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Cartilage Dec 2022To characterize the effects of parathyroid hormone (PTH) and alendronate (Alend) on the osteochondral tissue of temporomandibular joint (TMJ).
OBJECTIVE
To characterize the effects of parathyroid hormone (PTH) and alendronate (Alend) on the osteochondral tissue of temporomandibular joint (TMJ).
MATERIALS AND METHODS
Ninety-six male and female transgenic reporter mice, 4 to 5 weeks old were divided into 6 groups: (1) Control group: Saline was injected daily for 14 days; (2) PTH: PTH was injected daily for 14 days; (3) Alend: Alend was injected every alternate days for 14 days; (4) Combined PTH and Alend: PTH was injected daily and Alend injected every alternate days for 14 days; (5) PTH then Alend: PTH was injected daily for 14 days followed by Alend injections in alternate days for 14 days; and (6) PTH wait Alend: PTH was injected daily for 14 days. There was a waiting period of 1 week before administration of Alend in alternate days for 14 days. Mice were injected with 5-ethnyl-2'-deoxyuridine (EdU), 48 and 24 hours prior to euthanization.
RESULTS
There was significant increase in bone volume and decrease in osteoclastic activity in groups in which Alend was administered after PTH in both gender. There was significant increase in cartilage thickness with PTH or Alend alone in females, whereas in males, PTH alone led to increase in cartilage thickness. Chondrocyte apoptosis was significantly decreased with PTH or Alend alone in both male and female. Matrix metallopeptidase 13, and aggreganase-2 (ADAMTS5) expression were significantly decreased with PTH and Alend alone in both gender.
CONCLUSION
PTH and Alend administration causes anabolic effects in the osteochondral tissue of TMJ.
Topics: Male; Female; Mice; Animals; Alendronate; Parathyroid Hormone; Chondrocytes; Cartilage; Temporomandibular Joint
PubMed: 36239576
DOI: 10.1177/19476035221109229 -
Acta Odontologica Latinoamericana : AOL Sep 2016Bisphosphonates are the first choice therapy for the pharmaco logical treatment of osteoporosis. Following reports of cases of bisphosphonaterelated osteonecrosis of the...
Bisphosphonates are the first choice therapy for the pharmaco logical treatment of osteoporosis. Following reports of cases of bisphosphonaterelated osteonecrosis of the jaw and atypical femur fracture, the safety of longterm use of bisphosphonates has been evaluated, resulting in the proposal of strontium as an alternative drug. No experimental study using a sequential administration design has been reported to date. Hence, the aim of this study was to evaluate the effect on bone tissue of ovariectomized rats of administration of alendronate followed by strontium ranelate. Fortyeight female Wistar rats were ovariectomized on day 1 of the experiment. Beginning on day 30, they were administered 0.3 mg/kg/week of alendronate (ALN) or vehicle (VEH) for 8 weeks. Two groups (ALN and corresponding control) were euthanized at this time, and the remaining animals were divided into 4 groups and given 290 mg/kg/day of strontium ranelate (SR) in their drinking water (TW) or only water for 4 months. Experimental groups were: ALN+SR, ALN+TW, VEH+SR, VEH+TW, ALN and VEH. The tibiae and hemimandibles were resected for histomorphometric evaluation, and the right femur was used to perform biomechanical studies. ANOVA and Bonferroni test were applied. Diaphyseal stiffness, maximum elastic load and fracture load increased in animals that received alendronate, regardless of whether or not they received subsequent SR treatment. Fracture load also increased in VEH+ SR versus control (VEH+TW). Subchondral and interradicular bone volumes were significantly higher in animals that received ALN than in those that received vehicle. No difference was observed in cortical area or thickness of the tibia among treatments. The results obtained with the model presented here, evaluating tibial and mandibular interradicular bone, showed that the combination of ALN and SR and administration of ALN alone are equally effective in preventing bone loss associated with ovariectomyinduced estrogen depletion.
