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13 pages, 680 KiB

Open AccessArticle

Types of Injuries and the Severity of Shoulder Dysfunction Associated with Diabetes Mellitus in Patients with Functional Impairment: A Case–Control Study

by Mercedes Fuentes-Murguia, Karla B. Carrazco-Peña, Osiris G. Delgado-Enciso, Joel Castellanos-Gomez, Gustavo A. Hernandez-Fuentes, Fabian Rojas-Larios, Carmen A. Sanchez-Ramirez, Margarita L. Martinez-Fierro, Iram P. Rodriguez-Sanchez, José Guzmán-Esquivel, Idalia Garza-Veloz, José E. Del-Río-Valdivia, Jorge E. Plata-Florenzano and Iván Delgado-Enciso

Biomedicines 2024, 12(11), 2634; https://doi.org/10.3390/biomedicines12112634 - 18 Nov 2024

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Abstract

Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain [...] Read more.

Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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13 pages, 694 KiB

Open AccessArticle

A Clinical Evaluation of the Role of Autoimmunity in the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis

by Margaux Moret, Caroline Morizot, Marcelo de Carvalho Bittencourt, Edem Allado, Isabelle Chary-Valckenaere and Damien Loeuille

Biomedicines 2024, 12(10), 2376; https://doi.org/10.3390/biomedicines12102376 - 17 Oct 2024

Viewed by 570

Abstract

Background/objectives: Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. Methods: Patients fulfilling the [...] Read more.

Background/objectives: Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. Methods: Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. Results: A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ −2.5. A higher erosion score was associated with a lower BMD (value: −0.222; p = 0.009) and T-score (value −0.397; p < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04)). ACPA titers were associated with a lower BMD in the hip (value −0.216; p = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. Conclusions: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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19 pages, 15986 KiB

Open AccessArticle

Trehalose Rescues Postmenopausal Osteoporosis Induced by Ovariectomy through Alleviating Osteoblast Pyroptosis via Promoting Autophagy

by Xinli Hu, Wei Wang, Xiaolong Chen, Chao Kong, Xuan Zhao, Zheng Wang, Haojie Zhang and Shibao Lu

Biomedicines 2024, 12(10), 2224; https://doi.org/10.3390/biomedicines12102224 - 29 Sep 2024

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Abstract

Background: Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone [...] Read more.

Background: Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone mass recovery in ovariectomized rats and its underlying mechanisms remains unclear. In this study, trehalose was administered to ovariectomized rats to evaluate its therapeutic potential for osteoporosis following ovariectomy. Methods: Micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) and immunohistochemical staining techniques were utilized to evaluate the impact of trehalose on osteoporosis induced by ovariectomy (OVX) in mice, both in imaging and histological dimensions. Furthermore, the influence of trehalose on osteoblastogenesis and functional activity was quantified through Alizarin Red S (ARS) staining and immunoblotting assays. Results: Trehalose effectively mitigated bone loss, elevated autophagy and suppressed pyroptosis in ovariectomized rats. Furthermore, 3-methyladenine diminished the protective effects of trehalose, particularly in promoting autophagy and inhibiting pyroptosis. Conclusions: Trehalose demonstrates significant potential in treating osteoporosis by suppressing NLRP3 inflammasome-driven pyroptosis, primarily through autophagy promotion. This suggests that trehalose could be a promising, safer alternative treatment for osteoporosis. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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12 pages, 2195 KiB

Open AccessArticle

Platelet and Lymphocyte-Related Parameters as Potential Markers of Osteoarthritis Severity: A Cross-Sectional Study

by Francesca Salamanna, Stefania Pagani, Giuseppe Filardo, Deyanira Contartese, Angelo Boffa, Lucia Angelelli, Melania Maglio, Milena Fini, Stefano Zaffagnini and Gianluca Giavaresi

Biomedicines 2024, 12(9), 2052; https://doi.org/10.3390/biomedicines12092052 - 10 Sep 2024

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Abstract

Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering [...] Read more.

Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering age, sex, and body mass index (BMI). Methods: Patients aged ≥40 years were included in this cross-sectional study and divided into groups based on knee OA severity using the Kellgren–Lawrence (KL) grading system. A logistic regression model, adjusted for confounders, evaluated the ability of PLT, MPV, LINF, and PLR to categorize OA severity. Model performance in terms of accuracy, sensitivity, and specificity was assessed using ROC curves. Results: The study involved 245 OA patients (51.4% female, 48.6% male) aged 40–90 years, 35.9% with early OA (KL < 3) and 64.1% moderate/severe OA (KL ≥ 3). Most patients (60.8%) were aged ≥60 years, and BMI was <25 kg/m² in 33.9%. The model showed that a 25-unit increase in PLR elevates the odds of higher OA levels by 1.30 times (1-unit OR = 1.011, 95% CI [1.004, 1.017], p < 0.005), while being ≥40 years old elevates the odds by 4.42 times (OR 4.42, 95% CI [2.46, 7.95], p < 0.0005). The model’s accuracy was 73.1%, with 84% sensitivity, 52% specificity, and an AUC of 0.74 (95% CI [0.675, 0.805]). Conclusions: Higher PLR increases the likelihood of moderate/severe OA, suggesting that monitoring these biomarkers could aid in early detection and management of OA severity. Further research is warranted to cross-validate these results in larger populations. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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13 pages, 2255 KiB

Open AccessArticle

Interleukin-37 Inhibits Interleukin-1β-Induced Articular Chondrocyte Apoptosis by Suppressing Reactive Oxygen Species

by Seong-Kyu Kim, Boyoung Kim, Jung-Yoon Choe, Ji-Won Kim and Ki-Yeun Park

Biomedicines 2024, 12(9), 2025; https://doi.org/10.3390/biomedicines12092025 - 4 Sep 2024

Viewed by 665

Abstract

Objective: Chondrocyte apoptosis has been considered a crucial mechanism that is responsible for cartilage destruction in osteoarthritis (OA). The mechanism of interleukin-37 (IL-37) on chondrocyte apoptosis has not been clearly determined in the pathogenesis of OA. Here, we explored the role of [...] Read more.

Objective: Chondrocyte apoptosis has been considered a crucial mechanism that is responsible for cartilage destruction in osteoarthritis (OA). The mechanism of interleukin-37 (IL-37) on chondrocyte apoptosis has not been clearly determined in the pathogenesis of OA. Here, we explored the role of IL-37 in the regulation of cellular apoptosis in rat chondrocytes stimulated by IL-1β. Methods: Rat chondrocytes were used in in vitro study, and were stimulated with IL-1β (10 ng/mL) and/or recombinant IL-37 (rIL-37; 100 ng/mL) after cytotoxicity assessments using these cytokines were conducted. After rIL-37 treatment of chondrocytes stimulated with IL-1β, the cell proliferation assay, apoptosis assays, including expression of mitochondrial apoptosis-related markers, flow cytometry analysis of annexin V-FITC/propidium iodide (PI), cell cycle analysis, and Hoechst 33342 staining, and reactive oxygen species (ROS) measurement were used. Results: IL-1β induced expression of inflammatory cytokines and triggered degradation of the extracellular matrix of rat chondrocytes, but this effect was significantly attenuated by rIL-37 treatment. Enhanced ROS generation following IL-1β stimulation was reduced in a dose-dependent manner after stimulation with rIL-37. IL-1β induced pro-apoptotic markers and suppressed anti-apoptotic markers in rat chondrocytes. Flow cytometry using annexin V-FITC/PI revealed that IL-1β increased the apoptosis rate of rat chondrocytes, and that this effect was markedly reversed by treatment with rIL-37. Conclusions: IL-37 potently attenuated IL-1β-mediated apoptosis of rat chondrocytes by blocking ROS production. This study suggests that IL-37 can serve as a novel anti-cytokine therapy in OA by blocking chondrocyte apoptosis. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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20 pages, 15185 KiB

