Journal articles on the topic 'Bone fracture targeted drugs'
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1
De Martinis, Massimo, Maria Maddalena Sirufo, and Lia Ginaldi. "Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints." Current Medicinal Chemistry 27, no. 37 (November 6, 2020): 6356–72. http://dx.doi.org/10.2174/0929867326666190730113123.
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: Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Currently, there are basically two monoclonal antibodies for osteoporosis therapy: denosumab and romosozumab. Here, we focus on the modern approach to the osteoporosis management and in particular, on current and developing biologic drugs targeted to new immunological checkpoints, in the landscape of osteoimmunology.
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Hampson, Geeta, Grahame J. Elder, Martine Cohen-Solal, and Bo Abrahamsen. "A review and perspective on the assessment, management and prevention of fragility fractures in patients with osteoporosis and chronic kidney disease." Endocrine 73, no. 3 (May 11, 2021): 509–29. http://dx.doi.org/10.1007/s12020-021-02735-9.
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AbstractThis article aims to review the methods used for the assessment of fracture risk and the use of osteoporosis medications for fracture prevention in the population with CKD, and highlights the difficulties faced by clinicians in the management of these patients and the latest recommendations and guidelines. Chronic kidney disease (CKD) and osteoporosis often co-exist in older adults, and they present a major healthcare challenge. CKD mineral and bone disorder (CKD-MBD) occurs as renal function declines and this syndrome affects most patients in CKD stages 4 and 5. The biochemical abnormalities of CKD-MBD, renal bone disease and risk factors associated with age-related bone loss and osteoporosis lead to a cumulative effect on fracture risk and mortality. There is a need for routine evaluation of fracture risk and fracture prevention in this population. Measurement of bone mineral density (BMD) and the use of the FRAX tool have predictive value for incident fractures in the general population and in CKD. This enables physicians to identify CKD patients most at risk of sustaining a fragility fracture and allows a more targeted approach to fracture prevention. Data analysis from the pivotal trials of therapeutic agents used in osteoporosis show that these drugs can be considered in mild and moderate CKD (stages 1–3 CKD). Off-label drug use in patients with CKD-MBD and more severe renal impairment (CKD stages 4 and 5) could offer significant benefits to sub-groups of patients when carefully tailored to each individual’s bone turnover and calcium and phosphate balance. However, this requires a selective approach and treatment decisions based on inference from pathophysiology while we await further trials. Guidelines advocate the correction and/or reduction of the biochemical abnormalities of CKD-MBD before initiation of treatment with osteoporosis drugs and close monitoring during treatment.
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Adjei, Isaac, Madison Temples, Shannon Brown, and Blanka Sharma. "Targeted Nanomedicine to Treat Bone Metastasis." Pharmaceutics 10, no. 4 (October 25, 2018): 205. http://dx.doi.org/10.3390/pharmaceutics10040205.
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Bone metastases are common complications of solid tumors, particularly those of the prostate, breast, and lungs. Bone metastases can lead to painful and devastating skeletal-related events (SREs), such as pathological fractures and nerve compressions. Despite advances in treatment for cancers in general, options for bone metastases remain inadequate and generally palliative. Anticancer drugs (chemotherapy and radiopharmaceuticals) do not achieve therapeutic concentrations in the bone and are associated with dose-limiting side effects to healthy tissues. Nanomedicines, with their tunable characteristics, have the potential to improve drug targeting to bone metastases while decreasing side effects for their effective treatment. In this review, we present the current state of the art for nanomedicines to treat bone metastases. We also discuss new treatment modalities enhanced by nanomedicine and their effects on SREs and disease progression.
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Ferracini, Riccardo, Isabel Martínez Herreros, Antonio Russo, Tommaso Casalini, Filippo Rossi, and Giuseppe Perale. "Scaffolds as Structural Tools for Bone-Targeted Drug Delivery." Pharmaceutics 10, no. 3 (August 8, 2018): 122. http://dx.doi.org/10.3390/pharmaceutics10030122.
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Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair of large bone defects resulting from resection, trauma or non-union fractures still requires the implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial bones, synthetic substitutes and organ implants. In particular, recent advances in materials science have provided several innovations, underlying the increasing importance of biomaterials in this field. To address the increasing need for improved bone substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from organic or inorganic materials, incorporating drugs and growth factors, to induce new bone tissue formation. This review emphasizes recent progress in materials science that allows reliable scaffolds to be synthesized for targeted drug delivery in bone regeneration, also with respect to past directions no longer considered promising. A general overview concerning modeling approaches suitable for the discussed systems is also provided.
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Salave, Sagar, Dhwani Rana, and Derajram Benival. "Peptide Functionalised Nanocarriers for Bone Specific Delivery of PTH (1-34) in Osteoporosis." Current Nanomedicine 11, no. 3 (September 2021): 142–48. http://dx.doi.org/10.2174/2468187312666211220112324.
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: Osteoporosis represents a major public health burden especially considering the aging population worldwide. Treatment modalities for osteoporosis are classified into two categories based on the effect on bone remodelling: anabolic drugs and antiresorptive drugs. Anabolic drugs are preferred as it stimulates new bone formation. Currently, PTH (1-34) is the only peptide-based drug approved as an anabolic agent for the treatment of osteoporosis by both USFDA as well as EMA. However, its non-specific delivery results in prolonged kidney exposure, causing hypercalcemia. Nanotechnology-based drug delivery systems functionalized by conjugating it with homing moieties, such as peptides, offer an advantage of targeted delivery with reduced off-target effects. Here, we propose an innovative and targeted nanovesicle approach to efficiently deliver PTH (1-34) to the bone surface using peptides as a homing moiety. The proposed innovative delivery approach will augment the specific interaction between the drug and bone surface without producing side effects. This will reduce the off-target effects of PTH (1-34), and at the same time, it will also improve the outcome of anabolic therapy. Therefore, we postulate that the proposed innovative drug delivery approach for PTH (1-34) will establish as a promising therapy for osteoporotic patients, specifically in postmenopausal women who are at greater risk of bone fracture.
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Harris, Kira B., Kimberly L. Nealy, Delilah J. Jackson, and Phillip L. Thornton. "The Clinical Use of Denosumab for the Management of Low Bone Mineral Density in Postmenopausal Women." Journal of Pharmacy Practice 25, no. 3 (May 1, 2012): 310–18. http://dx.doi.org/10.1177/0897190012442061.
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Osteoporosis is a leading cause of debility and declining quality of life in postmenopausal women worldwide. Treatment of osteoporosis has been ubiquitous throughout the developed world since the mid-1990s, most notably with the introduction of bisphosphonates in 1995. Nonetheless, the incidence of hip fractures increased by 25% between 1990 and 2000, despite advances in osteoporosis therapy. Studies indicate that bone density increases over the first 3 years of bisphosphonate therapy and then plateaus or perhaps even declines, placing these patients at greater risk of fracture. Since hip fractures are associated with increased morbidity, mortality, and increased cost of health care, improvements in treating osteoporosis are critical. Denosumab is a novel monoclonal antibody targeted against the receptor activator of nuclear factor-κB ligand (RANKL) that inhibits osteoclast activity. Initial data suggest that denosumab increases bone mineral density for greater than 3 years. Of greater importance, denosumab has been shown to decrease vertebral fractures by 68%, nonvertebral fractures by 19%, and hip fractures by 42% for at least 36 months. Data also indicate that the safety profile of denosumab is equivalent to other drugs used in osteoporosis management, but potential risks of immunosuppression and cancer have been hypothesized.
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Genah, Shirley, Monica Monici, and Lucia Morbidelli. "The Effect of Space Travel on Bone Metabolism: Considerations on Today’s Major Challenges and Advances in Pharmacology." International Journal of Molecular Sciences 22, no. 9 (April 27, 2021): 4585. http://dx.doi.org/10.3390/ijms22094585.
