunction and osteoporosis after electrical burn. Burn. J. Int. Soc. Burn Inj. 2016, 42, 583–588. [Google Scholar] [CrossRef]
  58. Stephens, C.J.; McGibbon, D.H. Algodystrophy (reflex sympathetic dystrophy) complicating unilateral acrodermatitis continua. Clin. Exp. Dermatol. 1989, 14, 445–447. [Google Scholar] [CrossRef]
  59. Sato, T.; Miyazawa, K.; Suzuki, Y.; Mizutani, Y.; Uchibori, S.; Asaoka, R.; Arai, M.; Togari, A.; Goto, S. Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement. J. Dent. Res. 2014, 93, 807–812. [Google Scholar] [CrossRef] [Green Version]
  60. Zhang, W.; Kanehara, M.; Zhang, Y.; Wang, X.; Ishida, T. Beta-blocker and other analogous treatments that affect bone mass and sympathetic nerve activity in ovariectomized rats. Am. J. Chin. Med. 2007, 35, 89–101. [Google Scholar] [CrossRef]
  61. Wang, M.Y.; An, M.F.; Fan, M.S.; Zhang, S.S.; Sun, Z.R.; Zhao, Y.L.; Xiang, Z.M.; Sheng, J. FAEE exerts a protective effect against osteoporosis by regulating the MAPK signalling pathway. Pharm. Biol. 2022, 60, 467–478. [Google Scholar] [CrossRef] [PubMed]
  62. Ye, C.; Zhang, W.; Zhao, Y.; Zhang, K.; Hou, W.; Chen, M.; Lu, J.; Wu, J.; He, R.; Gao, W.; et al. Prussian Blue Nanozyme Normalizes Microenvironment to Delay Osteoporosis. Adv. Healthc. Mater. 2022, 11, e2200787. [Google Scholar] [CrossRef] [PubMed]
  63. Li, Y.; Zhuang, Q.; Tao, L.; Zheng, K.; Chen, S.; Yang, Y.; Feng, C.; Wang, Z.; Shi, H.; Shi, J.; et al. Urolithin B suppressed osteoclast activation and reduced bone loss of osteoporosis via inhibiting ERK/NF-κB pathway. Cell Prolif. 2022, 55, e13291. [Google Scholar] [CrossRef] [PubMed]
  64. He, M.; Lei, H.; He, X.; Liu, Y.; Wang, A.; Ren, Z.; Liu, X.; Yan, G.; Wang, W.; Wang, Y.; et al. METTL14 Regulates Osteogenesis of Bone Marrow Mesenchymal Stem Cells via Inducing Autophagy through m6A/IGF2BPs/Beclin-1 Signal Axis. Stem Cells Transl. Med. 2022, 11, 987–1001. [Google Scholar] [CrossRef] [PubMed]
  65. Zhang, L.; Zheng, Y.L.; Wang, R.; Wang, X.Q.; Zhang, H. Exercise for osteoporosis: A literature review of pathology and mechanism. Front. Immunol. 2022, 13, 1005665. [Google Scholar] [CrossRef] [PubMed]
  66. Gu, D.R.; Yang, H.; Kim, S.C.; Hwang, Y.H.; Ha, H. Water Extract of Piper longum Linn Ameliorates Ovariectomy-Induced Bone Loss by Inhibiting Osteoclast Differentiation. Nutrients 2022, 14, 3667. [Google Scholar] [CrossRef] [PubMed]
  67. Guo, H.; Sui, C.; Ge, S.; Cai, J.; Lin, D.; Guo, Y.; Wang, N.; Zhou, Y.; Ying, R.; Zha, K.; et al. Positive association of glucagon with bone turnover markers in type 2 diabetes: A cross-sectional study. Diabetes/Metab. Res. Rev. 2022, 38, e3550. [Google Scholar] [CrossRef]
  68. Qu, Z.; An, H.; Feng, M.; Huang, W.; Wang, D.; Zhang, Z.; Yan, L. Urolithin B suppresses osteoclastogenesis via inhibiting RANKL-induced signalling pathways and attenuating ROS activities. J. Cell. Mol. Med. 2022, 26, 4428–4439. [Google Scholar] [CrossRef]
  69. Wang, Z.; Liu, Y.; Zhang, J.; Lin, M.; Xiao, C.; Bai, H.; Liu, C. Mechanical loading alleviated the inhibition of β2-adrenergic receptor agonist terbutaline on bone regeneration. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2021, 35, e22033. [Google Scholar] [CrossRef]
  70. Wu, Y.; Zhang, Q.; Zhao, B.; Wang, X. Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration. Int. J. Mol. Med. 2021, 48, 191. [Google Scholar] [CrossRef]
  71. Yamada, T.; Ezura, Y.; Hayata, T.; Moriya, S.; Shirakawa, J.; Notomi, T.; Arayal, S.; Kawasaki, M.; Izu, Y.; Harada, K.; et al. β2 adrenergic receptor activation suppresses bone morphogenetic protein (BMP)-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells. J. Cell. Biochem. 2015, 116, 1144–1152. [Google Scholar] [CrossRef] [PubMed]