Open AccessArticle

Bioinformatics Identification and Experimental Verification of Disulfidptosis-Related Genes in the Progression of Osteoarthritis

by Siyang Cao, Yihao Wei, Yaohang Yue, Deli Wang, Ao Xiong, Jun Yang and Hui Zeng

Biomedicines 2024, 12(8), 1840; https://doi.org/10.3390/biomedicines12081840 - 13 Aug 2024

Viewed by 1031

Abstract

Background: Osteoarthritis (OA) is a disabling and highly prevalent condition affecting millions worldwide. Recently discovered, disulfidptosis represents a novel form of cell death induced by the excessive accumulation of cystine. Despite its significance, a systematic exploration of disulfidptosis-related genes (DRGs) in OA is [...] Read more.

Background: Osteoarthritis (OA) is a disabling and highly prevalent condition affecting millions worldwide. Recently discovered, disulfidptosis represents a novel form of cell death induced by the excessive accumulation of cystine. Despite its significance, a systematic exploration of disulfidptosis-related genes (DRGs) in OA is lacking. Methods: This study utilized three OA-related datasets and DRGs. Differentially expressed (DE)-DRGs were derived by intersecting the differentially expressed genes (DEGs) from GSE114007 with DRGs. Feature genes underwent screening through three machine learning algorithms. High diagnostic value genes were identified using the receiver operating characteristic curve. Hub genes were confirmed through expression validation. These hub genes were then employed to construct a nomogram and conduct enrichment, immune, and correlation analyses. An additional validation of hub genes was performed through in vitro cell experiments. Results: SLC3A2 and PDLIM1 were designated as hub genes, displaying excellent diagnostic performance. PDLIM1 exhibited low expression in early chondrocyte differentiation, rising significantly in the late stage, while SLC3A2 showed high overall expression, declining in the late differentiation stage. Cellular experiments corroborated the correlation of SLC3A2 and PDLIM1 with chondrocyte inflammation. Conclusions: Two hub genes, SLC3A2 and PDLIM1, were identified in relation to disulfidptosis, providing potential directions for diagnosing and treating OA. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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12 pages, 1321 KiB

Open AccessArticle

The Effects of Acute and Chronic Alcohol Administration and Withdrawal on Bone Microstructure, Mechanical Strength, and Remodeling Protein Expression and Their Relation to an Antioxidant and FGF23 In Vivo

by Syed Alhafiz Syed Hashim, Isa Naina Mohamed and Norazlina Mohamed

Biomedicines 2024, 12(7), 1515; https://doi.org/10.3390/biomedicines12071515 - 8 Jul 2024

Viewed by 900

Abstract

Alcohol’s detrimental effects on bone health are well established, yet some literature suggests moderate consumption may offer benefits. With alcohol use on the rise, we investigate the impact of acute and chronic alcohol administration, along with withdrawal, on male Wistar rat femurs. We [...] Read more.

Alcohol’s detrimental effects on bone health are well established, yet some literature suggests moderate consumption may offer benefits. With alcohol use on the rise, we investigate the impact of acute and chronic alcohol administration, along with withdrawal, on male Wistar rat femurs. We observed a transient cortical thickness increase with acute alcohol (AA) compared to chronic exposure (CA) but no significant changes in trabecular parameters or mechanical properties. High osteocalcin and osteopontin expression levels were noted in AA, alongside elevated RANKL expression. Conversely, CA showed low TRAP levels. FGF23 expression significantly increased during alcohol withdrawal (AW), while GPX decreased after chronic exposure but rose during withdrawal. Although mechanical strength changes were insignificant, biochemical shifts suggest alcohol exposure promotes bone resorption, reduces antioxidant protection, and potentially hampers active vitamin D and phosphate reabsorption via FGF23 upregulation. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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12 pages, 569 KiB

