- Cytotoxic and inflammatory effects of alendronate and zolendronate on human osteoblasts, gingival fibroblasts and osteosarcoma cells. [Journal Article]
- JCJ Craniomaxillofac Surg 2018 Jan 10
- CONCLUSIONS: ZOL and FOS could encourage cytotoxic and inflammatory reactions.
- Cost-effectiveness of teriparatide compared with alendronate and risedronate for the treatment of postmenopausal osteoporosis patients in Iran. [Journal Article]
- MJMed J Islam Repub Iran 2017; 31:39
- Background: Hip, vertebral and wrist fractures are the most common consequences of osteoporosis. This study aimed at analyzing the cost-effectiveness of teriparatide (CinnoPar®), ...
Background: Hip, vertebral and wrist fractures are the most common consequences of osteoporosis. This study aimed at analyzing the cost-effectiveness of teriparatide (CinnoPar®), compared with alendronate and risedronate, in the treatment of women aged 60 and over with postmenopausal osteoporosis in Iran.Methods: A decision tree model with a 2-year time horizon was used to compare treatment with teriparatide (CinnoPar®) with the following treatment strategies: two years of treatment with alendronate and two years of treatment with risedronate in women aged 60 years and over or those at risk of osteoporosis. Cost per QALY was calculated for 3 treatment strategies from the model. After base case analysis, one-way sensitivity analysis was performed on key parameters of the model to assess their impact on the study results and the cost-effectiveness of different treatment strategies and the model robustness. TreeAge Pro 2006 software was used for modeling and data analysis.Results: Incremental cost-effectiveness ratio (ICER) of alendronate and teriparatide than risedronate (base treatment) were US$- 2178.03 and US$483,783.67 per QALY, respectively. Therefore, the dominant and cost-effective treatment option was alendronate. In the one-way sensitivity analysis, the impact of annual 25% increase or decrease in the teriparatide cost on its ICER was remarkable. Also, reducing the discount rate from 0.03 to 0.0 had the greatest impact on the ICER of the teriparatide.Conclusion: The treatment strategy of teriparatide is more expensive than risedronate and alendronate and is associated with very little increase in QALYs. A significant reduction in teriparatide price and a limit in its use only for high-risk women and for acute and short-term treatment courses can contribute to its cost-effectiveness.
- Alendronate augments lipid A-induced IL-1β release and Smad3/NLRP3/ASC-dependent cell death. [Journal Article]
- LSLife Sci 2018 Feb 10
- Alendronate (ALN) is a nitrogen-containing bisphosphonate (NBP) that inhibits bone resorption. NBPs have inflammatory side effects, and ALN augments bacteria-induced interleukin (IL)-1β production. T...
Alendronate (ALN) is a nitrogen-containing bisphosphonate (NBP) that inhibits bone resorption. NBPs have inflammatory side effects, and ALN augments bacteria-induced interleukin (IL)-1β production. The present study aimed to examine whether ALN induces pyroptosis, a form of cell death associated with IL-1β release, in macrophage-like J774.1 cells incubated with lipid A, a component of gram-negative bacteria. Pretreatment of J774.1 cells with ALN increased lipid A-induced IL-1β production and cell death, but not IL-6 and TNF-α production. Ac-YVAD-CHO, a caspase-1 inhibitor, inhibited ALN-augmented IL-1β production induced by lipid A, although it did not affect ALN-induced cell death. Moreover, Ac-IETD-CHO, a caspase-8 inhibitor, and Z-VAD-FMK, a pan-caspase inhibitor, did not inhibit ALN-induced cell death, suggesting that the effects of ALN are exerted independently of caspase activation. We also demonstrate that a Smad3 inhibitor (SIS3) suppressed ALN-augmented IL-1β production. Moreover, SIS3 attenuated ALN-augmented release of LDH and caspase-1. These results suggest that ALN augments IL-1β production, cell death, and caspase-1 release in a manner dependent on Smad3. We then investigated whether ALN-augmented IL-1β production and cell death are dependent on apoptosis-associated speck-like protein containing a CARD (ASC) and NOD-like receptor pyrin domain containing-3 (NLRP3), which are associated with Smad3 activation. Both anti-ASC and anti-NLRP3 antibodies suppressed ALN-induced cell death and caspase-1 release, but only anti-ASC antibody inhibited ALN-augmented IL-1β production. Our findings suggest that ALN-augmented IL-1β production and cell death require Smad3 and ASC activation, and that SIS3 and anti-ASC antibodies may serve as palliative agents for necrotizing inflammatory diseases caused by ALN.
- Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review. [Review]
- EEndocrine 2018 Feb 06
- CONCLUSIONS: The presence of diabetes does not alter anti-osteoporotic treatment response, regarding BMD increase and vertebral fracture risk reduction.
- Influence of the teaching program on the learning in knowledge and practice of osteonecrosis of the jaws produced by antireasorptives in dental students of the Principality of Asturias (Spain). [Journal Article]
- JCJ Clin Exp Dent 2017; 9(12):e1402-e1407
- CONCLUSIONS: Training on medication-related osteonecrosis among dental students is susceptible to improvement. Introducing minor changes in the teachings allows this goal to be successfully achieved. Key words:Osteonecrosis of the jaw (ONJ), bisphosphonate-related osteonecrosis of the jaws (BRONJ), medication-related osteonecrosis of the jaw (MRONJ), dental education.
- Self-healing hydrogels formed by complexation between calcium ions and bisphosphonate-functionalized star-shaped polymers. [Journal Article]
- MMacromolecules 2017; 50(21):8698-8706
- Star-shaped poly(ethylene glycol) (PEG) chain termini were functionalized with alendronate to create transient networks with reversible crosslinks upon addition of calcium ions. The gelation ability ...
