Drugs for the treatment of metabolic bone diseases

Drake, Matthew T.; Cremers, Serge; Russell, R. G. G.; Bilezikian, John P.

doi:10.1111/bcp.13857

Cited by 5 publications

(5 citation statements)

References 23 publications

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Section: Orthopedic Diseases and Treatment Of Orthopedic Diseasesmentioning

confidence: 99%

“…Patients diagnosed with bone tumors not only need surgical removal of the tumors but may also require additional treatments, such as radiotherapy and chemotherapy, depending on the stage and severity of the bone cancer. [61] There is a growing body of clinical evidence suggesting that maintaining a balanced diet with proper nutritional supplements and making lifestyle improvements can significantly promote bone health. For the treatment of bone diseases, medical interventions such as drug therapy and surgical operations are commonly used.…”

Section: Treatment Of Orthopedic Diseasesmentioning

confidence: 99%

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Mesenchymal Stem Cells‐Derived Extracellular Vesicles in Orthopedic Diseases: Recent Advances and Therapeutic Potential

Wang,

Tian,

Yang

et al. 2023

Advanced Therapeutics

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Ever since the first application of mesenchymal stem cell (MSC) transplantation treating human hematologic malignancies in 1995, MSC‐based treatments have demonstrated great therapeutic potential in clinical settings. However, only a few MSC‐based cell therapy products have been clinically approved. Accumulating evidence suggests that the beneficial effects of MSCs are mainly attributed to the release of paracrine factors or extracellular vesicles (EVs) rather than their mesodermal differentiation potential. Therefore, MSC‐derived EVs, such as exosomes and microvesicles, have merged as promising alternatives to traditional cell‐based therapeutics in clinical practice. They offer several advantages such as better safety, lower immunogenicity, protection of cargoes from degradation, and the ability to overcome biological barriers. Moreover, there have been multiple clinical studies exploring the potential of MSC‐EVs for treating various diseases, including orthopedic disorders. However, there is no definitive “cure” for conditions such as osteoporosis and other bone disorders, but MSC‐EVs have displayed significant therapeutic potential for these orthopedic ailments. Therefore, the objective of this study is to conduct a systematic review of current knowledge related to MSC‐derived EVs (MSC‐EVs) and emphasize their potential application in treating orthopedic diseases, such as bone defects, osteoarthritis, osteoporosis, intervertebral disc degeneration, osteosarcoma and osteoradionecrosis.This article is protected by copyright. All rights reserved

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Section: Orthopedic Diseases and Treatment Of Orthopedic Diseasesmentioning

confidence: 99%

Section: Treatment Of Orthopedic Diseasesmentioning

confidence: 99%

Mesenchymal Stem Cells‐Derived Extracellular Vesicles in Orthopedic Diseases: Recent Advances and Therapeutic Potential

Wang,

Tian,

Yang

et al. 2023

Advanced Therapeutics

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“…Bisphosphonates are a large group of antiresorptive drugs that have been prescribed for treatment of bone disorders, mainly osteoporosis, for decades (Drake, Cremers et al 2019). Their antiresorptive action is due to their ability to prevent osteoclast function and enhance osteoclast apoptosis (Singh and Gonegandla 2019).…”

Section: Other Therapeutic Agents Used In Management Of Bone Diseasesmentioning

confidence: 99%

Wnt signaling pathway as a regulator of bone formation and healing.