Topics: Alendronate; Animals; Biomechanical Phenomena; Bone Density Conservation Agents; Bone and Bones; Female; Ovariectomy; Rats; Rats, Wistar; Thiophenes
PubMed: 27731487
DOI: No ID Found -
Journal of Applied Oral Science :... 2017The aim of this study was to evaluate the bone repair process at the bone/implant interface of osteoporotic rats treated with sodium alendronate through the analysis of...
OBJECTIVE
The aim of this study was to evaluate the bone repair process at the bone/implant interface of osteoporotic rats treated with sodium alendronate through the analysis of microtomography, real time polymerase chain reactions and immunohistochemistry (RUNX2 protein, bone sialoprotein (BSP), alkaline phosphatase, osteopontin and osteocalcin).
MATERIAL AND METHODS
A total of 42 rats were used and divided in to the following experimental groups: CTL: control group (rats submitted to fictitious surgery and fed with a balanced diet), OST: osteoporosis group (rats submitted to a bilateral ovariectomy and fed with a low calcium diet) and ALE: alendronate group (rats submitted to a bilateral ovariectomy, fed with a low calcium diet and treated with sodium alendronate). A surface treated implant was installed in both tibial metaphyses of each rat. Euthanasia of the animals was conducted at 14 (immunhostochemistry) and 42 days (immunohistochemistry, micro CT and PCR). Data were subjected to statistical analysis with a 5% significance level.
RESULTS
Bone volume (BV) and total pore volume were higher for ALE group (P<0.05). Molecular data for RUNX2 and BSP proteins were significantly expressed in the ALE group (P<0.05), in comparison with the other groups. ALP expression was higher in the CTL group (P<0.05). The immunostaining for RUNX2 and osteopontin was positive in the osteoblastic lineage cells of neoformed bone for the CTL and ALE groups in both periods (14 and 42 days). Alkaline phosphatase presented a lower staining area in the OST group compared to the CTL in both periods and the ALE at 42 days.
CONCLUSION
There was a decrease of osteocalcin precipitation at 42 days for the ALE and OST groups. Therefore, treatment with short-term sodium alendronate improved bone repair around the implants installed in the tibia of osteoporotic rats.
Topics: Alendronate; Alkaline Phosphatase; Animals; Bone Density; Bone Density Conservation Agents; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dental Implantation, Endosseous; Dental Implants; Female; Immunohistochemistry; Implants, Experimental; Osseointegration; Osteoblasts; Osteocalcin; Osteopontin; Osteoporosis; Ovariectomy; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Tibia; Time Factors; X-Ray Microtomography
PubMed: 28198975
DOI: 10.1590/1678-77572016-0165 -
Biochemical Pharmacology Sep 1997Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent bisphosphonate that inhibits osteoclastic bone resorption and has proven effective for the...
Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent bisphosphonate that inhibits osteoclastic bone resorption and has proven effective for the treatment of osteoporosis. Its molecular mechanism of action, however, has not been defined precisely. Here we report that alendronate is a potent inhibitor of the protein-tyrosine-phosphatase-meg1 (PTPmeg1). Two substrates were employed in this study: fluorescein diphosphate and the phosphotyrosyl peptide src-pY527. With either substrate, alendronate was a slow binding inhibitor of PTPmeg1. Among the other bisphosphonates studied, alendronate was more potent and selective for PTPmeg1. The hydrolysis of fluorescein diphosphate by PTP epsilon and PTPmeg1 was sensitive to alendronate, with IC50 values of less than 1 microM; PTPsigma, however, under the same conditions, was inhibited by only 50% with 141 microM alendronate. Similarly, with the src-pY527 substrate, alendronate inhibition was also PTP dependent. Alendronate inhibited PTPmeg1 with an IC50 value of 23 microM, PTPsigma with an IC50 value of 2 microM, and did not inhibit PTP epsilon at concentrations up to 1 mM. The alendronate inhibition of these three PTPs and two substrates is consistent with the formation of a ternary complex comprised of enzyme, substrate, and inhibitor. PTP inhibition by hisphosphonates or vanadate was diminished by the metal chelating agent EDTA, or by the reducing agent dithiothreitol, suggesting that a metal ion and the oxidation of a cysteine residue are required for full inhibition. These observations show substrate- and enzyme-specific PTP inhibition by alendronate and support the possibility that a certain PTP(s) may be the molecular target for alendronate action.