Star-shaped poly(ethylene glycol) (PEG) chain termini were functionalized with alendronate to create transient networks with reversible crosslinks upon addition of calcium ions. The gelation ability of alendronate-functionalized PEG was greatly dependent on the number of arms and arm molecular weight. After mixing polymer and calcium solutions, the formed hydrogels could be cut and then brought back together without any visible interface. After 2 minutes of contact, their connection was strong enough to allow for stretching without tearing through the previous fracture surface. Oscillatory rheology showed that the hydrogels recovered between 70 and 100% of the original storage and loss modulus after rupture. Frequency sweep measurements revealed a liquid-like behavior at lower frequencies and solid-like at high frequencies. Shifting frequency curves obtained at different calcium and polymer concentrations, all data collapsed in a single common master curve. This time-concentration superposition reveals a common relaxation mechanism intrinsically connected to the calcium-bisphosphonate complexation equilibrium.
- Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro. [Journal Article]
- COClin Oral Investig 2018 Feb 01
- CONCLUSIONS: The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate.Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.
- Osteoporosis: A Review of Treatment Options. [Journal Article]
- P TP T 2018; 43(2):92-104
- Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of frac...
Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of fractures.2 Osteoporosis-related fractures can increase pain, disability, nursing home placement, total health care costs, and mortality.3 The diagnosis of osteoporosis is primarily determined by measuring bone mineral density (BMD) using noninvasive dual-energy x-ray absorptiometry. Osteoporosis medications include bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogues, and calcitonin.3-6 Emerging therapies utilizing novel mechanisms include a cathepsin K inhibitor and a monoclonal antibody against sclerostin.7,8 While professional organizations have compiled recommendations for the management of osteoporosis in various populations, a consensus has yet to develop as to which is the gold standard; therefore, economic evaluations have been increasingly important to help guide decision-makers. A review of cost-effectiveness literature on the efficacy of oral bisphosphonates has shown alendronate and risedronate to be most cost-effective in women with low BMD without previous fractures.9 Guidelines are inconsistent as to the place in therapy of denosumab (Prolia, Amgen). In economic analyses evaluating treatment of postmenopausal women, denosumab outperformed risedronate and ibandronate; its efficacy was comparable to generic alendronate, but it cost more.10 With regard to older men with osteoporosis, denosumab was also found to be cost-effective when compared with bisphosphonates and teriparatide (Forteo, Lilly).11.
- Extracorporeal shock wave treatment can normalize painful bone marrow edema in knee osteoarthritis: A comparative historical cohort study. [Journal Article]
- MMedicine (Baltimore) 2018; 97(5):e9796
- Bone marrow edema (BME) represents a reversible but highly painful finding in magnetic resonance imaging (MRI) of patients with knee osteoarthritis. The aim of this retrospective study was to evaluat...
Bone marrow edema (BME) represents a reversible but highly painful finding in magnetic resonance imaging (MRI) of patients with knee osteoarthritis. The aim of this retrospective study was to evaluate the efficacy of extracorporeal shock wave treatment (ESWT) on painful BME in osteoarthritis of the knee.This study focuses on people who had early-to-mid stage osteoarthritis with knee pain and MRI findings of BME. Patients who underwent ESWT treatment or prescribed alendronate treatment in our department were analyzed. Knee pain and function were measured using the visual analog scale (VAS) for pain and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), respectively. The degree of BME was measured with MRI scans.A total of 126 patients who received ESWT treatment (Group A, n = 82) or alendronate treatment (Group B, n = 44) were included. All patients were followed up clinically and radiographically for a minimum of 12 months. The mean follow-up was 23.5 months (range, 12-38 months). The VAS and WOMAC score decreased more significantly after treatment in Group A than that in Group B (P <.01) within 3 months. In 6-month MRI follow-ups, there was higher incidence of distinct reduction and complete regression of BME of the affected knee in Group A than that in Group B (P <.01).ESWT is an effective, reliable, and noninvasive treatment in patients with painful BME in osteoarthritis of the knee followed by a rapid normalization of the MRI appearance. It has the potential to shorten the natural course of this disease.
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- Bone-targeting dendrimer for the delivery of methotrexate and treatment of bone metastasis. [Journal Article]
- JDJ Drug Target 2018 Feb 06; :1-11
- We developed a bone-targeting dendrimer for the delivery of anti-tumour agents and effective treatment of bone metastasis, in which alendronate (ALN), a bone-targeting moiety, is covalently bonded to...
We developed a bone-targeting dendrimer for the delivery of anti-tumour agents and effective treatment of bone metastasis, in which alendronate (ALN), a bone-targeting moiety, is covalently bonded to a polyethylene glycol (PEG)-conjugated polyamidoamine (PAMAM) dendrimer (PEG-PAMAM-ALN). Approximately 7.0 and 21.9% of the administered doses of [111In]PAMAM and PEG-PAMAM-ALN accumulated in the bones within 180 min after intravenous injection in mice, respectively. [3H]-labelled methotrexate (MTX) rapidly disappeared from the blood, and bone distribution was found to be only 1.1% of the administered dose at 180 min. In contrast, 21.5% of the administered dose of [3H]MTX-loaded PEG-PAMAM-ALN accumulated in the bones at 180 min after intravenous injection in mice, which was approximately 20-fold higher than that of [3H]MTX. In a bone metastatic tumour mouse model, in which B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice, the growth of metastatic tumour in the bones was significantly inhibited by intravenous injection of MTX-loaded PEG-PAMAM-ALN. These findings indicate that PEG-PAMAM-ALN is a promising bone-targeting carrier for the delivery of anti-tumour agents and treatment of bone metastasis.