Elseweidy

Elswefy

Baraka

et al. 2021

Zagazig Journal of Pharmaceutical Sciences

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Bone is a mineralized structure that is mainly made of a matrix that supports the various types of bone cells; osteoblasts, osteoclasts, osteocytes and bone lining cells. Bone mass is preserved as a result of the balance between bone forming osteoblasts and bone resorbing osteoclasts, in a process known as bone remodeling. Bone remodeling process occurs mainly in three steps: resorption, reversal and formation. These steps are controlled locally and systemically by numerous regulatory factors. Among these regulatory factors, wingless-related MMTV integration site (Wnt) signaling pathway plays a significant role in maintainig bone mass as well as regulating many cellular processes. Based on whether β-catenin is involved or not, Wnt signaling is categorized into two main pathways; the canonical and the non-canonical pathways. The actions exerted by the Wnt signaling pathway are achieved when Wnt ligands bind to specific transmembrane receptors such as the Frizzled family (Frz) members and low density lipoprotein receptor-related proteins (LRPs) and are inhibited when these ligands or receptors bind to Wnt signaling inhibitors such as Wnt inhibitory factor 1 (WIF1), secreted Frizzledrelated proteins (sFRPs), Dickkopf 1 (DKK1) and sclerostin. Improper synthesis of any of these ligands, receptors or inhibitors leads to disruption of different body functions and progression of various diseases including skeletal diseases. Therefore, the components of the Wnt signaling pathway can be targeted for developing novel therapeutic agents to manage different diseases.

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“…Metabolic, metastatic, and genetic bone diseases cause severe pain, reduced mobility, and increased socioeconomic costs and can also lead to secondary defects like fractures ( 1 ). Pharmacological drugs such as antiresorptive agents and osteoanabolics were developed for treating these debilitating diseases, and surgical grafts are also common in orthopedic practice to repair and rebuild damaged bones ( 2 ). However, clinical drug trials have limitations such as insufficient trial patients and a greater risk of unpredicted side effects ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Engineering three-dimensional bone macro-tissues by guided fusion of cell spheroids

Prabhakaran,

Melchels,

Murray

et al. 2023

Front. Endocrinol.

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IntroductionBioassembly techniques for the application of scaffold-free tissue engineering approaches have evolved in recent years toward producing larger tissue equivalents that structurally and functionally mimic native tissues. This study aims to upscale a 3-dimensional bone in-vitro model through bioassembly of differentiated rat osteoblast (dROb) spheroids with the potential to develop and mature into a bone macrotissue.MethodsdROb spheroids in control and mineralization media at different seeding densities (1 × 104, 5 × 104, and 1 × 105 cells) were assessed for cell proliferation and viability by trypan blue staining, for necrotic core by hematoxylin and eosin staining, and for extracellular calcium by Alizarin red and Von Kossa staining. Then, a novel approach was developed to bioassemble dROb spheroids in pillar array supports using a customized bioassembly system. Pillar array supports were custom-designed and printed using Formlabs Clear Resin® by Formlabs Form2 printer. These supports were used as temporary frameworks for spheroid bioassembly until fusion occurred. Supports were then removed to allow scaffold-free growth and maturation of fused spheroids. Morphological and molecular analyses were performed to understand their structural and functional aspects.ResultsSpheroids of all seeding densities proliferated till day 14, and mineralization began with the cessation of proliferation. Necrotic core size increased over time with increased spheroid size. After the bioassembly of spheroids, the morphological assessment revealed the fusion of spheroids over time into a single macrotissue of more than 2.5 mm in size with mineral formation. Molecular assessment at different time points revealed osteogenic maturation based on the presence of osteocalcin, downregulation of Runx2 (p < 0.001), and upregulated alkaline phosphatase (p < 0.01).DiscussionWith the novel bioassembly approach used here, 3D bone macrotissues were successfully fabricated which mimicked physiological osteogenesis both morphologically and molecularly. This biofabrication approach has potential applications in bone tissue engineering, contributing to research related to osteoporosis and other recurrent bone ailments.

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Drugs for the treatment of metabolic bone diseases

Cited by 5 publications

References 23 publications

Mesenchymal Stem Cells‐Derived Extracellular Vesicles in Orthopedic Diseases: Recent Advances and Therapeutic Potential

Mesenchymal Stem Cells‐Derived Extracellular Vesicles in Orthopedic Diseases: Recent Advances and Therapeutic Potential

Wnt signaling pathway as a regulator of bone formation and healing.

Engineering three-dimensional bone macro-tissues by guided fusion of cell spheroids

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