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Cureus Mar 2024Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant genetic disorder characterized by congenital great toe malformations and progressive ectopic...
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant genetic disorder characterized by congenital great toe malformations and progressive ectopic ossification. We report a typical case of FOP in a 22-year-old female patient presenting with limited movement of the left knee joint, which began following trauma in 2019. Clinical examination revealed a large mass behind the left knee, bilateral great toe deformities, and no palpable superficial lymph nodes, without systemic pain or other discomfort. Imaging and genetic testing further supported the diagnosis of FOP, demonstrating high-density ossification within soft tissues and a mutation in the gene. Treatment involved a combination of methylprednisolone and alendronate sodium vitamin D3 tablets, which yielded some therapeutic efficacy. The discussion emphasizes clinical diagnosis, pathogenesis, and treatment strategies for FOP, including injury prevention, rehabilitation exercises, and pharmacological interventions. Despite the lack of definitive treatment options, timely diagnosis and comprehensive management can effectively alleviate symptoms and improve the quality of life for affected individuals.
PubMed: 38576636
DOI: 10.7759/cureus.55528 -
Cureus Jul 2023The use of calcium sulfate beads (CSBs) as a carrier for local delivery of antibiotics is increasingly reported for the treatment of localized infections. They are used...
The use of calcium sulfate beads (CSBs) as a carrier for local delivery of antibiotics is increasingly reported for the treatment of localized infections. They are used most commonly in bone and joint infections, post-trauma infections, diabetes-related foot wounds, and vascular grafts. Hypercalcemia is rarely reported with CSB use but is an important safety concern, and patients at higher risk should be identified prospectively and followed carefully postoperatively. This case report details an 85-year-old male who developed severe, symptomatic postoperative hypercalcemia after antibiotic bead placement in the right knee. He presented with confusion, weakness, and lethargy, and was subsequently treated with fluids, calcitonin, and alendronate. The patient quickly returned to normal mental status, and calcium levels normalized, leading to discharge. The case report and review of the literature describe an incident of severe hypercalcemia attributed to the use of antibiotic-eluting CSBs and describe the risk factors and time course that may be expected.
PubMed: 37565095
DOI: 10.7759/cureus.41661 -
Archives of Osteoporosis Jul 2023Postmenopausal patients with osteoporosis who have a recent fracture are at very high risk of fracture, and this study finds that stratified treatment based on fracture...
UNLABELLED
Postmenopausal patients with osteoporosis who have a recent fracture are at very high risk of fracture, and this study finds that stratified treatment based on fracture risk would be a cost-effective treatment option for this population.
PURPOSE
To evaluate the cost-effectiveness of four anti-osteoporosis medications (denosumab, zoledronate, teriparatide, and alendronate) for postmenopausal osteoporotic women in mainland China, using a stratified treatment strategy recommended by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE).
METHODS
A microsimulation Markov model was used to compare the cost-effectiveness of the four treatments in postmenopausal osteoporotic patients of different ages (65, 70, 75, and 80 years), with a recent fracture from the Chinese healthcare perspective. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represent the incremental cost per quality-adjusted life-year (QALY) obtained. One-way deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of model findings.
RESULTS
Alendronate was dominated by denosumab-to-alendronate and zoledronate at all ages examined, indicating that the costs of the two drugs were lower, but QALYs was greater. However, teriparatide-to-alendronate yielded an ICER of $76,432.07/ QALY, compared with alendronate at age 65, which exceeded the pre-determined willingness-to-pay threshold of $37,653/ QALY. The results were similar at other ages. The DSA showed that the most sensitive parameters were drug efficacy for vertebral and wrist fractures, the relative risk of vertebral fractures, and the persistence of the drugs. The PSA showed that zoledronate had a 100% probability of being the most cost-effective treatment, with a willingness-to-pay threshold of $37,653/ QALY.
CONCLUSION
Stratified treatment based on very high fracture risk is more cost-effective than conventional pills in mainland China. Among the stratified treatments, zoledronate is the optimal option.
Topics: Humans; Female; Aged; Alendronate; Cost-Benefit Analysis; Bone Density Conservation Agents; Denosumab; Osteoporosis, Postmenopausal; Teriparatide; Zoledronic Acid; Cost-Effectiveness Analysis; Postmenopause; Osteoporosis; Fractures, Bone; Quality-Adjusted Life Years; Osteoporotic Fractures
PubMed: 37460858
DOI: 10.1007/s11657-023-01309-8 -
Bone Dec 2023Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such...
Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such adverse reactions result from the use of bisphosphonates (BPs). In this study, we assessed the correlation between TPLDs and the use of BPs via U.S. FDA Adverse Event Reporting System (FAERS) database. Bayesian and nonproportional analyses were applied to data retrieved from the FAERS database from the first quarter of 2004 to the third quarter of 2022. A total of 3202 reported cases of TPLDs were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, zoledronate), with statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC). Alendronate showed the highest association with tendinopathies and ligament disorders (ROR = 16.30, PRR = 15.47, IC = 3.88), while zoledronate had the lowest association (ROR = 2.13, PRR = 2.12, IC = 1.08), which was consistent with the results of top 10 preferred terms (PTs) under the narrow standardized MedDRA queries (SMQs) sorted by frequency of reports. Excluding zoledronate, over half of patients who reported BP-related TPLDs were hospitalized, either briefly or extendedly. This was especially true for alendronate, which showed the highest rate of hospitalization (83.25 %), however, the mortality rate reported by those taking alendronate were significantly lower than those of zoledronate and pamidronate. In addition, the clinical characteristics of BP-related TPLDs was analyzed. It is more common to reported in middle-aged and elderly females, the highest proportion was in 50-69 years old. Except for osteoporosis, osteopenia, and osteoporosis prophylaxis, cancer bone metastasis was also the indication of some BPs. The most often reported concomitant/prior medicines were calcium supplements, another BPs, antitumor agents, and nonsteroidal anti-inflammatory drugs. In conclusion, we provide a comprehensive overview of the correlation and clinical characteristics, and prognosis of BP-related TPLDs deserving continued surveillance and appropriate management.
PubMed: 37739298
DOI: 10.1016/j.bone.2023.116919 -
ACS Applied Bio Materials Dec 2023Bisphosphonate (BP)-based treatments have been extensively prescribed for bone-related conditions, particularly for osteoporosis. Their low bioavailability creates the...
Bisphosphonate (BP)-based treatments have been extensively prescribed for bone-related conditions, particularly for osteoporosis. Their low bioavailability creates the need for prescribed dosage increase to reach therapeutic levels but generates a plethora of undesirable side effects. A viable approach to alleviating these issues is to design and exploit controlled release strategies. Herein, the controlled release profiles of 15 structurally characterized BPs (actual drugs and structural analogs) were thoroughly studied from tablets containing three (cellulose, lactose, and silica) or two (cellulose, and silica) excipients in human stomach-simulated pH conditions. The BPs were of two types, alkyl-BPs and amino-BPs. Alkyl-BPs included four derivatives of etidronate (acid, disodium, tetra-sodium, and monopotassium forms), medronic acid, and three analogs of etidronate, in which the -CH group was replaced by the moieties -H, -CHCHCH, and -CHCHCHCHCH. Amino-BPs included the commercial drugs pamidronate, alendronate, neridronate, and ibandronate, as well as three analog compounds. Release curves were constructed based on data taken from H NMR peak integration and were expressed as "% BP release" vs time. The controlled release profiles (initial release rate, plateau value, etc.) were correlated with certain structural features (number of hydrogen and metal-oxygen bonds), showing that the molecular and crystal lattice features of each BP profoundly influence its release characteristics. It was concluded that for all BPs, in general, the initial rate became lower as the total number of lattice interactions increased. For the alkyl-BPs elongation of the alkyl side chain seems to decelerate the release. Amino-BPs, in general, show slower release than the alkyl-BPs. No adverse effects of alkyl- and amino-BP drugs on NIH3T3 cell viability were noted.
Topics: Mice; Animals; Humans; Delayed-Action Preparations; Etidronic Acid; NIH 3T3 Cells; Diphosphonates; Cellulose; Silicon Dioxide
PubMed: 37982716
DOI: 10.1021/acsabm.3c00770 -
Journal of Molecular Graphics &... Dec 2023In this paper we have studied the density functional theory of four drugs ibuprofen, alendronate, Sulfasalazine and paracetamol with quartz, propylamine, trimethylamine...
In this paper we have studied the density functional theory of four drugs ibuprofen, alendronate, Sulfasalazine and paracetamol with quartz, propylamine, trimethylamine functionalized quartz and carboxyl modified carbon nanotube. The attractive and repulsive interaction energies between drugs and quartz is obtained at various pH values. The attractive and repulsive energies are well correlated with experimental drug loading and releasing behavior by mesoporous silica nanoparticles. Further, a theoretical model is developed that accounts the electrostatic interaction between silica and drug and the model can predict the drug loading and releasing behavior by silica nanoparticles at various pH values. Sulfasalazine can be taken orally and loaded with trimethyl ammonium functionalized mesoporous silica nanoparticles, which keeps the drug in tact with the carrier in the acidic environment of the stomach and releases it into the neutral or basic medium of the small intestine. Alendronate may be loaded and released from propylamine functionalized mesoporous silica nanoparticles in the ranges of 1-5 and > 8, respectively. Ibuprofen is absorbed in an acidic environment and released in basic conditions for carboxyl modified carbon nanotube. The loading and releasing pH ranges for paracetamol in trimethylammonium functionalized mesoporous silica nanoparticles are 4-8 and >8, respectively. We also convert the pH-dependent variant of the diffusion-controlled Higuchi equation. We have changed the original Higuchi equation to produce the pH-dependent variation by incorporating the Nernst-Planck equation into Flick's first law. The updated equation could be used to forecast when medication particles with varying release times will emerge from a nanoparticles matrix.