Topics: Alendronate; DNA, Complementary; Enzyme Inhibitors; Humans; Protein Tyrosine Phosphatase, Non-Receptor Type 4; Protein Tyrosine Phosphatases; Substrate Specificity; Tumor Cells, Cultured
PubMed: 9310349
DOI: 10.1016/s0006-2952(97)00225-6 -
Journal of Bone and Mineral Research :... Mar 2012Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer...
Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50+) and 122,424 matched controls. Primary outcomes were esophageal cancer incidence and death because of esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 versus 1.7%, p < 0.001). Alendronate users had a lower risk of incident gastric cancer [odds ratio (OR) 0.61; 95% confidence interval (CI): 0.39-0.97) and no increased risk of esophageal cancer (OR 0.71; 95% CI: 0.43-1.19). Risk reductions were greater in users with 10+ prescriptions. The risk of dying of esophageal cancer was significantly reduced in alendronate users after 3 years OR 0.45 (95% CI: 0.22-0.92) but not after 9 years (OR 1.01; 95% CI: 0.52-1.95). An additional comparison with etidronate users revealed no statistically significant difference in outcomes. In conclusion, we found no excess in esophageal cancer deaths or incidence. The early decrease in esophageal cancer rates may relate to the greater use of endoscopy before starting alendronate. Longer term observations also indicated no excess risk of esophageal cancer death and a significantly decreased risk of gastric cancer death.
Topics: Adult; Aged; Alendronate; Bone Density Conservation Agents; Denmark; Esophageal Neoplasms; Etidronic Acid; Female; Humans; Incidence; Middle Aged; Stomach Neoplasms
PubMed: 22113985
DOI: 10.1002/jbmr.1481 -
Journal of Materials Chemistry. B Mar 2020The hydrothermal reaction between bioactive metal (Ca2+, Zn2+, and Mg2+) salts and a clinically utilized bisphosphonate, alendronate (ALEN), promotes the formation of...
The hydrothermal reaction between bioactive metal (Ca2+, Zn2+, and Mg2+) salts and a clinically utilized bisphosphonate, alendronate (ALEN), promotes the formation of several materials denominated as bisphosphonate-based coordination complexes (BPCCs). The systematic exploration of the effect of three variables, M2+/ALEN molar ratio, temperature, and pH, on the reaction yielded an unprecedented number of materials of enough crystal quality for structural elucidation. Five crystal structures were unveiled by single crystal X-ray diffraction (ALEN-Ca forms I and II, ALEN-Zn forms I and II, and ALEN-Mg) and their solid-state properties revealed in tandem with other techniques. The dissolution of these BPCCs was tested and contrasted to that of the commercially employed generic form of Fosamax® Alendronate Sodium, using fasted-state simulated gastric fluid and phosphate-buffered saline solution. Quantification of ALEN content was performed by derivatization with Cu2+, which produced a soluble complex suitable for quantification. The results show that these materials present a pH-dependent degradation. Moreover, a phase inversion temperature (PIT) nano-emulsion method was applied to the synthesis of ALEN-Ca form II. Size distribution analysis demonstrated the efficiency of the PIT-nano-emulsion method to decrease the particle size of this BPCC from ∼60 μm to ∼438 d nm. The cytotoxicity of ALEN, ALEN-Ca form II (bulk crystals), and nano-Ca@ALEN (nanocrystals) against the MDA-MB-231 cell line was investigated. Nano-Ca@ALEN form II presents higher cytotoxicity effects than ALEN and ALEN-Ca form II (bulk crystals), showing inhibition of cell proliferation at 7.5 μM. These results provide evidence of the structure, stability, dissolution and cytotoxicity properties of ALEN-based BPCCs and pave the way for better formulation strategies for this drug through the design of nano-sized BPCCs for the treatment of bone-related diseases.
