Search results for: bisphosphonates

Authors: Mohammad ASadian, Samira RajiAsadabadi

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Osteoporosis is very common, particularly in post-menopausal women and is characterized by a decrease in bone mass and strength. Osteoporosis also affects the jawbone and it is considered a potential contraindication to the placement of dental implants. The present paper reviews the literature regarding the effect of osteoporosis on the osseointegration of implants. Experimental models have shown that osteoporosis affects the process of osseointegration, which can be reversed by treatment. However, studies in subjects with osteoporosis have shown no differences in the survival of the implants compared to healthy individuals. Therefore, osteoporosis cannot be considered a contraindication for implant placement. Oral bisphosphonates are the most commonly used pharmacological agents in the treatment of osteoporosis. Although there have been cases of osteonecrosis of the jaw in patients treated with bisphosphonates, they are very rare and it is more usually associated with intravenous bisphosphonates in patients with neoplasms or other serious diseases. Nevertheless, patients treated with bisphosphonates must be informed in writing about the possibility of this complication and must give informed consent. Ceasing to use of bisphosphonates before implant placement does not seem to be necessary.

Keywords: Osteoporosis, dental implant, bisphosphonates, survival

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Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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Authors: Blessing Atim Aderibigbe

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A series of amine/ester-linked hybrid compounds containing pharmacophores, such as ursolic acid, oleanolic acid, ferrocene and bisphosphonates, were synthesized in an attempt to develop potent antibacterial and anticancer agents. Their structures were analyzed and confirmed using Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy, and mass spectroscopy. All the synthesized hybrid compounds were evaluated for their antibacterial activities against eleven selected bacterial strains using a serial dilution method. Some of the compounds displayed significant antibacterial activity against most of the bacterial and fungal strains. In addition, the in vitro cytotoxicity of these compounds was also performed against selected cancer cell lines. Some of the compounds were also found to be more active than their parent compounds, revealing the efficacy of designing hybrid molecules using plant-based bioactive agents.

Keywords: ursolic acid, hybrid drugs, oleanolic acid, bisphosphonates

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Authors: Esra Yuce, Isil D. S. Yamaner, Murude Yazan

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Aims and objective: Antiresorptive agents including bisphosphonates and denosumab as strong suppressors of osteoclasts are the most commonly used antiresorptive medications for the treatment of osteoporosis which counteract the negative quantitative alteration of trabecular and cortical bone by inhibition of bone turnover. Oral bisphosphonate therapy for the treatment of osteopenia, osteoporosis or Paget's disease is associated with the low-grade risk of osteonecrosis of the jaw, while higher-grade risk is associated with receiving intravenous bisphosphonates therapy in the treatment of multiple myeloma and bone metastases. On the other hand, there has been a remarkable increase in incidences of antiresorptive related osteonecrosis of the jaw (ARONJ) in oral bisphosphonate users. This clinical presentation will evaluate the healing outcomes via piezoelectric bone surgery under the irrigation of PVP-I solution irrigation in patients received bisphosphonate therapy. Material-Method: The study involved 8 female and 5 male patients that have been treated for ARONJ. Among 13 necrotic sites, 9 were in the mandible and 4 were in the maxilla. All of these 13 patients treated with surgical debridement via piezoelectric bone surgery under irrigation by solution with 3% PVP-I concentration in combination with long-term antibiotic therapy and 5 also underwent removal of mobile segments of bony sequestrum. All removable prosthesis in 8 patients were relined with soft liners during the healing periods in order to eliminate chronic minor traumas. Results: All patients were on oral bisphosphonate therapy for at least 2 years and 5 of which had received intravenous bisphosphonates up to 1 year before therapy with oral bisphosphonates was started. According to the AAOMS staging system, four cases were stage II, eight cases were stage I, and one case was stage III. The majority of lesions were identified at sites of dental prostheses (38%) and dental extractions (62%). All patients diagnosed with ARONJ stage I had used unadjusted removable prostheses. No recurrence of the symptoms was observed during the present follow-up (9–37 months). Conclusion: Despite their confirmed effectiveness, the prevention and treatment of osteonecrosis of the jaw secondary to oral bisphosphonate therapy remain major medical challenges. Treatment with piezoelectric bone surgery with irrigation of povidone-iodine solution was effective for management of bisphosphonate-related osteonecrosis of the jaw. Taking precautions for patients treated with oral bisphosphonates, especially also denture users, may allow for a reduction in the rate of developing osteonecrosis of the maxillofacial region.