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Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue homeostasis in microgravity is its capacity to regenerate following fractures due to weakening of the tissue and accidental events during the accomplishment of particularly dangerous tasks. Today, several pharmacological and non-pharmacological countermeasures to this problem have been proposed, including physical exercise, diet supplements and administration of antiresorptive or anabolic drugs. However, each class of pharmacological agents presents several limitations as their prolonged and repeated employment is not exempt from the onset of serious side effects, which limit their use within a well-defined range of time. In this review, we will focus on the various countermeasures currently in place or proposed to address bone loss in conditions of microgravity, analyzing in detail the advantages and disadvantages of each option from a pharmacological point of view. Finally, we take stock of the situation in the currently available literature concerning bone loss and fracture healing processes. We try to understand which are the critical points and challenges that need to be addressed to reach innovative and targeted therapies to be used both in space missions and on Earth.
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Henriksen, K., DJ Leeming, C. Christiansen, and MA Karsdal. "Use of Bone Turnover Markers in Clinical Osteoporosis Assessment in Women: Current Issues and Future Options." Women's Health 7, no. 6 (November 2011): 689–98. http://dx.doi.org/10.2217/whe.11.74.
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Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the last 20 years, biochemical markers of bone turnover have been implemented to a larger degree, and especially within the field of drug development. Numerous clinical studies have underscored that the markers have promise in terms of predicting patients at high risk of losing bone, future fracture events and importantly also the fracture efficacy of drugs in development. Furthermore, while classical methods often require years to monitor the changes, the bone turnover markers do so within a shorter time span. The aims of this article are to provide an update on the different biochemical markers of bone turnover, and to give an overview of their applications in epidemiological and clinical research especially in women. The main emphasis will be on their utility in clinical trials testing the efficacy of drugs for the treatment of osteoporosis, and their ability to supplement bone mass measurements. Finally, recent evidence suggests that biochemical markers may provide information on bone age that may indirectly relate to bone quality, and this is discussed together with future possibilities for measuring bone quality using bone turnover markers. In summary, a more targeted use of biomarkers could assist in the identification of high-risk patients, the process of drug discovery and monitoring of the efficacy of osteoporosis treatment in clinical settings.
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Brailova, N. V., V. A. Kuznetsova, E. N. Dudinskaya, and O. N. Tkacheva. "Aging bone." Russian Journal of Geriatric Medicine, no. 2 (May 26, 2020): 147–53. http://dx.doi.org/10.37586/2686-8636-2-2020-147-153.
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This review article deals with the topic of changes in bone tissue in the process of aging of the body. Adipogenesis and osteogenesis are affected at the molecular level, proteins and genes are described, in which somatic mutation can occur during the aging process, resulting in both minor changes and an active loss of bone mineral density. The factors that affect the change in bone mineral density mainly in the elderly, and existing drugs that can slow down osteoporosis are listed. Knowledge of the cellular and molecular mechanisms underlying the aging of bone tissue will contribute to the creation of targeted therapy for osteoporosis, which slows down bone aging and prevents falls and fractures in the elderly people.
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Andrews, Rebecca E., Janet E. Brown, Michelle A. Lawson, and Andrew D. Chantry. "Myeloma Bone Disease: The Osteoblast in the Spotlight." Journal of Clinical Medicine 10, no. 17 (September 2, 2021): 3973. http://dx.doi.org/10.3390/jcm10173973.
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Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a downregulation of bone formation (via reduced osteoblast (OB) activity), leading to phenotypic osteolysis. Treatments are limited, and currently exclusively target OCs. Despite existing bone targeting therapies, patients successfully achieving remission from their cancer can still be left with chronic pain, poor mobility, and reduced quality of life as a result of bone disease. As such, the field is desperately in need of new and improved bone-modulating therapeutic agents. One such option is the use of bone anabolics, drugs that are gaining traction in the osteoporosis field following successful clinical trials. The prospect of using these therapies in relation to myeloma is an attractive option, as they aim to stimulate OBs, as opposed to existing therapeutics that do little to orchestrate new bone formation. The preclinical application of bone anabolics in myeloma mouse models has demonstrated positive outcomes for bone repair and fracture resistance. Here, we review the role of the OB in the pathophysiology of myeloma-induced bone disease and explore whether novel OB targeted therapies could improve outcomes for patients.
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Rothe, Rebecca, Sandra Hauser, Christin Neuber, Markus Laube, Sabine Schulze, Stefan Rammelt, and Jens Pietzsch. "Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches." Pharmaceutics 12, no. 5 (May 6, 2020): 428. http://dx.doi.org/10.3390/pharmaceutics12050428.
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Bone defects of critical size after compound fractures, infections, or tumor resections are a challenge in treatment. Particularly, this applies to bone defects in patients with impaired bone healing due to frequently occurring metabolic diseases (above all diabetes mellitus and osteoporosis), chronic inflammation, and cancer. Adjuvant therapeutic agents such as recombinant growth factors, lipid mediators, antibiotics, antiphlogistics, and proangiogenics as well as other promising anti-resorptive and anabolic molecules contribute to improving bone healing in these disorders, especially when they are released in a targeted and controlled manner during crucial bone healing phases. In this regard, the development of smart biocompatible and biostable polymers such as implant coatings, scaffolds, or particle-based materials for drug release is crucial. Innovative chemical, physico- and biochemical approaches for controlled tailor-made degradation or the stimulus-responsive release of substances from these materials, and more, are advantageous. In this review, we discuss current developments, progress, but also pitfalls and setbacks of such approaches in supporting or controlling bone healing. The focus is on the critical evaluation of recent preclinical studies investigating different carrier systems, dual- or co-delivery systems as well as triggered- or targeted delivery systems for release of a panoply of drugs.
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Qiao, Rui-qi, Hao-Ran Zhang, Rong-Xing Ma, Rui-feng Li, and Yong-cheng Hu. "Prognostic Factors for Bone Survival and Functional Outcomes in Patients With Breast Cancer Spine Metastases." Technology in Cancer Research & Treatment 21 (January 2022): 153303382211226. http://dx.doi.org/10.1177/15330338221122642.
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According to the Global Cancer Statistics 2020 report, breast cancer is the most commonly diagnosed cancer worldwide. Patients with mammary cancer live longer due to the continuous optimization of chemotherapy, targeted drugs, and hormone therapy, which will inevitably lead to an increase in the prevalence of metastatic bone tumors. Bone metastasis affects approximately 8% of patients with mammary cancer, with the spine being the most common site. Metastatic neoplasms can invade the centrum and its attachments, leading to local pain, spinal instability, vertebral pathological fractures, spinal cord compression, impaired neurological function, and paralysis, ultimately reducing the quality of life. Multidisciplinary and personalized management using analgesic drugs, endocrine therapy, corticosteroid therapy, chemotherapy, bisphosphonates, immunotherapy, targeted drugs, radiotherapy, and surgery has been advocated for the treatment of spinal metastases. Multiple paradigms and systems have been proposed to determine suitable treatments. In the early stages, the occurrence of metastasis indicates a terminal stage of the tumor process in patients with malignant tumors, implying that their lifespan is limited. As a result, the choice of treatment is heavily influenced by longevity. However, with the development of treatment methods, the lifespan of patients with tumors has considerably increased in recent years. This leads to the choice of patient’s treatment, which depends not only on the patient’s survival, but also on the radiotherapy or postoperative functional outcomes. Nevertheless, they fall short of determining the variables that affect survival and functional outcomes in histology-specific subgroups of breast cancer. To accurately predict the bone survival and functional outcomes of patients with breast cancer spine metastases a review of prognostic factors was performed.
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Yakushevskaya, O. V. "Potential protective effect of zoledronic acid when switching from long-term therapy of osteoporosis with denosumab." Meditsinskiy sovet = Medical Council, no. 21 (January 17, 2021): 185–91. http://dx.doi.org/10.21518/2079-701x-2020-21-185-191.
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In accordance with the data of the Federal Clinical Recommendations for the Diagnosis, Treatment and Prevention of Osteoporosis, with the latter, antiresorptive drugs (denosumab, bisphosphonates) are used, which mainly suppress bone resorption, and anabolic compounds (teriparatide), which enhance bone formation. The vector of their pharmacological effect helps to prevent BMD loss and significantly reduces the risk of low-energy vertebral fractures and fractures of other localizations. The experience of clinical trials makes it possible to successfully carry out antiresorptive therapy with some drugs (denosumab) for up to 10 years, demonstrating good adherence and tolerance. Bisphosphonates remain in the bone matrix for a long time and are characterized by a period of a certain aftereffect. Denosumab and teriparatide show their effect only during the period of direct use. According to some data, when denosumab therapy is canceled in a situation where the targeted goal is achieved, the incidence of vertebral fractures increases, especially in patients with a history of low-traumatic fractures. The article will present the main provisions of the European Calcified Tissues Society, the European Medical Agency, the Russian Association for Osteoporosis regarding the timing of treatment and an analysis of clinical situations requiring the appointment of alternative antiresorptive therapy. According to the resolution of the Council of Experts of the Russian Association on Osteoporosis, bisphosphonates are recommended for all patients to prevent an increased risk of vertebral fractures 6 months after patients had their last subcutaneous injection of denosumab. Oral bisphosphonates should be taken immediately, and zoledronic acid injection should be delayed for another 65 days following a missed denosumab injection.
