scholarly journals Bisphosphonate-Based Conjugates and Derivatives as Potential Therapeutic Agents in Osteoporosis, Bone Cancer and Metastatic Bone Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 6869
Author(s):  
Zintle Mbese ◽  
Blessing A. Aderibigbe
Keyword(s):  
Side Effects ◽  
Bone Cancer ◽  
Bone Diseases ◽  
Drug Uptake ◽  
Treatment Of Osteoporosis ◽  
Therapeutic Outcomes ◽  
Main Class ◽  
Skeletal Related Events ◽  
Prostate Cancers ◽  
Biological Outcomes

Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited due to severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the main class of drugs utilized to inhibit metastatic bone cancer. It is also used for the treatment of osteoporosis and other bone diseases. However, bisphosphonate also suffers from serious side effects. Thus, there is a serious need to develop bisphosphonate conjugates with promising therapeutic outcomes for treating metastatic bone cancer and osteoporosis. This review article focuses on the biological outcomes of designed bisphosphonate-based conjugates for the treatment of metastatic bone cancer and osteoporosis.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk

2019 ◽  
Vol 17 (6) ◽  
pp. 610-617 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Luigi Barrea ◽  
Barbara Altieri ◽  
Carolina Di Somma ◽  
Harjit pal Bhattoa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Side Effects ◽  
Secondary Hyperparathyroidism ◽  
Calcium Supplementation ◽  
Physiological Role ◽  
Bone Diseases ◽  
Current Evidence ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Muscle Health

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.

A hybrid for pain, i.e. bifunctional analgesics in neuropathy

Ból ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 17-24
Author(s):  
Joanna Starnowska-Sokół
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Pain Therapy ◽  
Analgesic Efficacy ◽  
Hybrid Structure ◽  
Multimodal Approach ◽  
Pharmacological Profile ◽  
Hybrid Compounds ◽  
Therapeutic Outcomes ◽  
Promising Perspective

The need of developing new neuropathic pain therapies results from limited potency of currently available treatments, which is underlain by low efficacy of conventional analgesics, complex etiology and pathogenesis of neuropathy, diversity of its symptoms, as well as heightened side effects risk that accompanies the polypharmaceutical strategy, employed commonly to improve the therapeutic outcomes. Designing hybrid compounds, i.e. multimodal molecules that present the affinity to more than one receptor target, offers a promising perspective in this context. The multimodal approach allows to increase the analgesic efficacy of a given compound thanks to aiming at the very pathomechanisms specific for neuropathic pain, and to optimize the pharmacological profile of the drug. Thanks to the hybrid structure, analgesic properties of its moieties can be maximized, even if their action as separate pharmacophores tends to be limited or inconsistent under nerve injury conditions, such as in the case of opioid agonists. The present review discusses selected targets of hybrid compounds in the view of potential neuropathic pain therapy, along with the gains, limitations and challenges related to the use of hybrid compounds.

scholarly journals Comparative evaluation of clinical effectivity and side effects of two different parenteral agents used in the treatment of osteoporosis

2014 ◽  
Vol 1 (1) ◽  
pp. 1 ◽  
Author(s):  
Ahmet Aslan ◽  
Ahmet Özmeriç ◽  
Ökkeş Bilal ◽  
Fatih Doğar ◽  
Zübeyde Özkaya ◽  
...  
Keyword(s):  
Side Effects ◽  
Comparative Evaluation ◽  
Treatment Of Osteoporosis

scholarly journals Effect of Plastrum Testudinis Extracts on the Proliferation and Osteogenic Differentiation of rBMSCs by Regulating p38 MAPK-Related Genes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Qi Shang ◽  
Xiang Yu ◽  
Hui Ren ◽  
Gengyang Shen ◽  
Wenhua Zhao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Osteogenic Differentiation ◽  
Mrna Expression ◽  
P38 Mapk ◽  
Bone Diseases ◽  
Treatment Of Osteoporosis ◽  
Osteogenic Induction ◽  
Rat Bone