  72. Choi, Y.J.; Lee, J.Y.; Lee, S.J.; Chung, C.P.; Park, Y.J. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation. Biochem. Biophys. Res. Commun. 2011, 416, 232–238. [Google Scholar] [CrossRef] [PubMed]
  73. Li, H.; Fong, C.; Chen, Y.; Cai, G.; Yang, M. beta2- and beta3-, but not beta1-adrenergic receptors are involved in osteogenesis of mouse mesenchymal stem cells via cAMP/PKA signaling. Arch. Biochem. Biophys. 2010, 496, 77–83. [Google Scholar] [CrossRef] [PubMed]
  74. Ma, Y.; Krueger, J.J.; Redmon, S.N.; Uppuganti, S.; Nyman, J.S.; Hahn, M.K.; Elefteriou, F. Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis. J. Biol. Chem. 2013, 288, 30105–30113. [Google Scholar] [CrossRef] [Green Version]
  75. He, J.Y.; Zheng, X.F.; Jiang, S.D.; Chen, X.D.; Jiang, L.S. Sympathetic neuron can promote osteoblast differentiation through BMP signaling pathway. Cell. Signal. 2013, 25, 1372–1378. [Google Scholar] [CrossRef]
  76. Uemura, T.; Ohta, Y.; Nakao, Y.; Manaka, T.; Nakamura, H.; Takaoka, K. Epinephrine accelerates osteoblastic differentiation by enhancing bone morphogenetic protein signaling through a cAMP/protein kinase A signaling pathway. Bone 2010, 47, 756–765. [Google Scholar] [CrossRef]
  77. Faulkner, B.; Astleford, K.; Mansky, K.C. Regulation of Osteoclast Differentiation and Skeletal Maintenance by Histone Deacetylases. Molecules 2019, 24, 1355. [Google Scholar] [CrossRef] [Green Version]
  78. Arnett, T.R.; Orriss, I.R. Metabolic properties of the osteoclast. Bone 2018, 115, 25–30. [Google Scholar] [CrossRef] [Green Version]
  79. Ginnetti, A.T.; Paone, D.V.; Nanda, K.K.; Li, J.; Busuek, M.; Johnson, S.A.; Lu, J.; Soisson, S.M.; Robinson, R.; Fisher, J.; et al. Lead optimization of cathepsin K inhibitors for the treatment of Osteoarthritis. Bioorganic Med. Chem. Lett. 2022, 74, 128927. [Google Scholar] [CrossRef]
  80. Ongprakobkul, N.; Ishida, Y.; Hatano-Sato, K.; Li, K.; Petdachai, S.; Usumi-Fujita, R.; Hosomichi, J.; Mahatumarat, K.; Ono, T. Effects of local vs systemic administration of CXCR4 inhibitor AMD3100 on orthodontic tooth movement in rats. Am. J. Orthod. Dentofac. Orthop. Off. Publ. Am. Assoc. Orthod. Const. Soc. Am. Board Orthod. 2022, 162, 182–192. [Google Scholar] [CrossRef]
  81. Yu, F.; Huo, F.; Li, F.; Zuo, Y.; Wang, C.; Ye, L. Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption. Int. J. Oral Sci. 2022, 14, 6. [Google Scholar] [CrossRef] [PubMed]
  82. Ewanchuk, B.W.; Arnold, C.R.; Balce, D.R.; Premnath, P.; Orsetti, T.L.; Warren, A.L.; Olsen, A.; Krawetz, R.J.; Yates, R.M. A non-immunological role for γ-interferon-inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption. Sci. Adv. 2021, 7, eabd3684. [Google Scholar] [CrossRef] [PubMed]
  83. Hadjiargyrou, M. Effects of bisphosphonates on appendicular fracture repair in rodents. Bone 2022, 164, 116542. [Google Scholar] [CrossRef] [PubMed]
  84. Kim, A.S.; Girgis, C.M.; McDonald, M.M. Osteoclast Recycling and the Rebound Phenomenon Following Denosumab Discontinuation. Curr. Osteoporos. Rep. 2022, 20, 505–515. [Google Scholar] [CrossRef] [PubMed]
  85. Hume, D.A.; Batoon, L.; Sehgal, A.; Keshvari, S.; Irvine, K.M. CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple. Curr. Osteoporos. Rep. 2022, 20, 516–531. [Google Scholar] [CrossRef]
  86. Martens, A.; Hertens, P.; Priem, D.; Rinotas, V.; Meletakos, T.; Gennadi, M.; Van Hove, L.; Louagie, E.; Coudenys, J.; De Muynck, A.; et al. A20 controls RANK-dependent osteoclast formation and bone physiology. EMBO Rep. 2022, 23, e55233. [Google Scholar] [CrossRef]