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Zhao, Xuefeng, Peng Deng, Ramiro Iglesias-Bartolome, Panomwat Amornphimoltham, Dana J. Steffen, Yunyun Jin, Alfredo A. Molinolo, et al. "Expression of an active Gαs mutant in skeletal stem cells is sufficient and necessary for fibrous dysplasia initiation and maintenance." Proceedings of the National Academy of Sciences 115, no. 3 (December 27, 2017): E428—E437. http://dx.doi.org/10.1073/pnas.1713710115.
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Fibrous dysplasia (FD) is a disease caused by postzygotic activating mutations of GNAS (R201C and R201H) that encode the α-subunit of the Gs stimulatory protein. FD is characterized by the development of areas of abnormal fibroosseous tissue in the bones, resulting in skeletal deformities, fractures, and pain. Despite the well-defined genetic alterations underlying FD, whether GNAS activation is sufficient for FD initiation and the molecular and cellular consequences of GNAS mutations remains largely unresolved, and there are no currently available targeted therapeutic options for FD. Here, we have developed a conditional tetracycline (Tet)-inducible animal model expressing the GαsR201C in the skeletal stem cell (SSC) lineage (Tet–GαsR201C/Prrx1-Cre/LSL-rtTA-IRES-GFP mice), which develops typical FD bone lesions in both embryos and adult mice in less than 2 weeks following doxycycline (Dox) administration. Conditional GαsR201C expression promoted PKA activation and proliferation of SSCs along the osteogenic lineage but halted their differentiation to mature osteoblasts. Rather, as is seen clinically, areas of woven bone admixed with fibrous tissue were formed. GαsR201C caused the concomitant expression of receptor activator of nuclear factor kappa-B ligand (Rankl) that led to marked osteoclastogenesis and bone resorption. GαsR201C expression ablation by Dox withdrawal resulted in FD-like lesion regression, supporting the rationale for Gαs-targeted drugs to attempt FD cure. This model, which develops FD-like lesions that can form rapidly and revert on cessation of mutant Gαs expression, provides an opportunity to identify the molecular mechanism underlying FD initiation and progression and accelerate the development of new treatment options.
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Abdelsamie, Ahmed S., Steven Herath, Yannik Biskupek, Carsten Börger, Lorenz Siebenbürger, Mohamed Salah, Claudia Scheuer, et al. "Targeted Endocrine Therapy: Design, Synthesis, and Proof-of-Principle of 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors in Bone Fracture Healing." Journal of Medicinal Chemistry 62, no. 3 (January 15, 2019): 1362–72. http://dx.doi.org/10.1021/acs.jmedchem.8b01493.
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Raoul, Jean-Luc, Julien Edeline, Victor Simmet, Camille Moreau-Bachelard, Marine Gilabert, and Jean-Sébastien Frénel. "Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper." Cancers 14, no. 5 (February 24, 2022): 1156. http://dx.doi.org/10.3390/cancers14051156.
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Multikinase inhibitors (MKIs), and particularly tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs), are currently some of the major breakthroughs in cancer treatment. Proton pump inhibitors (PPIs) revolutionised the treatment of acid-related diseases, but are frequently overused for epigastric pain or heartburn. However, long-term acid suppression from using PPIs may lead to safety concerns, and could have a greater impact in cancer patients undergoing therapy, like bone fractures, renal toxicities, enteric infections, and micronutrient deficiencies (iron and magnesium). Moreover, acid suppression may also affect the pharmacokinetics of drugs (at least during acid suppression) and decrease the absorption of many molecularly-targeted anticancer therapies, which are mostly weak bases with pH-dependent absorption. This type of drug-drug interaction may have detrimental effects on efficacy, with major clinical impacts described for some orally administrated targeted therapies (erlotinib, gefitinib, pazopanib, palbociclib), and conflicting results with many others, including capecitabine. Furthermore, the long-term use of PPIs results in severe alterations to the gut microbiome and recent retrospective analyses have shown that the benefit of using CPIs was suppressed in patients treated with PPIs. These very expensive drugs are of great importance because of their efficacy. As the use of PPIs is not essential, we must apply the precautionary principle. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician.
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Vittrup, Sofus Ørbæk, Pelle Hanberg, Martin Bruun Knudsen, Sara Kousgaard Tøstesen, Josephine Olsen Kipp, Jakob Hansen, Nis Pedersen Jørgensen, Maiken Stilling, and Mats Bue. "Tibial bone and soft-tissue concentrations following combination therapy with vancomycin and meropenem – evaluated by microdialysis in a porcine model." Bone & Joint Research 11, no. 2 (February 1, 2022): 112–20. http://dx.doi.org/10.1302/2046-3758.112.bjr-2021-0321.r1.
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Aims Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem. Methods Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results Across the targeted ECOFF values, vancomycin displayed longer T > MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T > MIC. For the low MIC targets and across compartments, mean T > MIC ranged between 208 and 449 minutes (46% to 100%) for vancomycin and between 189 and 406 minutes (42% to 90%) for meropenem. For the high MIC targets, mean T > MIC ranged between 30 and 446 minutes (7% to 99%) for vancomycin and between 45 and 181 minutes (10% to 40%) for meropenem. Conclusion The differences in the T > MIC between the low and high targets illustrate how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contamination, or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T > MIC in all the exposed tissues, and thereby lower the risk of acquiring an infection after open tibial fractures. Cite this article: Bone Joint Res 2022;11(2):112–120.
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Chen, Jia-Feng, Chung-Yuan Hsu, Shan-Fu Yu, Chi-Hua Ko, Wen-Chan Chiu, Han-Ming Lai, Ying-Chou Chen, Yu-Jih Su, and Tien-Tsai Cheng. "The impact of long-term biologics/target therapy on bone mineral density in rheumatoid arthritis: a propensity score-matched analysis." Rheumatology 59, no. 9 (January 25, 2020): 2471–80. http://dx.doi.org/10.1093/rheumatology/kez655.
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Abstract Objectives To investigate changes in BMD in RA patients receiving 3-year biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or conventional synthetic DMARD (csDMARD). Methods Patients with RA were recruited from September 2014 until March 2019. Clinical characteristics, BMD and evidence of fragility fractures at enrolment were documented. Participants were treated according to the National Institute for Health and Care Excellence (NICE) guidelines over a 3-year observation period. Repeated BMD was measured at the end of the study period. Participants were grouped into those receiving b/tsDMARD or csDMARD and by propensity score matching (1:2). Results A total of 388 participants completed the 3-year follow-up. After propensity score matching, 92 and 184 participants were allocated to the b/tsDMARD (Group I) and csDMARD (Group II), respectively. After 3 years, BMD remained stable at the femoral neck (FN), hip (total) (TH) and lumbar vertebra (L1-4) (P =0.09, 0.15, 0.87) in Group I. However, BMD decreased significantly in Group II (P=0.045, <0.001, 0.004) at corresponding sites. Participants receiving combined b/tsDMARD and anti-osteoporosis therapy experienced a greater BMD preserving effect than other subgroups. Conclusion Long-term b/tsDMARDs therapy had protective effects on bone loss for patients with RA. Patients receiving concomitant anti-osteoporosis therapy and b/tsDMARDs therapy experienced the greatest BMD preserving effect.
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Feng, Site, Jiahao Li, Jingjing Tian, Sheng Lu, and Yu Zhao. "Application of Single-Cell and Spatial Omics in Musculoskeletal Disorder Research." International Journal of Molecular Sciences 24, no. 3 (January 23, 2023): 2271. http://dx.doi.org/10.3390/ijms24032271.