Extracts from plastrum testudinis (PTE) are active compounds that have been used to treat bone diseases in traditional Chinese medicine for thousands of years. In previous studies, we demonstrated their effects on glucocorticoid-induced osteoporosis both in vivo and in vitro. However, the mechanisms by which PTE regulates the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) in vitro remain poorly understood. In this study, rBMSCs were treated with medium (CON), PTE, osteogenic induction (OI), and a combination of PTE and OI (PTE+OI) over a 21-day period. We found that PTE significantly promoted rBMSCs osteogenic differentiation and mineralisation after 21 days of culturing. Moreover, PTE+OI further enhanced the differentiation and mineralisation process. PTE upregulated STE20, IGF1R, and p38 MAPK mRNA expression and downregulated TRAF6 mRNA expression. The extracts inhibited TRAF6 protein expression and promoted STE20, IGF1R, and phosphorylated p38 MAPK protein expression. Our results imply that PTE promotes the proliferation and osteogenic differentiation of rBMSCs by upregulating p38 MAPK, STE20, and IGF1R and downregulating TRAF6 expression, which may provide experimental evidence of the potential of PTE in the treatment of osteoporosis.

Review of normal gastrointestinal tract, ulcerative colitis, proctitis and rectal medication adherence

2020 ◽  
Vol 29 (14) ◽  
pp. 805-811
Author(s):  
Pineshwari Naeck-Boolauky ◽  
Jitka Adio ◽  
Jennie Burch
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Gastrointestinal Tract ◽  
Side Effects ◽  
Rectal Mucosa ◽  
Gi Tract ◽  
Therapeutic Outcomes ◽  
Rectal Medication ◽  
Inflammatory Bowel

The gastrointestinal (GI) tract has a number of functions—ingestion, digestion, absorption and elimination. When the GI tract is working normally, it is efficient. However, this can change when disease, such as inflammatory bowel disease (IBD) occurs. IBD is a long-term relapsing and remitting autoimmune disease; it incorporates ulcerative colitis (UC). In UC, part or all the mucosa lining the rectum and colon becomes inflamed and ulcerated. UC that affects the rectum only is called proctitis. Effective treatment is essential. It is better to target the rectal mucosa directly in proctitis, using topical rectal medications in enemas or suppositories, as these have fewer side-effects and resolve symptoms more quickly than systemic drugs. However, patients may not feel clear about aspects of their IBD care and can find it difficult to initiate and comply with treatment and maintenance regimens. Nurses need to educate and support them to achieve optimal therapeutic outcomes in both the immediate and long terms.

scholarly journals Bisphosphonates in the treatment of metabolic bone diseases

2010 ◽  
Vol 54 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Henrique Pierotti Arantes ◽  
André Gonçalves da Silva ◽  
Marise Lazaretti-Castro
Keyword(s):  
Bone Resorption ◽  
Bone Diseases ◽  
Low Bone Mass ◽  
Metabolic Bone Diseases ◽  
Treatment Of Osteoporosis ◽  
Good Safety Profile ◽  
Metabolic Bone ◽  
Prevention And Treatment ◽  
High Bone ◽  
Osteonecrosis Of Jaw

Osteoporosis is a disease characterized by low bone mass associated with the deterioration of microarchitecture, due to an imbalance either in high bone resorption or low bone formation or in both, leading to a high risk of fractures. Bisphosphonates are medications which reduce the ability of osteoclasts to induce bone resorption and consequently improve the balance between resorption and formation. There are bisphosphonates approved for the prevention and treatment of osteoporosis. Administration can be oral (daily, weekly or monthly) or intravenous (quarterly or yearly). These medications are well tolerated and with the correct instructions of administration have a good safety profile. Serious side effects, such as, osteonecrosis of jaw is very rare. Bisphosphonates are the most prescribed medication for the treatment of osteoporosis.

scholarly journals Side effects of disodium aminohydroxypropylidenediphosphonate (APD) during treatment of bone diseases.