Topics: Alendronate; Antineoplastic Agents; Bone Neoplasms; Cell Proliferation; Coordination Complexes; Diphosphonates; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Osteoclasts; Particle Size; Surface Properties; Tumor Cells, Cultured
PubMed: 32095795
DOI: 10.1039/c9tb01857c -
Scientific Reports Sep 2023Nitrogen-containing bisphosphonates (NBPs), compounds that are widely used in the treatment of bone disorders, may cause side effects related to endothelial dysfunction....
Nitrogen-containing bisphosphonates (NBPs), compounds that are widely used in the treatment of bone disorders, may cause side effects related to endothelial dysfunction. The aim of our study was to investigate the effects of chronic 6-day exposure to two common bone-preserving drugs, alendronate and zoledronate, on endothelial function and oxidative metabolism of cultured human endothelial cells (EA.hy926). NBPs reduced cell viability, induced oxidative stress and a pro-inflammatory state and downregulated the prenylation-dependent ERK1/2 signaling pathway in endothelial cells. In addition, NBPs induced increased anaerobic respiration and slightly increased oxidative mitochondrial capacity, affecting mitochondrial turnover through reduced mitochondrial fission. Moreover, by blocking the mevalonate pathway, NBPs caused a significant decrease in the level of coenzyme Q10, thereby depriving endothelial cells of an important antioxidant and mitochondrial electron carrier. This resulted in increased formation of reactive oxygen species (ROS), upregulation of antioxidant enzymes, and impairment of mitochondrial respiratory function. A general decrease in mitochondrial respiration occurred with stronger reducing fuels (pyruvate and glutamate) in NBP-treated intact endothelial cells, and significantly reduced phosphorylating respiration was observed during the oxidation of succinate and especially malate in NBP-treated permeabilized endothelial cells. The observed changes in oxidative metabolism caused a decrease in ATP levels and an increase in oxygen levels in NBP-treated cells. Thus, NBPs modulate the energy metabolism of endothelial cells, leading to alterations in the cellular energy state, coenzyme Q10 redox balance, mitochondrial respiratory function, and mitochondrial turnover.
Topics: Humans; Diphosphonates; Alendronate; Zoledronic Acid; Endothelial Cells; Antioxidants
PubMed: 37758809
DOI: 10.1038/s41598-023-43377-3 -
Technology and Health Care : Official... 2020In our study, the influence of PEMF on skeleton morphology and bone metabolism on rats with disuse osteoporosis was investigated, and the possibility of using it for the...
OBJECTIVE
In our study, the influence of PEMF on skeleton morphology and bone metabolism on rats with disuse osteoporosis was investigated, and the possibility of using it for the treatment of disuse osteoporosis was explored.
METHODS
The rats in the ALN group were treated with alendronate, and the rats in the PEMF group were exposed to pulsed electromagnetic fields (3.82 mT, 10 Hz) for 40 mind-1. Rats were sacrificed by the end of 2, 4, 8 and 12 weeks, and serum and right leg bones were collected. Serum BMP-2, BGP concentrations and bone metabolism and biomechanical parameters were measured.
RESULTS
The bone structural mechanical indices and material mechanical indices of the right femur in all groups of mice during weeks 2 and 4 were decreased. At week 8 the bone structural mechanical index and maximum stress of the right femur in the ALN group were markedly raised compared with the CON group (P< 0.01). Only maximum stress and strain were improved in the ALN group and had a significant difference (P< 0.05) at week 12. The serum BGP and BMP-2 concentration in the PEMF and ALN groups was increased (P< 0.05) at week 2, but this increase was not synchronized. After 8 weeks, BGP and BMP-2 level in the PEMF group was observably elevated (P<0.01) in contrast to the ALN group.
