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Antioxidants (Basel, Switzerland) Jan 2024The prolonged use of exogenous glucocorticoids, such as dexamethasone (Dex), is the most prevalent secondary cause of osteoporosis, known as glucocorticoid-induced...
The prolonged use of exogenous glucocorticoids, such as dexamethasone (Dex), is the most prevalent secondary cause of osteoporosis, known as glucocorticoid-induced osteoporosis (GIO). The current study examined the preventative and synergistic effect of aqueous chicory extract (ACE) and ethanolic purslane extract (EPE) on GIO compared with Alendronate (ALN). The phytochemical contents, elemental analysis, antioxidant scavenging activity, and ACE and EPE combination index were evaluated. Rats were randomly divided into control, ACE, EPE, and ACE/EPE MIX groups (100 mg/kg orally), Dex group (received 1.5 mg Dex/kg, Sc), and four treated groups received ACE, EPE, ACE/EPE MIX, and ALN with Dex. The bone mineral density and content, bone index, growth, turnover, and oxidative stress were measured. The molecular analysis of RANK/RANKL/OPG and Nrf2/HO-1 pathways were also evaluated. Dex causes osteoporosis by increasing oxidative stress, decreasing antioxidant markers, reducing bone growth markers (OPG and OCN), and increasing bone turnover and resorption markers (NFATc1, RANKL, ACP, ALP, IL-6, and TNF-α). In contrast, ACE, EPE, and ACE/EPE MIX showed a prophylactic effect against Dex-induced osteoporosis by modulating the measured parameters and the histopathological architecture. In conclusion, ACE/EPE MIX exerts a powerful synergistic effect against GIO by a mode of action different from ALN.
PubMed: 38247490
DOI: 10.3390/antiox13010066 -
Experimental Biology and Medicine... Dec 2023With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations;...
With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.
Topics: Animals; Female; Rats; Alendronate; Autophagy; Bone Density; Bone Density Conservation Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Osteoporosis; Osteoporosis, Postmenopausal; Ovariectomy; Quercetin; X-Ray Microtomography
PubMed: 38240215
DOI: 10.1177/15353702231211977 -
BioMed Research International 2023[This retracts the article DOI: 10.1155/2022/1213278.].
[This retracts the article DOI: 10.1155/2022/1213278.].
PubMed: 38188785
DOI: 10.1155/2023/9817304 -
Medicina Oral, Patologia Oral Y Cirugia... Dec 2023To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
BACKGROUND
To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
MATERIAL AND METHODS
Observational studies that evaluated the occurrence of BAONJ in individuals with RA (BAONJ-RA) were considered for inclusion. Electronic searches were performed up to December 2022 in six databases and in the grey literature. The study selection, data extraction, and quality assessment of the included studies according to the Joanna Briggs Institute Critical Appraisal Checklists was performed. The certainty of evidence was evaluated using the GRADE approach.
RESULTS
Five studies were included three cohort and two cross-sectional. The sample size of subjects with RA ranged from 16 to 3201. Together, the studies presented 36 cases of BAONJ-RA. Prevalence of BAONJ-RA ranged from 0.094% to 56.25%. The incidence ranged from 0.4% to 2.21. Women between the 6th and 8th decade of life were the most affected. Alendronate (n=5) and zoledronic acid (n=9), orally and intravenously, respectively, were the most used bisphosphonates. The duration of bisphosphonates use ranged from 2.7 to 8 years. The certainty of evidence was very low.
CONCLUSIONS
The occurrence of BAONJ-RA is low. However, the certainty of the evidence was very low for this outcome.
PubMed: 38150601
DOI: 10.4317/medoral.26373 -
Experimental and Therapeutic Medicine Jan 2024Methotrexate-related other iatrogenic immunodeficiency-associated lymphoproliferative disorder (MTX-OIIA-LPD) is prone to extranodal involvement but rarely involves the...
Methotrexate‑related other iatrogenic immunodeficiency‑associated lymphoproliferative disorder in the CNS and medication‑related osteonecrosis of the jaw occurring simultaneously: A case report.
Methotrexate-related other iatrogenic immunodeficiency-associated lymphoproliferative disorder (MTX-OIIA-LPD) is prone to extranodal involvement but rarely involves the central nervous system (CNS). The present study reports a case of MTX-OIIA-LPD of the CNS discovered during medication-related osteonecrosis of the jaw (MRONJ) treatment in a 76-year-old woman with rheumatoid arthritis (RA). The chief complaint of the patient was bone exposure and pain in the right mandibular molar. The patient had been receiving MTX for RA and alendronate sodium hydrate for osteoporosis, followed by denosumab. Treatment was initiated based on a diagnosis of MRONJ. However, the patient experienced lightheadedness and floating dizziness afterwards. Examinations revealed scattered neoplastic lesions in the brain. The histopathological diagnosis was diffuse large B-cell lymphoma. A systemic search also revealed adrenal involvement. Since the patient was taking MTX, a diagnosis of MTX-OIIA-LPD was made and MTX was discontinued. Chemotherapeutic agents were administered since the central lesions became symptomatic. The MTX-OIIA-LPD lesions in the brain and adrenal glands completely resolved 8 months after onset. The physical condition of the patient improved, and the bone-exposed areas became epithelialized. Reports on MTX-LPD in the oral and maxillofacial region are few, which may delay its diagnosis. Therefore, biopsy of oral lesions in patients with MRONJ who are taking MTX and collaboration with related diagnostic departments, such as rheumatology and hematology, must be done to initiate the diagnosis and treatment of extraoral MTX-LPD.
