Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis

Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.

The Application of Tannic Acid in Orthopedics

Tannic acid (TA) is a naturally occurring polyphenol compound commonly found in tea, wine, and fruits. Because of the excellent structural and functional properties afforded by TA, materials based on the structure of polyhydroxyphenols have great value, particularly for orthopedic transplantation. This compound, for example, can form a strong interaction with metals and can form a stable coating on their surfaces, thus, improving the physical and chemical properties of bone–implant surfaces and boosting implantation success rates. TA can also inhibit the activity of osteoclasts, thus, playing a potential role in the treatment of osteoporosis. Furthermore, if the body becomes polluted with heavy metals, TA can chelate the ions to protect bone morphology and structure. It also has a significant antibacterial effect and can reduce infections caused by surgical implantation and inhibit a variety of tumor cells, thereby promoting its potential application in spinal metastasis surgery. Furthermore, it can also slow the corrosion caused by magnesium alloys, thereby greatly improving the development of degradable orthopedic metal fixatives. Importantly, TA is cheap and easy to obtain, making it extremely valuable for use in orthopedics. This review focuses on the research status and practical applications of TA, and prospects for its future application for orthopedics (Figure 1).

Role of zoledronic acid in treatment of osteoporosis and prevention of fractures

Introduction. One of the causes of primary disability and high mortality, among patients with osteoporosis, are fractures that occur with minimal trauma, as a rule, it is a fall from the height of one’s own height. The final link in the chain of preventive measures to reduce the frequency of osteoporosis and fractures on its background is the introduction of pharmacological correction of bone deficiency into the practical activity of an orthopedic traumatologist. Currently, there are several drugs that can change the disturbed metabolism. For example, the use of zoledronic acid significantly reduces the risk of fractures.Aim: to study the effect of zoledronic acid on bone mineral density in patients with osteoporosis complicated by a fracture of proximal end of the femur.Materials and methods. In a prospective cohort study, 14 patients received zoledronic acid for 2 years.Results. When comparing BMD L2-L4, it was revealed that a year after the start of treatment, its increase relative to the baseline value was 4.6%, but was statistically insignificant (0.86 ± 0.078 g/cm2 versus 0.90 ± 0.08 g/cm2, p > 0.05). After 2 years of treatment, the BMD of this segment increased, relative to the baseline values, by 12% and the differences became statistically significant (0.86 ± 0.078 g/cm2 compared to 0.97 ± 0.076 g/cm2, p < 0.05). The increase in BMD for the second year of treatment by 6% was statistically significantly different from the increase for the first year of treatment (0.90 ± 0.08 g/cm2 compared to 0.97 ± 0.076 g/cm2, p < 0.05).A comparative analysis of the basic units of the IPC hip after 1 and 2 years of treatment did not reveal significant differences: 0.7075 ± 0.046 g/cm2 compared to 0.7079 ± 0.034 g/cm2 and 0.70751 ± 0.046 g/cm2 compared to 0.6630 ± 0.97 g/cm2, p > 0.05. In any case, for 2 years not marked new vertebral body fractures. Only one patient had a fracture of the radius in the distal third. The quality of life, after 2 years, significantly improved on the scale of “habitual daily activities” (p = 0.007), decreased indicators on the scale of “anxiety” and “depression” (p > 0.05).Discussion. The study confirmed that even in the presence of pronounced bone loss, pharmacological correction of impaired remodeling reduces the risk of new fractures and improves the quality of life.Conclusion. Pharmacotherapy with zoledronic acid, in our study, confirmed its effectiveness in the treatment of osteoporosis.

The problem of low adherence to antiresorptive therapy with bisphosphonates: solutions

Over the past several decades, there has been a global aging of the population around the world. The demographic situation in the Russian Federation is no exception, being a natural result of an increase in the life expectancy of the population. In clinical practice, geriatric diseases have been identified and are widely studied, which deserve priority attention due to a sharp decline in the quality of life of elderly patients. Osteoporosis is called a “silent epidemic” among elderly and senile patients. This disease is associated with a high risk of low-traumatic fractures of various localization. The imperfect rehabilitation program after complex fractures and its insufficient funding are forcing clinicians to focus on more cost-effective solutions to this problem – the prevention and treatment of osteoporosis. Osteomodifying agents are widely used by physicians of various specialties. Bisphosphonates effectively reduce the risk of low-traumatic fractures against the background of an increase in bone mineral density. The level of effectiveness of bisphosphonates depends on the patient’s adherence to antiresorptive therapy and the degree of compensation for vitamin D and serum calcium. Low adherence to osteoporosis therapy is based on the need for long-term use of bisphosphonates and a different spectrum of adverse events. In the article, using alendronate as an example, the problem of low adherence to antiresorptive therapy will be considered and ways to solve it are presented.

Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.

Exploring the potential therapeutic effect of Eucommia ulmoides–Dipsaci Radix herbal pair on osteoporosis based on network pharmacology and molecular docking technology

This study elaborated the multi-component, multi-target, and multi-pathway interaction mechanism of Eucommia ulmoides-Dipsaci Radix herbal pair in the treatment of osteoporosis.

Identification and Analysis of Chemical Constituents and Rat Serum Metabolites in Gushuling Using UPLC-Q-TOF/MS Coupled with Novel Informatics UNIFI Platform

Gushuling (GSL), a well-known hospital preparation composed of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of osteoporosis (OP) for decades due to its remarkable therapeutic effect. However, the chemical constituents of GSL are still unclear so far, which limits the in-depth study of its pharmacodynamic material basis and further restricts its clinical application. In this study, we developed a strategy for qualitative analysis of the chemical constituents of GSL in vitro and in vivo. Based on the results of ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) and the UNIFI informatics platform, the chemical constituents of GSL can be determined quickly and effectively. By comparing the retention time, accurate mass, and fragmentation spectrum of the compounds in GSL, a total of 93 compounds were identified or preliminarily identified, including flavonoids, terpenoids, phenylpropanoids, steroids, etc. Among them, nine compounds have been confirmed by standard substances, namely epimedin A, epimedin B, epimedin C, icariin, ecdysterone, calycosin, calycosin-7-glucoside, ononin, and ginsenoside Ro. Fragment patterns and characteristic ions of representative compounds with different chemical structure types were analyzed. At the same time, 20 prototype compounds and 42 metabolites were detected in rat serum. Oxidation, hydration, reduction, dehydration, glutathione S-conjugation, and acetylcysteine conjugation were the main transformation reactions of GSL in rat serum. In this research, the rapid method to characterize the in vitro and in vivo chemical constituents of GSL can not only be used for the standardization and quality control of GSL but also be helpful for further research on its pharmacodynamic material basis.

17p-estradiol (1 mg daily) in continuous combination with dydrogesterone (5.10 or 20 mg daily) increases bone mineral density in postmenopausal women

Although the minimal dose of 17/3-estradiol in hormone replacement regimens was originally considered to be 2 mg a day, it is now increasingly accepted that a lower dose of 1 mg a day is effective in protecting women from the detrimental effects of the menopause. A 1-year, multicentre, double-blind, randomized study was conducted in 214 healthy postmenopausal women in order to assess the effect of 17(3-estradiol (1 mg a day) continuously combined with dydrogesterone (5,10 or 20 mg/day) in preventing bone loss. Bone mineral density (BMD) was evaluable in 177 women who completed the study. In all women, a statistically significant increase from baseline in lumbar vertebrae (L.2~L4) BMD was seen after 6 months (+ 2,4%; p0,01); this increase was somewhat greater after 12 months (+ 3,6%;p 0,01). Similar effects were seen in the hip. After 6 months, BMD in the femoral neck, Wards triangle and trochanter had increased by 0,20% (not significant [n.s.]), 0,32% (n.s.)and 1,08% (p0,01), respectively, compared with baseline. Greater increases were again seen after 12 months (+1,16%, + 1,62% and +2,83%, respectively), all of which were statistically significant (p0,01) compared with baseline. The change in BMD from baseline did not diff er significantly between the three dydrogesterone dosages for either L.2~L4 or hip. All dosages were well tolerated and amenorrhoea was achieved in over 70%. In conclusion, 17(3-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) results in a significant increase in lumbar vertebrae and hip BMD in postmenopausal women. The lower dose of oestrogen and the avoidance of cyclical bleeding make this a particularly suitable regimen for the prevention and treatment of osteoporosis in older women.