  87. Elefteriou, F.; Ahn, J.D.; Takeda, S.; Starbuck, M.; Yang, X.; Liu, X.; Kondo, H.; Richards, W.G.; Bannon, T.W.; Noda, M.; et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005, 434, 514–520. [Google Scholar] [CrossRef]
  88. Cao, H.; Kou, X.; Yang, R.; Liu, D.; Wang, X.; Song, Y.; Feng, L.; He, D.; Gan, Y.; Zhou, Y. Force-induced Adrb2 in periodontal ligament cells promotes tooth movement. J. Dent. Res. 2014, 93, 1163–1169. [Google Scholar] [CrossRef] [Green Version]
  89. Aitken, S.J.; Landao-Bassonga, E.; Ralston, S.H.; Idris, A.I. Beta2-adrenoreceptor ligands regulate osteoclast differentiation in vitro by direct and indirect mechanisms. Arch. Biochem. Biophys. 2009, 482, 96–103. [Google Scholar] [CrossRef]
  90. Frediani, U.; Becherini, L.; Lasagni, L.; Tanini, A.; Brandi, M.L. Catecholamines modulate growth and differentiation of human preosteoclastic cells. Osteoporos. Int. 1996, 6, 14–21. [Google Scholar] [CrossRef]
  91. Takeuchi, T.; Tsuboi, T.; Arai, M.; Togari, A. Adrenergic stimulation of osteoclastogenesis mediated by expression of osteoclast differentiation factor in MC3T3-E1 osteoblast-like cells. Biochem. Pharmacol. 2001, 61, 579–586. [Google Scholar] [CrossRef] [PubMed]
  92. Taylor, E.A.; Donnelly, E.; Yao, X.; Johnson, M.L.; Amugongo, S.K.; Kimmel, D.B.; Lane, N.E. Sequential Treatment of Estrogen Deficient, Osteopenic Rats with Alendronate, Parathyroid Hormone (1-34), or Raloxifene Alters Cortical Bone Mineral and Matrix Composition. Calcif. Tissue Int. 2020, 106, 303–314. [Google Scholar] [CrossRef] [PubMed]
  93. Barrionuevo, P.; Kapoor, E.; Asi, N.; Alahdab, F.; Mohammed, K.; Benkhadra, K.; Almasri, J.; Farah, W.; Sarigianni, M.; Muthusamy, K.; et al. Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis. J. Clin. Endocrinol. Metab. 2019, 104, 1623–1630. [Google Scholar] [CrossRef] [PubMed]
  94. Eastell, R.; Rosen, C.J.; Black, D.M.; Cheung, A.M.; Murad, M.H.; Shoback, D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2019, 104, 1595–1622. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Cheng, C.; Shoback, D. Mechanisms Underlying Normal Fracture Healing and Risk Factors for Delayed Healing. Curr. Osteoporos. Rep. 2019, 17, 36–47. [Google Scholar] [CrossRef] [PubMed]
  96. Khalid, S.; Calderon-Larranaga, S.; Sami, A.; Hawley, S.; Judge, A.; Arden, N.; Van Staa, T.P.; Cooper, C.; Abrahamsen, B.; Javaid, M.K.; et al. Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: A meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database. Osteoporos. Int. 2022, 33, 1579–1589. [Google Scholar] [CrossRef] [PubMed]
  97. Sharma, S.; Porwal, K.; Kulkarni, C.; Pal, S.; Sihota, P.; Kumar, S.; Tiwari, M.C.; Katekar, R.; Kumar, A.; Singh, P.; et al. Diosmin, a citrus fruit-derived phlebotonic bioflavonoid protects rats from chronic kidney disease-induced loss of bone mass and strength without deteriorating the renal function. Food Funct. 2022, 13, 2184–2199. [Google Scholar] [CrossRef]
  98. Fixen, C.W.; Fixen, D.R. Renal safety of zoledronic acid for osteoporosis in adults 75 years and older. Osteoporos. Int. 2022, 33, 2417–2422. [Google Scholar] [CrossRef]
  99. de Roij van Zuijdewijn, C.; van Dorp, W.; Florquin, S.; Roelofs, J.; Verburgh, K. Bisphosphonate nephropathy: A case series and review of the literature. Br. J. Clin. Pharmacol. 2021, 87, 3485–3491. [Google Scholar] [CrossRef]
  100. de Sousa, V.C.; Sousa, F.R.N.; Vasconcelos, R.F.; Martins, C.S.; Lopes, A.P.; Alves, N.M.; Viana, D.; Alves, K.; Leitão, R.; Brito, G.A.C.; et al. Atorvastatin reduces zoledronic acid-induced osteonecrosis of the jaws of rats. Bone 2022, 164, 116523. [Google Scholar] [CrossRef]