Topics: Silicon Dioxide; Quartz; Nanotubes, Carbon; Acetaminophen; Alendronate; Ibuprofen; Sulfasalazine; Drug Delivery Systems; Hydrogen-Ion Concentration
PubMed: 37647724
DOI: 10.1016/j.jmgm.2023.108609 -
Journal of Pediatric Endocrinology &... Apr 2006
Topics: Humans; Alendronate; Child; Adolescent; Osteoporosis; Bone Density Conservation Agents; Female; Administration, Oral; Male; Bone Density; Treatment Outcome
PubMed: 38742779
DOI: 10.1515/jpem-2006-190410 -
Orthopedic Research and Reviews 2024While osteoporosis increases the risk of fragility fractures, bisphosphonate has been proven to increase bone strength and reduce the risk of vertebral and non-vertebral...
BACKGROUND
While osteoporosis increases the risk of fragility fractures, bisphosphonate has been proven to increase bone strength and reduce the risk of vertebral and non-vertebral fractures. In addition to its efficacy, substituting the brand with generic medication is a strategy to optimize healthcare expenditures. This study aimed to evaluate the efficacy of generic alendronate treatment and assess potential adverse events in patients with osteoporosis.
MATERIALS AND METHODS
A retrospective review was conducted on 120 patients who met the indications for osteoporosis treatment, received weekly generic alendronate (70 mg) for >1 year, and underwent evaluation through standard axial dual-energy X-ray absorptiometry (DXA). The outcomes of this study were the percent change in bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip after one year of treatment. The major adverse events occurring during medication that led to the discontinuation of drug administration were documented.
RESULTS
Most patients were female (96.7%) with an average age of 69.0 ± 9.3 years. The percent change in BMD increased at all sites after one year of generic alendronate treatment (lumbar spine: 5.6 ± 13.7, -value <0.001; femoral neck: 2.3 ± 8.3, -value = 0.023; total hip: 2.1 ± 6.2, -value = 0.003), with over 85% of patients experiencing increased or stable BMD. Three patients discontinued the medication due to adverse effects: two had dyspepsia, and one had persistent myalgia.
CONCLUSION
Generic alendronate may be considered an effective antiresorptive agent for osteoporosis treatment with a low incidence of adverse effects.
PubMed: 38410814
DOI: 10.2147/ORR.S445202 -
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 -
Materials (Basel, Switzerland) Jun 2024The surface modification of dental implants plays an important role in establishing a successful interaction of the implant with the surrounding tissue, as the...
The surface modification of dental implants plays an important role in establishing a successful interaction of the implant with the surrounding tissue, as the bioactivity and osseointegration properties are strongly dependent on the physicochemical properties of the implant surface. A surface coating with bioactive molecules that stimulate the formation of a mineral calcium phosphate (CaP) layer has a positive effect on the bone bonding process, as biomineralization is crucial for improving the osseointegration process and rapid bone ingrowth. In this work, the spontaneous deposition of calcium phosphate on the titanium surface covered with chemically stable and covalently bound alendronate molecules was investigated using an integrated experimental and theoretical approach. The initial nucleation of CaP was investigated using quantum chemical calculations at the density functional theory (DFT) level. Negative Gibbs free energies show a spontaneous nucleation of CaP on the biomolecule-covered titanium oxide surface. The deposition of calcium and phosphate ions on the alendronate-modified titanium oxide surface is governed by Ca-phosphonate (-POH) interactions and supported by hydrogen bonding between the phosphate group of CaP and the amino group of the alendronate molecule. The morphological and structural properties of CaP deposit were investigated using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy. This integrated experimental-theoretical study highlights the spontaneous formation of CaP on the alendronate-coated titanium surface, confirming the bioactivity ability of the alendronate coating. The results provide valuable guidance for the promising forthcoming advancements in the development of biomaterials and surface modification of dental implants.
PubMed: 38893965
DOI: 10.3390/ma17112703