Keywords: antiresorptive drug related osteonecrosis, bisphosphonate therapy, piezoelectric bone surgery, povidone iodine

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Authors: Mai Ashraf Talaat

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Objectives: The aim of this review article is to assess the success of dental implants in breast cancer patients receiving bisphosphonate therapy and to evaluate the risk of developing bisphosphonate-related osteonecrosis of the jaw following dental implant surgery. Materials and Methods: A thorough search was conducted, with no time or language restriction, using: PubMed, PubMed Central, Web of Science, and ResearchGate electronic databases. Medical Subject Headings (MeSH) terms such as “bisphosphonate”, “dental implant”, “bisphosphonate-related osteonecrosis of the jaw (BRONJ)”, “osteonecrosis”, “breast cancer, MRONJ”, and their related entry terms were used. Eligibility criteria included studies and clinical trials that evaluated the impact of bisphosphonates on dental implants. Conclusion: Breast cancer patients undergoing bisphosphonate therapy may receive dental implants. However, the risk of developing BRONJ and implant failure is high. Risk factors such as the type of BP received, the route of administration, and the length of treatment prior to surgery should be considered. More randomized controlled trials with long-term follow-ups are needed to draw more evidence-based conclusions.

Keywords: dental implants, breast cancer, bisphosphonates, osteonecrosis, bisphosphonate-related osteonecrosis of the jaw

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Authors: Alexandru Grigorescu, Alexandra Protesanu

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Background: Approximately 34-67 percent of cancer patients experience an episode of uncontrolled pain during the course of their disease, depending on the stage. The aim is to provide evidence-based data for pain prevalence, diagnosis and treatment recommendations on an integrative model of medical oncology and palliative care for patients with cancer diagnostic in a day hospital. Patients and method: Consultation registers and electronic records of 166 Patients (Pts) were studied from April 2022 to March 2023. Pts with pain syndrome were selected. The pain was objectified by the visual pain scale. To elucidate the causes of the pain, investigations were carried out: bone scintigraphy, CT scan, and PET-CT. The analgesic treatments were represented by weak and strong morphine, radiotherapy, and bisphosphonates. Result: During the mentioned period, 166 oncological patients (74 women and 92 men) were treated in the oncology day hospitalization service. There were 1,500 consultations, 40 of which were only for pain. The neoplastic locations were: gynecological, malignant melanoma, breast, gastric, bronchopulmonary, colorectal, liver, pancreatic, bladder, and kidney. 70 Pts presented pain syndrome. The causes of the pain were represented by bone metastases, compressive tumors, and post-surgical status. Drug treatment: Tramadol 47 Pts, of which 10 switched to a major opioid (Oxycodonum, Morphine sulfate), 20 Pts were treated with Oxycodonum as the first intention. In 5 patients ry to rotated morphine, 20 Pts received palliative radiotherapy, 10 Pts were treated with bisphosphonates. 2 Pts required neurosurgery consultation for an antalgic intervention. 5 Pts had important adverse reactions to morphine. All patients and their families were advised by a medical oncologist and psychologist for a lifestyle change. Conclusions: The prevalence of pain was similar to that described in the literature. In most cases, the pain could be managed in the day hospital. Weak and strong morphine represented the main pain therapy. Palliative radiotherapy was the second most effective therapy. Treatment with bisphosphonates was useful. Surgical interventions were rarely indicated. Discussions with patients and their families regarding the lifestyle change were important.

Keywords: cancer pain, opioids, medical oncology, palliative care

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Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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Authors: Seyedeh Faranak Baniahmad, Soroor Yousefi

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Osteoporosis is a bone disease which increases the bone fracture risk, reduces the bone mineral density (BMD) and alters the amount and variety of proteins in bones. Antiresorptive therapy is one the most popular Osteoporosis treatment methods. In this method the bisphosphonates, hormones, calcitonin or the selective estrogen receptor modulators is replaced. In order to reduce undesirable effects and to increase the bioavailability of drug agents, the controlled drug delivery systems have been utilized. In current study, the controlled release of Alendronate from LDH-PCL with (0, 5, 10, 15 % wt. of LDH) was investigated. The results showed that the release of alendronate from the lamellar LDH incorporated into the PCL matrix is much slower than the release of alendronate from the PCL. Therefore such systems are very promising, in which the antiresorptive drug has to remain in the matrix for longer time and can be released in controlled manner.

Keywords: osteoporosis, alendronate, poly (ε–caprolactone), layered double hydroxide

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Authors: S. Alireza Mirghasemi, Elly Trepman, Mohammad Saleh Sadeghi, Narges Rahimi Gabaran, Shervin Rashidinia

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Bone marrow edema syndrome (BMES) is an uncommon and self-limited syndrome characterized by atraumatic extremity pain with unknown of etiology. Symptom onset may include sudden or gradual swelling and pain at rest or during activity, usually at night. This syndrome mostly affects middle-aged men and younger women who have pain in the lower extremities. The most common sites involved with BMES, in decreasing order of frequency, are the bones about the hip, knee, ankle, and foot. The diagnosis of BMES is made with magnetic resonance imaging to exclude other causes of bone marrow edema. The correct diagnosis often is delayed because of the low prevalence and nonspecific signs in the foot and ankle. This delay may intensify bone pain and impair patient function and quality of life. The goal of BMES treatment is to relieve pain and shorten disease duration. Treatment options are limited and may include symptomatic treatment, pharmacologic treatment, and surgery.