  101. Hadad, H.; Kawamata de Jesus, L.; Piquera Santos, A.F.; Rinaldi Matheus, H.; de Souza Rodrigues, L.G.; Paolo Poli, P.; Marcantonio Junior, E.; Pozzi Semeghini Guastaldi, F.; Maiorana, C.; Milanezi de Almeida, J.; et al. Beta tricalcium phosphate, either alone or in combination with antimicrobial photodynamic therapy or doxycycline, prevents medication-related osteonecrosis of the jaw. Sci. Rep. 2022, 12, 16510. [Google Scholar] [CrossRef] [PubMed]
  102. Nordstrom, B.L.; Cai, B.; De Gregorio, F.; Dhalwani, N.; Fraeman, K.H.; Yoshida, Y.; Gibbs, T. Incidence of venous thromboembolism among postmenopausal women prescribed ospemifene, selective estrogen receptor modulators for noncancer indications, or untreated vulvar and vaginal atrophy. Menopause 2020, 27, 864–871. [Google Scholar] [CrossRef] [PubMed]
  103. Pazhekattu, R.; Lau, A.N.; Adachi, J.D. The Tissue-Selective Estrogen Complex: A Review of Current Evidence. Rheumatol. Ther. 2015, 2, 47–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  104. Vestergaard, P. New strategies for osteoporosis patients previously managed with strontium ranelate. Ther. Adv. Musculoskelet. Dis. 2014, 6, 217–225. [Google Scholar] [CrossRef] [Green Version]
  105. Rozenberg, S.; Di Pietrantonio, V.; Vandromme, J.; Gilles, C. Menopausal hormone therapy and breast cancer risk. Best Pract. Research. Clin. Endocrinol. Metab. 2021, 35, 101577. [Google Scholar] [CrossRef]
  106. Edey, K.A.; Rundle, S.; Hickey, M. Hormone replacement therapy for women previously treated for endometrial cancer. Cochrane Database Syst. Rev. 2018, 5, Cd008830. [Google Scholar] [CrossRef]
  107. Vermeulen, R.F.M.; Beurden, M.V.; Korse, C.M.; Kenter, G.G. Impact of risk-reducing salpingo-oophorectomy in premenopausal women. Climacteric J. Int. Menopause Soc. 2017, 20, 212–221. [Google Scholar] [CrossRef]
  108. Yamamoto, J.; Nakazawa, D.; Nishio, S.; Ishikawa, Y.; Makita, M.; Kusunoki, Y.; Nagai, S.; Fujieda, Y.; Takahata, M.; Yamada, K.; et al. Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study. Ther. Apher. Dial. Off. Peer-Rev. J. Int. Soc. Apher. Jpn. Soc. Apher. Jpn. Soc. Dial. Ther. 2020, 24, 146–153. [Google Scholar] [CrossRef]
  109. Naik-Panvelkar, P.; Norman, S.; Elgebaly, Z.; Elliott, J.; Pollack, A.; Thistlethwaite, J.; Weston, C.; Seibel, M.J. Osteoporosis management in Australian general practice: An analysis of current osteoporosis treatment patterns and gaps in practice. BMC Fam. Pract. 2020, 21, 32. [Google Scholar] [CrossRef] [Green Version]
  110. Chew, C.K.; Clarke, B.L. Abaloparatide: Recombinant human PTHrP (1-34) anabolic therapy for osteoporosis. Maturitas 2017, 97, 53–60. [Google Scholar] [CrossRef]
  111. Chen, H.; Hu, B.; Lv, X.; Zhu, S.; Zhen, G.; Wan, M.; Jain, A.; Gao, B.; Chai, Y.; Yang, M.; et al. Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis. Nat. Commun. 2019, 10, 181. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  112. Shimizu, H.; Nakagami, H.; Yasumasa, N.; Mariana, O.K.; Kyutoku, M.; Koriyama, H.; Nakagami, F.; Shimamura, M.; Rakugi, H.; Morishita, R. Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel. Hypertens. Res. Off. J. Jpn. Soc. Hypertens. 2012, 35, 77–81. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  113. Shimizu, W.; Ohe, T.; Kurita, T.; Kawade, M.; Arakaki, Y.; Aihara, N.; Kamakura, S.; Kamiya, T.; Shimomura, K. Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome. J. Am. Coll. Cardiol. 1995, 26, 1299–1309. [Google Scholar] [CrossRef] [PubMed]
Biomedicines 11 00033 g001 550
Figure 1. PRISMA flowchart showing the process of study selection.
