Title: Exploring the Link Between Type 1 Diabetes and Osteoporosis: A Comprehensive Literature

Review

In the realm of medical research, understanding the intricate relationship between Type 1 Diabetes
and Osteoporosis poses a significant challenge. Scholars and healthcare professionals delve into a
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to clinical manifestations and treatment modalities.

Moreover, the complexity of the subject matter often leads to conflicting findings and interpretations
within the literature. While some studies suggest a direct association between Type 1 Diabetes and
an increased risk of osteoporosis, others propose more nuanced relationships influenced by factors
such as glycemic control, insulin therapy, and bone metabolism.

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Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is
not guaranteed or endorsed by the publisher. It has been observed that the DCs can potentially trans-
differentiate and fuse to form OCs, and this fusion is faster and efficient than monocyte fusion.
Osteoporosis is characterized by bone mass reduction related to the poor supply of bone marrow
stromal cells, which are a heterogeneous population of cells. Diabetes occurs when the pancreas is no
longer able to make the hormone insulin (as in the less common type 1 diabetes), or when the body
cannot make good use of the insulin it produces (as in type 2 diabetes).1 Insulin helps glucose pass
from the blood stream into the cells in the body in order to produce energy. Eosinophilic Esophagitis:
Update on Diagnosis and Treatment in Pediatric Patients. Year 3 1.06 0.20 (331) 0.99 0.17 (4839)
0.89 0.16 (331) 0.84 0.13 (4831). Findings From A Systematic Review Of The Literature. BMD was
measured in lumbar spine and femoral neck by dual-energy X-ray absorptiometry. All articles
published by MDPI are made immediately available worldwide under an open access license. No
special. The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil
Pathogenicity in Mucocutaneous Disease. The true challenge is patients with diabetes who have
normal or borderline bone mineral density but still sustain fractures. Accordingly, circulating
monocyte plays some crucial role by serving as osteoclast precursor and participating in bone
remodeling by producing cytokines ( 33, 34 ). Study finds link between type 1 diabetes and increased
risk of bone fractures in men A Norwegian study has established that men with type 1 diabetes are
more likely to suffer bone fractures because of lower bone density, poorer bone quality and a lower
rate of bone growth. In addition, osteoporosis (OP) is a silent disease with a harmful impact on
morbidity and mortality. Enrichment of ILC3 is also found in the gut, in the peripheral blood, bone
marrow, and SF of patients with ankylosing spondylitis. He is an avid basketball enthusiast, both as
a player and a fan, and enjoys following the sport at both the professional and amateur levels. Bone
health of postpartum women: Unexpected high prevalence of a health probl. Researchers are yet to
fully understand the mechanism to explain why people with type 1 diabetes have a lower bone
density but one hypothesis is that insulin may play a part as our bones are known to play a part in
the regulation of blood sugar levels. Daswani et al. provided further insight into monocyte
proteomics, which revealed the involvement of phosphorylated heat-shock protein 27 (HSP27) in
low BMD subjects ( 107 ). Recent evidence suggested that glucose transporter expression depends
on RANKL ( 74 ). During aging, epigenetic-metabolic changes in physiology drive chronic
inflammation in the body resulting in osteoporosis ( 5 ). Interleukin-22 Mediates Early Host Defense
Against Attaching and Effacing Bacterial Pathogens. Because of the vast number of people affected,
the relationship between diabetes and osteoporosis is of special concern. Excessive intake of
calcium, therefore, has no benefit for bone health. Alendronate and risedronate are the most
commonly used for the treatment of osteoporosis. Density and Microstructure at Distal Tibia in
Healthy. Choo YY, Tran PT, Min BS, Kim O, Nguyen HD, Kwon SH, et al. Aging Enhances the
Production of Reactive Oxygen Species and Bactericidal Activity in Peritoneal Macrophages by
Upregulating Classical Activation Pathways. An alternative study revealed that the duration of
diabetes also plays a role in bone health. This presence of insulin receptors on bone cells raises
questions about the potential impact of diabetes on bone metabolism.