CONCLUSION
From the experimental time interval analysis, PEMF can improve the mechanical stability of bone structure more gently and permanently than alendronate.
Topics: Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Disease Models, Animal; Female; Magnetic Field Therapy; Osteoporosis; Rats; Rats, Sprague-Dawley
PubMed: 32364143
DOI: 10.3233/THC-209006 -
International Journal of Molecular... Nov 2022Synthetic implants are used to treat large bone defects that are often unable to regenerate, for example those caused by osteoporosis. It is necessary that the materials...
Synthetic implants are used to treat large bone defects that are often unable to regenerate, for example those caused by osteoporosis. It is necessary that the materials used to manufacture them are biocompatible and resorbable. Polymer-ceramic composites, such as those based on poly(L-lactide) (PLLA) and calcium phosphate ceramics (Ca-P), are often used for these purposes. In this study, we attempted to investigate an innovative strategy for two-step (dual) modification of composites and their components to improve the compatibility of composite components and the adhesion between PLA and Ca-P whiskers, and to increase the mechanical strength of the composite, as well as improve osteological bioactivity and prevent bone resorption in composites intended for bone regeneration. In the first step, Ca-P whiskers were modified with a saturated fatty acid namely, lauric acid (LA), or a silane coupling agent γ-aminopropyltriethoxysilane (APTES). Then, the composite, characterized by the best mechanical properties, was modified in the second stage of the work with an active chemical compound used in medicine as a first-line drug in osteoporosis-sodium alendronate, belonging to the group of bisphosphonates (BP). As a result of the research covered in this work, the composite modified with APTES and alendronate was found to be a promising candidate for future biomedical engineering applications.
Topics: Humans; Silanes; Alendronate; Porosity; Polyesters; Osteoblasts; Osteoporosis
PubMed: 36430791
DOI: 10.3390/ijms232214315 -
Polish Journal of Pharmacology 2004Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of... (Comparative Study)
Comparative Study
Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate sodium and retinol are used concurrently. There are no reports on the interaction between alendronate sodium and retinol. The aim of the present study was to investigate the effect of concurrent administration of alendronate sodium and retinol on bone remodeling in ovariectomized rats. The histomorphometric parameters of long bones were studied. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I (C) - sham operated control rats, II (OVX) - ovariectomized control rats, III (OVX + ALN) - ovariectomized rats + alendronate sodium (3 mg/kg po), IV (OVX + R-1) - ovariectomized rats + retinol (700 IU/kg po), V (OVX + R-2) - ovariectomized rats + retinol (3500 IU/kg po), VI (OVX + ALN + R-1) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (700 IU/kg po), VII (OVX + ALN + R-2) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (3500 IU/kg po). The drugs were administered to the rats daily by oral gavage (alendronate sodium in the morning, retinol in the afternoon) for 28 days. Body mass gain, bone mass, mineral content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, area of the transverse cross section of the bone marrow cavity and the cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Alendronate sodium administered at a dose of 3 mg/kg po daily inhibited the development of changes induced by ovariectomy in the skeletal system of rats. Retinol, especially administered at the dose of 3500 IU/kg daily, intensified the changes in the osseous system caused by estrogen deficiency in rats. Retinol administered concurrently with alendronate sodium attenuated the antiresorptive effect of alendronate sodium on the skeletal system in ovariectomized rats.
Topics: Alendronate; Animals; Bone Remodeling; Calcification, Physiologic; Drug Combinations; Estrogens; Female; Femur; Intubation, Gastrointestinal; Lumbar Vertebrae; Ovariectomy; Rats; Rats, Wistar; Tibia; Vitamin A
PubMed: 15591645
DOI: No ID Found