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Musculoskeletal disorders, including fractures, scoliosis, heterotopic ossification, osteoporosis, osteoarthritis, disc degeneration, and muscular injury, etc., can occur at any stage of human life. Understanding the occurrence and development mechanism of musculoskeletal disorders, as well as the changes in tissues and cells during therapy, might help us find targeted treatment methods. Single-cell techniques provide excellent tools for studying alterations at the cellular level of disorders. However, the application of these techniques in research on musculoskeletal disorders is still limited. This review summarizes the current single-cell and spatial omics used in musculoskeletal disorders. Cell isolation, experimental methods, and feasible experimental designs for single-cell studies of musculoskeletal system diseases have been reviewed based on tissue characteristics. Then, the paper summarizes the latest findings of single-cell studies in musculoskeletal disorders from three aspects: bone and ossification, joint, and muscle and tendon disorders. Recent discoveries about the cell populations involved in these diseases are highlighted. Furthermore, the therapeutic responses of musculoskeletal disorders, especially single-cell changes after the treatments of implants, stem cell therapies, and drugs are described. Finally, the application potential and future development directions of single-cell and spatial omics in research on musculoskeletal diseases are discussed.
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Jagessar, RC. "Nanotechnology and Nanoparticles in Contemporary Sciences." Journal of Nanosciences Research & Reports 3, no. 1 (March 31, 2021): 1–7. http://dx.doi.org/10.47363/jnsrr/2021(3)118.
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Nonotechanology has been a rapidly growing field of advanced science at the inception of this century. Many problematic endeavours in sciences have been successfully overcome using nanoparticles. For example, a low risk solution using antibody modified bismuth nanoparticle, in combination with an X-ray dose equivalent to a chest X-ray specifically, has been shown to kill the common bacterium Pseudomonas aeruginosa in a set up designed to resemble a deep wound in human tissue. Nanosized gold particle could catalyse the oxidation of carbon monoxide better than anything previously known. Heparin functionalized nanoparticles have been use for targeted delivery of anti-malarial drugs. Heparin is abundant and cheap compared to treatments that involve antibodies, an important consideration, since malaria is most common in developing countries. A bone repairing nano-particle paste has been developed that promises faster repair of fractures and breakages. DNA containing two growth genes is encapsulated inside synthetic calcium phosphate nanoparticles. In a remarkable demonstration of the extreme limits of nanoscale engineering, researchers have used the tip of a scanning tunnelling microscope to cleave and form selected chemical bonds in a complex molecule. Many medicinal and industrial endeavours have seen the use of Nanotechnology. These and other more recent advances in nanotechnology will be presented at this conference
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Soldatos, Theodoros G., Ioannis Iakovou, and Christos Sachpekidis. "Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data." Medicina 55, no. 5 (May 16, 2019): 149. http://dx.doi.org/10.3390/medicina55050149.
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Background and Objective: Radium-223 dichloride (Xofigo®) is a calcium mimetic agent approved for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. This targeted, α-particle-emitting therapy has demonstrated significant survival benefit accompanied by a favorable safety profile. Nevertheless, recent evidence suggests that its combined use with abiraterone and prednisone/prednisolone may be associated with increased risk of death and fractures. While the precise pathophysiologic mechanisms of these events are not yet clear, collecting evidence from more clinical trials and translational studies is necessary. The aim of our present study is to assess whether accessible sources of patient outcome data can help gain additional clinical insights to radium-223 dichloride’s safety profile. Materials and Methods: We performed a retrospective analysis of cases extracted from the FDA Adverse Event Reporting System and characterized side effect occurrence by using reporting ratios. Results: A total of ~1500 prostate cancer patients treated with radium-223 dichloride was identified, and side effects reported with the use of radium-223 dichloride alone or in combination with other therapeutic agents were extracted. Our analysis demonstrates that radium-223 dichloride may often come with hematological-related reactions, and that, when administered together with other drugs, its safety profile may differ. Conclusions: While more prospective studies are needed to fully characterize the toxicological profile of radium-223 dichloride, the present work constitutes perhaps the first effort to examine its safety when administered alone and in combination with other agents based on computational evidence from public real-world post marketing data.
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Wiebe, E., D. Freier, D. Huscher, G. Dallagiacoma, R. Biesen, S. Hermann, G. R. Burmester, and F. Buttgereit. "OP0300 A CROSS-SECTIONAL, MATCHED-PAIR ANALYSIS OF ACPA POSITIVE AND ACPA NEGATIVE RHEUMATOID ARTHRITIS PATIENTS COMPARING THE PREVALENCE OF OSTEOPOROSIS, FRAGILITY FRACTURES AND UNDERLYING RISK FACTORS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 186.1–187. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4391.
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Background:Rheumatoid arthritis (RA) is associated with increased systemic bone loss, leading to a high risk for fragility fractures. Especially anti-citrullinated protein antibody (ACPA) positivity is considered a risk factor for local bone erosions and systemic bone loss1.Objectives:The purpose of this study was to compare ACPA positive versus ACPA negative RA patients in terms of the prevalence of osteoporosis and fragility fractures and to identify differences in underlying risk factors that influence bone health.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic rheumatic diseases or psoriasis treated with glucocorticoids (GC). In this cross-sectional analysis, we performed a matched-pair analysis, matching 114 ACPA positive to 114 ACPA negative RA patients according to age (5-year-steps), sex, and body mass index (BMI, 2-unit-steps). Descriptive analyses were performed, with values displayed as mean ± standard deviation for continuous variables. Non-parametric tests were used at a two-sided significance level of 5% to compare differences in underlying and potential risk factors without adjustment for multiple testing.Results:At same mean age (63.9 ±10.2 years) and BMI (27.9 ±5.6kg/m2), the matched groups had a female proportion of 82.5%. APCA positive patients had a significantly longer mean disease duration (13.9 vs 9.9 years, p<0.001), a higher mean cumulative GC-dose (22.3 vs 13.2g, p<0.01) and mean duration of GC therapy (10.1 vs 6.6 years, p<0.01). There was no significant difference in the prevalence of osteoporosis as defined by dual-energy X-ray absorptiometry (DXA) (18.4 vs 20.2%), nor in the prevalence of vertebral (7.0 vs 5.3%) or non-vertebral fractures (31.6 vs 29.8%). C-reactive protein levels as a marker of disease activity were significantly higher in ACPA positive patients (mean: 8.8 vs 4.3mg/l, p= 0.02), while mean disease activity score (DAS)28 levels were slightly lower in ACPA positive patients (2.4 vs 2.7, p= 0.05). No difference in health assessment questionnaire (HAQ) score was found. RA-specific treatments were similar, especially concerning current mean daily GC-dose (6.7 vs 4.9mg/day), except for Rituximab and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) which were more commonly used in ACPA positive patients (9.6 vs 2.6%, p=0.05) and (5.3 vs 0%, p=0.029), respectively. ACPA positive patients did not differ significantly from ACPA negative patients in specific anti-osteoporotic treatment, nor in the prevalence of comorbidities or concomitant medication. There were no significant differences in bone-specific laboratory parameters.Conclusion:In a cross-sectional analysis of our cohort, the prevalence of osteoporosis and fragility fractures was similar between ACPA positive and ACPA negative RA patients, despite longer disease duration and GC-treatment in ACPA positive patients. This is remarkable since it implies that ACPA negative patients are at a similar risk for osteoporosis and associated fractures. Optimal management of disease activity with or without GCs may represent a mainstay in preventing disease-related comorbidities such as osteoporosis.References:[1]Steffen, U., Schett, G., & Bozec, A. (2019). How Autoantibodies Regulate Osteoclast Induced Bone Loss in Rheumatoid Arthritis. Frontiers in immunology, 10, 1483. doi:10.3389/fimmu.2019.01483Disclosure of Interests:Edgar Wiebe: None declared, Desiree Freier: None declared, Dörte Huscher: None declared, gloria dallagiacoma: None declared, Robert Biesen: None declared, Sandra Hermann: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.
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Terpos, Evangelos, Nikolaos Kanellias, Eftathios Kastritis, Maria Gavriatopoulou, Vassilis Koutoulidis, Ioannis Ntanasis-Stathopoulos, Aristea-Maria Papanota, et al. "Natural History of Skeletal Related Events in Patients with Multiple Myeloma Who Received First- and Second- Line Therapy with Novel Agents: Results from a Single Center Analysis in 620 Patients." Blood 134, Supplement_1 (November 13, 2019): 4326. http://dx.doi.org/10.1182/blood-2019-123606.
