- Protective effect of low-dose risedronate against osteocyte apoptosis and bone loss in ovariectomized rats. [Journal Article]
- PlosPLoS One 2017; 12(10):e0186012
- Osteocyte apoptosis is the first reaction to estrogen depletion, thereby stimulating osteoclastic bone resorption resulting in bone loss. We investigated the effects of two different risedronate (RIS...
Osteocyte apoptosis is the first reaction to estrogen depletion, thereby stimulating osteoclastic bone resorption resulting in bone loss. We investigated the effects of two different risedronate (RIS) doses (high and low) on osteocyte apoptosis, osteoclast activity and bone loss in ovariectomized rats. Forty rats with ovariectomy (OVX) and sham ovariectomy (SHAM) were divided into 4 groups: 1) SHAM rats treated with saline (SHAM); 2) OVX rats treated with saline (OVX); 3) OVX rats treated with low-dose RIS (OVX-LR, 0.08 μg/kg/day); 4) OVX rats treated with high-dose RIS (OVX-HR, 0.8 μg/kg/day). All animals were sacrificed 90 days after surgery for the examinations of osteocyte apoptosis by caspase-3 staining, osteoclast activity by TRAP staining and bone volume by micro-CT scanning in lumbar vertebral cancellous bone. Both low and high dose RIS significantly reduced caspase-3 positive osteocytes, empty lacunae and TRAP positive osteoclasts in OVX rats. Although the difference in caspase-3 positive osteocytes was not significant between the OVX-LR and OVX-HR groups, numerically these cells were significantly more prevalent in OVX-HR (not OVX-LR) group than in SHAM group. TRAP positive osteoclasts were significantly higher in OVX-LR group than in SHAM or OVX-HR group. There was no significant difference in bone volume among the OVX-LR, OVX-HR and SHAM groups, but lower in OVX group alone. However, significant increase in trabecular thickness only occurred in OVX-LR group. We conclude that both low and high dose RIS significantly inhibit osteocyte apoptosis and osteoclast activity in OVX rats, but the low-dose RIS has weaker effect on osteoclast activity. However, low-dose RIS preserves cancellous bone mass and microarchitecture as well as high-dose RIS after estrogen depletion.
- Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis. [Journal Article]
- PlosPLoS One 2017; 12(9):e0184904
- Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclas...
Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG-/-) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG-/-mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG-/-mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/β-catenin signaling and induced alveolar bone formation in OPG-/-mice. Expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was significantly lower in tibiae of OPG-/-mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG-/-mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG-/-mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG-/-mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis.
- Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors. [Journal Article]
- IJInt J Nanomedicine 2017; 12:5633-5642
- Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Four...
Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, solid-state nuclear magnetic resonance, wavelength dispersive X-ray fluorescence, and inductively coupled plasma optical emission spectrometry. SeHA was then used to develop the selenium-containing hydroxyapatite/alginate (SeHA/ALG) composite granules. Risedronate sodium (RIS) was introduced to the obtained spherical microgranules of a size of about 1.1-1.5 mm in 2 ways: during the granules' preparation (RIS solution added to a suspension of ALG and SeHA), and as a result of SeHA/ALG granules soaking in aqueous RIS solution. The analysis made using 13C and 31P cross-polarization magic angle spinning nuclear magnetic resonance confirmed the presence of RIS and its interaction with calcium ions. Then, the release of selenium (inductively coupled plasma optical emission spectrometry) and RIS (high-performance liquid chromatography) from microgranules was examined. Moreover, cytotoxicity of fabricated granules was assessed by MTT test. Selenium release was biphasic: the first stage was short and ascribed to a "burst release" probably from a hydrated surface layer of SeHA crystals, while the next stage was significantly longer and ascribed to a sustained release of selenium from the crystals' interior. The study showed that the method of obtaining microgranules containing RIS significantly affects its release profile. Performed cytotoxicity test revealed that fabricated granules had high antitumor activity against osteosarcoma cells. However, because of the "burst release" of selenium during the first 10 h, the granules significantly reduced viability of normal osteoblasts as well.
- Comparison of the properties of implantable matrices prepared from degradable and non-degradable polymers for bisphosphonate delivery. [Journal Article]
- IJInt J Pharm 2017 Nov 30; 533(2):364-372
- The aim of the present study was the development of directly compressed tablets for implantable delivery of risedronate sodium for osteoporosis treatment and the comparison of the mechanism and kinet...