ILCs Innate lymphoid-like cells or ILCs are the heterogeneous populations of cells that arise from
the lymphoid lineage ( 173 ). The International Diabetes Federation estimates that there are more
than 382 million people with diabetes worldwide, and this number is likely to increase by 55% by
2035. In clinical trials, salmon or eel calcitonin are widely used because of their enhanced potent
activity compared to human calcitonin. Preserving Bone Health With Type 2 Diabetes Maintaining
strong bones is an important part of managing diabetes. Publisher’s Note All claims expressed in this
article are solely those of the authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the reviewers. Characterization of Functional
Reprogramming During Osteoclast Development Using Quantitative Proteomics and mRNA
Profiling. And it may be that other 'lifestyle' diseases such as joint pain and even obesity are
contagious, too. As a result, glucose builds up in the blood and may overflow into the urine where it
is excreted from the body. Additionally, the researchers found that in patients with renal function
insufficiency and clinical albuminuria (two conditions that are linked to insulin insufficiency), bone
mineral density was lowered in the patients with type 2 diabetes. IMAGING IN
OSTEOPOROSIS.pptx IMAGING IN OSTEOPOROSIS.pptx A Retrospective Study to Investigate
Association among Age, BMI and BMD in th. Thus, neutrophils interact with both innate and
adaptive arms of the immune system and differentially respond depending on the context. However,
calcium is a threshold mineral, that is, surplus ions are excreted. Geissler S, Textor M, Stumpp S,
Seitz S, Lekaj A, Brunk S, et al. Monitoring of Blood Vessels and Tissues by a Population of
Monocytes With Patrolling Behavior. The aim of the paper is to present the present state of scientific
knowledge about the osteoporosis risk in diabetic patient. Cellular studies revealed that ANXA2 is
important in monocyte migration across the endothelial barrier. Thus, the elevation of ANXA2
probably stimulates the higher migration rate of monocyte from blood to the bone tissue and then
differentiate to OCs and contribute to bone-resorbing activity ( Figure 2B ) ( 104 ). Insulin is a
hormone produced by the pancreas, an organ located behind the stomach. Researchers wrote an
article after they reviewed new information on osteoporosis and fracture risk in people with type 2
diabetes. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the
fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both
types of diabetes. Although they lack antigen-specific receptors, upon tissue damage or pathogen
invasion, they can sense changes in the local milieu by cytokine receptors and modulate subsequent
antigen-specific lymphocyte responses. It is also observed that there is an increase in serum IL-31
level in post-menopausal women with a decrease in BMD, correlating with age ( 38 ). One of the
typical osteoporosis treatmentsanti-resorptive treatmentswont work in this patient population.
Interestingly, eosinophils are the source of IL-31 in an inflammatory skin condition called Bullous
pemphigoid (BP) ( 144 ). Therefore, active forms of vitamin D 3, including calcitriol, alphacalcidol
(1?-hydroxyvitamin D 3, a prodrug of calcitriol), and eldecalcitol (2?-3-hydroxypropyloxy-calcitriol,
an analog of calcitriol that was developed in Japan) are mainly used in clinical trials. Omata Y, Frech
M, Primbs T, Lucas S, Andreev D, Scholtysek C, et al. In this review, we have discussed the role of
the innate immune cells in great detail and divided these cells into different sections in a systemic
manner. Poubelle PE, Chakravarti A, Fernandes MJ, Doiron K, Marceau AA. Thats why staying
physically active is so important as you age it not only helps keep diabetes complications at bay, but
also helps maintain strong bones. Further, studying the cross talk between gut microbiota and ILCs
and intestinal cells could be important in immunoporosis and of great clinical value.
This class of drugs has been associated with both progressive bone loss and a higher risk for
fractures. Transcriptome study identified the downregulation of two apoptosis-inducing genes, death-
associated protein 6 (DAXX) and polo-like kinase 3 (PLK3), in low BMD subjects ( 108 ). As the
cartilage goes away, the bones can rub against each other and cause pain, stiffness, and swelling.
Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing. Year 3 1.06 0.20
(331) 0.99 0.17 (4839) 0.89 0.16 (331) 0.84 0.13 (4831). Insulin is a hormone produced by the
pancreas that plays a pivotal role in regulating blood sugar levels. Kindstedt E, Koskinen Holm C,
Palmqvist P, Sjostrom M, Lejon K, Lundberg P. Age-Related Changes to Macrophages Are
Detrimental to Fracture Healing in Mice. In addition, osteoporosis (OP) is a silent disease with a
harmful impact on morbidity and mortality. Different Types of Heart Surgery Offered at Gokuldas
Hospital Exploring Treat. Multiple requests from the same IP address are counted as one view.
Exosomes can then directly activate cell surface receptors via protein and bioactive lipid ligands,
transfer cell surface receptors or deliver effectors including transcription factors, oncogenes and
infectious particles into target cells. The Role of Dendritic Cells Derived Osteoclasts in Bone
Destruction Diseases. Ignatius A, Schoengraf P, Kreja L, Liedert A, Recknagel S, Kandert S, et al.
These studies suggest that the monocyte can participate in the inflammatory process directly apart
from acting as precursors only. Furthermore, adequate glycemic control and the prevention of
diabetic complications are the starting point of therapy in T1DM. Evidence that there are significant
alterations in serum parathyroid hormone levels or function is lacking. Choo YY, Tran PT, Min BS,
Kim O, Nguyen HD, Kwon SH, et al. Nursing Care of Patients with Life Threatening Conditions,
High Acuity Situat. Recent studies have focused on the combination of calcium and vitamin D. Shen
G, Ren H, Shang Q, Zhang Z, Zhao W, Yu X, et al. TNF-Alpha Contributes to Postmenopausal
Osteoporosis by Synergistically Promoting RANKL-Induced Osteoclast Formation. Kasagi S, Chen
W. TGF-Beta1 on Osteoimmunology and the Bone Component Cells. Those with type 2 diabetes
have a higher risk for fractures than those without type 2 diabetes. Subscribe to receive issue release
notifications and newsletters from MDPI journals. Other risk factors for osteoporosis include being
older in age, being Caucasian or Asian, bone structure, body weight, family history, history of broken
bones, cigarette smoking, caffeine consumption, certain diseases and medications. The Association
of monocyte with post-menopausal osteoporosis in Caucasian women was shown by Zhang et al. (
29, 102, 103 ). Network-based proteomics analysis of peripheral blood monocytes (PBM) showed
significant downregulation of proteins encoded by four genes, namely, LOC654188, PPIA,
TAGLN2, YWHAB whereas, upregulation of proteins encoded by three genes, namely LMNB1,
ANXA2P2, ANXA2, in extremely low- versus high-BMD subjects ( 103 ). These two reports
suggested that inhibition of polarization of macrophage enhances osteoclast differentiation. Nursing
Care of Patients with Life Threatening Conditions, High Acuity Situat. Bone structure refers to the
organization of bone tissue at a microscopic level.
Whether in the operating room, behind the desk, or on the stage, he is driven by a passion for
excellence and a commitment to making a positive impact in the world. The Effects of
Immunomodulation by Macrophage Subsets on Osteogenesis In Vitro. Dr. M.C. Zillikens IWO
bijeenkomst - 14 april - Prof. We also highlighted the studies regarding the impact of physiological
and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing,
ultimately triggering osteoporosis. Thus, NK cells can control or augment osteoporosis depending on
the tissue microenvironment. Bone Resorbing Activity in Supernatant Fluid From Cultured Human
Peripheral Blood Leukocytes. Type 1 Diabetes and Osteoporosis: From Molecular Pathways to Bone
Phenotype 1Department of Medicine, Western University, London, ON, Canada 2Division of
Endocrinology and Metabolism, St. National Osteoporosis Society Metabolic abnormalities observed
in osteoarthritis of knee: A single center e. In the 1970s, NK cells were described as large granular
lymphocytes with the ability of “natural cytotoxicity” against various tumor cells. Researchers are yet
to fully understand the mechanism to explain why people with type 1 diabetes have a lower bone
density but one hypothesis is that insulin may play a part as our bones are known to play a part in
the regulation of blood sugar levels. This article aims to delve into the intricate connection between
diabetes and its impact on bone mineral density (BMD) and bone structure. ILC1 is the more
predominant ILCs in SF of RA patients ( 180 ). These increases were significantly larger than those
observed in alendronate and teriparatide treatment groups. In addition to his love of sports and the
arts, Dr Markandaiya has a talent for communication and public speaking. Their recruitment to the
inflammatory site is predominantly CCR2 dependent ( 94 ). Sarkar S, Fox DA. Dendritic Cells in
Rheumatoid Arthritis. Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review.