Keywords: transient osteoporosis, bone marrow edema syndrome, iloprost, bisphosphonates

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Authors: Soyeon Kang, Youn-Jee Chung, Jung Namkung

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Objective: This retrospective study investigated the association between uric acid level and bone mineral density (BMD) in the postmenopausal period. Methods: The study included 328 menopausal women (mean age, 57.3 ± 6.5 years; mean serum uric acid level, 4.6 ± 1.0 mg/dL). Patients were divided into three groups by tertile of serum uric acid level. Patients who used hormone treatment (HT), bisphosphonates, or lipid-lowering agents were included. Results: Blood urea nitrogen, serum creatinine, and serum triglyceride levels were significantly higher in the upper uric acid tertiles. No significant difference was found in the mean uric acid levels between medication users and non-users. Distinct HT regimens showed different mean serum uric acid levels. In a cross-sectional analysis, higher serum uric acid levels showed a tendency toward increased BMD in the spine and femoral neck. Longitudinal analysis of 186 women who underwent follow-up examination at a mean interval of 14.6 months revealed a trend toward a smaller reduction in femoral neck BMD in women in the upper serum uric acid tertiles. Conclusion: A positive correlation exists between serum uric acid levels and BMD in menopausal women.

Keywords: menopause, antioxidant, uric acid, bone mineral density

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Authors: Mark T. Hanson, Alan T. Varughese

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Osteoporosis is a disease affecting bone quality which in turn can increase the risk of low energy fractures. Treatment of osteoporosis using Bisphosphonates has the beneficial effect of increasing bone mass while at the same time has been linked to the formation of atypical femoral fractures. This has led to the increased study of micro-fractures in bones of patients using Bisphosphonate treatment. One of the mechanics related issues which have been identified in this regard is the loss in stiffness of bones containing one or many micro-fractures. Different theories have been put forth using fracture mechanics to determine the effect of crack presence on elastic properties such as modulus. However, validation of these results in a deterministic way has not been forthcoming. The present analysis seeks to provide this deterministic evaluation of fracture’s effect on the elastic modulus. In particular, the effect of crack size, crack orientation and crack number on elastic modulus is investigated. In particular, the Finite Element method is used to explicitly determine the elastic modulus reduction caused by the presence of cracks in a representative volume element. Single cracks of various lengths and orientations are examined as well as cases of multiple cracks. Cracks in tension as well as under shear stress are considered. Although the focus is predominantly two-dimensional, some three-dimensional results are also presented. The results obtained show the explicit reduction in modulus caused by the parameters of crack size, orientation and number noted above. The present results allow the interpretation of the various theories which currently exist in the literature.

Keywords: cracks, elastic, fracture, modulus

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Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

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Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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Authors: Arezoo Rahmani, Rinez Thapa, Juha-Matti Aalto, Petri Turhanen, Jouko Vepsalainen, Vesa-PekkaLehto, Joakim Riikonen

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Production of Scandium (Sc) is a complicated process because Sc is found only in low concentrations in ores and the concentration of Sc is very low compared with other metals. Therefore, utilization of typical extraction processes such as solvent extraction is problematic in scandium extraction. The Adsorption/desorption method can be used, but it is challenging to prepare materials, which have good selectivity, high adsorption capacity, and high stability. Therefore, efficient and environmentally friendly methods for Sc extraction are needed. In this study, the nanoporous composite material was developed for extracting Sc from an Sc ore. The nanoporous composite material offers several advantageous properties such as large surface area, high chemical and mechanical stability, fast diffusion of the metals in the material and possibility to construct a filter out of the material with good flow-through properties. The nanoporous silicon material was produced by first stabilizing the surfaces with a silicon carbide layer and then functionalizing the surface with bisphosphonates that act as metal chelators. The surface area and porosity of the material were characterized by N₂ adsorption and the morphology was studied by scanning electron microscopy (SEM). The bisphosphonate content of the material was studied by thermogravimetric analysis (TGA). The concentration of metal ions in the adsorption/desorption experiments was measured with inductively coupled plasma mass spectrometry (ICP-MS). The maximum capacity of the material was 25 µmol/g Sc at pH=1 and 45 µmol/g Sc at pH=3, obtained from adsorption isotherm. The selectivity of the material towards Sc in artificial solutions containing several metal ions was studied at pH one and pH 3. The result shows good selectivity of the nanoporous composite towards adsorption of Sc. Scandium was less efficiently adsorbed from solution leached from the ore of Sc because of excessive amounts of iron (Fe), aluminum (Al) and titanium (Ti) which disturbed the adsorption process. For example, the concentration of Fe was more than 4500 ppm, while the concentration of Sc was only three ppm, approximately 1500 times lower. Precipitation methods were developed to lower the concentration of the metals other than Sc. Optimal pH for precipitation was found to be pH 4. The concentration of Fe, Al and Ti were decreased by 99, 70, 99.6%, respectively, while the concentration of Sc decreased only 22%. Despite the large reduction in the concentration of other metals, more work is needed to further increase the relative concentration of Sc compared with other metals to efficiently extract it using the developed nanoporous composite material. Nevertheless, the developed material may provide an affordable, efficient and environmentally friendly method to extract Sc on a large scale.

Keywords: adsorption, nanoporous silicon, ore solution, scandium

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