The aim of the present study was the development of directly compressed tablets for implantable delivery of risedronate sodium for osteoporosis treatment and the comparison of the mechanism and kinetics of drug release from biogradable (chitosan) and non-degradable (PVC) polymer matrices. The compositions and process parameters were optimized in accordance to a mixed 2 and 3 level full factorial design. Critical Quality Attributes (CQA), such as diametral breaking hardness, porosity and speed of drug dissolution were investigated. The results revealed significant differences between the behaviours of the two polymers. Chitosan exhibited poor compressibility, which resulted in poor mechanical properties and the fast disintegration of chitosan based tablets. Nevertheless, despite the fast disintegration, the chitosan based matrices exhibited one-week-long continuous drug release, which can be due to a strong drug-carrier interaction. The presence of intermolecular hydrogen bonds was confirmed with FT-IR and NIR measurements. In contrast, PVC based compositions exhibited excellent compressibility, good tablet hardness and low porosity. The tablets remained intact during the dissolution and exhibited a slower release rate than what was measured in the case of chitosan based matrices. There was no sign of intermolecular association on NIR spectra, suggesting that the dissolution rate is basically determined by the porosity of tablets, but FT-IR measurements revealed some details of the molecular background of drug release mechanism.
- Poly(vinyl alcohol)/hydroxyapatite Monolithic In-Needle Extraction (MINE) device: Preparation and examination of drug affinity. [Journal Article]
- EJEur J Pharm Sci 2017 Jul 15; 105:195-202
- Polymer-ceramic materials based on poly(vinyl alcohol) (PVA) and hydroxyapatite were applied as sorption material in Monolithic In-Needle Extraction (MINE) device. The presented device provides new p...
Polymer-ceramic materials based on poly(vinyl alcohol) (PVA) and hydroxyapatite were applied as sorption material in Monolithic In-Needle Extraction (MINE) device. The presented device provides new possibilities for the examination of bisphosphonates affinity for bone and will be a helpful tool in evaluation of potential antiresorptive drugs suitability. A ceramic part of monoliths was prepared by incorporation of hydroxyapatite (HA) into the reaction mixture or by using a soaking method (mineralization of HA on the PVA). The parameters of synthesis conditions were optimized to achieve a monolithic material having the appropriate dimensions after the soaking process enabling placing of the monolithic material inside the needle. Furthermore, the material must have had optimal dimensions after the re-soaking process to fit perfectly to the needle. Among the sixteen monolithic materials, eight of them were selected for further study, and then four of them were selected as a sorbent material for the MINE device. The material properties were examined on the basis of several parameters: swelling ratio, initial mass reversion and initial diameter reversion, mass growth due to the HA formation, and antiresorptive drug sorption. The MINE device might be then used as a tool for examination of interactions between bisphosphonate and bone. The simulated body fluid containing sodium risedronate (RSD) as a standard compound was passed through the MINE device. The obtained device allowed for sorption about 0.38mg of RSD. The desorption process was carried out in five steps allowing insightful analysis. The MINE device turned out to be a helpful tool for determination of the bisphosphonates affinity to the ceramic part of sorbent (hydroxyapatite) and to assess the usefulness of them as antiresorptive drugs in the future.
- BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD. [Journal Article]
- EPEndocr Pract 2017; 23(7):787-793
- CONCLUSIONS: In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers.
- CLINICAL EVALUATION OF COST EFFICACY OF DRUGS FOR TREATMENT OF OSTEOPOROSIS: A META-ANALYSIS. [Review]
- EPEndocr Pract 2017; 23(7):841-856
- CONCLUSIONS: The most cost-effective initial therapy of postmenopausal osteoporosis is generic oral alendronate or generic parenteral zoledronate. There is no statistically significant difference in efficacy of available drugs to prevent hip fractures. There are limited data to suggest switching drugs after sustaining an osteoporotic fracture while on oral alendronate therapy, although generic zoledronate may be considered on the basis of side effects or questions of medication adherence.
- Osteoporosis Treatment Efficacy for Men: A Systematic Review and Meta-Analysis. [Review]
- JAJ Am Geriatr Soc 2017; 65(3):490-495
- CONCLUSIONS: Bisphosphonates reduce the risk of vertebral and possibly nonvertebral fractures for men with osteoporosis. Further studies are needed to evaluate the efficacy of bisphosphonates for reducing nonvertebral fracture risk and the efficacy of nonbisphosphonates for reducing vertebral and nonvertebral fracture risk in men with osteoporosis.
- Efficacy and safety of medical therapy for low bone mineral density in patients with Crohn disease: A systematic review with network meta-analysis. [Review]
- MMedicine (Baltimore) 2017; 96(11):e6378
- CONCLUSIONS: Zoledronate might have the highest probability to be the best therapeutic strategy for increasing LSBMD. For the safety assessment, risedronate showed the greatest trend to decrease the risk of AEs. In the future, more RCTs with higher qualities are needed to make head-to-head comparison between 2 or more treatments.
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- Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States. [Journal Article]
- AOArch Osteoporos 2017; 12(1):22
- CONCLUSIONS: Patients initiating injectable therapies had greater persistence and compliance at 2 years than those initiating oral therapies. Patients initiating an every-6-month injection had significantly higher persistence compared with those initiating more frequently dosed (e.g., daily and weekly) oral or injectable agents.