Int. J. Mol. Sci. 2019, 20, 2557. Neutrophils are also involved in the pathophysiology of various
diseases, including inflammation-mediated bone loss ( 131 ). Metabolic abnormalities observed in
osteoarthritis of knee: A single center e. Year 6 1.07 0.21 (253) 1.00 0.18 (4203) 0.87 0.16 (261) 0.84
0.13 (4262). Bordbar A, Mo ML, Nakayasu ES, Schrimpe-Rutledge AC, Kim YM, Metz TO, et al.
Author links open overlay panel Khalid I.KhoshhalABOSa Type 1 diabetes mellitus (T1DM) in
children often starts before the achievement of peak bone mass. Role of Regulatory authorities in
Quality education, practice, and rights of. Conflict of Interest The authors declare that the research
was conducted in the absence of any commercial or financial relationships that could be construed as
a potential conflict of interest. On the other hand, OCs, giant multinucleated cells of HSCs origin,
demineralize the bone by releasing substances like hydrochloric acid and proteolytic enzymes, thus
keep in check the anabolic activity of OBs ( 1 ). Innate Lymphoid Cells Promote Lung-Tissue
Homeostasis After Infection With Influenza Virus. These two reports suggested that inhibition of
polarization of macrophage enhances osteoclast differentiation. Department of Endocrinology and
Diabetes, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom. Fasting glucose
and CGM Blood Glucose Monitoring aris 20 1 HBA1C results - confused, please help Type 2
Diabetes Maggie75 106 5 ADHD, anyone. Bone mineral density (BMD) was done using DXA
apparatus.
If you have osteoporosis, it may be advisable to take part in low impact physical activity such as:
Walking Swimming Yoga These activities are advisable over higher impact activity such as running
or activities involving jumping. Anti-resorptive drugs, which suppress bone resorption, include
calcitonin, estrogen and selective estrogen receptor modulators (SERMs), bisphosphonates (BPs),
and anti-RANKL antibody. Treatment Duration Aderence Compliance and Concordance and
Management Of Oste. Help improve your cardiovascular health and your quality of life by joining us
as we investigate a variety of heart health hacks. All articles published by MDPI are made
immediately available worldwide under an open access license. No special. Taken together, calcitonin
may be a preferred treatment for acute osteoporotic fractures. 5.3. Adverse Events The most
common side effects involve nausea, reduced appetite, diarrhea, abdominal pain, and discomfort.