Open AccessArticle

The Effect of Denosumab on Rotator Cuff Repair in Women Aged 60 and over with Osteoporosis: A Prospective Observational Study

by Ki-Tae Kim, Sanghyeon Lee, Ho-Won Lee, Shi-Hyun Kim and Yong-Beom Lee

Biomedicines 2024, 12(5), 1069; https://doi.org/10.3390/biomedicines12051069 - 12 May 2024

Viewed by 1342

Abstract

Background: In previous studies, denosumab, a RANKL human monoclonal antibody used in osteoporosis treatment, has shown efficacy in tendon healing after rotator cuff repair. This prospective study investigated the effects of denosumab on tendon healing, re-tear rates, and clinical outcomes post rotator cuff [...] Read more.

Background: In previous studies, denosumab, a RANKL human monoclonal antibody used in osteoporosis treatment, has shown efficacy in tendon healing after rotator cuff repair. This prospective study investigated the effects of denosumab on tendon healing, re-tear rates, and clinical outcomes post rotator cuff repair in women with osteoporosis. Method: This was a prospective, observational study, employing propensity score matching for the control group. From March 2018 to March 2023, female patients over the age of 60 with normal bone density undergoing arthroscopic rotator cuff repair were selected as controls through propensity score matching (PSM) and compared with female patients of the same age group with osteoporosis who were receiving denosumab treatment. The control group was matched using 1-to-2 propensity score matching. Radiological examinations and functional outcomes were assessed preoperatively and at 6 months postoperatively. Results: In the final analysis, the study comprised 34 patients in the denosumab treatment group (Group 1) and 68 patients in the control group (Group 2). The functional scores showed significant improvement at 6 months post-surgery in both groups. No significant difference in the functional scores was observed among the groups. The re-tear rate, defined according to Sugaya’s classification (types IV and V) as re-tear, was slightly higher in Group 1 at 16.7% (6 of 34) compared to Group 2 at 11.7% (8 of 68), but the difference was not statistically significant (p = 0.469). The re-tear patterns, classified according to Rhee’s classification, also showed no significant difference among the groups (Group 1: 2/4 of 6; Group 2: 4/4 of 8; p = 0.571). The occurrence of type I re-tear exhibited no significant difference between the two groups (5.9% vs. 5.9%; p = 1.000). Conclusions: The administration of denosumab following arthroscopic rotator cuff repair in women aged 60 and over with osteoporosis resulted in a re-tear rate that was similar to that observed in patients without osteoporosis. This result suggests that denosumab administration might be beneficial for rotator cuff healing, particularly in the context of osteoporosis, a known risk factor for increased retear rates. Therefore, comprehensive osteoporosis screening and treatment should be considered in conjunction with rotator cuff repair surgery in middle-aged women. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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11 pages, 1206 KiB

Open AccessArticle

Cartilage Collagen Neoepitope C2C Expression in the Articular Cartilage and Its Relation to Joint Tissue Damage in Patients with Knee Osteoarthritis

by Taavi Torga, Siim Suutre, Kalle Kisand, Marina Aunapuu and Andres Arend

Biomedicines 2024, 12(5), 1063; https://doi.org/10.3390/biomedicines12051063 - 11 May 2024

Cited by 1 | Viewed by 910

Abstract

Pathological cleavage of type II collagen (Col2) and generation of Col2 neoepitopes can serve as useful molecular markers of the progression of osteoarthritis (OA). One of such potential biomarkers is type II collagen neoepitope C2C. The aim of this study was to correlate [...] Read more.

