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The Journal of Histochemistry and... Feb 2022Osteoclasts are cells whose main function is the resorption of bone matrix. However, several factors, including medications, can interfere with the resorption process....
Osteoclasts are cells whose main function is the resorption of bone matrix. However, several factors, including medications, can interfere with the resorption process. Alendronate (ALN), a nitrogen-containing type of bisphosphonate, and dexamethasone (DEX), a glucocorticoid, are drugs that may affect the resorption activity. The aim of this study is to investigate the effects of ALN, and/or DEX on osteoclast gene expression and resorption activity in primary mouse marrow cultures stimulated with 1,25-dihydroxyvitamin D3, a model for the bone microenvironment. Cultures were treated only with ALN (10 M), DEX (10 M), and with a combination of both agents. Viability assays performed at days 5, 7, and 9 showed the highest number of viable cells at day 7. All the following assays were then performed at day 7 of cell culture: tartrate resistant acid phosphatase (TRAP) histochemistry, receptor activator of nuclear factor kappa B ligand (RANKL) immunofluorescence, osteoprotegerin (OPG), and RANKL gene expression by qPCR and resorption analysis by scanning electron microscopy. Treatment with ALN, DEX, and the combination of both did not promote significant changes in the number of TRAP+ cells, although larger giant cells were detected in groups treated with DEX. DEX treatment increased the gene expression of RANKL and reduced OPG. The treatment with ALN reduced the depth of the resorption pits, but their inhibitory effect was less effective when administered with DEX.
Topics: Alendronate; Animals; Bone Marrow; Bone Resorption; Cattle; Cell Survival; Cells, Cultured; Dexamethasone; Dose-Response Relationship, Drug; Mice; Mice, Inbred BALB C; Osteoclasts
PubMed: 34915746
DOI: 10.1369/00221554211063519 -
Ugeskrift For Laeger Jul 2022The inflammatory side effects of bisphosphonates are well-known. We report a case of orbital and ocular inflammation secondary to the use of intravenous zoledronic acid...
The inflammatory side effects of bisphosphonates are well-known. We report a case of orbital and ocular inflammation secondary to the use of intravenous zoledronic acid and a case of scleritis secondary to oral alendronate. Bisphosphonate-induced inflammation can present as uveitis, (epi)scleritis, and orbital inflammation. The course is typically self-limiting after cessation of bisphosphonate therapy, but resolution can be further promoted by steroid therapy. The ocular side effects of bisphosphonates should be duly considered.
Topics: Alendronate; Bone Density Conservation Agents; Diphosphonates; Humans; Inflammation; Scleritis
PubMed: 35959811
DOI: No ID Found -
Anatomical Science International Jan 2023Osteoporosis increases bone fragility and fractures. Preptin hormone is regulated by moderate exercise training and increases bone formation. Therefore, this study was...
Osteoporosis increases bone fragility and fractures. Preptin hormone is regulated by moderate exercise training and increases bone formation. Therefore, this study was conducted to see how estradiol administration and moderate exercise training affected osteoporotic changes in ovariectomized (OVX) rats. To achieve this aim, 36 healthy adult female Wistar albino rats were randomized into Sham, OVX, ovariectomized estradiol-treated (OVX + E) (OVX + E rats were treated using subcutaneous estradiol benzoate 2.5 μg/kg body weight/day), ovariectomized practicing moderate exercise training, ovariectomized estradiol-treated and practiced a moderate exercise training, and ovariectomized alendronate-treated (OVX + Alen) (OVX + Alen rats were treated orally with alendronate 3 mg/kg body weight/week) groups. Alendronate was used as a standard anti-osteoporotic drug. Moderate exercise training, including therapy with estradiol and alendronate for OVX rats began on the fourth week and lasted for six weeks. Results showed that OVX rats had estrogen and preptin deficiency in serum. These deficiencies were associated with a significant increase in bone resorption biomarkers (urinary deoxypyridinoline and hydroxyproline), and bone formation biomarkers (serum osteocalcin and bone-specific alkaline phosphatase). Also, serum pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) were increased, while bone osteopontin (OPN) expression was decreased. Subsequently, the osteoporotic alterations were verified based on histopathological changes. From the results, estradiol therapy and moderate exercise training significantly improved these findings to the same extent as that of the standard alendronate treatment. Therefore, through their anti-inflammatory properties, increasing bone OPN expression, and regulating serum preptin; estradiol therapy and moderate exercise training can reduce osteoporotic alterations in OVX rats. Thus, combined estradiol therapy and moderate exercise training could be a promising potential therapeutic protocol to reduce postmenopausal osteoporosis. Also, targeting serum preptin and bone osteopontin regulation could have a critical role in the treatment of postmenopausal osteoporosis.