This article will discuss some of the potential causes for this associated increased risk and will make
some suggestions for prevention of osteoporosis and bone fractures. Geissler S, Textor M, Stumpp S,
Seitz S, Lekaj A, Brunk S, et al. Hence, T-cells could act as a balance switch in mediating DC-OC
trans-differentiation. However, because diabetics can suffer from osteoporosis at an earlier age, they
are more at risk of suffering a fracture from a fall. A therapy that affects the activities of MSCs,
osteoblasts and osteoclasts by influencing intercellular communication would, therefore, be a
potential future treatment. Small interfering RNA (siRNA) therapies are one of the therapies based
on gene engineering. RANK-Independent Osteoclast Formation and Bone Erosion in Inflammatory
Arthritis. Ukon, Yuichiro, Takahiro Makino, Joe Kodama, Hiroyuki Tsukazaki, Daisuke Tateiwa,
Hideki Yoshikawa, and Takashi Kaito. Neutrophils respond to different signals in the inflammatory
milieu by producing cytokines and chemokines, which can regulate inflammation and other pro-
inflammatory cells ( 128, 129 ). Long-term compliance may be a factor that limits the efficacy. To aid
these activities ( 63 ), they show a great degree of plasticity and hence can undergo a transition
between M1 and M2 phenotype depending on the microenvironment ( 64 ). Please note that many of
the page functionalities won't work as expected without javascript enabled. The Multifaceted
Biology of Plasmacytoid Dendritic Cells. There are key evidences that suggested the involvement of
ILCs in inflammatory bone diseases such as spondylarthritis (SA) ( 180 ). Iking-Konert C, Ostendorf
B, Sander O, Jost M, Wagner C, Joosten L, et al. Kasagi S, Chen W. TGF-Beta1 on
Osteoimmunology and the Bone Component Cells. In bone tissue engineering, exosomes loaded with
materials offer unique advantages in patients with osteoporosis following a fracture. M1 macrophage
serves as a precursor of osteoclast ( 28 ). Diabetic women (n) Nondiabetic women (n) Diabetic
women (n) N ondiabetic women (n). Takaki-Kuwahara A, Arinobu Y, Miyawaki K, Yamada H,
Tsuzuki H, Irino K, et al. Children diagnosed with T1DM for 3 years or more without signs of
puberty were included in the diabetic group. The increase in fractures poses an increased mortality
rate among patients with osteoporosis. People with type 1 diabetes have been found to have, on
average, lower bone mineral density. Numerous studies suggested a role of M2 macrophages in
osteogenesis.
Mundy GR, Luben RA, Raisz LG, Oppenheim JJ, Buell DN. ROS has been shown to increase
osteoclastic activities and bone loss ( 196 ). Pathak JL, Bakker AD, Verschueren P, Lems WF, Luyten
FP, Klein-Nulend J, et al. In addition to his medical expertise, he is also an author with a passion for
writing on a variety of topics. Role of Regulatory authorities in Quality education, practice, and
rights of. Dendritic Cells Dendritic cells are majorly antigen-presenting cells (APCs) endowed with
abilities to activate the adaptive immune response. There are also reports suggesting a more direct
role of DCs in osteoclastogenesis. These drugs usually cause adverse effects, and consequently result
in decreased adherence. This ability comes from the presence of a broad range of pattern recognition
receptors (PRRs) such as toll-like receptors (TLRs), nod-like receptors (NLRs), etc., as well as
scavenger receptors (SRs) ( 57 ). Regarding recommendations, we adopted the grading system
introduced by the American College of Physicians. Inflammatory mediators such as reactive oxygen
species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the
bone cells and play a role in the pathogenesis of osteoporosis. This is reflected in a decrease in serum
markers of bone formation, such as osteocalcin. Indeed, few reports suggested that there was increase
in number of mast cells in the patient with reduced bone density and associated with post-
menopausal osteoporosis ( 149, 150 ). Study finds link between type 1 diabetes and increased risk of
bone fractures in men A Norwegian study has established that men with type 1 diabetes are more
likely to suffer bone fractures because of lower bone density, poorer bone quality and a lower rate of
bone growth. Journal of Manufacturing and Materials Processing (JMMP). Innate cells of lymphoid
lineage, such as NK cells and innate lymphoid cells (ILCs), also contribute to the manifestation of
osteoporosis, majorly as producers of pro-inflammatory mediators ( 26, 27 ). The FREEDOM
extension study evaluated the effect of 3 or 6 years of denosumab treatment; 6 out of 4550
participants experienced events of osteonecrosis of the jaw, whereas one participant developed an
atypical femoral fracture. TNF-Alpha Contributes to Postmenopausal Osteoporosis by Synergistically
Promoting RANKL-Induced Osteoclast Formation. The immune system is intricately involved in
bone physiology as well as pathologies. Metformin Should Remain the Foundation Therapy for Type