BMJ ◽  
1984 ◽  
Vol 288 (6420) ◽  
pp. 828-829 ◽  
Author(s):  
C A Mautalen ◽  
C A Casco ◽  
D Gonzalez ◽  
G R Ghiringhelli ◽  
C Massironi ◽  
...  
Keyword(s):  
Side Effects ◽  
Bone Diseases

scholarly journals Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1556 ◽  
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Anticancer Drugs ◽  
Water Solubility ◽  
Review Article ◽  
High Rate ◽  
Therapeutic Outcomes ◽  
Biological Outcomes

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers to result in promising therapeutic outcomes in cancer treatment. Curcumin exhibits good anticancer activity but its poor bioavailability has resulted in its incorporation into several polymer-based nanocarriers resulting in good biological outcomes. Furthermore, the incorporation of curcumin together with other anticancer drugs have been reported to result in excellent therapeutic outcomes in vivo and in vitro. Due to the potential of polymer-based nanocarriers, this review article will be focused on the design of polymer-based nanocarriers loaded with curcumin together with other anticancer drugs.

scholarly journals Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

2020 ◽  
Vol 9 (1) ◽  
pp. 139 ◽  
Author(s):  
Greg Hutchings ◽  
Lisa Moncrieff ◽  
Claudia Dompe ◽  
Krzysztof Janowicz ◽  
Rafał Sibiak ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Bone Diseases ◽  
Basic Knowledge ◽  
Growth Factor Delivery ◽  
Bone Homeostasis ◽  
Skeletal Health ◽  
Paracrine Factors ◽  
Regeneration Rate ◽  
Biomimetic Scaffolds

The deterioration of the human skeleton’s capacity for self-renewal occurs naturally with age. Osteoporosis affects millions worldwide, with current treatments including pharmaceutical agents that target bone formation and/or resorption. Nevertheless, these clinical approaches often result in long-term side effects, with better alternatives being constantly researched. Mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue are known to hold therapeutic value for the treatment of a variety of bone diseases. The following review summarizes the latest studies and clinical trials related to the use of MSCs, both individually and combined with other methods, in the treatment of a variety of conditions related to skeletal health. For example, some of the most recent works noted the advantage of bone grafts based on biomimetic scaffolds combined with MSC and growth factor delivery, with a greatly increased regeneration rate and minimized side effects for patients. This review also highlights the continuing research into the mechanisms underlying bone homeostasis, including the key transcription factors and signalling pathways responsible for regulating the differentiation of osteoblast lineage. Paracrine factors and specific miRNAs are also believed to play a part in MSC differentiation. Furthering the understanding of the specific mechanisms of cellular signalling in skeletal remodelling is key to incorporating new and effective treatment methods for bone disease.

scholarly journals Bisphosphonates in Dentistry – State of the Art

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tamara Vučićević ◽  
Suzana Živanović ◽  
Miloš Papić ◽  
Aleksandra Lukić
Keyword(s):  
Side Effects ◽  
Bone Resorption ◽  
Alveolar Bone ◽  
State Of The Art ◽  
Bone Diseases ◽  
Oral Diseases ◽  
Periapical Lesions ◽  
Bone Preservation ◽  
Effective Drugs

Abstract Bisphosphonates remain the most used and most effective drugs for the treatment of systemic bone diseases followed by bone resorption. Although their side effects in a form of alveolar bone osteonecrosis have been reported, bisphosphonates have a potential of being used in the treatment of the most common oral diseases followed by alveolar bone resorption such as peri-implantitis, periapical lesions, and periodontitis. The aim of this article was to review the most recent research regarding the use of bisphosphonates in the field of dentistry. The results of studies indicate that bisphosphonate use in the treatment of peri-implantitis, periapical lesions, and periodontitis can reduce alveolar bone resorption and contribute to bone preservation. However, the most beneficial way of their application in the treatment of these oral diseases remain to be determined.

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