PubMed: 38125353
DOI: 10.3892/etm.2023.12329 -
International Journal of Clinical... Apr 2024Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world evidence has been published evaluating the anti-nonvertebral fracture effect of ibandronate.
AIM
This meta-analysis of observational studies assessed the effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis.
METHOD
Pubmed/Embase databases were searched for observational studies. Risks of nonvertebral fractures and hip fractures were the outcomes. Meta-analyses were performed pooling rate ratios (RRs), using random-effects models. Data were reanalysed in sensitivity analyses considering Knapp-Hartung method and Bayesian random-effects.
RESULTS
Six cohort studies were included. Overall, once-monthly 150 mg oral ibandronate reduced the risk of nonvertebral fractures (RR 0.84; 95% CI 0.76-0.94). Similar results were obtained when the comparison was restricted to once-monthly 150 mg risedronate, but no differences were found when the comparator was other oral bisphosphonates (weekly alendronate/risedronate). Ibandronate didn't significantly change the risk of hip fractures (RR 1.25; 95% CI 0.89-1.76). The risk of hip fracture was comparable between once monthly, 150 mg oral ibandronate and other oral bisphosphonates. Intravenous ibandronate was not effective in reducing hip fractures comparing to intravenous zoledronate. The low number of studies diminished the robustness of sensitivity analyses.
CONCLUSION
Results suggest that once-monthly 150 mg oral ibandronate may be as effective as other oral bisphosphonates in reducing the risk of nonvertebral fractures. However, uncertainty associated to the small number of included studies, which are characterized by heterogeneous demographics and methodologies, precluded definitive conclusions.
Topics: Female; Humans; Ibandronic Acid; Risedronic Acid; Bone Density Conservation Agents; Diphosphonates; Bayes Theorem; Osteoporosis; Hip Fractures; Osteoporosis, Postmenopausal; Observational Studies as Topic
PubMed: 38112890
DOI: 10.1007/s11096-023-01666-x -
Trials Dec 2023Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear...
Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial.
BACKGROUND
Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes.
METHODS
This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ - 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100-125 mg/dL, (ii) a 2-hour plasma glucose level of 140-199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7-6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months.
DISCUSSION
This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations.
TRIAL REGISTRATION
This study had been registered in the Chinese Clinical Trials Registry.
REGISTRATION NUMBER
ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn .
Topics: Female; Humans; Blood Glucose; Bone Density; Bone Density Conservation Agents; Denosumab; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Multicenter Studies as Topic; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Prediabetic State; Randomized Controlled Trials as Topic; RANK Ligand
PubMed: 38111052
DOI: 10.1186/s13063-023-07769-0 -
Frontiers in Endocrinology 2023Hormonal therapy (HT) blocks the hormone-mediated growth signal dramatically reducing estrogenic levels with aromatase inhibitors (AIs) becoming a crucial component of... (Observational Study)
Observational Study
The role of bone modifying agents for secondary osteoporosis prevention and pain control in post-menopausal osteopenic breast cancer patients undergoing adjuvant aromatase inhibitors.
INTRODUCTION
Hormonal therapy (HT) blocks the hormone-mediated growth signal dramatically reducing estrogenic levels with aromatase inhibitors (AIs) becoming a crucial component of the treatment mainstay in patients with early breast cancer (BC). Postmenopausal BC patients receiving HT present with a significant risk of secondary osteoporosis with AIs further reducing estrogen levels and ultimately leading to an accelerated rate of bone resorption and thus decreased bone mineral density (BMD). This was an observational retrospective clinical study that consecutively enrolled early BC patients with osteopenia to compare the impact of alendronate versus denosumab on secondary osteoporosis prevention and pain control.
METHODS
We identified two groups of patients treated with denosumab 60 mg by subcutaneous injection once every six months or alendronate 70 mg orally once a week. All the patients underwent a baseline physiatric evaluation (T0) and underwent a follow-up visit after 18 months (T1) together with femoral and vertebral Dual-Energy X-ray Absorptiometry (DEXA) exam evaluating T-Score marks. From September 2015 to December 2019 a total of 50 early (stage I-III) BC patients were considered eligible and consecutively enrolled in our study if they met pre-specified inclusion criteria.
