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15 pages, 2443 KiB  
Article
Bone Microstructural Deterioration and miR-155/RHOA-Mediated Osteoclastogenesis in Type 2 Diabetes Mellitus
by Mouza M. Alaleeli, Suneesh Kaimala, Ernest Adeghate and Sahar Mohsin
Int. J. Mol. Sci. 2025, 26(17), 8159; https://doi.org/10.3390/ijms26178159 - 22 Aug 2025
Abstract
Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone [...] Read more.
Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone remodeling imbalances in T2DM through miR-155 and RHOA expression profiling. Three-month-old female Wistar rats were fed a high-calorie diet for 3 weeks, followed by intraperitoneal injections of two lower doses of streptozotocin at weekly intervals to induce T2DM. Bone analysis from diabetic rats tested using qRT-PCR showed significantly reduced miR-155 levels and elevated RHOA. Histological analysis showed a 12.65% increase in Tb.Sp, 10.07% decrease in Tb.Th, and significant increase (p < 0.05) in apoptotic osteocytes. The bone turnover marker CTx-1 level was increased by 20.84%, and RANKL levels were significantly increased in T2DM. IL-1β and TNF-α were increased in T2DM. Bone resorption is more likely to occur in T2DM as both IL-1β and TNF-α work synergistically to promote osteoclastogenesis. MiR-155 could be an important modulator of bone remodeling in T2DM and a potential therapeutic target for diabetic osteopathy. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Molecular Pathophysiology and Treatment)
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13 pages, 824 KiB  
Review
Recent Updates on Diabetes and Bone
by Giacomina Brunetti
Int. J. Mol. Sci. 2025, 26(17), 8140; https://doi.org/10.3390/ijms26178140 - 22 Aug 2025
Viewed by 40
Abstract
Diabetes represents one of the major challenges in preserving health in the 21st century. It has been estimated that in 2050, 853 million subjects will live with diabetes. It was also reported that 3.4 million adults died from diabetes and related comorbidities. Chronic [...] Read more.
Diabetes represents one of the major challenges in preserving health in the 21st century. It has been estimated that in 2050, 853 million subjects will live with diabetes. It was also reported that 3.4 million adults died from diabetes and related comorbidities. Chronic hyperglycemia, if not properly managed, leads to skeletal fragility with fracture risk that augments with age. In type 1 diabetes (T1D), the augmented fracture risk can be partially explained by lower areal bone mineral density (aBMD). Interestingly, in type 2 diabetes (T2D), the risk of fractures increases with normal or elevated aBMD. In this review, the recent updates on diabetes and bone health (2023–2025) are reported, thus describing bone quality and the role of mediators involved in diabetes pathogenesis. Consequently, the role of Vitamin D, Incretins, Glucagon-like peptide-2 (GLP-2), neurotensin, asprosin, irisin, and Thioredoxin-interacting protein (TXNIP) will be described considering the interplay between diabetes and bone health. The importance of monitoring diabetic patients’ bone health is underlined, together with the therapeutic approaches to avoid fractures. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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18 pages, 402 KiB  
Article
Effectiveness of Proprioceptive Training on Postural Stability and Chronic Pain in Older Women with Osteoporosis: A Six-Month Prospective Pilot Study
by Katya Mollova, Steliyana Valeva, Nazife Bekir, Pavlina Teneva and Kaloyan Varlyakov
J. Funct. Morphol. Kinesiol. 2025, 10(3), 316; https://doi.org/10.3390/jfmk10030316 - 15 Aug 2025
Viewed by 322
Abstract
Background: Osteoporosis is the most prevalent metabolic bone disease, characterized by decreased bone mineral density, which leads to increased bone fragility, back pain, impaired postural stability, and a heightened risk of fractures. Proprioceptive exercises have been identified as an effective approach for [...] Read more.