Topics: Animals; Humans; Rats; Female; Bone Density; Alendronate; Osteoporosis, Postmenopausal; Osteopontin; Rats, Wistar; Estradiol; Body Weight; Biomarkers; Ovariectomy
PubMed: 35507276
DOI: 10.1007/s12565-022-00666-7 -
Toxicology and Applied Pharmacology Oct 2023Alendronate, a nitrogen-containing bisphosphonate, has reported long-term clinical success in the management of distinct bone-related conditions, particularly in the...
Alendronate, a nitrogen-containing bisphosphonate, has reported long-term clinical success in the management of distinct bone-related conditions, particularly in the modulation of post-menopausal osteoporosis. Nonetheless, whether the inhibitory activity over osteoclastic cells' functionality is widely acknowledged, contradictory evidence arises from the assessment of alendronate activity over osteoblastic populations. This may be of particular relevance in situations in which bone formation exceeds bone resorption, with further emphasis on embryonic development, since alendronate can cross the placental barrier and alendronate-based therapies are being extended into women of reproductive age. Accordingly, the present study aims to assess the effects of alendronate, at distinct concentrations (1.5EM to 1.5EM) on bone tissue development, within a translational animal model - the embryonic chicken development model. Embryos, at the beginning of osteogenesis (day 7) were exposed to different alendronate concentrations for 4 days. Embryos were following characterized for skeletal development by histomorphometric analysis upon histochemical staining, microtomographic analysis, and gene expression assessment of genes related to osteoclastogenic/osteoclastic and osteoblastogenic/osteogenic differentiation, as well as to the immuno-inflammatory activation. The findings revealed that exposure to alendronate had a dose-dependent impact on skeletal growth and mineralization. This effect was evidenced by diminished bone volume and reduced bone surface parameters, with the 1.5EM concentration leading to a remarkable reduction of over 50%. Additionally, a decreased osteoclastogenic/osteoclastic gene expression was verified, associated with a diminished osteoblastogenic/osteogenic program - within the 30-50% range for 1.5E-7 M, supporting the diminished bone formation process. An increased inflammatory activation may contribute, at least in part, to the attained outcomes. Overall present findings suggest a negative influence of alendronate on the embryonic bone development process in a dose-dependent manner, highlighting the potential risk of alendronate use during embryonic development.
Topics: Female; Pregnancy; Animals; Chick Embryo; Alendronate; Osteogenesis; Chickens; Placenta; Embryonic Development
PubMed: 37652309
DOI: 10.1016/j.taap.2023.116673 -
Archivos de La Sociedad Espanola de... Sep 2022We aimed to investigate ocular involvement findings in female osteoporosis patients using oral bisphosphonate (BP).
OBJECTIVE
We aimed to investigate ocular involvement findings in female osteoporosis patients using oral bisphosphonate (BP).
METHODS
A total of 51 female osteoporosis patients aged 50-75 years using oral BP for at least one year for the study group and 64 age-matched non-osteoporosis female patients for the control group were included in the study. The BP type and exposure time were noted. The ophthalmic examination findings and measurements of the flare of the patients who received oral BP due to osteoporosis and the controls were evaluated.
RESULTS
The mean duration of BP use was 3.96 years. In the study group, it was detected four of 51 patients were diagnosed with meibomian gland dysfunction (MGD) (7.8%), seven of 102 eyes had erythematous, irregular, thickened lid margin or telangiectasia around the glandular orifices. There were no pathological findings on fundus examination. The mean value of measurements of the flare (ph/ms) was 7.90±7.96 in the study group, and 5.02±0.81 in the control group. When the mean values were compared, there was a significant difference between the two groups (P=.001). A significant difference was found in the mean value of measurements of the flare between the patients using alendronate, and ibandronate with the control group (P=.001; P=.005, respectively).
CONCLUSION
Our study showed that the flare in the anterior chamber associated with chronic ocular inflammation can be seen higher rate in patients using oral alendronate, and ibandronate compared to those who do not. Morever it can be said that oral BPs may cause similar ocular side effects like as intravascular BPs.
Topics: Administration, Oral; Alendronate; Diphosphonates; Female; Humans; Ibandronic Acid
PubMed: 35787381
DOI: 10.1016/j.oftale.2022.06.006 -
Journal of Korean Medical Science Feb 2019
Topics: Alendronate; Cell Differentiation; Cell Proliferation; Clay; Osteogenesis
PubMed: 30718995
DOI: 10.3346/jkms.2019.34.e44 -
Journal of Bone and Mineral Metabolism Sep 2020Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been...
INTRODUCTION
Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment.
MATERIALS AND METHODS
In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months.
RESULTS
The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar.
CONCLUSION
The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.
Topics: Alendronate; Aromatase Inhibitors; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Breast Neoplasms; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Retrospective Studies
PubMed: 32405760
DOI: 10.1007/s00774-020-01111-3 -
Colloids and Surfaces. B, Biointerfaces Jun 2016In this article, the synthesis of a novel calcification-targeting nanoparticle (NP) is reported, which is realized through dopamine self-polymerization on the...
