Anti-osteoporotic Drugs Research Articles

Calcium Phosphate/Hyaluronic Acid Composite Hydrogels for Local Antiosteoporotic Drug Delivery.

Despite the bone ability of self-regeneration, large bone defects require surgical intervention. Likewise, when it comes to osteoporotic bone fractures, new approaches should be considered a supportive mechanism for the surgery. In recent years, more and more attention has been attracted to advanced drug delivery systems for local osteoporosis treatment, combining appropriate biomaterials with antiosteoporotic drugs, allowing simultaneously to regenerate the bone and locally treat the osteoporosis. Within the current research, hyaluronic acid/strontium ranelate (HA/SrRan), HA/calcium phosphate nanoparticles (HA/CaP NPs), and HA/CaP NPs/SrRan hydrogels were prepared. The effect of CaP and SrRan presence in the composites on the swelling behavior, gel fraction, molecular structure, microstructure, and SrRan and Sr2+ release, as well as in vitro cell viability was evaluated. Obtained results revealed that the route of CaP nanoparticle incorporation into the HA matrix had a significant effect on the hydrogel gel fraction, rheological properties, swelling behavior, and microstructure. Nevertheless, it had a negligible effect on the release kinetics of SrRan and Sr2+. The highest cell (3T3) viability (>80%) was observed for HA hydrogels, with and without SrRan. Moreover, the positive effect of SrRan on 3T3 cells was also demonstrated, showing a significant increase (up to 50%) in cell viability if the used concentrations of SrRan were in the range of 0.05–0.2 μg/ml.

Anti-osteoporotic treatment and COVID-19 risk: is there an association?

Introduction. Despite the recent ASBMR, AACE, Endocrine Society, ECTS&NOF guidelines for osteoporosis management in the era of COVID-19 the impact of antiosteoporotic drugs on disease risk and severity is insufficiently studied. The purpose of this study was to assess the COVID-19 risk for the patients receiving the parenteral bisphosphonate or Denosumab treatment, and the severity of its course in patients with systemic osteoporosis. Materials and methods. We performed the phone survey and studied the results of 195 patients (92 % women; mean age – 62.7±10.8 years) with systemic osteoporosis depending on the current use of parenteral antiresorptive drugs (Zoledronic, Ibandronic acids, or Denosumab, n = 125) and compared the results with data of the patients with osteoporosis who did not use any anti-osteoporotic drugs previously (n = 70). Results. The group of patients with COVID-19 included 32.9 % of patients who did not receive previously any anti-osteoporotic treatment and 33.3 % of osteoporotic patients treated with parenteral antiresorptive drugs. The share of the patients taking the Zoledronic acid who fell ill with COVID-19 was 29.2 %, the share of those taking the Ibandronic acid was 34.4%, and the share of those taking Denosumab was 42.9 %. We did not reveal any significant differences in the COVID-19 frequency and severity depending on the presence and type of parenteral anti-osteoporotic therapy. Additionally, there were no differences depending on the patients' age, gender, obesity, and other osteoporosis risk factors. The risk of COVID-19 in the patients with systemic osteoporosis did not differ depending on antiresorptive drug use, amounting (odds ratio (OR) 95 % CI) 1.1 (0.6-2.0), or on the use of the definite anti-osteoporotic drug (for the Zoledronic acid – 0.9 (0.4-2.0), the Ibandronic acid – 1.1 (0.5-2.3), and for the Denosumab – 1.6 (0.5-5.2). Conclusions. Parenteral anti-osteoporotic drugs (Zoledronic acid, Ibandronic acid, or Denosumab) do not have any influence on COVID-19 frequency and severity and can be recommended for the continuation of the treatment of patients with osteoporosis.

Dispensing anti-osteoporotic drugs changed during the COVID-19 pandemic.

ObjectivesCaring for osteoporosis patients has proven challenging during the COVID-19 pandemic due to repeated lockdowns in Austria. The distinct possibility of insufficient treatment regimens is therefore a matter of pressing concern. The aim of the study was to assess alterations in dispensing anti-osteoporotic drugs during the COVID-19 pandemic.Patients/methodsThis study was a nationwide retrospective register-based observational study which included all patients in Austria aged ≥50 who received at least one prescription for anti-osteoporotic medication between January 2016 and November 2020. Pseudonymised individual-level patients' data were obtained from social insurance authorities. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) to predict drug dispensing.ResultsThere were 2,884,374 dispensations of anti-osteoporotic drugs to 224,598 patients between 2016 and 2020. The mean monthly prescriptions for oral bisphosphonates (−14.5 %) and SERMs (−12.9 %) decreased during the COVID-19 pandemic when compared to the non-COVID-19 period. Dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased. Prescriptions for DMAB decreased during the first lock-down, however increased by 29.1 % for the total observation time.The Arima models showed that in March 2020 (beginning of the 1st COVID-19 lockdown), there was a decrease of 778 dispensings, with a further increase of 14 dispensings every month for denosumab; a decrease by 178 dispensings, with a further increase of 23 dispensings every month for zolendronic acid; a decrease by 2950 dispensings, but with a further increase of 236 dispensings every other month for ibandronate and a decrease by 1443 dispensing with a further decrease of 29 dispensings for alendronate than predicted, had the lockdown not occurred.ConclusionsThe total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during first COVID-19 lockdown. The observed decrease of DMAB during the first lockdown rebounded in the following months. Considering the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even during a pandemic.

