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EDITORIAL
Year : 2023  |  Volume : 6  |  Issue : 1  |  Page : 1-2

“Osteomicrobiology,” “Osteoimmunology,” and “Immunoporosis”- promising frontiers to study bone health and homeostasis


Department of Orthopaedics, Government Medical College, Haldwani, Uttarakhand, India

Date of Submission16-Sep-2022
Date of Decision21-Nov-2022
Date of Acceptance21-Nov-2022
Date of Web Publication27-Dec-2022

Correspondence Address:
Ganesh Singh Dharmshaktu
Department of Orthopaedics, Government Medical College, Haldwani - 263 139, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jodp.jodp_80_22

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How to cite this article:
Dharmshaktu GS. “Osteomicrobiology,” “Osteoimmunology,” and “Immunoporosis”- promising frontiers to study bone health and homeostasis. J Orthop Dis Traumatol 2023;6:1-2

How to cite this URL:
Dharmshaktu GS. “Osteomicrobiology,” “Osteoimmunology,” and “Immunoporosis”- promising frontiers to study bone health and homeostasis. J Orthop Dis Traumatol [serial online] 2023 [cited 2023 Jan 30];6:1-2. Available from: https://jodt.org/text.asp?2023/6/1/1/365295



Human bone is a dynamic tissue that is a constant “work in progress” when it comes to its functions and physiology. It serves key functions by being a storehouse for hematopoietic cells and marrow, keeping the stringent balance of calcium in the body through complex biochemical processes, and by being part of the skeletal system to provide human form and structure. The attachment of muscles and tendons facilitates human movement and functions. The formation of joints of various types enables complex postures, functions, and dexterity in humans. Its reparative properties are unmatched and this is the only tissue replaced by the bone itself following the healing after the injury.

As the scientific evidence is gathered, newer discoveries lead to newer perspectives with regard to bone metabolism and homeostasis. A few notable frontiers in this context are not only promising to offer greater insights but also hold solutions to many disorders affecting human bone in the future.


  Osteomicrobiology Top


It is an old axiom that a healthy gut is the key to optimal health. More and more discoveries regarding the effect of tiny little creatures thriving inside the human gut on various physiological functions and their implications on human diseases and recovery have turned spotlights on an intriguing habitat within us. Many known and unknown facets of human health and functioning are directly or indirectly linked to gut bacteria which are not only many in number but equally enigmatic in their types, behavior, and functions.

The gut microbiome (GM) is a collective term used for nearly 100 trillion microorganisms inhabiting symbiotically within the gut from the duodenum to the distal colon. These include many species of Gram-positive and negative bacteria, archaea, eukarya, and viruses. These constitute 90% of human cells with a heterogeneous population of 1014 bacteria, 5000 species, and 5 million genes.[1] The gut microbes impact overall bone health and it is believed that a “gut–bone axis” exists and functions within us. Researchers believe that these little creatures might modulate key hormones to indirectly affect bone physiology and propose another theory of a possible “gut–brain–bone axis.”[2] Biological interactions between the immune and skeletal systems are drawing international attention and providing more and more insights into deciphering this complex interplay. A new interdisciplinary area of “osteomicrobiology” is also suggested to understand the complex and interdependent interplay of bone homeostasis, immunology, microbiology, and gastrointestinal contents.[3] The research from these disciplines is certainly going to provide newer insights into mechanisms, treatment targets, and treatment molecules in the future. The manipulation of microbiota by pre and probiotics can have a significant influence in improving bone health and further knowledge in this regard holds potential for newer therapeutic options in the future.[4] The overall idea of GM affecting important homeostasis functions in the body, the fact that gets strengthened by each newer research, is heartening and a welcome step. As we are not able to fathom the complexities of the microbiome inside us, we must not rule out the endless possibilities it can offer for one and all. Our scientific fraternity should invest more time and energy in this arena to unearth fresh gems. It seems, although a bit philosophical, that the idea of “looking within” for solutions has a new meaning.


  Osteoimmunology Top


The immune system is a key regulator of bone turnover that affects many skeletal disorders such as postmenopausal osteoporosis and inflammatory bone loss. GM by regulating the immune system can thus also affect bone health and the need for a new subspecialty of “osteoimmunology” is important for their thorough study.[5]

Osteoimmunology is the new term, as previously described, pertaining to the study of the complex interplay of the immune and skeletal systems.[6] Receptor activator of nuclear factor-kappa B (RANK), RANK ligand (RANKL), and osteoprotegrin (OPG) take part in complex interplay in regulating the remodeling process. Bone remodeling is a continuous process that maintains blood calcium levels within desirable limits. Osteoporosis is the result of net bone loss due to increased osteoclast activity. Evolution of the RANK/RANKL/OPG axis and resultant osteoclastic activity thus is a decisive factor in the causation of osteoporosis. Bone cells (both osteoblasts and osteoclasts) regulate the immune cells by contributing to what is called the “endosteal niche” by engraftment or mobilization of hematopoietic stem cells (HSCs).[7] Key players in bone–immune interrelation are HSCs, osteoblasts, osteoclasts, osteomacs, dendritic cells, neutrophils, T and B lymphocytes. RANKL, function of immune cells in the formation of bone cells and cytokines, transcription factors, and chemokine shared by both the cells of bone and immunity are important discoveries and more future research shall reveal comprehensive details.[5]