Background: Osteoporosis is the most prevalent metabolic bone disease, characterized by decreased bone mineral density, which leads to increased bone fragility, back pain, impaired postural stability, and a heightened risk of fractures. Proprioceptive exercises have been identified as an effective approach for reducing the risk of falls and adverse events. Objective: Our aim was to conduct a pilot exploratory study evaluating the effectiveness of proprioceptive training in improving coordination and balance, and in reducing chronic thoracolumbar back pain in older women diagnosed with osteoporosis. Methods: Quantitative ultrasound bone densitometry was performed on 144 women over the age of 60, followed by the implementation of a proprioceptive training program. The One-Leg Stance balance test and the Visual Analog Scale for pain intensity were administered before and after a six-month training intervention. Results: ANOVA revealed significant improvements in balance, with the OLS duration increasing from 2.49 s at baseline to 7.31 s following the intervention. Participants aged over 70 years demonstrated a positive, though comparatively lower increase in stability and balance. Chi-squared (χ2) analysis indicated that 83.9% of the variance in OLS performance was attributable to proprioceptive training (Cramer’s V = 0.839, p = 0.001). A significant reduction in VAS pain scores was observed, with 48.1% of the variance explained by the moderate effect of proprioceptive training (Cramer’s V = 0.481, p = 0.001). Conclusions: Proprioceptive training has the potential to improve postural stability, balance, and coordination and stimulate pain intensity in the thoracolumbar region. Despite promising results, the absence of a control group limits our ability to draw definitive causal conclusions. Full article
(This article belongs to the Section Functional Anatomy and Musculoskeletal System)
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15 pages, 984 KiB  
Article
Epidemiology and Management of Ankle Fractures Prior to, During, and Following the COVID-19 Pandemic in an Italian Tertiary Hospital
by Gianluca Testa, Francesco Leonforte, Marco Sapienza, Martina Ilardo, Stefania Garozzo, Maria Agata Musumeci, Michela Marchetti, Andrea Vescio, Antonio Mistretta and Vito Pavone
Medicina 2025, 61(8), 1439; https://doi.org/10.3390/medicina61081439 - 10 Aug 2025
Viewed by 312
Abstract
Background and Objectives: Ankle fractures represent one of the most common injuries to the lower limb, particularly impacting women and the elderly. The coronavirus disease 2019 (COVID-19) pandemic greatly disrupted both the incidence of these fractures and their treatment patterns globally. This [...] Read more.
Background and Objectives: Ankle fractures represent one of the most common injuries to the lower limb, particularly impacting women and the elderly. The coronavirus disease 2019 (COVID-19) pandemic greatly disrupted both the incidence of these fractures and their treatment patterns globally. This retrospective epidemiological study analyzed 1010 cases of ankle fractures treated at the Orthopedics Department of Policlinico University Hospital in Catania from 2018 to 2023. The study aimed to evaluate trends in incidence, patient demographics, fracture types, treatment modalities, and hospital stay across the pre-COVID-19, COVID-19, and post-COVID-19 periods. Materials and Methods: A retrospective observational study was conducted including all patients diagnosed with ankle fractures from 1 January 2018 to 31 December 2023. Data were collected from hospital medical records using ICD-9-CM codes and radiographic classification systems (Danis–Weber, Lauge-Hansen, and AO/OTA). Variables analyzed included demographics, fracture type and side, treatment modality, and hospitalization details. Statistical analyses were performed using t-tests, chi-square tests, and linear regression, with significance set at p < 0.05. Results: In 2020, there was a 31.7% decrease in fracture incidence. Although overall fracture rates rebounded after COVID-19, they did not reach pre-pandemic levels. During the pandemic, trimalleolar fractures increased significantly, occurring more frequently in older women, likely due to bone fragility. The rate of surgical treatments rose during and after the pandemic, with a distinct shift from ORIF to external fixation. Hospital stays were longer, especially for patients with cardiovascular risk factors. Conclusions: The pandemic significantly altered the epidemiology, treatment strategies, and outcomes of ankle fractures. These findings highlight the necessity for adaptable care models and preventive strategies, particularly for vulnerable populations such as older women. Full article
(This article belongs to the Section Orthopedics)
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14 pages, 587 KiB  
Article
Which Patients in the FLS Should Be Prioritised for a DXA Scan Within 12 Weeks?
by Hege Nysted, Oda Horpestad and Ane Djuv
J. Clin. Med. 2025, 14(16), 5619; https://doi.org/10.3390/jcm14165619 - 8 Aug 2025
Viewed by 344
Abstract
At Stavanger University Hospital (SUH), patients aged 50 years and above with a fracture after a fall are included in our Fracture Liaison Service (FLS) at the orthopaedic department, due to their high imminent fracture risk. The FLS at SUH keeps a quality [...] Read more.