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Introduction: Skeletal-related events (SREs) that include pathological fractures, spinal cord compression (SCC) and need for radiotherapy or surgery to the bone are frequent complications of multiple myeloma (MM). Although the incidence of SREs at diagnosis is well-documented, there is limited information for the natural history of SREs during treatment with novel agents. Thus, we evaluated the SRE rate in MM patients who received frontline and second line therapy with proteasome inhibitors (PIs) or immunomodulatory drug (IMiD)-based therapies and explored possible correlations with disease or genetic features and type of treatment. Methods: MM patients who received frontline therapy in our center (Department of Clinical Therapeutics, University of Athens, Greece), between 2007-2017, were included in this analysis. Patients had a whole-body skeletal survey using either conventional radiography (WBXR) or low-dose CT (WBLDCT) at diagnosis and then at the time of relapse or whenever clinically indicated. Magnetic Resonance Imaging (MRI) of the spine and pelvis at diagnosis was recorded when available. SNPs in genes that are involved in bone destruction in osteoporosis were also evaluated: LRP5 (rs4988321), GC vitamin D (rs4588), TNFRSF11A (rs3018362), DKK1 (rs1569198), RANKL (rs9594759), OPG (rs6469804) and ERS1 (rs1038304). Results: In total, 620 consecutive patients with symptomatic MM (316M/304F, median age: 65 years) were studied. The median follow-up was 54 months. At diagnosis, osteolytic disease was present in 408 (66%) patients. MRI was available in 390 patients: 149 (38%) patients had focal, 139 (36%) diffuse, 81 (21%) normal and 21 (5%) variegated pattern of marrow involvement. SREs were observed in 271 (44%) patients at diagnosis: 213 (34%) presented with pathological fractures (183 with vertebral fractures, 18 with rib fractures and 15 with long bone fractures; 32 patients had both vertebral and long bone or rib fractures), while 34 (5.5%) patients needed surgery to bone, 45 (7.2%) radiotherapy and 31 (5%) patients presented with SCC. The incidence of SREs was higher in patients with osteolytic lesions (76.4% vs. 12.4%, p<0.0001) or abnormal MRI pattern (49% vs. 11.3%, p<0.0001) at diagnosis. No correlation was found between the presence of SREs at diagnosis and a specific SNP of those studied. Frontline therapy with IMiD-based regimens was given in 38% of patients; 27% patients received bortezomib-based regimens and 28% both IMiD and bortezomib-based therapies (VTD or VRD); 7% received only conventional chemo. Bisphosphonates (BPs) were given to 465 patients (75%) at diagnosis; the vast majority (91%) received zoledronic acid. The remaining 155 patients did not receive upfront BPs, mainly due to renal insufficiency. During first line treatment, 39 (6.3%) patients developed a SRE: 25/341 (7.3%) on bortezomib- (including combos with an IMiD) and 14/235 (6%) on IMiD-based regimens. At the time of first relapse, 4.5% of patients presented with new fractures and 12% required local radiotherapy to bone (SRE rate: 16.5%). The rate of SREs at first progression was much higher in patients who did not receive upfront BPs (92.3% vs. 7.7%). There was no difference in the incidence of SREs at first relapse between patients who received PI- vs. non-PI-based regimens as first line therapy (54.2% vs. 45.8%, p=0.544). During second line therapy, 12.2% of patients developed a SRE, with no difference regarding the second line therapy (PI- or IMiD-based regimens). In total, 126 (20.3%) patients developed at least one SRE, during the course of the first and second line of therapy; this was more common in those who presented with an SRE at diagnosis (33% vs 12%; p<0.03). Conclusions: Our data, which constitutes one of the few systematic reports on the incidence and characteristics of SREs in the era of novel agents, indicate that SREs remain a significant complication in MM. Despite high response rates after first line therapy and the broad use of BPs, more than 20% of patients develop a new SRE during the first and second line treatment or at the time of first relapse. Importantly, patients who do not receive BPs due to renal impairment develop very frequently SREs, suggesting an unmet need in this setting. More effective frontline therapies or more potent bone-targeted agents (denosumab or anti-sclerostin drugs) may manage to further reduce the SREs rate in MM patients, especially in those who cannot receive BPs. Disclosures Terpos: Celgene: Honoraria; Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria. Kastritis:Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Gavriatopoulou:Amgen: Honoraria; Takeda: Honoraria, Other: Travel expenses; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses. Dimopoulos:Sanofi Oncology: Research Funding.
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Gibbs, Sarah N., Jiyoon Choi, Ibrahim Khilfeh, K. Hamzah Ahmed, Irina Yermilov, and Eric Segal. "The Humanistic and Economic Burden of Pediatric Focal Seizures in the United States." Journal of Child Neurology 35, no. 8 (March 30, 2020): 543–55. http://dx.doi.org/10.1177/0883073820911785.
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Objective: To better understand the humanistic and economic burden of focal seizures in children 2-12 years old. Methods: We conducted a targeted literature review by searching MEDLINE for English-language publications reporting on children 2-12 years old with focal seizures published in the United States since 2008. Results: Thirty-five publications were included. Incidence of focal seizures was 23.2 to 47.1 per 100,000 children per year; prevalence was 2.0 per 1,000 children, and ranged from 1.6 - 2.6 per 1,000 in patients of any age. Life expectancy was 47.3-61.8 years among children 3-12 years old. Patients took several antiepileptic drugs and experienced frequent seizures, sleep disorders, mood disorders, migraine, and seizure-related injuries (eg, bone fractures, sprains, open wounds). Children with focal seizures scored below average on cognitive assessments and up to 42%, 16%, and 19% had depression, anxiety, and attention-deficit disorder, respectively. Patients of any age had about 10 outpatient visits (2 epilepsy-related), 2 inpatient visits (less than 1 epilepsy-related), and 24 procedures (1 epilepsy-related) per year. Medication adherence was low: only half of pediatric patients maintained ≥90% adherence over 6 months. Annual total health care costs among patients of any age ranged from $18,369 - 38,549; first-year total health care costs for children were $19,883. Conclusions: Incidence and prevalence of focal seizures is high and the humanistic and economic burdens are significant. Future studies focused exclusively on children with focal seizures are needed to more precisely describe the burden. We also suggest further research and implementation of methods to improve medication adherence as an approach to lessen burden on these young patients.
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Brådland, S., A. Kavanaugh, and G. Haugeberg. "POS1085 OSTEOPOROSIS IN PSORIATIC ARTHRITIS: A 5 YEAR PROSPECTIVE STUDY OF AN OUTPATIENT CLINIC COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 821.2–822. http://dx.doi.org/10.1136/annrheumdis-2021-eular.4038.