2 Diabetes. YX, BM, and GL critically reviewed the manuscript for relevant intellectual content.
This adsorption to bone surface enables BPs to make close contact with osteoclasts and inhibit bone
resorption ( Figure 1 ). One of the necessary and key changes observed in macrophage to osteoclast
differentiation is the changes in energy metabolism. In addition to various innate immune cells, we
also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. Thus, stem cells
are believed to be the best source for cell replacement therapy of bone disease. There are key
evidences that suggested the involvement of ILCs in inflammatory bone diseases such as
spondylarthritis (SA) ( 180 ). Cline-Smith A, Axelbaum A, Shashkova E, Chakraborty M, Sanford J,
Panesar P, et al. Alterations in bone structure can compromise bone strength and integrity. BPs are
classified into two groups; non-nitrogen-containing and nitrogen-containing. DCs contribute to
inflammation-mediated osteoclastogenesis and take part in inflammatory bone disease.
Metabolic abnormalities observed in osteoarthritis of knee: A single center e. Researchers explored
these questions in a study, The relationship between insulin resistance and osteoporosis in elderly
male type2 diabetes mellitus and diabetic nephropathy. Interestingly, insulin receptors are not only
present on fat and muscle cells but also on bone cells, including osteoblasts and osteoclasts. Heart
Health Hacks: How to Identify and Tackle Cardiac Disease Symptoms Like a Pro If you want to
live a longer, better, and happier life, take ownership of your heart health. Feng S, Madsen SH, Viller
NN, Neutzsky-Wulff AV, Geisler C, Karlsson L, et al. The serum levels of bone resorption markers
were significantly higher in the diabetic group. Similar to other immune cells, mast cells are also
abundantly found in inflamed synovial joints of RA patients. Type 1 Diabetes and Osteoporosis:
From Molecular Pathways to Bone Phenotype 1Department of Medicine, Western University,
London, ON, Canada 2Division of Endocrinology and Metabolism, St. This clinical study is still in
the process of recruiting ( ClinicalTrials.gov identifier: NCT02566655). Human Dendritic Cell-
Derived Osteoclasts With High Bone Resorption Capacity and T Cell Stimulation Ability. Similar to
macrophages, monocytes also undergo metabolic changes like, increase in glucose uptake, oxidative
phosphorylation etc. Radiological follow-up and functional assessment were performed. The
Macrophage Polarization Regulates MSC Osteoblast Differentiation In Vitro. A more in-depth study
is required to understand the full potential of DCs in the induction of immunoporosis. Flow chart of
data extraction for T2DM cohort and case-control. However, Jakubzick et al., in their study, reported
that monocytes can retain their markers or their identity without differentiating into macrophages and
DCs while moving through tissues ( 97 ). Otaki F, Daniel W, Geno DM, Tholen C, Alexander JA.
Diabetes, a chronic metabolic disorder characterized by elevated blood glucose levels, has long been
associated with various complications such as cardiovascular diseases, neuropathy, and retinopathy.
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers.
However, the profound effect of DCs on bone metabolism has been widely recognized recently.
Unfortunately, they close over the winter (we are a touris. Phagocytosis of Apoptotic Neutrophils
Regulates Granulopoiesis via IL-23 and IL-17. The Effect of Biologic Agents on Bone Homeostasis
in Chronic Inflammatory Rheumatic Diseases. IL-17 also drives inflammatory response by recruiting
cells to the site of inflammation ( 179 ). This form of the disease typically appears in children and
young adults, but it can develop at any age. Researchers arent certain as to why type 1 diabetes
contributes to bone loss but theories are based on animal and cellular models. Poorly controlled
diabetes can lead to increased bone fragility. Deletion of ER? in osteoblasts had differential effects at
different stages of differentiation of the osteoblast lineage. Bone remodeling occurs in several
specific spaces in the bone called bone remodeling compartments (BRC) ( 2 ). Buckley MG, Walters
C, Wong WM, Cawley MI, Ren S, Schwartz LB, et al.