Pathological cleavage of type II collagen (Col2) and generation of Col2 neoepitopes can serve as useful molecular markers of the progression of osteoarthritis (OA). One of such potential biomarkers is type II collagen neoepitope C2C. The aim of this study was to correlate the degree of articular cartilage damage in OA patients with C2C expression in histological samples of tissues removed during total knee replacement. Cartilage samples were obtained from 27 patients ranging in age from 55 to 66 years. In each patient, medial and lateral tibia plateau samples were analyzed according to the OARSI histopathology grading system. The C2C expression was evaluated on histological slides by semi-quantitative analysis using ImageJ Fiji 2.14.0 software. Spearman’s rank correlation analysis revealed a positive weak correlation (rho = 0.289, p = 0.0356) between the histological grade of tissue damage and the percentage of C2C staining. In addition, a highly significant positive correlation (rho = 0.388, p = 0.0041) was discovered between the osteoarthritis score (combining the histological grade of damage with the OA macroscopic stage) and the percentage of C2C staining in the samples. The C2C expression was detected in all the regions of the articular cartilage (i.e., the superficial zone, mid zone, deep zone and tidemark area, and the zone of calcified cartilage). Our findings imply that local expression of C2C correlates with the articular cartilage damage in OA-affected knees. This confirms that C2C can be used as a prospective marker for assessing pathological changes in the OA course and OA clinical trials. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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16 pages, 2481 KiB

Open AccessArticle

Using Macrophage Polarization in Human Platelet Lysate to Test the Immunomodulatory Potential of Cells for Clinical Use

by Silvia Lopa, Francesca Libonati, Katia Mareschi, Giuseppe Talò, Stefania Brambilla, Vincenzo Raffo, Luciana Labanca, Luigi Zagra, Matteo Moretti, Laura de Girolamo and Alessandra Colombini

Biomedicines 2024, 12(4), 833; https://doi.org/10.3390/biomedicines12040833 - 9 Apr 2024

Cited by 1 | Viewed by 1384

Abstract

Macrophage-based co-cultures are used to test the immunomodulatory function of candidate cells for clinical use. This study aimed to characterize a macrophage polarization model using human platelet lysate (hPL) as a GMP-compliant alternative to Fetal Bovine Serum (FBS). Primary human monocytes were differentiated [...] Read more.

Macrophage-based co-cultures are used to test the immunomodulatory function of candidate cells for clinical use. This study aimed to characterize a macrophage polarization model using human platelet lysate (hPL) as a GMP-compliant alternative to Fetal Bovine Serum (FBS). Primary human monocytes were differentiated into unpolarized (M0) or polarized (M1, M2a, and M2c) macrophages in an hPL- or FBS-based medium. The protein secretion profiles and expression of phenotypic markers (CD80 for M1, CD206 for M2a, and CD163 for M2c) were analyzed. Subsequently, chondrocytes were tested in an hPL-based co-culture model to assess their immunomodulatory function in view of their possible use in patients with osteoarthritis. The results showed similar marker regulation between hPL and FBS cultures, but lower basal levels of CD206 and CD163 in hPL-cultured macrophages. Functional co-culture experiments with chondrocytes revealed increased CD206 expression both in hPL and in FBS, indicating an interaction between macrophages and chondrocytes. While markers in FBS-cultured macrophages were confirmed in hPL-cultured cells, the interpretation of marker modulation in immunomodulatory assays with hPL-based cultures should be carried out cautiously due to the observed differences in the basal marker levels for CD206 and CD163. This research underscores the utility of hPL as a GMP-compliant alternative to FBS for macrophage-based co-cultures and highlights the importance of understanding marker expressions in different culture conditions. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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Review

Jump to: Research

22 pages, 2171 KiB

Open AccessReview

Beyond the Surface: Uncovering Secondary Causes of Osteoporosis for Optimal Management

by Rasheed Hosein-Woodley, Rahim Hirani, Ali Issani, Anum S. Hussaini, Olivia Stala, Abbas Smiley, Mill Etienne and Raj K. Tiwari

Biomedicines 2024, 12(11), 2558; https://doi.org/10.3390/biomedicines12112558 - 8 Nov 2024

Viewed by 507

Abstract

Osteoporosis (OP), a condition marked by reduced bone mineral density and increased fracture risk, can arise either as a primary disorder or secondary to other diseases and medications. While primary OP typically relates to age-related or postmenopausal changes, secondary OP results from underlying [...] Read more.