Figure 1. PRISMA flowchart showing the process of study selection.
Biomedicines 11 00033 g001
Table
Table 1. Sympathetic regulation of osteogenesis.
Table 1. Sympathetic regulation of osteogenesis.
ScholarsViewsResearch ModelMechanismsReferences
Ziyan Wang et al.inhibit osteogenesismiceβ2-adrenergic receptor agonist[69]
Yupeng Wu et al.inhibit osteogenesisrabbitsβ-receptor antagonist[70]
Takayuki Yamada et al.inhibit osteogenesiscellβ2-adrenergic receptor agonist[71]
Yoon Jung Choi et al.inhibit osteogenesiscellα receptor antagonist[72]
Yun Ma et al.inhibit osteogenesismiceβ2-adrenergic receptor agonist[52]
Haifang Li et al.inhibit osteogenesiscellβ2 and β3 adrenergic receptor agonist[73]
Yun Ma et al.promote osteogenesismicenorepinephrine [74]
Ji-Ye He et al.promote osteogenesiscellbone morphogenetic protein[75]
Takuya Uemura et al.promote osteogenesiscellepinephrine[76]
Table
Table 2. Sympathetic regulation of osteoclasts.
Table 2. Sympathetic regulation of osteoclasts.
ScholarsViewsResearch ModelMechanismsReferences
Florent Elefteriou et al.promote osteoclastmiceβ2-adrenergic receptor agonist[87]
H Cao et al.promote osteoclastratsβ2-adrenergic receptor agonist[88]
Sarah J Aitken et al.promote osteoclastcellβ2-adrenergic receptor agonist[89]
U Frediani et al.promote osteoclastcellβ2-adrenergic receptor agonist[90]
T Takeuchi et al.promote osteoclastcellβ-receptor agonist[91]
Yuka Okada et al.promote osteoclastratsβ-receptor agonist[54]
Table
Table 3. Potential drugs inhibit osteoporosis through sympathetic nerves.
Table 3. Potential drugs inhibit osteoporosis through sympathetic nerves.
Potential DrugsScholarsResearch ModelMechanismsReferences
propranololHao Chen et al.miceβ2-adrenergic antagonist[111]
butoxamineT Sato et al.ratsselective beta2-adrenergic antagonist[59]
cilnidipineHideo Shimizu et al.ratsinhibiting sympathetic nerve activity[112]
propranololWenping Zhang et al.ratsbeta-blocker[60]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Zhang, W.; Liu, Y.; Xu, J.; Fan, C.; Zhang, B.; Feng, P.; Wang, Y.; Kong, Q. The Role of Sympathetic Nerves in Osteoporosis: A Narrative Review. Biomedicines 2023, 11, 33. https://doi.org/10.3390/biomedicines11010033

AMA Style

Zhang W, Liu Y, Xu J, Fan C, Zhang B, Feng P, Wang Y, Kong Q. The Role of Sympathetic Nerves in Osteoporosis: A Narrative Review. Biomedicines. 2023; 11(1):33. https://doi.org/10.3390/biomedicines11010033

Chicago/Turabian Style

Zhang, Weifei, Yuheng Liu, Jixuan Xu, Chen Fan, Bin Zhang, Pin Feng, Yu Wang, and Qingquan Kong. 2023. "The Role of Sympathetic Nerves in Osteoporosis: A Narrative Review" Biomedicines 11, no. 1: 33. https://doi.org/10.3390/biomedicines11010033

APA Style

Zhang, W., Liu, Y., Xu, J., Fan, C., Zhang, B., Feng, P., Wang, Y., & Kong, Q. (2023). The Role of Sympathetic Nerves in Osteoporosis: A Narrative Review. Biomedicines, 11(1), 33. https://doi.org/10.3390/biomedicines11010033

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop