Search Results (127)

Post-traumatic osteoarthritis (PTOA) is a distinct form of knee osteoarthritis characterized by accelerated joint degeneration following injury. It poses unique challenges in post-menopausal women due to hormonal changes and altered bone metabolism that create complex pathophysiological environments. This retrospective cohort study compared the effectiveness of different anti-osteoporotic medications in preventing total knee replacement (TKR) in 6155 postmenopausal women with PTOA treated between 2011 and 2021. We compared raloxifene and denosumab, with alendronate serving as the reference group. The primary outcome was TKR occurrence. Cox proportional hazards regression and inverse probability of treatment weighting (IPTW) were performed to estimate hazard ratios, with Kaplan–Meier survival analysis for time-to-event assessment. Participants’ mean (SD) age was 69.4 (10.0) years. Given the retrospective nature and typical delayed presentation of PTOA symptoms, cohort entry was defined as the concurrent diagnosis of PTOA and osteoporosis requiring anti-resorptive therapy. Over a mean follow-up of 5.47 years, 26 patients (0.42%) underwent TKR. Raloxifene was associated with a significantly reduced TKR risk compared to alendronate (IPTW-HR 0.81, 95% CI 0.67–0.99, p = 0.040), representing a 19% relative risk reduction. Kaplan–Meier analysis demonstrated raloxifene maintained the lowest cumulative TKR incidence compared to alendronate and denosumab over time, particularly beyond 5 years. These findings suggest that raloxifene may offer superior joint protection compared with alendronate and denosumab in postmenopausal women with PTOA, supporting its potential as a disease-modifying therapeutic option for this vulnerable population. Full article

Background/Objectives: Postmenopausal osteoporosis disrupts magnesium homeostasis and hematological balance, contributing to systemic inflammation and metabolic alterations. This study aimed to assess the effects of dietary interventions—tempeh, daidzein, probiotics, and their combinations—on magnesium status and hematological ratios in a postmenopausal osteoporotic Wistar rat model. Methods: Sixty-four rats were divided into one sham group (n = 8) and seven ovariectomized (OVX) groups (n = 56), with different modified diets administered for six weeks. In addition, one of the groups received alendronate bisphosphonate as a pharmacological reference to benchmark the dietary interventions against standard anti-osteoporotic therapy. Magnesium levels in the tissues and feces, along with blood hematological ratios (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and triglyceride-to-glucose index (TyG)), were evaluated. Results: The results revealed that a combination of tempeh and probiotics (OTL) significantly increased magnesium levels in the feces, spleen, and hair, while reducing liver magnesium levels. Compared to the standard groups (S and O), the hematological analysis revealed that the daidzein group (OD) had the highest MLR, while the OTL group exhibited the lowest TyG index. The alendronate bisphosphonate (OB) intervention showed no significant effect on tissue magnesium levels, feces magnesium levels, or hematological ratios. Correlation analysis revealed a strong negative association between spleen magnesium levels and the PLR (r = −0.626) and a positive relationship between liver magnesium levels and TyG (r = 0.422). Conclusions: The authors of this study concludes that while ovariectomy significantly altered magnesium status and hematological ratios, the dietary combination of tempeh, daidzein, and probiotics did not demonstrate an apparent beneficial effect on magnesium status or inflammatory ratios in a postmenopausal osteoporotic rat model. However, the findings highlight interesting aspects of magnesium status and its correlations with metabolic and inflammatory parameters, warranting further investigation. Full article

This study sought to evaluate the inhibitory effect of pulsed electromagnetic field (PEMF) therapy on bone resorption in a mouse model of lipopolysaccharide (LPS)-induced osteoporosis. A total of 40 mice were divided into four groups: control, LPS, LPS + alendronate, and LPS + PEMF. Blood and spleen samples were analyzed using RT-PCR and ELISA, while calvaria and femurs were assessed by micro-computed tomography (CT) and histological analysis. Serum analysis revealed that, compared with the control group, calcium levels in the PEMF group showed no significant difference, but alkaline phosphatase (ALP) levels were significantly increased, whereas tartrate-resistant acid phosphatase (TRAP) levels were significantly decreased. Moreover, blood cytokine analysis showed reduced expression of TNF-α and IL-1β and increased expression of BMP-2 in the PEMF group. Spleen tissue analysis further demonstrated significant upregulation of IFN-γ and IL-10 expression in the PEMF group. Micro-CT confirmed that PEMF inhibited femoral bone loss and promoted bone regeneration in calvarial defects. Histological evaluation with hematoxylin and eosin and Masson–Goldner trichrome staining confirmed enhanced bone formation in both the femur and calvaria. In conclusion, PEMF effectively alleviates bone loss and promotes bone regeneration in LPS-induced osteoporosis. Furthermore, PEMF exhibits anti-osteoclastogenic activity by reducing inflammatory cytokines and enhancing IFN-γ and IL-10 expression in the spleen. Full article

Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an increased risk of osteonecrosis of the jaw (ONJ). This systematic review aimed to assess the incidence and risk of ONJ in osteoporotic patients treated with ZA or AA and evaluate the impact of treatment duration. Material and Methods: The systematic literature review was conducted following PRISMA guidelines. The keywords “Zoledronic acid,” “Alendronic acid,” “Osteoporosis,” and “Osteonecrosis” were searched in PubMed and ScienceDirect databases. Selection criteria included studies on humans written in English, published from 2014. The systematic review protocol was registered in the PROSPERO register under the following number: CRD42024587046. Results: A total of 7 studies with 98,717 osteoporotic patients met the criteria, showing a higher ONJ incidence with ZA than AA. Six studies linked longer BP use to increased ONJ risk, which quadrupled after 5 years of AA use. A positive correlation was found between BP use (≥3 years) and ONJ in OP patients, primarily affecting females over 60. ONJ appeared after 1 year with AA, increasing over time, while ZA-related ONJ emerged as early as 5 months with a higher overall incidence. Conclusions: ZA poses a higher ONJ risk and incidence and earlier onset than AA, occurring within 5 months versus 1 year for AA. These findings emphasize the need for careful monitoring, especially in long-term BP therapy with additional risk factors. Full article

Background: We report the successful formulation of a bone-targeted vancomycin-loaded liposomal carrier. Method: The basic liposomal structure is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dicetyl phosphate (DCP) in a molar ratio of 3:1:0.25, respectively. The dehydration–rehydration method was used to maximize the liposomal-encapsulation efficiency of vancomycin after the initial preparation using thin-film hydration. Results: Sodium alendronate was used as a targeting moiety and was successfully conjugated to DSPE–PEG–COOH via carbodiimide chemistry, as was confirmed using IR spectroscopy. The resulting conjugate, DSPE–PEG-alendronate, was subsequently used in the formulation of bone-targeting vancomycin-loaded liposomes. In vitro binding assays with hydroxyapatite demonstrated preferential binding of the surface-modified liposomes to hydroxyapatite crystals. Furthermore, ex vivo studies revealed that the surface-modified liposomes exhibited enhanced binding affinity to the tibial bone tissue of 4-week-old male CD1 mice, in comparison to unmodified liposomes. Conclusions: The successfully formulated surface-modified vancomycin loaded liposomes showed enhanced bone affinity with a great potential for targeting the antibiotic to infected bones. Full article

Introduction: Bone health optimization is a key component of the preoperative management of spine surgery patients, as poor bone quality increases the odds of mechanical complications. The present study aimed to achieve the following: (1) compare the relative efficacy of current osteoporosis medications in improving bone quality; (2) identify factors influencing treatment response in preoperative spine surgery patients. Methods: Patients treated at a single, multisite institution who received osteoporosis treatment were identified. Data were gathered on pre- and post-treatment lumbar spine Hounsfield Unit (HU) measurements, patient demographics, frailty scores (modified Frailty Index/mFI, risk analysis index/RAI), and pharmacologic treatment details. The primary outcome was a ≥7 point improvement in lumbar HU, and baseline and logistic regression models were utilized to identify factors associated with this improvement. Medications were grouped as anabolic (teriparatide, romosozumab) and antiresorptive (denosumab, alendronate) therapies. Results: A total of 267 patients were included (median age: 74 years; IQR [66–81]; 67.3% female), with 127 (47.6%) improving by ≥7 HU. The treatment agents used were alendronate (95), denosumab (113), romosozumab (31), and teriparatide (28). Univariable comparisons revealed significant differences across medication groups in age (p < 0.001), sex (p < 0.001), mFI (p < 0.001), RAI (p = 0.004), BMI (p < 0.001), pre-treatment HU (p = 0.022), and treatment duration (p < 0.001). The highest HU improvement rates (ΔHU ≥ 7) were observed in patients receiving the anabolic medications romosozumab (67.7%) and teriparatide (60.7%). Univariable logistic regression identified male sex (OR 0.54, p = 0.019), higher pre-treatment HU (OR 0.99, p = 0.006), and longer treatment duration (OR 0.97, p = 0.003) as factors associated with lower odds of HU improvement. Only romosozumab was associated with significantly higher odds of HU improvement relative to alendronate (OR 3.02, p = 0.012). In our multivariable analysis, male sex (OR 0.53, p = 0.028) and higher pre-treatment HU (OR 0.99, p = 0.002) remained significant predictors of HU improvement. However, medication type was not significant in the multivariable analysis. Conclusions: Our study highlights that male sex and higher pre-treatment HU were independently associated with lower odds of HU improvement, while medication type was not a significant predictor. Additionally, anabolic agents offered superior improvement relative to antiresorptive therapies. Full article

Background/Objectives: Bisphosphonates are effective in preventing osteoporotic fractures. However, the risk of atypical femur fractures (AFFs) increases with long-term bisphosphonate use. There are few existing publications on the analysis of clinical outcomes of atypical femur fracture cases in Chinese patients. Our objective was to review the clinical outcomes of AFF cases managed in a tertiary center in Hong Kong, China. Methods: Cases of AFF managed in the Prince of Wales Hospital from 2010 to 2024 were included. Data on demographics, type and duration of bisphosphonate use prior to AFF, fixation method, and mobility 1 year post-operation were retrospectively retrieved. One-way ANOVA was used to compare the duration of use prior to the development of AFF between different types of bisphosphonates. Results: Sixty-nine cases of AFF were included, with a mean age of 73.8 ± 9.7 years. A total of 95.6% of patients had a history of bisphosphonate use, with a mean duration of usage of 6.8 ± 5.6 years prior to the occurrence of AFF. The duration of bisphosphonate use prior to the development of AFF was comparable between alendronate, ibandronate, and a history of using more than one type of anti-resorptive agent. A non-union rate of 5.8% was observed in the current cohort, with 48.2% returning to pre-morbid mobility 1 year post-operation. Conclusions: AFF is more commonly seen in female patients with a history of bisphosphonate use. Considering the high success rate demonstrated in the current cohort, treating AFF with closed reduction followed by fixation with a long cephalomedullary device in dynamic locking together with immediate full-weight-bearing rehabilitation post-operation may be effective. Full article

Metastatic endometrial cancer continues to be a common cause of death as of 2024, even after maximal use of all currently available standard treatments. To address this problem of metastatic cancer generally in 2025, the drug repurposing movement within oncology identifies medicines in common general medical use that have clinical or preclinical experimental data indicating that they interfere with or inhibit a specific growth driving element identified in a given cancer. The drug repurposing movement within oncology also uses data from large scale in vitro screens of thousands of drugs, looking for simple empirical growth inhibition in a given cancer type. This paper outlines the data showing that five drugs from general medical practice meet these evidence criteria for inhibition of endometrial cancer growth, the EC5 regimen. The EC5 regimen uses the osteoporosis treatment drug, alendronate; the analgesic drug, celecoxib; the antifungal drug, itraconazole; the sleep aid, ramelteon; and the cholesterol lowering drug, simvastatin. Side effects seen with these drugs are usually minimal and easily tolerated by patients. Full article

Objectives: This study evaluated the efficacy of teriparatide (TPTD) and alendronate (ALN) in mitigating bone loss, enhancing bone structure, and facilitating motor function recovery following spinal cord injury (SCI). Methods: All the rats were allocated into four groups: a sham surgery group (SHAM group), a normal saline group (SCI + NS group), a TPTD treatment group after SCI (SCI + TPTD group), and an ALN treatment group after SCI (SCI + ALN group). The Basso, Beattie, and Bresnahan (BBB) scores and gait analyses were used to assess the motor abilities of rats following SCI and the effects of treatment. HE staining, Masson’s trichrome staining, and LFB staining were performed to evaluate the extent of spinal cord tissue damage. Micro-CT was used to measure 12 bone-related parameters of the proximal tibia and create 3D images, and structural changes in the proximal tibial bone tissue were observed under a light microscope after HE staining. Results: After 12 weeks of treatment, the micro-CT data indicated that TPTD significantly increased key bone indicators, such as bone mineral density, after SCI (p < 0.01), whereas ALN did not significantly improve these indicators (p > 0.05). Compared with the SCI + NS group, the SCI + TPTD group presented significantly greater BBB scores and near-normal gait parameters (p < 0.05). Analyses of pathological sections revealed that TPTD significantly reduced the cavity area in the spinal cord after SCI, decreased the proportion of scar tissue, and increased the retention of neural myelin (p < 0.05). However, ALN had no significant effect on these indicators (p > 0.05). Conclusions: TPTD was more effective than ALN at mitigating bone loss and promoting motor function recovery after SCI, and it demonstrated significant advantages in reducing spinal cord damage and improving tissue structure. Full article

The widespread use of thiamethoxam has led to pesticide residues that have sparked global concerns regarding ecological and human health risks. A pressing requirement exists for a detection method that is both swift and sensitive. Herein, we introduced an innovative fluorescence biosensor constructed from alendronic acid (ADA)-modified upconversion nanoparticles (UCNPs) linked with magnetic nanoparticles (MNPs) via aptamer recognition for the detection of thiamethoxam. Through base pairing, thiamethoxam-specific aptamer-functionalized MNPs (apt-MNPs) were integrated with complementary DNA-functionalized UCNPs (cDNA-UCNPs) to create the MNPs@UCNPs fluorescence biosensor. Thiamethoxam specifically attached to apt-MNPs, leading to their separation from cDNA-UCNPs, which in turn led to a reduction in fluorescence intensity at 544 nm following separation by an external magnetic field. The change in fluorescence intensity (ΔI) was directly correlated with the concentration of thiamethoxam, enabling the quantitative analysis of the pesticide. With optimized detection parameters, the biosensor was capable of quantifying thiamethoxam within a concentration span of 0.4–102.4 ng·mL⁻¹, and it achieved a detection limit as minute as 0.08 ng·mL⁻¹. Moreover, leveraging the swift magnetic concentration properties of MNPs, the assay duration could be abbreviated to 25 min. The research exhibited a swift and precise sensing platform that yielded promising results in samples of cucumber, cabbage, and apple. Full article

Background/Objectives: Pulmonary fibrosis (PF) results in a progressive decline of lung function due to scarring. Drugs are among the most common causes of PF. The objective of our study was to reveal the structure of drugs involved in PF development. Methods: we performed a retrospective descriptive pharmacoepidemiologic study on spontaneous reports (SRs) with data on PF registered in the Russian National Pharmacovigilance database for the period from 4 January 2019 to 31 May 2024. Results: A total of 1308 SRs on PF were finally identified with patients mean age of 59.3 ± 23.4 years. Death was reported in 30.7% (n = 401) with mean age of 59.9 ± 13.8 years. In the structure of culprit drugs, the following groups were leaders: antineoplastic and immunomodulating agents (51.9%); systemic hormonal preparations, excluding sex hormones and insulins (7.4%); drugs affecting nervous system (7.1%); respiratory system (7.1%); alimentary tract and metabolism (6.5%); and cardiovascular system (5.5%). In the total sample, the top ten drugs were rituximab (5.5%), methotrexate (4.4%), etanercept (4.2%), leflunomide (4.0%), adalimumab (3.7%), tocilizumab (3.3%), abatacept (3.0%), alendronic acid (2.7%), secukinumab (2.6%), and infliximab (2.4%). The number of SRs per year nearly doubled from 2021 to 2022 and from 2022 to 2023 with a maximum peak expected for 2024. Conclusions: Our study demonstrated increased reporting on PF in the National Pharmacovigilance database from 2019 to 2024. We revealed outstanding results for the role of antineoplastic and immunomodulating agents in PF development. Full article

Objectives: To assess the number of new cases of Medication-Related Osteonecrosis of the Jaw (MRONJ) among patients with osteoporosis and other non-malignant bone diseases in Northwestern Italy between 2007 and 2022. Methods: MRONJ cases were collected from referral centers in a population of 4.5 million. We analysed the number of new MRONJ cases per year, type of disease, administered drugs, duration of therapy (when available), and onset time of disease. Results: We analysed 198 cases (out of 1071 total MRONJ cases); diseases included osteoporosis (87%), rheumatoid arthritis (5%), their association (4%), Paget’s disease, and other various diseases (4%). Patients received bisphosphonates alone (74%), or denosumab alone (6%), or a sequence of different drugs (20%). The number of new cases increased over five years from 2 (2003–2007) to 51 (2008–2012), 65 (2013–2017), and 79 (2018–2022), and the percentage increased from 1% to 14%, 20%, and 29% of the total cases. Conclusions: The number of new MRONJ cases per year among patients with non-malignant diseases is rapidly increasing all around the world, though underestimation cannot be excluded. In this study, we describe epidemiological and clinical characteristics of patients, and the drug most frequently involved in MRONJ cases in our region over a long period, allowing a comprehensive view of the progression of the disease. Greater collaboration among specialists is needed for correct and early diagnosis to improve measures potentially reducing disease incidence and to limit quality of life deterioration in patients with osteoporosis and other non-malignant diseases. Full article

American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects approximately 6–7 million people worldwide. However, its pharmacological treatment causes several uncomfortable side effects, causing patients’ treatment abandonment. Therefore, there is a need for new and better treatments. In this work, the molecular docking of nine hundred twenty-four FDA-approved drugs on three different sites of trypanothione reductase of T. cruzi (TcTR) was carried out to find potential trypanocidal agents. Finally, biological evaluations in vitro and in vivo were conducted with the selected FDA-approved drugs. Digoxin, alendronate, flucytosine, and dihydroergotamine showed better trypanocidal activity than the reference drugs benznidazole and nifurtimox in the in vitro evaluation against the trypomastigotes form. Further, these FDA-approved drugs were able to reduce 20–50% parasitemia in a short time in an in vivo model, although with less efficiency than benznidazole. Therefore, the results suggest a combined therapy of repurposed and canonical drugs against T. cruzi infection. Full article

Acute myeloid leukemia (AML) is characterized by the abnormal proliferation and differentiation arrest of myeloid progenitor cells. The clinical treatment of AML remains challenging. Promoting AML cell differentiation is a valid strategy, but effective differentiation drugs are lacking for most types of AML. In this study, we generated Tg(drl:hoxa9) zebrafish, in which hoxa9 overexpression was driven in hematopoietic cells and myeloid differentiation arrest was exhibited. Using Tg(drl:hoxa9) embryos, we performed chemical screening and identified four FDA-approved drugs, ethacrynic acid, khellin, oxcarbazepine, and alendronate, that efficiently restored myeloid differentiation. The four drugs also induced AML cell differentiation, with ethacrynic acid being the most effective. By an RNA-seq analysis, we found that during differentiation, ethacrynic acid activated the IL-17 and MAPK signaling pathways, which are known to promote granulopoiesis. Furthermore, we found that ethacrynic acid enhanced all-trans retinoic acid (ATRA)-induced differentiation, and both types of signaling converged on the IL-17/MAPK pathways. Inhibiting the IL-17/MAPK pathways impaired ethacrynic acid and ATRA-induced differentiation. In addition, we showed that ethacrynic acid is less toxic to embryogenesis and less disruptive to normal hematopoiesis than ATRA. Thus, the combination of ethacrynic acid and ATRA may have broader clinical applications. In conclusion, through zebrafish-aided screening, our study identified four drugs that can be repurposed to induce AML differentiation, thus providing new agents for AML therapy. Full article

Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis. Full article