Osteoporosis (OP), a condition marked by reduced bone mineral density and increased fracture risk, can arise either as a primary disorder or secondary to other diseases and medications. While primary OP typically relates to age-related or postmenopausal changes, secondary OP results from underlying conditions or drug exposures, complicating diagnosis and management. This review explores the pathophysiology, prevalence, and treatment approaches for secondary OP arising from endocrine, renal, gastrointestinal, hematological, and autoimmune disorders, as well as medication side effects. The findings highlight that secondary OP is frequently undiagnosed, particularly in premenopausal women and men, with conditions such as chronic kidney disease, glucocorticoid use, and diabetes among the primary contributors. Management strategies must be tailored to address the underlying conditions to effectively reduce fracture risk and improve outcomes. Ultimately, this review underscores the necessity for increased clinical awareness and more targeted interventions for optimal management of secondary OP. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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28 pages, 825 KiB

Open AccessReview

From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches

by Qingmei Li, Jihan Wang and Congzhe Zhao

Biomedicines 2024, 12(10), 2389; https://doi.org/10.3390/biomedicines12102389 - 18 Oct 2024

Viewed by 787

Abstract

Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies—genomics, transcriptomics, proteomics, and metabolomics—have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic [...] Read more.

Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies—genomics, transcriptomics, proteomics, and metabolomics—have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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15 pages, 1284 KiB

Open AccessReview

Exploring the Interconnection between Metabolic Dysfunction and Gut Microbiome Dysbiosis in Osteoarthritis: A Narrative Review

by Hui Li, Jihan Wang, Linjie Hao and Guilin Huang

Biomedicines 2024, 12(10), 2182; https://doi.org/10.3390/biomedicines12102182 - 25 Sep 2024

Viewed by 999

Abstract

Osteoarthritis (OA) is a prevalent joint disorder and the most common form of arthritis, affecting approximately 500 million people worldwide, or about 7% of the global population. Its pathogenesis involves a complex interplay between metabolic dysfunction and gut microbiome (GM) alterations. This review [...] Read more.

Osteoarthritis (OA) is a prevalent joint disorder and the most common form of arthritis, affecting approximately 500 million people worldwide, or about 7% of the global population. Its pathogenesis involves a complex interplay between metabolic dysfunction and gut microbiome (GM) alterations. This review explores the relationship between metabolic disorders—such as obesity, diabetes, and dyslipidemia—and OA, highlighting their shared risk factors, including aging, sedentary lifestyle, and dietary habits. We further explore the role of GM dysbiosis in OA, elucidating how systemic inflammation, oxidative stress, and immune dysregulation driven by metabolic dysfunction and altered microbial metabolites contribute to OA progression. Additionally, the concept of “leaky gut syndrome” is discussed, illustrating how compromised gut barrier function exacerbates systemic and local joint inflammation. Therapeutic strategies targeting metabolic dysfunction and GM composition, including lifestyle interventions, pharmacological and non-pharmacological factors, and microbiota-targeted therapies, are reviewed for their potential to mitigate OA progression. Future research directions emphasize the importance of identifying novel biomarkers for OA risk and treatment response, adopting personalized treatment approaches, and integrating multiomics data to enhance our understanding of the metabolic–GM–OA connection and advance precision medicine in OA management. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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12 pages, 1777 KiB

Open AccessReview

Diagnosis and Treatment of Acute Periprosthetic Infections with the BioFire^® System within a Time-Dependent and Bacterium-Dependent Protocol: Review and Prosthesis-Saving Protocol

by Rudy Sangaletti, Luca Andriollo, Alice Montagna, Simone Franzoni, Paolo Colombini, Loris Perticarini, Francesco Benazzo and Stefano Marco Paolo Rossi