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Background:Data addressing whether patients with psoriatic arthritis (PsA) are at increased risk of osteoporosis have been inconclusive (1). Most studies have reported cross sectional data, and there is a lack of longer-term studies. We have previously reported bone density data from an outpatient PsA clinic cohort (2). Herein, we present 5-year follow up data from that same cohort.Objectives:To explore longer-term change in bone mineral density (BMD) at femoral neck and spine (L1-4) in an outpatient PsA cohort.Methods:140 PsA patients were at baseline examined with dual energy x-ray absorptiometry (DXA) with measurements at femoral neck and spine (L1-4). Trained nurses performed the DXA scans. The DXA machines used at baseline (Lunar Prodigy) and at 5 year follow-up (Lunar iDXA) were stable over the measurement periods. Cross calibration using a spine phantom was performed between the two DXA machines (BMD of the old phantom in the new machine and the old phantom in the old machine, with 55 measurement over a time period of 2 weeks) had a difference of less than 1%. Demographic, disease measures and treatment data was collected at the same day or within 14 days to the date of DXA assessment. For group comparison, we used paired student t-test.Results:After 5 years, 114 PsA patients (50.4% women) were re-examined. Baseline mean (SD) was for age 51.4 (9.4) years, BMI 28.1 (3.4) kg/m2, disease duration 9.1 (6.7) years.Disease characteristics at baseline and follow-up presented as mean (SD) were: DAS28 3.05 (1.1) and 2.4 (0.8); CRP 4.3 (6.7) and 5.1 (12.2) mg/dl, ESR 14.9 (11.1) and 10.9 (12.9) mm/hr; mHAQ 0.40 (0.35) and 0.38 (0.37).The proportions of patients as baseline and follow up using conventional synthetic disease modifying anti-rheumatic drugs (DMARD) were 61.4% vs. 46.5%; for biological DMARDs 37.7% vs. 48.2%; for prednisolone 5.3% vs. 10.5%, for targeted osteoporosis medication 0.9% vs. 3.5%; for calcium and vitamin-D 11.4% vs. 26.3%. As shown in the table, no significant change in femoral neck and spine BMD and T-scores was found for the 114 patients. However for Z-scores (age and weight adjusted T-score) a significant increase was found both at femoral neck and lumbar spine. When gender was examined separately no significant reduction in bone density was found in men whereas in women a significant reduction during follow up was only found for right femoral neck BMD.Baseline5 yearsP valueBMD spine L1-41.22 (0.17)1.23 (0.17)0.13T-score spine L1-40.21 (1.42)0.32 (2.01)0.42Z-score spine L1-40.20 (1.32)0.78 (2.05)<0.001BMD Femoral neck L0.98 (0.14)0.97 (0.14)0.09T-score Femoral neck L-0.59 (1.15)-0.50 (1.02)0.14Z-score Femoral neck L-0.06 (1.02)0.37 (1.04)<0.001BMD Femoral neck R0.98 (0.14)0.98 (1.16)0.57T-score Femoral neck R-0.59 (1.10)-0.52 (0.94)0.22Z-score Femoral neck R-0.08 (1.02)0.35 (0.90)<0.001Conclusion:No reduction in BMD at femoral neck and spine was found in our PsA outpatient clinic cohort at baseline or over 5 years follow up. Rather, we found a statistically significant increase in age adjusted bone density (Z-score) both at femoral neck and spine over time. Our data thus adds evidence that PsA patients treated in ordinary clinical practice do not seem to be at an increased risk of developing osteoporosis.References:[1]Tai-li Chen, et al. Bone Mineral Density, Osteoporosis, and Fracture Risk in Adult Patients with Psoriasis and Psoriatic Arthritis: A systematic Review and Meta-Analysis of Observational Studies, J Clin Med 2020;9:3712[2]Agnete Malm Gulati, et al. Osteoporosis in psoriatic arthritis: a cross-sectional study of an outpatient clinic population. RMD Open 2018;4:1Acknowledgements:Research nurse Hanne Vestaby and osteoporosis nurses at -Division of Rheumatology, Kristiansand.Disclosure of Interests:Serina Brådland: None declared, Arthur Kavanaugh: None declared, Glenn Haugeberg Grant/research support from: Unrestricted Research Grant from Pfizer Norway.
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Wang, Mingding, Soie Park, Yoonhee Nam, Jeffery Nielsen, Stewart A. Low, Madduri Srinivasarao, and Philip S. Low. "Bone-Fracture-Targeted Dasatinib-Oligoaspartic Acid Conjugate Potently Accelerates Fracture Repair." Bioconjugate Chemistry 29, no. 11 (October 31, 2018): 3800–3809. http://dx.doi.org/10.1021/acs.bioconjchem.8b00660.
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Tkacheva, Olga N., Natalia V. Brailova, Ekaterina N. Dudinskaya, and Veronika A. Kuznesova. "Osteoporosis drug treatment after fracture." Osteoporosis and Bone Diseases 23, no. 4 (June 6, 2021): 30–36. http://dx.doi.org/10.14341/osteo12694.
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The prevalence of osteoporosis, especially among the elderly, is increasing exponentially, leading to an increase in the number of fractures and disability. As a result, new requirements for anti-osteoporotic therapy appear, associated with its influence not only on the remodeling of healthy bone, but also on the acceleration of fracture consolidation. The article provides a brief overview of the effect of various anti-osteoporotic drugs on the healing of bone fractures. An assessment of the consolidating effect of antiresorptive drugs — bisphosphonates and denosumab, and anabolic drug — teriparatide, monoclonal antibodies blocking the protein sclerostin, strontium ranelate is given. The use of antiresorptive drugs did not affect, according to the literature, the slowing down of consolidation after fractures of various parts of the skeleton (hip, vertebrae, distal radius). The introduction of anabolic drugs, in particular teriparatide, is accompanied by faster healing of fractures in comparison with the timing of natural bone regeneration or the intake of bisphosphonates, causing an improvement in the formation of callus. The use of drugs that block sclerostin also increases bone formation and bone strength. Based on the available data, it can be concluded that fractures should not be considered as a contraindication to the use of these drugs and be the reason for the late initiation of drug treatment of osteoporosis.
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Smith, Robert G. "Fracture Healing." Journal of the American Podiatric Medical Association 105, no. 2 (March 1, 2015): 160–72. http://dx.doi.org/10.7547/0003-0538-105.2.160.
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Background Recognizing the existence of adverse drug effects of frequently prescribed drugs can empower a clinician with knowledge to avoid dangerous adverse effects that may result in hazardous, negative patient outcomes on either fracture healing or bone health. Pharmacovigilance reports have described the influence of medications, allowing for bone health to be quite unpredictable. Methods First, mechanisms found in the medical literature of potential drug adverse effects regarding fracture healing are presented. Second, the 100 most frequently prescribed medications in 2010 are reviewed regarding adverse effects on fracture healing. These reported adverse effects are evaluated for medical causation. Last, a data table describing the 100 reviewed medications and their reported effects on fracture healing is provided. Results The actual number of different medications in the review was 72. Reported drug adverse effects on bone and fracture healing occurred with 59 of the 72 drugs (81.9%). These adverse effects are either described as a definitive statement or represented by postmarketing case reports. Thirteen of the 72 review drugs (18.1%) did not have any description of the possible effects on bone health. A total of 301 cases reports describing delayed union, malunion, and nonunion of fractures represent 31 of the 72 medications reviewed (43.1%). Conclusions This review offers the health-care provider information regarding potential adverse drug effects on bone health. Empowered with this information, clinicians may assist their patients in maximizing pharmacologic outcomes by avoiding these reported harmful adverse effects.
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Rosenberg, Karen. "Drugs Reduce Bone Fracture Risk; Adverse Effects Vary." AJN, American Journal of Nursing 115, no. 2 (February 2015): 56. http://dx.doi.org/10.1097/01.naj.0000460694.25134.cf.
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Brandi, Maria Luisa. "Healing of the bone with anti-fracture drugs." Expert Opinion on Pharmacotherapy 14, no. 11 (June 17, 2013): 1441–47. http://dx.doi.org/10.1517/14656566.2013.801959.
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Vannucci, Letizia, and Maria Luisa Brandi. "Healing of the bone with anti-fracture drugs." Expert Opinion on Pharmacotherapy 17, no. 17 (October 11, 2016): 2267–72. http://dx.doi.org/10.1080/14656566.2016.1241765.
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Toriumi, Shinya, Akinobu Kobayashi, Hitoshi Sueki, Munehiro Yamamoto, and Yoshihiro Uesawa. "Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database." Pharmaceuticals 14, no. 12 (December 13, 2021): 1299. http://dx.doi.org/10.3390/ph14121299.
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Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms.
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Leslie, W. D., S. N. Morin, L. M. Lix, and N. Binkley. "Targeted bone density testing for optimizing fracture prevention in Canada." Osteoporosis International 31, no. 7 (February 12, 2020): 1291–97. http://dx.doi.org/10.1007/s00198-020-05335-x.
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Hozain, Sarah, and Jessica Cottrell. "CDllb+ targeted depletion of macrophages negatively affects bone fracture healing." Bone 138 (September 2020): 115479. http://dx.doi.org/10.1016/j.bone.2020.115479.
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Willson, Timothy M., Paul S. Charifson, Anthony D. Baxter, and Nora G. Geddie. "Bone targeted drugs 1. Identification of heterocycles with hydroxyapatite affinity." Bioorganic & Medicinal Chemistry Letters 6, no. 9 (May 1996): 1043–46. http://dx.doi.org/10.1016/0960-894x(96)00164-3.
