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

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.

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

Journal of Clinical Medicine ◽

10.3390/jcm9010139 ◽

2020 ◽

Vol 9 (1) ◽

pp. 139 ◽

Cited By ~ 6

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.

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Bisphosphonates in Dentistry – State of the Art

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2020-0061 ◽

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

International Journal of Molecular Sciences ◽

10.3390/ijms22136869 ◽

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.

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Amifostine Suppresses the Side Effects of Radiation on BMSCs by Promoting Cell Proliferation and Reducing ROS Production

Stem Cells International ◽

10.1155/2019/8749090 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Bo Huang ◽

Tao He ◽

Qianqian Yao ◽

Liang Zhang ◽

Yang Yao ◽

...

Keyword(s):

Cell Proliferation ◽

Side Effects ◽

Bone Diseases ◽

Ros Production ◽

Radiation Group ◽

Group A ◽

Effects Of Radiation ◽

Group B ◽

Group D ◽

Stromal Stem Cells

This study is aimed at investigating the effect of amifostine (AMI) on rat bone marrow stromal stem cells (BMSCs) exposed to 2 Gy radiation. The BMSCs were divided into four groups, namely, group A that received 0 Gy radiation, group B that received 0 Gy radiation and AMI, group C that received 2 Gy radiation, and group D that received 2 Gy radiation and AMI. The proliferation, apoptosis, and distribution of BMSCs in the cell cycle, along with their osteogenesis ability, adipogenesis ability, and ROS production, were subsequently examined. The levels of ALP, PPARγ, P53, and TNFα were determined by Western blotting. The results demonstrated that the proliferation of BMSCs and the levels of ALP in group C were much lower than those in group A. The production of ROS and levels of PPARγ, P53, and TNFα in the group that received 2 Gy radiation were much higher than those in group A. Furthermore, the production of ROS and the levels of PPARγ, P53, and TNFα were much lower in group D than in group C. Additionally, the levels of ALP and extent of cell proliferation were much higher in group D than in group C. The results demonstrated the potential of AMI in reducing the side effects of radiation in BMSCs and in treatment of bone diseases caused by radiation.

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Bisphosphonates in Bone Diseases Treatment

Revista de Chimie ◽

10.37358/rc.17.2.5429 ◽

2017 ◽

Vol 68 (2) ◽

pp. 246-249 ◽

Cited By ~ 2

Author(s):

Adela Cristina Lazar ◽

Mariana Pacurar ◽

Radu Septimiu Campian

Keyword(s):

Side Effects ◽

Carbon Atom ◽

Oxygen Atom ◽

Binding Capacity ◽

Chemical Compounds ◽

Bone Diseases ◽

The Other ◽

Complex Chemical ◽

The One ◽

Cancer Diseases

Bisphosphonates are the most frequently used drugs in the treatment of various bone and cancer diseases. They are complex chemical compounds, having a structure similar to that of pyrophosphates, but with certain differences: i.e., bisphosphonates have P-C-P in their composition; instead of an oxygen atom, a carbon atom is present. The R1 and R2 chains bind to the carbon atom and thus, the antiresorptive capacity of bisphosphonates on the one hand, and their bone-binding capacity on the other hand are stimulated. Through their action, they favor the treatment of diseases for which they have been prescribed, but they can also favor a number of undesired side effects.

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H2S Donor and Bone Metabolism

Frontiers in Pharmacology ◽

10.3389/fphar.2021.661601 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yanming Hao ◽

Hongzhen Wang ◽

Lingna Fang ◽

Jinsong Bian ◽

Yan Gao ◽

...

Keyword(s):

