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Journal of Bone and Mineral Metabolism May 2024The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk.
MATERIALS AND METHODS
Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD.
RESULTS
A total of 559 participants were selected. BMD ≥ -2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD.
CONCLUSION
During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.
Topics: Humans; Alendronate; Female; Teriparatide; Bone Density; Aged; Middle Aged; Bone Density Conservation Agents; Japan; Osteoporosis; Osteoporosis, Postmenopausal; Spinal Fractures; Lumbar Vertebrae; East Asian People
PubMed: 38755328
DOI: 10.1007/s00774-024-01515-5 -
Bioactive Materials Sep 2024Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis...
Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.
PubMed: 38846529
DOI: 10.1016/j.bioactmat.2024.05.037 -
Materials Today. Bio Jun 2024Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance...
Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance the healing of bone defects through the synergistic regulation of osteogenesis and osteoclastogenesis is still a challenging task in the field of bone tissue engineering. The aim of this study was to create a dual-drug release-based core-shell nanofibers with the intent of achieving a time-controlled release to facilitate bone regeneration. We fabricated core-shell P/PCL nanofibers using coaxial electrospinning, where alendronate (ALN) was incorporated into the core layer and hydroxyapatite (HA) into shell. The surface of the nanofiber construct was further modified with mussel-derived polydopamine (PDA) to induce hydrophilicity and enhance cell interactions. Surface characterizations confirmed the successful synthesis of PDA@PHA/PCL-ALN nanofibers endowed with excellent mechanical strength (20.02 ± 0.13 MPa) and hydrophilicity (22.56°), as well as the sustained sequential release of ALN and Ca ions. experiments demonstrated that PDA-functionalized core-shell PHA/PCL-ALN scaffolds possessed excellent cytocompatibility, enhanced cell adhesion and proliferation, alkaline phosphatase activity and osteogenesis-related genes. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity and osteoclastogenesis-related gene expression. After 12-week of implantation, it was observed that PDA@PHA/PCL-ALN nanofiber scaffolds, in a rat cranial defect model, significantly promoted bone repair and regeneration. Microcomputed tomography, histological examination, and immunohistochemical analysis collectively demonstrated that the PDA-functionalized core-shell PHA/PCL-ALN scaffolds exhibited exceptional osteogenesis-inducing and osteoclastogenesis-inhibiting effects. Finally, it may be concluded from our results that the bio-inspired surface-functionalized multifunctional, biomimetic and controlled release core-shell nanofiber provides a promising strategy to facilitate bone healing.
PubMed: 38779556
DOI: 10.1016/j.mtbio.2024.101088 -
ACS Omega Jan 2024Titanium nanotube (TNT) arrays manufactured via electrochemical anodization have been widely used as local drug carriers due to their excellent biocompatibility and...
Titanium nanotube (TNT) arrays manufactured via electrochemical anodization have been widely used as local drug carriers due to their excellent biocompatibility and customizable nanotubular structures. However, the uncontrollable and abrupt drug release at the early stage decreases the drug release duration, leading to excessive drug concentration at the implantation site. In this study, a continuous drug delivery system based on TNTs was created. Initially, a basic ultrasound-assisted approach was utilized to deposit a polydopamine (PDA) coating onto TNTs to obtain PDA-modified TNTs. Next, TNTs-PDA were submerged in a calcium chloride solution to include Ca through Ca coordination between the PDA layer's catechol groups. Sodium alendronate (NaAL) was used as a model drug and loaded onto TNTs-PDA-Ca by immersing them in an NaAL solution. In the final step, NaAL was covalently attached to TNTs-PDA-Ca through coordination bonds with Ca. The samples underwent characterization through the use of various techniques, including field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction patterning, X-ray photoelectron spectroscopy, and inductively coupled plasma emission spectrometry. The results indicated that the bioactivity of TNTs improved, and there was an enhancement in drug loading capacity and release performance due to modification with PDA and Ca. Furthermore, acidic conditions can cause significant drug release due to the cleavage of coordination bonds between the drug and Ca ions. Thus, the aforementioned drug delivery system represents a potentially promising approach for achieving sustained and controllable drug release.
PubMed: 38313478
DOI: 10.1021/acsomega.3c08772 -
Bone Reports Jun 2024This study aimed to analyze the current medication treatment status for women with osteoporosis (OP) based on real-world prescription data from 2016 to 2021 in Chinese...
PURPOSE
This study aimed to analyze the current medication treatment status for women with osteoporosis (OP) based on real-world prescription data from 2016 to 2021 in Chinese nine cities' tertiary Grade A hospital and systematically describe the medication treatment patterns in women with OP.
METHODS
Prescription information for female OP patients in nine cities (Beijing, Shanghai, Guangzhou, Hangzhou, Tianjin, Zhengzhou, Chengdu, Shenyang, Harbin) was extracted from the Hospital Prescription Analysis Collaboration Project Database of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. Statistical analysis was conducted to evaluate demographic characteristics and medication treatment patterns.