At Stavanger University Hospital (SUH), patients aged 50 years and above with a fracture after a fall are included in our Fracture Liaison Service (FLS) at the orthopaedic department, due to their high imminent fracture risk. The FLS at SUH keeps a quality registry, including index fractures, fall from standing/walking, preventive factors, Dual Absorptiometry X-ray (DXA) results and treatment status, in addition to risk factors such as chronic diseases. As in many other hospitals and countries, the capacity of the DXA scanner at SUH does not meet the needs of the ageing population. As such, FLS patients should be prioritised for DXA scanning according to their need for anti-osteoporotic treatment. The aims of this study were (1) to identify whether any risk factors are more strongly associated with osteoporosis than others, and (2) to use this information as a tool to prioritise patients for which the decision to initiate anti-osteoporotic treatment should be assessed by a DXA scan. Method: We used software from CheckWare to keep a structured health record, submitting journal text to the health record and data to our fracture quality registry from 1 June 2022 to 31 December 2024. The fracture coverage of the registry, as part of the medical record, was 100%. Both men and women aged over 50 years with fragility-related fractures were included in the analysis, with index fracture having been reported within 24 months prior to FLS assessment. Exclusion criteria: short life expectancy (<3 years), already started on anti-osteoporotic treatment, living in nursing home, age >97 years, or multi-trauma patients. Statistics were calculated using SPSS and logistic regression. The results are presented as odds ratio (OR) and 95% confidence interval (95% CI). Significant differences were considered at a p-value of <0.05. Results: A total of 6974 patients were included, 81% of which were female. After the DXA scan, 5307 of the patients were started on anti-osteoporotic treatment (76%). Patients aged 50–70 years were the largest group. Female patients or those aged 80 years or older had an increased odds ratio (OR) of starting treatment after a fracture. The index fractures included in the logistic regression analysis and were most likely to initiate anti-osteoporotic treatment in the FLS, were vertebral fracture (p < 0.000, OR 3.1, 95% CI: 2.4–4.0), hip fracture (p < 0.000, OR 2.60, 95% CI: 1.9–3.5), costa fracture (p-value = 0.028, OR:1.3, 95% CI:1.0–1.5), pelvic fracture (p-value < 0.000, OR 3.1, 95% CI: 1.8–5.1). Patients with lack of sufficient vitamin D had increased odds with OR of 1.7 (p-value < 0.00, 95% CI: 1.3–2.2) for having osteoporosis compared to the other FLS patients. Fall from standing, walking or sitting increased the odds for osteoporosis treatment (p-value < 0.000, OR 2.8, 95% CI: 2.3–3.3). Conclusions: The listed risk factors for needing treatment were high for most fractures, especially vertebral, hip, and pelvic fractures. Patients aged 80+ years and with a fracture from standing/walking could also start treatment directly, without waiting for a DXA scan. Thus, these patients should be shifted rapidly to FLS and started on treatment without delay. In this way, DXA scanning can be prioritised for patients for whom supporting information is needed regarding the decision to initiate anti-osteoporotic treatment, such as those with proximal humerus, wrist, or ankle fractures. Time to DXA scan could be shortened for these patients and 12 weeks may be achievable. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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26 pages, 701 KiB  
Review
Skeletal Health in Pituitary and Neuroendocrine Diseases: Prevention and Treatments of Bone Fragility
by Flavia Costanza, Antonella Giampietro, Laura De Marinis, Antonio Bianchi, Sabrina Chiloiro and Alfredo Pontecorvi
Targets 2025, 3(3), 26; https://doi.org/10.3390/targets3030026 - 8 Aug 2025
Viewed by 270
Abstract
Bone loss is common in patients affected by pituitary and neuroendocrine disorders as both hormone excess and hormone deficiency can affect bone structure. There is increasing evidence that pituitary hormones directly influence bone cells turnover by bypassing endocrine organs. Osteopenia, osteoporosis, and vertebral [...] Read more.
Bone loss is common in patients affected by pituitary and neuroendocrine disorders as both hormone excess and hormone deficiency can affect bone structure. There is increasing evidence that pituitary hormones directly influence bone cells turnover by bypassing endocrine organs. Osteopenia, osteoporosis, and vertebral fractures often result from these skeletal changes; however, diagnosing and managing bone frailty in pituitary and neuroendocrine disorders is still challenging because of the unpredictable outcomes in terms of fracture risk, even after the improvement of pituitary dysfunction, and the limited evidence for the use of bone-active drugs in these pathologies. The use of vitamin D supplements for fracture prevention is still debated in these secondary forms of bone frailty, although some studies have shown similar benefits to those derived in the general population. This review offers an overview on the characteristics of bone fragility in different pituitary and neuroendocrine diseases, and focuses on the prevention and treatment of skeletal disorders with bone-active drugs and vitamin D formulations currently available in this setting. Full article
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20 pages, 1388 KiB  
Article
Beyond Bone Mineral Density: Real-World Fracture Risk Profiles and Therapeutic Gaps in Postmenopausal Osteoporosis
by Anamaria Ardelean, Delia Mirela Tit, Roxana Furau, Oana Todut, Gabriela S. Bungau, Roxana Maria Sânziana Pavel, Bogdan Uivaraseanu, Diana Alina Bei and Cristian Furau
Diagnostics 2025, 15(15), 1972; https://doi.org/10.3390/diagnostics15151972 - 6 Aug 2025
Viewed by 404
Abstract
Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal [...] Read more.
Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal women undergoing DXA screening. Methods: We analyzed data from 1669 postmenopausal women aged 40–89 years who underwent DXA evaluation. BMD status was categorized as normal, osteopenia, or osteoporosis. Treatment status was classified based on active antiosteoporotic therapy, calcium/vitamin D supplementation, hormonal therapy (historical use), or no treatment. Logistic regression models were used to explore independent predictors of osteoporosis and treatment uptake. Results: A total of 45.0% of women had osteoporosis and 43.5% had osteopenia. Despite this, 58.5% of the population, over half of women with osteoporosis, were not receiving any active pharmacologic treatment. Bisphosphonates were the most prescribed therapy (17.9%), followed by calcium/vitamin D supplements (20.6%). A prior history of fragility fractures and radiological bone lesions were significantly associated with lower BMD (p < 0.05). Historical hormone replacement therapy (HRT) use was not associated with current BMD (p = 0.699), but women with HRT use reported significantly fewer fractures (p < 0.001). In multivariate analysis, later menopause age and low BMD status predicted higher odds of receiving active treatment. Conclusions: Our findings highlight a substantial care gap in osteoporosis management, with treatment primarily initiated reactively in more severe cases. Improved screening and earlier intervention strategies are urgently needed to prevent fractures and reduce the long-term burden of osteoporosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Osteoporosis)
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11 pages, 782 KiB  
Article
Exploring the Association Between Platelet Count, the Systemic Immune Inflammation Index, and Fracture Risk in Postmenopausal Women with Osteoporosis: A Cross-Sectional Study
by Cecilia Oliveri, Anastasia Xourafa, Rita Maria Agostino, Valentina Corigliano, Antonino Botindari, Agostino Gaudio, Nunziata Morabito, Alessandro Allegra and Antonino Catalano
J. Clin. Med. 2025, 14(15), 5453; https://doi.org/10.3390/jcm14155453 - 2 Aug 2025
Viewed by 603
Abstract
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution [...] Read more.
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution width (PDW), platelet crit, percentage of large platelets (P-LCR), platelet–lymphocyte ratio, and the SII, calculated as (NxP)/L, where N, P, and L represented neutrophils, platelets and lymphocytes counts, respectively, were evaluated. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Results: A total of 124 women (mean age 68.4 ± 9 years) were stratified into two groups based on the median platelet count; the “lower platelet count group” (n = 58) had a count of 200,000 (174,000 to 226,000), while the “higher platelet count group” (n = 66) had a count of 281,500 (256,500 to 308,500). The higher platelet count group showed a higher hip fracture risk (7.4 vs. 4.5%, p = 0.08) and lower lumbar spine BMD (0.773 vs. 0.83 gr/cm2, p = 0.03). By dividing the participants into two groups with higher SSI (950,848.6 ± 746,097.99) (n = 61) and lower SII (355,751.2 ± 88,662.6) (n = 63), the group with the higher SII showed the higher hip fracture risk (7.4 vs. 3.6%, p = 0.01). Univariate regression analysis revealed correlations between chronological age and PDW (r = 0.188, p = 0.047), and P-LCR (r = 0.208, p = 0.03), as well as associations between vitamin D status and P-LCR (r = −0.301, p = 0.034), and between SII and hip fracture risk (r = 0.12, p = 0.007). Conclusions: Platelet count and SII were associated with fracture risk in postmenopausal women undergoing osteoporosis assessment. Given their reproducibility and cost-effectiveness, these markers warrant further investigation in future prospective studies focused on bone fragility. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, Prevention and Rehabilitation in Osteoporosis)
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16 pages, 948 KiB  
Review
Oxytocin: From Biomarker to Therapy for Postmenopausal Osteoporosis
by Tiago Franca, Joana Fonseca Ferreira, Melissa Mariana and Elisa Cairrao
Women 2025, 5(3), 27; https://doi.org/10.3390/women5030027 - 1 Aug 2025
Viewed by 268
Abstract
Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown [...] Read more.
Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article
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22 pages, 2239 KiB  
Article
10-Year Fracture Risk Assessment with Novel Adjustment (FRAXplus): Type 2 Diabetic Sample-Focused Analysis
by Oana-Claudia Sima, Ana Valea, Nina Ionovici, Mihai Costachescu, Alexandru-Florin Florescu, Mihai-Lucian Ciobica and Mara Carsote
Diagnostics 2025, 15(15), 1899; https://doi.org/10.3390/diagnostics15151899 - 29 Jul 2025
Viewed by 477
Abstract
Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover [...] Read more.
Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m2; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article
(This article belongs to the Special Issue Diagnosis and Management of Metabolic Bone Diseases: 2nd Edition)
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14 pages, 1588 KiB  
Article
Ageing and BMI in Focus: Rethinking Risk Assessment for Vertebral Fragility and Pedicle Screw Loosening in Older Adults
by Jun Li, André Strahl, Beate Kunze, Stefan Krebs, Martin Stangenberg, Lennart Viezens, Patrick Strube and Marc Dreimann
J. Clin. Med. 2025, 14(15), 5296; https://doi.org/10.3390/jcm14155296 - 27 Jul 2025
Viewed by 592
Abstract
Background/Objectives: Pathological vertebral fragility (path-VF) increases the risk of osteoporotic fractures and pedicle screw loosening (PSL) after posterior instrumented spinal fusion (PISF). While WHO body mass index (BMI) categories broadly identify risks related to underweight and obesity, fixed thresholds may inadequately reflect [...] Read more.
Background/Objectives: Pathological vertebral fragility (path-VF) increases the risk of osteoporotic fractures and pedicle screw loosening (PSL) after posterior instrumented spinal fusion (PISF). While WHO body mass index (BMI) categories broadly identify risks related to underweight and obesity, fixed thresholds may inadequately reflect vertebral fragility risks among elderly patients, especially within the normal-weight range. This study investigates whether current BMI classifications sufficiently capture the risk of path-VF in older adults. Methods: This retrospective study included 225 patients who underwent kyphoplasty or PISF (2022–2023). Path-VF was defined by non-tumorous fractures, screw reinforcement, or PSL within six months without prior reinforcement. Patients were grouped into the path-VF (n = 94) and control (n = 131) groups. HU and BMI values, BMI-related ORs, and age trends were analysed, and a logistic regression was performed. Results: Mean HU values were significantly lower in the path-VF group (71.37 ± 30.50) than in controls (130.35 ± 52.53, p < 0.001). Path-VF females (26.26 ± 5.38) had a lower BMI than the control females (29.33 ± 5.98, p = 0.002); no difference was found in males. Normal-weight females showed a borderline risk for path-VF (OR 2.03, p = 0.0495). Obesity (ORmale 0.31/ORfemale 0.37) and being male and overweight (OR 0.21) were protective (all p < 0.05). BMI declined with age in path-VF males (p = 0.001) but increased in the controls (p = 0.023). A logistic regression identified a BMI < 22.5 kg/m2 and age > 67.5 years as significant risk thresholds. Notably, 20.2% of path-VF patients over 67.5 had a normal weight, suggesting a potentially overlooked subgroup. Conclusions: The current WHO lower limit for normal BMI (18.5 kg/m2) may underestimate the risk of path-VF in patients older than 67.5 years, potentially overlooking 24.7% of cases. The results offer a new approach for clinicians to interpret BMI values at the lower end of the normal range (<22.5 kg/m2) with caution in elderly patients undergoing spinal surgery. Full article
(This article belongs to the Special Issue Current Progress and Future Directions of Spine Surgery)
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14 pages, 1687 KiB  
Article
Bone Health and Endocrine Therapy with Ovarian Function Suppression in Premenopausal Early Breast Cancer: A Real-Life Monocenter Experience with Denosumab
by Angelachiara Rotondi, Valentina Frescura, Giorgia Arcuri, Giovanna Garufi, Letizia Pontolillo, Luca Mastrantoni, Elena Di Monte, Noemi Maliziola, Maria Antonia Fucile, Francesca Salvatori, Rita Mondello, Ilaria Poli, Gaia Rachele Oliva, Ginevra Mongelli, Antonella Palazzo, Alessandra Fabi, Emilio Bria, Giampaolo Tortora and Armando Orlandi
Curr. Oncol. 2025, 32(8), 421; https://doi.org/10.3390/curroncol32080421 - 26 Jul 2025
Viewed by 327
Abstract
Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli [...] Read more.
Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article
(This article belongs to the Special Issue Advances in Personalized Therapy for Breast Cancer)
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12 pages, 1502 KiB  
Article
Long-Term Impact of COVID-19 on Osteoporosis Risk Among Patients Aged ≥50 Years with New-Onset Overweight, Obesity, or Type 2 Diabetes: A Multi-Institutional Retrospective Cohort Study
by Sheng-You Su, Yi-Fan Sun and Jun-Jun Yeh
Medicina 2025, 61(8), 1320; https://doi.org/10.3390/medicina61081320 - 22 Jul 2025
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Abstract
Background and Objectives: COVID-19 may have long-term adverse effects on bone health, particularly in individuals aged ≥50 years with obesity or diabetes, who are predisposed to impaired bone quality. Materials and Methods: This retrospective cohort study used TriNetX data from 141 [...] Read more.
Background and Objectives: COVID-19 may have long-term adverse effects on bone health, particularly in individuals aged ≥50 years with obesity or diabetes, who are predisposed to impaired bone quality. Materials and Methods: This retrospective cohort study used TriNetX data from 141 healthcare organizations across North America and Western Europe. Patients aged ≥50 years with overweight (body mass index 25–30 kg/m2), obesity (body mass index ≥ 30 kg/m2), or type 2 diabetes (T2DM) and COVID-19 (2019–2024) were propensity score-matched to non-COVID-19 controls. Exclusion criteria included prior overweight, obesity, diabetes, osteoporosis, T-score ≤ −2.5, Z score ≤ −2.0, fractures, pneumonia, tuberculosis, and cancer. Outcomes included new-onset osteoporosis, fragility fractures, and low T-scores (≤−2.5). Cox regression estimated hazard ratios (HRs); sensitivity analyses assessed lag effects (1–4 years). Results: Among 327,933 matched pairs, COVID-19 was linked to increased osteoporosis risk at 3 years (HR, 1.039; 95% CI, 1.003–1.077) and 6 years (HR, 1.095; 95% CI, 1.059–1.133). Sensitivity analysis showed rising risk with longer lag times: HRs were 1.212, 1.379, 1.563, and 1.884 at 1 to 4 years, respectively. Subgroup analyses confirmed consistent trends. Conclusions: COVID-19 is independently associated with elevated long-term osteoporosis risk in older adults with new-onset overweight, obesity, or T2DM, peaking at 4 years post-infection and persisting through 6 years. Full article
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23 pages, 4725 KiB  
Tutorial
Fragility Fractures of the Pelvis—Current Understanding and Open Questions
by Amber Gordon, Michela Saracco, Peter V. Giannoudis and Nikolaos K. Kanakaris
J. Clin. Med. 2025, 14(14), 5122; https://doi.org/10.3390/jcm14145122 - 18 Jul 2025
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Abstract
Fragility fractures of the pelvis (FFPs) are common in elderly patients, particularly those with osteoporosis. FFPs can be associated with high mortality, morbidity, and functional decline. Known risk factors include being over 80 years old and delays in surgical intervention when this is [...] Read more.