Osteoblast-mediated suppression in the settings of hematopoietic malignancies and the relationship between bone and remote malignancies have also extended the spectrum of osteoimmunology.[8]

In fracture also, the presence of immune cells throughout the healing process assures defense against pathogens and also regulates bone modeling. Similarly, rheumatoid arthritis and osteoporosis have immune systems contributing to various presentations of the diseases, and prosthesis failures are also examples of underlying immune system activation against particle debris.[9] Bone loss is seen in autoimmune disorders and cancer also has excessive immune interplay with bone homeostasis. Cells regulating bone turnover share a common precursor with inflammatory immune cells.[10] Future research shall certainly make path-breaking discoveries in not only various aspects of osteoimmunology but also unearth treatment strategies based on the evidence.


  Immunoporosis Top


The growing knowledge and awareness of the interrelation between the immune system and bone health is gaining momentum. A complex interplay of various immune factors such as interleukins and other factors is linked to skeletal homeostasis. The term “immunoporosis” is rightly used recently to highlight the importance of the immune system on the osteoporosis mechanism.[11] Both innate (innate immune cells being a major player) and adaptive immune systems contribute to bone health. Upon being triggered by inflammatory markers, these cells produce pro-inflammatory mediators. Cells of myeloid lineage (like macrophages, monocytes, and dendritic cells) act by producing pro-inflammatory cytokines and at times differentiate into osteoclasts. The inflammation is triggered by cells of the innate immune system and the inflammation has been associated with many skeletal disorders.[12] Aging, also has a huge impact on the immune system, and a state of chronic low-grade inflammation is found in aged patients, the process also referred to as “inflammaging.” Interleukin (IK)-6, IL-10, IL-17, tumor necrosis factor-alpha, and RANKL are well-known factors linked to have an impact on bone cells such as osteoblasts and osteoclasts.[13] As the world is facing an important silent epidemic of osteoporosis that shall only grow larger, the need for comprehensive knowledge of various factors involved in the causation and diagnosis is an unmet need. Robust scientific initiatives are the need of the hour and welcome steps to a healthier future.



 
  References Top

1.
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science 2005;308:1635-8.  Back to cited text no. 1
    
2.
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature 2007;449:804-10.  Back to cited text no. 2
    
3.
Ohlsson C, Sjögren K. Osteomicrobiology: A new cross-disciplinary research field. Calcif Tissue Int 2018;102:426-32.  Back to cited text no. 3
    
4.
Hsu E, Pacifici R. From osteoimmunology to osteomicrobiology: How the microbiota and the immune system regulate bone. Calcif Tissue Int 2018;102:512-21.  Back to cited text no. 4
    
5.
Rauner M, Sipos W, Pietschmann P. Osteoimmunology. Int Arch Allergy Immunol 2007;143:31-48.  Back to cited text no. 5
    
6.
Arron JR, Choi Y. Bone versus immune system. Nature 2000;408:535-6.  Back to cited text no. 6
    
7.
Ponzetti M, Rucci N. Updates on osteoimmunology: What's new on the cross-talk between bone and immune system. Front Endocrinol (Lausanne) 2019;10:236.  Back to cited text no. 7
    
8.
Tsukasaki M, Takayanagi H. Osteoimmunology: Evolving concepts in bone-immune interactions in health and disease. Nat Rev Immunol 2019;19:626-42.  Back to cited text no. 8
    
9.
Guder C, Gravius S, Burger C, Wirtz DC, Schildberg FA. Osteoimmunology: A current update of the interplay between bone and the immune system. Front Immunol 2020;11:58.  Back to cited text no. 9
    
10.
Walsh MC, Kim N, Kadono Y, Rho J, Lee SY, Lorenzo J, et al. Osteoimmunology: Interplay between the immune system and bone metabolism. Annu Rev Immunol 2006;24:33-63.  Back to cited text no. 10
    
11.
Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of osteoporosis-role of T Cells. Front Immunol 2018;9:657.  Back to cited text no. 11
    
12.
Saxena Y, Routh S, Mukhopadhaya A. Immunoporosis: Role of innate immune cells in osteoporosis. Front Immunol 2021;12:687037.  Back to cited text no. 12
    
13.
Srivastava RK, Sapra L. The rising era of “Immunoporosis”: Role of immune system in the pathophysiology of osteoporosis. J Inflamm Res 2022;15:1667-98.  Back to cited text no. 13
    




 

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Osteomicrobiology
Osteoimmunology
Immunoporosis
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