Biomedicines 2024, 12(9), 2082; https://doi.org/10.3390/biomedicines12092082 - 12 Sep 2024

Viewed by 699

Abstract

Despite ongoing efforts to enhance diagnostic and treatment processes, the success rate for eradicating infections, particularly prosthetic joint infections (PJIs), currently stands at around 50%. For acute infections occurring shortly after arthroplasty, guidelines recommend a treatment known as DAIR (debridement, antibiotics, and implant [...] Read more.

Despite ongoing efforts to enhance diagnostic and treatment processes, the success rate for eradicating infections, particularly prosthetic joint infections (PJIs), currently stands at around 50%. For acute infections occurring shortly after arthroplasty, guidelines recommend a treatment known as DAIR (debridement, antibiotics, and implant retention). This approach is suggested for infections within 30 days post-arthroplasty or with less than 3 weeks of symptoms, provided that there is a stable implant and adequate soft-tissue mass. Several authors have suggested extending the use of DAIR beyond the initial 3-week period in specific cases. This extension practice seems increasingly feasible due to the rapid diagnostic capabilities offered by BioFire^®. This technology allows for quick pathogen identification, aiding in the exclusion of cases that do not fit the criteria for the DAIR/DAPRI (debridement, antibiotic pearls and retention of the implant) protocol based on pathogen identification. The aim of this review is to re-examine the current literature on acute infections and present our proposed “prosthesis-saving” protocol, which integrates the BioFire^® molecular diagnostic system. Continued research and assessment of the efficacy and safety of these protocols, especially regarding extended treatment timelines, are crucial for advancing the management of acute infections and enhancing outcomes for PJI patients. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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22 pages, 7125 KiB

Open AccessReview

Advances in Shear Stress Stimulation of Stem Cells: A Review of the Last Three Decades

by Qiyuan Lin, Zhen Yang, Hao Xu, Yudi Niu, Qingchen Meng and Dan Xing

Biomedicines 2024, 12(9), 1963; https://doi.org/10.3390/biomedicines12091963 - 29 Aug 2024

Viewed by 881

Abstract

Stem cells are widely used in scientific research because of their ability to self-renew and differentiate into a variety of specialized cell types needed for body functions. However, the self-renewal and differentiation of stem cells are regulated by various stimuli, with mechanical stimulation [...] Read more.

Stem cells are widely used in scientific research because of their ability to self-renew and differentiate into a variety of specialized cell types needed for body functions. However, the self-renewal and differentiation of stem cells are regulated by various stimuli, with mechanical stimulation being particularly notable due to its ability to mimic the physical environment in the body. This study systematically collected 2638 research papers published between 1994 and 2024, employing tools such as VOSviewer, CiteSpace, and GraphPad Prism to uncover research hotspots, publication trends, and collaboration networks. The results indicate a yearly increase in global research on the shear stress stimulation of stem cells, with significant contributions from the United States and China in terms of research investment and output. Future research directions include a deeper understanding of the mechanisms underlying mechanical stimulation’s effects on stem cell differentiation, the development of new materials and scaffold designs to better replicate the natural cellular environment, and advancements in regenerative medicine. Despite considerable progress, challenges remain in translating basic research findings into clinical applications. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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Open AccessReview

Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review

by Nyruz Ramadan Elahmer, Sok Kuan Wong, Norazlina Mohamed, Ekram Alias, Kok-Yong Chin and Norliza Muhammad

Biomedicines 2024, 12(8), 1635; https://doi.org/10.3390/biomedicines12081635 - 23 Jul 2024

Cited by 1 | Viewed by 4142

Abstract

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients’ quality of life. This review synthesizes the current understanding of the [...] Read more.

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients’ quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis. Full article

(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)

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