Side Effects ◽

Bone Metabolism ◽

Metabolic Diseases ◽

Biological Effects ◽

Bone Diseases ◽

The Body ◽

Metabolic Bone Diseases ◽

Physiological Processes ◽

Metabolic Bone ◽

And Function

Hydrogen sulfide (H2S) has been recognized as the third gasotransmitter, following nitric oxide and carbon monoxide, and it exerts important biological effects in the body. Growing evidence has shown that H2S is involved in many physiological processes in the body. In recent years, much research has been carried out on the role of H2S in bone metabolism. Bone metabolic diseases have been linked to abnormal endogenous H2S functions and metabolism. It has been found that H2S plays an important role in the regulation of bone diseases such as osteoporosis and osteoarthritis. Regulation of H2S on bone metabolism has many interacting signaling pathways at the molecular level, which play an important role in bone formation and absorption. H2S releasing agents (donors) have achieved significant effects in the treatment of metabolic bone diseases such as osteoporosis and osteoarthritis. In addition, H2S donors and related drugs have been widely used as research tools in basic biomedical research and may be explored as potential therapeutic agents in the future. Donors are used to study the mechanism and function of H2S as they release H2S through different mechanisms. Although H2S releasers have biological activity, their function can be inconsistent. Additionally, donors have different H2S release capabilities, which could lead to different effects. Side effects may form with the formation of H2S; however, it is unclear whether these side effects affect the biological effects of H2S. Therefore, it is necessary to study H2S donors in detail. In this review, we summarize the current information about H2S donors related to bone metabolism diseases and discuss some mechanisms and biological applications.

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Gastric Ulcers Produced by Cisplatin

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099337 ◽

1981 ◽

Vol 39 ◽

pp. 582-583

Author(s):

S.K. Aggarwal ◽

J. San Antonio

Keyword(s):

Electron Microscopy ◽

Single Dose ◽

Side Effects ◽

Antitumor Agent ◽

Gastric Ulcers ◽

Enzyme Cytochemistry ◽

Intestinal Toxicity ◽

Ovarian Cancers ◽

Inner Surface

Cisplatin (cis-dichlorodiammineplatinum(II)) a potent antitumor agent is now available for the treatment of testicular and ovarian cancers. It is however, not free from its serious side effects including nephrotoxicity, gastro intestinal toxicity, myelosuppression, and ototoxicity. Here we now report that the drug produces peculiar bloating of the stomach in rats and induces acute ulceration.Wistar-derived rats weighing 200-250 g were administered cisplatin(9 mg/kg) ip as a single dose in 0.15 M NaCl. After 3 days the animals were sacrificed by decapitation. The stomachs were removed, the contents analyzed for pepsin and acidity. The inner surface was examined with a dissecting microscope after a moderate stretching for ulcers. Affected areas were fixed and processed for routine electron microscopy and enzyme cytochemistry.The drug treated animals kept on food and water consistently showed bloating and lesions (Fig. 1) with a frequency of 6-70 ulcers in the rumen section of the stomachs.

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Effects of cisplatin treatment on the rat neurohypophysis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142256 ◽

1986 ◽

Vol 44 ◽

pp. 122-123

Author(s):

J.M. Fadool ◽

P.J. Boyer ◽

S.K. Aggarwal

Keyword(s):

Side Effects ◽

Urine Output ◽

Morphological Changes ◽

Limiting Factor ◽

Antineoplastic Drugs

Cisplatin (CDDP) is currently one of the most valuable antineoplastic drugs available. However, it has severe toxic side effects of which nephrotoxicity is the major dose limiting factor in its use. It induces morphological changes in the kidney with hampered urine output. The present study is an effort to determine the influence of the drug on the neurohypophysis for any antidiuretic effects on the kidney.

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Severe Drooling and Treatment With Botulinum Toxin

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd21.1.15 ◽

2012 ◽

Vol 21 (1) ◽

pp. 15-21

Author(s):

Merete Bakke ◽

Allan Bardow ◽

Eigild Møller

Keyword(s):

Botulinum Toxin ◽

Side Effects ◽

Health Risk ◽

Flow Rate ◽

Clinical Evidence ◽

Acetylcholine Release ◽

Psychosocial Problems ◽

Rate Reduction ◽

Local Inhibition ◽

Surgical Treatments

Severe drooling is associated with discomfort and psychosocial problems and may constitute a health risk. A variety of different surgical and non-surgical treatments have been used to diminish drooling, some of them with little or uncertain effect and others more effective but irreversible or with side effects. Based on clinical evidence, injection with botulinum toxin (BTX) into the parotid and submandibular glands is a useful treatment option, because it is local, reversible, and with few side effects, although it has to be repeated. The mechanism of BTX is a local inhibition of acetylcholine release, which diminishes receptor-coupled secretion and results in a flow rate reduction of 25–50% for 2–7 months.

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