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Molecular Advances in Osteoporosis Research
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Molecular Advances in Osteoporosis Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 38578

Special Issue Editor

Dr. Alberto Falchetti

E-Mail Website
Guest Editor
Unit of Endocrinology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
Interests: osteoporosis; metabolic bone diseases; parathyroid diseases; multiple endocrine neoplasia; genetic diseases of bone
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteoporosis still represents a pathological condition that remains largely underdiagnosed and undertreated mainly due to the low frequency of screening and to the controversies in BMD testing standards. Testosterone, estrogens, SHBG, and FSH levels interact in determining the bone mass accrual, BMD maintenance, and lifetime decrease.

Fragility fractures are increasingly recognized as an important complication of T2DM. Osteoporosis is often an underdiagnosed T2DM related complication. Appropriate early diagnosis of osteoporosis is mandatory in order to start adequate treatment of these subjects, representing a very important step in clinical practice as it may impact on mortality more than in women.

This Special Issue aims to update the pathophysiology and preclinical approach to osteoporosis. We welcome both original research and review articles covering significant developments in the pathogenesis of osteoporosis, as well as novel medicines or strategies that hold promise in the prevention and/or treatment of this disease.

Dr. Alberto Falchetti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • osteoporosis
  • fractures in T2DM
  • molecular mechanisms
  • signaling pathways
  • preclinical and instrumental diagnostic tools of bone fragility
  • pathogenesis of bone fragility, in general and according to a specific clinical scenario
  • biomarkers predictive of bone mass reduction as also of bone fragility
  • the role of antidiabetic drugs on bone health and fracture rate
  • the effects of antiosteoporotic drugs, in general and according to a specific clinical scenario

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Related Special Issue

Published Papers (5 papers)

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Research

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18 pages, 3544 KiB  
Article
Proteomics Profiling of Osteoporosis and Osteopenia Patients and Associated Network Analysis
by Mysoon M. Al-Ansari, Shereen M. Aleidi, Afshan Masood, Eman A. Alnehmi, Mai Abdel Jabar, Maha Almogren, Mohammed Alshaker, Hicham Benabdelkamel and Anas M. Abdel Rahman
Int. J. Mol. Sci. 2022, 23(17), 10200; https://doi.org/10.3390/ijms231710200 - 5 Sep 2022
Cited by 18 | Viewed by 3560
Abstract
Bone mass reduction due to an imbalance in osteogenesis and osteolysis is characterized by low bone mineral density (LBMD) and is clinically classified as osteopenia (ON) or osteoporosis (OP), which is more severe. Multiple biomarkers for diagnosing OP and its progression have been [...] Read more.
Bone mass reduction due to an imbalance in osteogenesis and osteolysis is characterized by low bone mineral density (LBMD) and is clinically classified as osteopenia (ON) or osteoporosis (OP), which is more severe. Multiple biomarkers for diagnosing OP and its progression have been reported; however, most of these lack specificity. This cohort study aimed to investigate sensitive and specific LBMD-associated protein biomarkers in patients diagnosed with ON and OP. A label-free liquid chromatography-mass spectrometry (LC-MS) proteomics approach was used to analyze serum samples. Patients’ proteomics profiles were filtered for potential confounding effects, such as age, sex, chronic diseases, and medication. A distinctive proteomics profile between the control, ON, and OP groups (Q2 = 0.7295, R2 = 0.9180) was identified, and significant dysregulation in a panel of proteins (n = 20) was common among the three groups. A comparison of these proteins showed that the levels of eight proteins were upregulated in ON, compared to those in the control and the OP groups, while the levels of eleven proteins were downregulated in the ON group compared to those in the control group. Interestingly, only one protein, myosin heavy chain 14 (MYH14), showed a linear increase from the control to the ON group, with the highest abundance in the OP group. A significant separation in the proteomics profile between the ON and OP groups (Q2 = 0.8760, R2 = 0.991) was also noted. Furthermore, a total of twenty-six proteins were found to be dysregulated between the ON and the OP groups, with fourteen upregulated and twelve downregulated proteins in the OP, compared to that in the ON group. Most of the identified dysregulated proteins were immunoglobulins, complement proteins, cytoskeletal proteins, coagulation factors, and various enzymes. Of these identified proteins, the highest area under the curve (AUC) in the receiver operating characteristic (ROC) analysis was related to three proteins (immunoglobulin Lambda constant 1 (IGLC1), RNA binding protein (MEX3B), and fibulin 1 (FBLN1)). Multiple reaction monitoring (MRM), LC-MS, was used to validate some of the identified proteins. A network pathway analysis of the differentially abundant proteins demonstrated dysregulation of inflammatory signaling pathways in the LBMD patients, including the tumor necrosis factor (TNF), toll-like receptor (TL4), and interferon-γ (IFNG) signaling pathways. These results reveal the existence of potentially sensitive protein biomarkers that could be used in further investigations of bone health and OP progression. Full article
(This article belongs to the Special Issue Molecular Advances in Osteoporosis Research)
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11 pages, 1760 KiB  
Article
Using a Polygenic Score to Predict the Risk of Developing Primary Osteoporosis
by Bulat Yalaev, Anton Tyurin, Inga Prokopenko, Aleksandra Karunas, Elza Khusnutdinova and Rita Khusainova
Int. J. Mol. Sci. 2022, 23(17), 10021; https://doi.org/10.3390/ijms231710021 - 2 Sep 2022
Cited by 10 | Viewed by 2360
Abstract
Osteoporosis (OP) is a multifactorial bone disease belonging to the metabolic osteopathies group. Using the polygenic score (PGS) approach, we combined the effects of bone mineral density (BMD) DNA loci, affecting osteoporosis pathogenesis, based on GEFOS/GENOMOS consortium GWAS meta-analysis. We developed models to [...] Read more.
Osteoporosis (OP) is a multifactorial bone disease belonging to the metabolic osteopathies group. Using the polygenic score (PGS) approach, we combined the effects of bone mineral density (BMD) DNA loci, affecting osteoporosis pathogenesis, based on GEFOS/GENOMOS consortium GWAS meta-analysis. We developed models to predict the risk of low fractures in women from the Volga-Ural region of Russia with efficacy of 74% (AUC = 0.740; OR (95% CI) = 2.9 (2.353–3.536)), as well as the formation of low BMD with efficacy of 79% (AUC = 0.790; OR (95% CI) = 3.94 (2.993–5.337)). In addition, we propose a model that predicts fracture risk and low BMD in a comorbid condition with 85% accuracy (AUC = 0.850; OR (95% CI) = 6.6 (4.411–10.608)) in postmenopausal women. Full article
(This article belongs to the Special Issue Molecular Advances in Osteoporosis Research)
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Review