Fragility fractures of the pelvis (FFPs) are common in elderly patients, particularly those with osteoporosis. FFPs can be associated with high mortality, morbidity, and functional decline. Known risk factors include being over 80 years old and delays in surgical intervention when this is required. While the role of surgery in FFPs remains less defined than in proximal femoral fractures in the elderly, studies indicate that surgical fixation offers improved survival and functional outcomes. Similarly, the choice of fixation method, whether posterior or anterior, and their combinations, vary between clinicians. It depends on the fracture type and patient-specific factors, such as bone quality and comorbidities, as well as the surgeon’s experience and the availability of resources. Additionally, orthobiologic adjuncts such as cement augmentation and sacroplasty can enhance the stability of an osteoporotic fracture during surgical intervention. Furthermore, medical treatments for osteoporosis, especially the use of teriparatide, have demonstrated beneficial effects in reducing fractures and promoting healing of the FFPs. Return to pre-injury activities is often limited, with independence rates remaining low at mid-term follow-up. Factors that influence clinical outcomes include fracture type, with Type III and IV fractures generally leading to poorer outcomes, and patient age, functional reserve, and comorbidities. The present tutorial aims to summarise the relevant evidence on all aspects of FFPs, inform an updated management strategy, and provide a template of the reconstruction ladder referring to the most available surgical techniques and treatment methods. Further research, based on large-scale studies, is needed to address the open questions described in this manuscript and refine surgical techniques, as well as determine optimal treatment pathways for this vulnerable patient population. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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30 pages, 2419 KiB  
Systematic Review
Rehabilitation Protocols for Surgically Treated Acetabular Fractures in Older Adults: Current Practices and Outcomes
by Silviya Ivanova, Ondrej Prochazka, Peter V. Giannoudis, Theodoros Tosounidis, Moritz Tannast and Johannes D. Bastian
J. Clin. Med. 2025, 14(14), 4912; https://doi.org/10.3390/jcm14144912 - 10 Jul 2025
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Abstract
Background/Objectives: Acetabular fractures in older adults pose significant challenges due to bone fragility, complex fracture patterns, and increased comorbidities. Surgical management, including isolated open reduction and internal fixation (ORIF) and ORIF combined with acute total hip arthroplasty (THA) (combined hip procedure—CHP), have [...] Read more.
Background/Objectives: Acetabular fractures in older adults pose significant challenges due to bone fragility, complex fracture patterns, and increased comorbidities. Surgical management, including isolated open reduction and internal fixation (ORIF) and ORIF combined with acute total hip arthroplasty (THA) (combined hip procedure—CHP), have advanced considerably. Nevertheless, optimal postoperative rehabilitation and particularly weight-bearing (WB) recommendations remain controversial and inconsistent. This review aims to assess rehabilitation protocols, focusing on WB strategies following the surgical treatment of acetabular fractures in older adults. It also examines differences in WB restrictions by surgical technique (ORIF vs. CHP) and their impact on recovery, complications, reoperations, and mortality. Methods: A systematic review of PubMed, Embase, and the Cochrane Library (2006–2024) included studies involving patients aged ≥65 years treated surgically for displaced acetabular fractures. Data included WB protocols (full, partial, toe-touch), length of stay (LOS), healing, functional outcomes (mobility, Harris and Oxford Hip Scores), complications, reoperations, delayed THA, compliance, readmission, and mortality. Due to heterogeneity, findings were narratively synthesized. Risk of bias was assessed using ROBINS-I and RoB2. Results: Twenty studies involving 929 patients (530 isolated ORIF, 399 CHP) were analyzed. The overall mean follow-up was 3.5 years (range: 1–5.25 years). Postoperative WB protocols were reported in 19 studies (95%). Immediate full WB was permitted in 0% of isolated ORIF studies (0/13), with partial WB recommended by 62% (8/13) for durations typically between 6 and 12 weeks. On the other hand, immediate full WB was allowed in 53% (9/17) of CHP studies. Functional outcomes were moderate following isolated ORIF (mean HHS: 63–82 points), with delayed THA conversion rates ranging from 16.5% to 45%. CHP demonstrated superior functional outcomes (mean HHS: 70–92 points), earlier independent ambulation, and higher patient satisfaction (74–90%), yet increased orthopedic complications, including dislocations (8–11%) and implant loosening (up to 18%). LOS varied from 12 to 21 days (mean 16 days) for isolated ORIF and from 8 to 25 days (mean 17 days) for CHP. Readmission within 30 days was not explicitly reported in any study. Mortality at 1 year varied significantly (ORIF: 0–25%; CHP: 0–14%), increasing markedly at long-term follow-up (up to 42% ORIF, up to 70% CHP at five years). Compliance with WB restrictions was monitored in only two studies (11%). Conclusions: Postoperative rehabilitation after acetabular fracture surgery in older adults remains inconsistent and lacks standardization. Combining ORIF with acute THA may enable earlier weight-bearing and improved short-term function but carries risks such as dislocation and implant loosening. In contrast, isolated ORIF avoids these implant-related complications but often requires prolonged weight-bearing restrictions. Robust evidence is still missing. Future trials are essential to establish standardized protocols that balance mechanical protection and functional recovery. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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