In this article, the synthesis of a novel calcification-targeting nanoparticle (NP) is reported, which is realized through dopamine self-polymerization on the poly(lactic-co-glycolic acid) (PLGA) particle surface and subsequent alendronate conjugation. Cell viability and proliferation tests confirmed that such particle has low cytotoxicity and good biocompatibility. Experiments were designed to observe whether the synthesized NPs can pass through an obstructive hydrogel and directly bind themselves to hydroxyapatite (HA) NPs (mimicking calcified spots) and HA porous scaffolds (mimicking calcified tissues); and the result was positive, indicating ingenious targeting of NPs on calcifications. The calcification-targeting NPs are expected to be with promising applications on calcification-related disease diagnoses and therapies.
Topics: Alendronate; Animals; Bone Density Conservation Agents; Calcification, Physiologic; Cell Proliferation; Cell Survival; Dopamine; Drug Carriers; Durapatite; Humans; Hydrogels; Lactic Acid; Mice; NIH 3T3 Cells; Nanoparticles; Particle Size; Permeability; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymerization
PubMed: 26970822
DOI: 10.1016/j.colsurfb.2016.03.015 -
Clinical Oral Investigations Feb 2019The objectives of this study were to analyze the effect of pH on the growth and activity of osteoclasts treated with different doses of two nitrogen-containing BPs,...
OBJECTIVES
The objectives of this study were to analyze the effect of pH on the growth and activity of osteoclasts treated with different doses of two nitrogen-containing BPs, zoledronate and alendronate.
MATERIALS AND METHODS
Murine osteoclasts cultured on dentine disks were treated with zoledronate (50 or 500 nM) or alendronate (500 or 5 μM) at two different pH values (7.4 or 7.0). Osteoclasts were counted with transmitted light microscopy, apoptosis/necrosis was studied with flow cytometry and confocal microscopy, and resorption pit number and depth were calculated using reflected light and scanning electron microscopy.
RESULTS
The osteoclast count on dentine disks was significantly (p < 0.001) reduced by zoledronate or alendronate treatment at pH 7.0 in comparison to treatment with the same doses at pH 7.4 and untreated disks (controls). The percentage of apoptotic cells was significantly increased by treatment with 500 nM zoledronate or 5 μM alendronate at pH 7.0 in comparison to the same doses at pH 7.4. The number and depth of resorption pits were significantly lower in disks treated at each BP dose studied than in untreated controls at pH 7.0.
CONCLUSIONS
Zoledronate and alendronate at therapeutic doses have an adverse effect on the viability and resorptive activity of osteoclasts when the local medium pH is reduced.
CLINICAL RELEVANCE
These findings suggest that periodontal or peri-implant oral cavity infection may be a key trigger of the cascade of events that lead to BRONJ.
Topics: Alendronate; Animals; Bone Density Conservation Agents; Cells, Cultured; Dentin; Flow Cytometry; Hydrogen-Ion Concentration; In Vitro Techniques; Mice; Microscopy, Confocal; Microscopy, Electron, Scanning; Osteoclasts; Zoledronic Acid
PubMed: 29876664
DOI: 10.1007/s00784-018-2505-z -
International Journal of Biological... Dec 2023A novel co-hybrid nano-apatite (n-HA) by introducing lignin derivatives (LDs) and alendronate (ALE) was designed to reinforce poly(lactide-co-glycolide) (PLGA). The...
A novel co-hybrid nano-apatite (n-HA) by introducing lignin derivatives (LDs) and alendronate (ALE) was designed to reinforce poly(lactide-co-glycolide) (PLGA). The effect of different addition methods and contents of LDs, lignin derivatives sorts of lignosulfonate (LS), alkali lignin (AL) and carboxymethyl lignin (CML), and the addition order of ALE on the dispersion of hybrid n-HA, and reinforce effective for PLGA were investigated by FTIR, XRD, TEM, TGA, XPS, N adsorption/desorption, zeta potential, dispersion experiments, universal testing machine, SEM, DSC and POM. The results showed that the addition order could regulate the growth of n-HA crystal planes by binding with Ca, and co-hybrid HA by LDs and ALE possessed better dispersion owing to the synergistic effect. Moreover, 10 wt% LS-ALE-n-HA displayed the best reinforce effect, and the tensile strength of composite was 24.43 % higher than that of PLGA, even 15 wt% LS-ALE-n-HA was added, it still exhibited reinforce effect for PLGA. In vitro soaking in simulated body fluid (SBF) results indicated that LS-ALE-n-HA delayed tensile strength reduce of PLGA and promoted bone-like apatite deposition. The cell proliferation results demonstrated that the hybrid n-HA by the introduction of ALE endowed PLGA with better cell adhesion and proliferation.
Topics: Durapatite; Polylactic Acid-Polyglycolic Acid Copolymer; Alendronate; Polyglycolic Acid; Polyglactin 910; Lignin; Lactic Acid
PubMed: 37696379
DOI: 10.1016/j.ijbiomac.2023.126785