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27 pages, 878 KiB  
Review
Current Status of the Diagnosis and Management of Osteoporosis
by Agustín Aibar-Almazán, Ana Voltes-Martínez, Yolanda Castellote-Caballero, Diego Fernando Afanador-Restrepo, María del Carmen Carcelén-Fraile and Elena López-Ruiz
Int. J. Mol. Sci. 2022, 23(16), 9465; https://doi.org/10.3390/ijms23169465 - 21 Aug 2022
Cited by 142 | Viewed by 18161
Abstract
Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting mainly postmenopausal women and older adults. Osteoporosis is characterized by an imbalance between bone resorption and bone [...] Read more.
Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting mainly postmenopausal women and older adults. Osteoporosis is characterized by an imbalance between bone resorption and bone production. It is diagnosed through different methods such as bone densitometry and dual X-rays. The treatment of this pathology focuses on different aspects. On the one hand, pharmacological treatments are characterized by the use of anti-resorptive drugs, as well as emerging regenerative medicine treatments such as cell therapies and the use of bioactive hydrogels. On the other hand, non-pharmacological treatments are associated with lifestyle habits that should be incorporated, such as physical activity, diet and the cessation of harmful habits such as a high consumption of alcohol or smoking. This review seeks to provide an overview of the theoretical basis in relation to bone biology, the existing methods for diagnosis and the treatments of osteoporosis, including the development of new strategies. Full article
(This article belongs to the Special Issue Molecular Advances in Osteoporosis Research)
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23 pages, 3284 KiB  
Review
Roles of Non-Canonical Wnt Signalling Pathways in Bone Biology
by Jasna Lojk and Janja Marc
Int. J. Mol. Sci. 2021, 22(19), 10840; https://doi.org/10.3390/ijms221910840 - 7 Oct 2021
Cited by 46 | Viewed by 4561
Abstract
The Wnt signalling pathway is one of the central signalling pathways in bone development, homeostasis and regulation of bone mineral density. It consists of numerous Wnt ligands, receptors and co-receptors, which ensure tight spatiotemporal regulation of Wnt signalling pathway activity and thus tight [...] Read more.
The Wnt signalling pathway is one of the central signalling pathways in bone development, homeostasis and regulation of bone mineral density. It consists of numerous Wnt ligands, receptors and co-receptors, which ensure tight spatiotemporal regulation of Wnt signalling pathway activity and thus tight regulation of bone tissue homeostasis. This enables maintenance of optimal mineral density, tissue healing and adaptation to changes in bone loading. While the role of the canonical/β-catenin Wnt signalling pathway in bone homeostasis is relatively well researched, Wnt ligands can also activate several non-canonical, β-catenin independent signalling pathways with important effects on bone tissue. In this review, we will provide a thorough overview of the current knowledge on different non-canonical Wnt signalling pathways involved in bone biology, focusing especially on the pathways that affect bone cell differentiation, maturation and function, processes involved in bone tissue structure regulation. We will describe the role of the two most known non-canonical pathways (Wnt/planar cell polarity pathways and Wnt/Ca2+ pathway), as well as other signalling pathways with a strong role in bone biology that communicate with the Wnt signalling pathway through non-canonical Wnt signalling. Our goal is to bring additional attention to these still not well researched but important pathways in the regulation of bone biology in the hope of prompting additional research in the area of non-canonical Wnt signalling pathways. Full article
(This article belongs to the Special Issue Molecular Advances in Osteoporosis Research)
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22 pages, 15823 KiB  
Review
Vitamin D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review
by Massimo De Martinis, Alessandro Allegra, Maria Maddalena Sirufo, Alessandro Tonacci, Giovanni Pioggia, Martina Raggiunti, Lia Ginaldi and Sebastiano Gangemi
Int. J. Mol. Sci. 2021, 22(16), 8855; https://doi.org/10.3390/ijms22168855 - 17 Aug 2021
Cited by 41 | Viewed by 8544
Abstract
Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a [...] Read more.
Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a VD receptor, including the brain, heart, stomach, pancreas, skin, gonads, and immune cells, and a deficiency may modify the function of these organs. Thus, the wide-ranging actions of VD help to explain why a reduction in VD amount has been correlated with numerous chronic diseases. In fact, VD deficiency increases the risk of osteoporosis and several other diseases and complications characterized by impaired bone metabolisms, such as autoimmune diseases, inflammatory bowel diseases, allergy, endocrinological diseases, hematological malignancies, and bone marrow transplantation. This review aims to investigate the link between VD deficiency, osteoporosis, and its concomitant diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases; however, adequate vitamin supplementation and restoration of metabolic normality could be useful for better management of these pathologies. Full article
(This article belongs to the Special Issue Molecular Advances in Osteoporosis Research)
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