RESULTS
In the entire observed population, the addition of treatment with alendronate or denosumab led to a significant T-score improvement at the lumbar spine level (-1.92 vs -1.52, p=0.03), with a comparable contribution from alendronate (-1.60 vs -1.45, p=0.07) and denosumab (-2.26 vs -1.58, p=0.07). Regarding the femoral region, neither alendronate (-0.98 vs -1.07, p=0.23) nor denosumab (-1.39 vs -1.34, p=0.81) were able to produce any statistically relevant effect. However, concerning pain control, BMAs had a significant impact on reducing NRS scoresin the general population (T1 3.94 vs. baseline 4.32, p=0.007), with a likelyspecific contribution from alendronate (T1 3.52 vs. baseline 3.88, p=0.004) compared to denosumab (T1 4.36 vs baseline 4.76, p=0.12), without any differences in analgesic therapy assumption over time (p=0.93).
DISCUSSION
Both alendronate and denosumab significantly contributed to preventing secondary osteoporosis in early BC patients with low BMD undergoing AIs, mostly at the lumbar spine level. Moreover, alendronate seemed to significantly impact pain control in such patients further supporting alendronate as a cost-effective option in this frail setting, although BMAs particularities should be carefully considered on an individual basis according to specific clinical contexts.
Topics: Female; Humans; Alendronate; Aromatase Inhibitors; Bone Density; Bone Density Conservation Agents; Breast Neoplasms; Denosumab; Osteoporosis; Pain; Postmenopause; Retrospective Studies
PubMed: 38075057
DOI: 10.3389/fendo.2023.1297950 -
AACE Clinical Case Reports 2023Osteogenesis imperfecta (OI) is a genetic disorder that affects type 1 collagen synthesis causing increased bone fragility, low bone mass, and skeletal deformity....
BACKGROUND/OBJECTIVE
Osteogenesis imperfecta (OI) is a genetic disorder that affects type 1 collagen synthesis causing increased bone fragility, low bone mass, and skeletal deformity. Bisphosphonates are recommended for treatment of OI patients; however, the efficacy of sclerostin inhibitors such as romosozumab has not been determined in OI patients with osteoporosis.
CASE REPORT
A 52-year-old G2P2 clinically diagnosed with OI, with a history of multiple fractures beginning in childhood presented with low bone mass. On physical examination, blue sclera was observed. She was previously treated with alendronate therapy from April 2014 to June 2015 without significant improvement in bone mineral density (BMD). After the onset of menopause, she began romosozumab 210 mg subcutaneous therapy once a month for 12 months. Repeat dual-energy X-ray absorptiometry showed an increase of 10.3% in BMD of the spine and a 5.4% increase in BMD of the right hip. The trabecular bone score increased by 5.2%.
DISCUSSION
Current literature is limited regarding the use of sclerostin inhibitors in OI patients. Our patient's improvement in BMD of the spine and right hip after romosozumab therapy was significant at a 95% confidence level, compared to treatment initiation. Her trabecular bone score also improved significantly. Six months into our patient's treatment course, a case in Japan of a male with severe osteoporotic OI and recurrent fractures showed improvement in BMD after romosozumab therapy.
CONCLUSION
This case highlights our patient's significant response to romosozumab and warrants further investigation of romosozumab as a potential treatment option for OI patients with osteoporosis.
PubMed: 38045794
DOI: 10.1016/j.aace.2023.10.002 -
Frontiers in Bioengineering and... 2023Electrospun composite nanofiber scaffolds are well known for their bone and tissue regeneration applications. This research is focused on the development of PVP and PVA...
Multifunctional electrospun nanofibrous scaffold enriched with alendronate and hydroxyapatite for balancing osteogenic and osteoclast activity to promote bone regeneration.
Electrospun composite nanofiber scaffolds are well known for their bone and tissue regeneration applications. This research is focused on the development of PVP and PVA nanofiber composite scaffolds enriched with hydroxyapatite (HA) nanoparticles and alendronate (ALN) using the electrospinning technique. The developed nanofiber scaffolds were investigated for their physicochemical as well as bone regeneration potential. The results obtained from particle size, zeta potential, SEM and EDX analysis of HA nanoparticles confirmed their successful fabrication. Further, SEM analysis verified nanofiber's diameters within 200-250 nm, while EDX analysis confirmed the successful incorporation of HA and ALN into the scaffolds. XRD and TGA analysis revealed the amorphous and thermally stable nature of the nanofiber composite scaffolds. Contact angle, FTIR analysis, Swelling and biodegradability studies revealed the hydrophilicity, chemical compatibility, suitable water uptake capacity and increased degradation making it appropriate for tissue regeneration. The addition of HA into nanofiber scaffolds enhanced the physiochemical properties. Additionally, hemolysis cell viability, cell adhesion and proliferation by SEM as well as confocal microscopy and live/dead assay results demonstrated the non-toxic and biocompatibility behavior of nanofiber scaffolds. Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) assays demonstrated osteoblast promotion and osteoclast inhibition, respectively. These findings suggest that developed HA and ALN-loaded PVP/PVA-ALN-HA nanofiber composite scaffolds hold significant promise for bone regeneration applications.
PubMed: 38026845
DOI: 10.3389/fbioe.2023.1302594