RESULTS
A total of 669,505 prescriptions for medication treatment of female OP patients were included in this study. The majority of patients were aged 60 to 99 years (69.79 %) followed by 50 to 59 years (18.81 %) and 40 to 49 years (6.69 %). Geographically, the highest concentration of patients was in North China (Beijing, Tianjin) (43.05 %) followed by East China (Shanghai, Hangzhou) (31.43 %). The top three prescribed medications were active vitamin D and its analogs (40.78 %), calcium supplements (32.51 %), and bisphosphonates (18.75 %). The prescription frequency of menopausal hormone therapy (MHT) was 0.31 %. The proportion of female OP patients receiving monotherapy and two drug combinations therapy is equivalent (about 37 %).
CONCLUSION
The diagnosis and treatment of female OP patients in China showed regional variations. The most commonly prescribed medications for this population were calcitriol, calcium carbonate with vitamin D3, and alendronate sodium with vitamin D3. The use of MHT was relatively limited.
PubMed: 38939472
DOI: 10.1016/j.bonr.2024.101778 -
Hip & Pelvis Mar 2024We report on the case of a 52-year-old female who presented with a stress fracture after undergoing an endoscopic resection of the lesser trochanter in ischiofemoral...
We report on the case of a 52-year-old female who presented with a stress fracture after undergoing an endoscopic resection of the lesser trochanter in ischiofemoral impingement, which was resistant to maximal conservative treatment. To the best of our knowledge, this complication has not been previously described. Non-weight-bearing and intravenous alendronic acid were prescribed for management. No additional surgery was required. The patient was pain free with the ability to perform sports on the same level as before and had no complaints.
PubMed: 38420740
DOI: 10.5371/hp.2024.36.1.70 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Feb 2024To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of...
[Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages].
OBJECTIVE
To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs.
METHODS
Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated.
RESULTS
This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant ( < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance ( < 0.001).
CONCLUSION
The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.
Topics: Male; Humans; Female; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Zoledronic Acid; Mandible; Sutures; Diphosphonates
PubMed: 38318896
DOI: 10.19723/j.issn.1671-167X.2024.01.009 -
PloS One 2024Pretargeting, which is the separation of target accumulation and the administration of a secondary imaging agent into two sequential steps, offers the potential to...
Pretargeting, which is the separation of target accumulation and the administration of a secondary imaging agent into two sequential steps, offers the potential to improve image contrast and reduce radiation burden for nuclear imaging. In recent years, the tetrazine ligation has emerged as a promising approach to facilitate covalent pretargeted imaging due to its unprecedented kinetics and bioorthogonality. Pretargeted bone imaging with TCO-modified alendronic acid (Aln-TCO) is an attractive model that allows the evaluation of tetrazines in healthy animals without the need for complex disease models or targeting regimens. Recent structure-activity relationship studies of tetrazines evaluated important parameters for the design of potent tetrazine-radiotracers for pretargeted imaging. However, limited information is available for 99mTc-labeled tetrazines. In this study, four tetrazines intended for labeling with fac-[99mTc(OH2)3 (CO)3]+ were synthesized and evaluated using an Aln-TCO mouse model. 3,6-bis(2-pyridyl)-1,2,4,5-Tz without additional linker showed higher pretargeted bone uptake and less background activity compared to the same scaffold with a PEG8 linker or 3-phenyl-1,2,4,5-Tz-based compounds. Additionally, improved bone/blood ratios were observed in pretargeted animals compared to animals receiving directly labeled Aln-TCO. The results of this study implicate 3,6-bis(2-pyridyl)-1,2,4,5-Tz as a promising scaffold for potential 99mTc-labeled tetrazines.
Topics: Animals; Mice; Tomography, X-Ray Computed; Tomography, Emission-Computed, Single-Photon; Heterocyclic Compounds; Cell Line, Tumor; Radiopharmaceuticals; Positron-Emission Tomography
PubMed: 38626058
DOI: 10.1371/journal.pone.0300466 -
Molecules (Basel, Switzerland) May 2024Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in...
Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.
Topics: Micelles; Cholecalciferol; Nanostructures; Bone and Bones; Alendronate; Polyethylene Glycols; Humans; Drug Delivery Systems; Luminescence; Nanoparticles; Drug Carriers; Quantum Dots
PubMed: 38792228
DOI: 10.3390/molecules29102367 -
Materials Today. Bio Jun 2024Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic...
Injectable and high-strength PLGA/CPC loaded ALN/MgO bone cement for bone regeneration by facilitating osteogenesis and inhibiting osteoclastogenesis in osteoporotic bone defects.
Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg (from nMgO) and Ca (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN . Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects . Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.
PubMed: 38873105
DOI: 10.1016/j.mtbio.2024.101092