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Willson, Timothy M., Brad R. Henke, Tanya M. Momtahen, Deanna T. Garrison, Linda B. Moore, Nora G. Geddie, and Philip G. Baer. "Bone targeted drugs 2. synthesis of estrogens with hydroxyapatite affinity." Bioorganic & Medicinal Chemistry Letters 6, no. 9 (May 1996): 1047–50. http://dx.doi.org/10.1016/0960-894x(96)00165-5.
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Nam, Nguyen Hoai, and Naruepon Kampa. "An Overview of Drug Effects on Bone Healing on Animal Research Models." Vietnam Journal of Agricultural Sciences 4, no. 1 (June 18, 2021): 978–88. http://dx.doi.org/10.31817/vjas.2021.4.1.08.
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Bone fracture is a common health problem in humans and animals, and the healing of the bone fracture is a complicated process. Several drugs may be used concurrently with the treatment of fractures, but they may interfere with the healing process of the bone. The present research reviewed previously published studies with the objective to enhance the understandings of the effects of different drugs on bone healing. There is clear evidence that antibiotics, corticosteroids, non-steroidal inflammatory drugs, and chemotherapeutic drugs all affect bone healing. By contrast, the effect of anticoagulants on bone healing is controversial, so more research is needed to determine its efficacy. In addition, there is no direct evidence to approve the effect of anesthetics on bone healing, so this is another area in need of further research.
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Deeba, Farah, Sidra Younis, Nida Qureshi, Tahmina Mustafa, Nadia Iqbal, and Saira Hussain. "Effect of Diabetes Mellitus and Anti-Diabetic Drugs on Bone Health-A Review." Journal of Bioresource Management 8, no. 2 (May 26, 2021): 131–48. http://dx.doi.org/10.35691/jbm.1202.0187.
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Osteoporosis and diabetes mellitus (DM) are widespread diseases and have a significant health burden. Type-1 diabetes mellitus (T1DM) and Type-2 diabetes mellitus (T2DM) are associated with an increased bone fracture. In T1DM, the increased risk of bone fracture is associated with low bone mass. In patients with T2DM, the risk of fracture of the bone is increased due to low quality of bone, despite increased bone mineral density (BMD). In type 2 diabetic patients, bone fragility depends on the quality of bone instead of a reduction in bone mass. Thiazolidinediones (TZD) cause differentiation of adipocytes and inhibit differentiation of osteoblast and bone marrow stromal stem cells (BMSC). In this review, we have described the effect of anti-diabetic drugs and diabetes mellitus on bone health and our finding shows that sulfonylureas and metformin have no negative effect on bone health and protect bones against fractures.
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Zhou, Wu, Ze Lin, Yuan Xiong, Hang Xue, Wen Song, Tao Yu, Lang Chen, et al. "Dual-Targeted Nanoplatform Regulating the Bone Immune Microenvironment Enhances Fracture Healing." ACS Applied Materials & Interfaces 13, no. 48 (November 19, 2021): 56944–60. http://dx.doi.org/10.1021/acsami.1c17420.
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Howard Nielsen, Jeffery Jay, Stewart A. Low, and Philip S. Low. "3505 Fracture Targeted Parathyroid Hormone Agonist As An Effective Pharmaceutical For Bone Repair in Mouse and Canine Models." Journal of Clinical and Translational Science 3, s1 (March 2019): 105–6. http://dx.doi.org/10.1017/cts.2019.241.
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OBJECTIVES/SPECIFIC AIMS: The primary objective of this study was to evaluate the performance of a bone fracture targeted systemically administrable bone anabolic as a potential therapeutic for bone fracture repair. Currently all bone fracture repair therapeutic require local administration during surgery. However, the population that need the most assistance in repair bone fractures are not eligible for surgery. So, it was our goal to design an inject-able therapeutic to assist in bone fracture repair to reduce the invasiveness. The injectable nature of it allows for repair administration of the bone anabolic and for therapeutic effect throughout the entire bone fracture healing process. Targeting it to the bone fracture site reduces the toxicity and increases the efficacy. METHODS/STUDY POPULATION: METHODS To achieve the above objective, a bone mineral-(hydroxyapatite-) targeting oligopeptide was conjugated to the non-signaling end of an engineered parathyroid hormone related protein fragment 1-46 with substitutions at Glu22,25, Leu23,28,31, Aib29, Lys26,30 (ePTHrP). The negatively charged oligopeptide has been shown to target raw hydroxyapatite with remarkable specificity, while the attached PTHrP has been demonstrated to induce sustained and accelerated bone growth under control of endogenous morphogenic regulatory factors. The conjugate’s specificity arises from the fact that raw hydroxyapatite is only exposed whenever a bone is fractured, surgically cut, grafted, or induced to undergo accelerated remodeling. The hydroxyapatite-targeted conjugate can therefore be administered systemically (i.e. without invasive surgery or localized injection) and still accumulate on the exposed hydroxyapatite at the fracture site where it accelerates the healing process Murine in vivo experiments were conducted on female Swiss Webster mice (10 per group). Femoral fractures were induced with a 3-point bending device and stabilized. Mice were dosed with 3 nmol/kg/d of targeted-ePTHrP, non-conjugated (free) ePTHrP, or saline. Following a 4-week study, fracture callus densities were measured using microCT. Canine in vivo experiments were conducted on 1-year-old male beagles. Beagles underwent a 10 mm bilateral ulnar ostectomy. Two dogs in the treatment group and Three dogs in the control group were dosed daily with either targeted-ePTHrP 0.5nmol/kg/d or saline respectively. Dogs were x-rayed weekly for the first 6 weeks and then every other week thereafter. One tailed ANOVA followed by Dunnett’s post-hoc test was used to establish significance. All animal experiments were conducted as described in approved IACUC protocols. P<0.05 was considered significant. RESULTS/ANTICIPATED RESULTS: RESULTS SECTION: In the murine studies we observed a marked increase in fracture callus size and a 2-fold increase in bone deposition was observed in the targeted-ePTHrP group over the saline group (P<0.01). A significant doubling in bone density was also observed. Targeted-ePTHrP group fractured femurs were able to achieve their pre-fracture strength as early as 3 weeks compared to 9 weeks in the saline mice representing a 66% reduction in healing time. In the canine studies, we observe a significantly higher closure of the ostectomy gap than saline controls (P<0.05). In addition, no significant differences in weight are observed in the treatment vs. saline controls. No significant difference between the control group and treatment groups was found in a histological investigation of the organs. DISCUSSION/SIGNIFICANCE OF IMPACT: DISCUSSION: Although attempts have been made in developing a systemically administered fracture therapeutic for fracture repair, i.e. teriparatide, to date, no such anabolics have been approved for this use. In these studies there is evidence that anabolic activity was occurring at the fracture site, but at a level that did not meet FDA required end-points.2 It is plausible that if sufficient drug were to be delivered to a fracture site then improved fracture repair would be possible. In previous studies, we demonstrated fracture specific accumulation bone anabolics can be achieved by modifying the drug with acidic oligopeptides.3 Here, by modifying a safe, clinically proven, parathyroid hormone receptor agonist with an acidic oligopeptide we observe improved bone deposition and strength in mice. Furthermore, when administered to canine critical sized defect ostectomies, a more relevant and difficult model, we observe improved ostectomy closure. CLINICAL RELEVANCE:: The ability to accelerate bone fracture repair is a fundamental need that has not been addressed by conventional methods. By targeting bone anabolic agents to bone fractures, we can deliver sufficient concentrations of anabolic agent to the fracture site to accelerate healing, thus avoiding surgery and any ectopic bone growth associated with locally-applied bone anabolic agents.
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Wang, Jun, Arielle Elkrief, Wei Guo, Neerav Shukla, Mrinal Gounder, and Marc Ladanyi. "Prospects for Epigenetic Targeted Therapies of Bone and Soft-Tissue Sarcomas." Sarcoma 2021 (July 26, 2021): 1–7. http://dx.doi.org/10.1155/2021/5575444.
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Targeted therapies have revolutionized cancer treatment. It is well established that alterations of chromatin configuration and modifications affect tumorigenesis of some, possibly most, bone and soft-tissue sarcomas. As epigenetic regulators play a major role in the development of bone and soft-tissue sarcomas, epigenetic drugs provide a novel potential avenue for rational targeted therapies for these aggressive cancers. The present review summarizes the application of epigenetic drugs for clinical utilization in bone and soft-tissue sarcomas and provides an overview of clinical trials currently evaluating epigenetic therapies in this space.
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Borges, Roger, Agatha Maria Pelosine, Ana Carolina Santos de Souza, Joel Machado, Giselle Zenker Justo, Lionel Fernel Gamarra, and Juliana Marchi. "Bioactive Glasses as Carriers of Cancer-Targeted Drugs: Challenges and Opportunities in Bone Cancer Treatment." Materials 15, no. 24 (December 19, 2022): 9082. http://dx.doi.org/10.3390/ma15249082.
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The treatment of bone cancer involves tumor resection followed by bone reconstruction of the defect caused by the tumor using biomaterials. Additionally, post-surgery protocols cover chemotherapy, radiotherapy, or drug administration, which are employed as adjuvant treatments to prevent tumor recurrence. In this work, we reviewed new strategies for bone cancer treatment based on bioactive glasses as carriers of cancer-targeted and other drugs that are intended for bone regeneration in conjunction with adjuvant treatments. Drugs used in combination with bioactive glasses can be classified into cancer-target, osteoclast-target, and new therapies (such as gene delivery and bioinorganic). Microparticulated, nanoparticulated, or mesoporous bioactive glasses have been used as drug-delivery systems. Additionally, surface modification through functionalization or the production of composites based on polymers and hydrogels has been employed to improve drug-release kinetics. Overall, although different drugs and drug delivery systems have been developed, there is still room for new studies involving kinase inhibitors or antibody-conjugated drugs, as these drugs have been poorly explored in combination with bioactive glasses.
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Najim, Soukaina, Kawtar Nassar, Wafae Rachidi, Saadia Janani, and Ouafa Mkinsi. "What approach should be followed in case of fractures in patients receiving treatment for osteoporosis." Batna Journal of Medical Sciences (BJMS) 1, no. 2 (December 31, 2014): 59–63. http://dx.doi.org/10.48087/bjmsra.2014.1204.
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Osteoporosis is a systemic disease of the skeleton characterized by low bone mineral density and changes in bone microarchitecture increasing the risk of fracture. Its management is codified and must comply with official recommendations. However, it is problematic when an osteoporotic fracture happens in a patient under treatment with anti-osteoporotic drugs. In the absence of consensus for care, the management of this situation varies according to the experience of different centers. We tried to establish practice management guidelines in case of the occurrence of a fracture under antiosteoporotic drugs, on the basis of a literature review.
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Balu, Abhinav, Rong Huang, Kristin Molitoris, and Gurpreet Baht. "Apolipoprotein E impairs aged bone fracture healing." Innovation in Aging 5, Supplement_1 (December 1, 2021): 662. http://dx.doi.org/10.1093/geroni/igab046.2499.
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Abstract Bone fracture healing and osteoblast differentiation are impaired with advanced age. Using a combination of parabiosis and proteomic models, we identified apolipoprotein E (ApoE) to be an aging factor in bone regeneration. Circulating levels of ApoE increased with age in patients and in mice. ApoE impaired bone fracture healing by decreasing bone deposition in the fracture callus which subsequently decreased the mechanical strength of healed tissue. Osteoblasts serve as the sole bone forming cells within the body. In tissue culture models, ApoE treatment decreased osteoblast differentiation and activity which led to decreased matrix formation and mineralization. This inhibition of osteoblast differentiation relied on down-regulation of the Wnt/β-catenin pathway. In mouse models, aged bone repair was rejuvenated when we lowered circulating ApoE levels using a hepatotropic AAV-siRNA model – serving as a proof of concept that ApoE can be targeted to improve bone repair in an older population. While promising, knockdown of circulating ApoE in such a fashion is likely not translatable to patient care. Thus, current work in our laboratory is focused on developing treatment strategies that temporally decrease circulating ApoE levels and consequently improve bone healing after acute injury and/or surgical orthopedic procedure in the geriatric population.
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Kimelman-Bleich, Nadav, Gadi Pelled, Yoram Zilberman, Ilan Kallai, Olga Mizrahi, Wafa Tawackoli, Zulma Gazit, and Dan Gazit. "Targeted Gene-and-host Progenitor Cell Therapy for Nonunion Bone Fracture Repair." Molecular Therapy 19, no. 1 (January 2011): 53–59. http://dx.doi.org/10.1038/mt.2010.190.
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Erdogan, Bulent, and Irfan Cicin. "Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs." Asian Pacific Journal of Cancer Prevention 15, no. 4 (February 28, 2014): 1503–10. http://dx.doi.org/10.7314/apjcp.2014.15.4.1503.
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Cottrell, Jessica, Sarah Hozain, and Danielle Touma. "Targeted Deletion of CD11b+ Macrophage Subtypes alter the Acute Inflammatory Cytokine Response In Bone Healing." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 58.14. http://dx.doi.org/10.4049/jimmunol.202.supp.58.14.
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Abstract Any immunological or inflammatory dysregulation can impair the bone healing process. Macrophages (MØ) are immune cells specialized for phagocytosis and assist in all stages of bone repair. MØs are often divided into two main subsets, MØ1, pro-inflammatory M1 macrophages and MØ2, anti-inflammatory or resolving M2 macrophages. Our preliminary data demonstrates that MØ1 to MØ2 polarization occurs following femur fracture during the first 7 days post-fracture and is associated with a specific cytokine expression profile over time. Other studies have demonstrated that dysregulated inflammation can impair fracture healing outcomes in normal mice. We hypothesize that targeted depletion of CD11b+ MØ cells will reduce the acute inflammatory response, alter the normal cytokine expression profile, and interfere with the bone healing response. Therefore, the bone marrow of mice depleted of CD11b+ MØ cells were compared to normal mice following femur fracture at days 0, 1, 2, and 4 using established methods. MØ subtypes were identified using flow cytometry and cytokine expression was quantified using Luminex. The data demonstrated that after fracture, the CD11b+ MØ depleted group had significantly less MØ1s, F480+/CD86+/MHC classII+/CD11b+ cells when compared to controls at all timepoints. MØ cytokine expression profiles were found to be altered in the control fractures when compared to the CD11b+ MØ depleted fractures. Our results demonstrate that MØ subsets contribute substantially to the signaling mechanisms that guide the acute inflammatory phase of bone healing. Proper modulation of macrophage polarization may be useful to develop novel treatment strategies to improve healing when the immune system or inflammation is dysregulated.
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Russow, Gabriele, Denise Jahn, Jessika Appelt, Sven Märdian, Serafeim Tsitsilonis, and Johannes Keller. "Anabolic Therapies in Osteoporosis and Bone Regeneration." International Journal of Molecular Sciences 20, no. 1 (December 26, 2018): 83. http://dx.doi.org/10.3390/ijms20010083.
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Osteoporosis represents the most common bone disease worldwide and results in a significantly increased fracture risk. Extrinsic and intrinsic factors implicated in the development of osteoporosis are also associated with delayed fracture healing and impaired bone regeneration. Based on a steadily increasing life expectancy in modern societies, the global implications of osteoporosis and impaired bone healing are substantial. Research in the last decades has revealed several molecular pathways that stimulate bone formation and could be targeted to treat both osteoporosis and impaired fracture healing. The identification and development of therapeutic approaches modulating bone formation, rather than bone resorption, fulfils an essential clinical need, as treatment options for reversing bone loss and promoting bone regeneration are limited. This review focuses on currently available and future approaches that may have the potential to achieve these aims.
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Kanis, J. A., O. Johnell, B. Gullberg, E. Allander, G. Dilsen, C. Gennari, A. A. Lopes Vaz, G. P. Lyritis, G. Mazzuoli, and L. Miravet. "Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture." BMJ 305, no. 6862 (November 7, 1992): 1124–28. http://dx.doi.org/10.1136/bmj.305.6862.1124.
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Mazzuoli, G. F., C. Gennari, M. Passeri, M. Acca, A. Camporeale, and G. Pioli. "Hip fracture in Italy: Epidemiology and preventive efficacy of bone-active drugs." Bone 14 (January 1993): 81–84. http://dx.doi.org/10.1016/8756-3282(93)90356-f.
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