Prevalence and patterns of anti-osteoporotic drug use based on 2019 real-world nationwide data in Greece.

Based on the 2019 European scorecard (SCOPE), osteoporosis is diagnosed in an estimated 683,679 individuals in Greece, with the direct cost of incident fractures being €694.7 million, although further relevant real-world data are scarce. The e-Government Center for Social Security Services prescription database, which covers almost 100% of the Greek population, was used to capture all individuals on anti-osteoporotic treatment during 2019. A total of 288,983 among 8,641,341 people, corresponding to 3.3% of the total adult Greek population, had filled at least one anti-osteoporotic prescription (6.0% and 0.36% for females and males, respectively). Prevalence of anti-osteoporotic treatment increased with age, from 0.15% in those younger than 50 to 8.6% in those older than 70years. Oral bisphosphonates were more frequently prescribed (58.8%), followed by denosumab (39.4%). Alendronate was more frequently prescribed in males and in people younger than 60years. Denosumab was more frequently prescribed in females and in people older than 60years. Selective estrogen-receptor modulators, teriparatide, and parenteral bisphosphonates accounted for 1.1%, 1.0%, and 0.02% of all prescriptions, respectively. Orthopedic surgeons (39.6%), endocrinologists (19.6%), general practitioners (19%), and rheumatologists (9.3%) prescribed the vast majority of anti-osteoporotic regimens, with significant differences in prescription patterns. The annual cost of treatment per patient increased significantly with age, being on average €323.33. Less than half of the estimated number of individuals with osteoporosis in 2019 in Greece received treatment, with the total annual cost being far less than the estimated cost of incident-fragility fractures. The impact of this undertreatment on related health care costs merits further investigation.

Association Between Antiosteoporotic Drugs and Risk of Acute Kidney Injury: A Cross-Sectional Study Using Disproportional Analysis and a Pharmacovigilance Database.

The number of fractures related to osteoporosis is expected to increase. Therefore, clarifying the risk of acute kidney injury (AKI) associated with each type of antiosteoporotic drug may avoid discontinuation of osteoporosis pharmacotherapy due to onset of AKI. This cross-sectional study using disproportional analysis and a pharmacovigilance database assessed the risk of AKI with various antiosteoporotic drugs by analyzing data entered into the US Food and Drug Administration's Adverse Event Reporting System from April 2014 to March 2021 and the Medical Data Vision database in Japan in November 2021. All antiosteoporotic drugs were investigated, including bisphosphonates, selective estrogen receptor modulators, denosumab, romosozumab, abaloparatide, and teriparatide. In the analysis of US Food and Drug Administration's Adverse Event Reporting System data, disproportionality for decreasing AKI was observed for oral ibandronate (reporting odds ratios [ROR], 0.22; 95%CI, 0.09-0.45; P < .01), bazedoxifene (ROR, 0.26; 95%CI, 0.05-0.77; P = .01), and intravenous ibandronate (ROR, 0.39; 95% CI, 0.14-0.86; P = .01). In the analysis of the Medical Data Vision data, the incidence of AKI was lower in patients taking intravenous ibandronate (odds ratio, 0.22; 95%CI, 0.06-0.89; P = .03), and the incidence of AKI was higher in patients taking oral alendronate (odds ratio, 2.40; 95%CI, 2.08-2.77; P < .01). Risk of AKI may differ even among oral antiosteoporotic drugs, and the evidence of this association should be assessed further in future drug safety studies.

Experience in using teriparatide for the treatment of postoperative hypoparathyroidism in hemodialysis patients

The frequency of chronic postoperative hypoparathyroidism after total parathyroidectomy for secondary and tertiary hyperparathyroidism in patients with end-stage renal failure, according to various authors, can reach 20% or more. Prescribing active metabolites of vitamin D and calcium it is not always sufficient for achievement of target goals. This dictates the need for replacement therapy with recombinant parathyroid hormone. Teriparatide is the only drug of this series approved by the American Food and Drug Administration (FDA) and registered in the Russian Federation. However, it is registered as an anabolic anti-osteoporotic drug and is not indicated for the treatment of chronic hypoparathyroidism. The use of teriparatide in postoperative hypoparathyroidism in patients receiving renal replacement therapy with programmed hemodialysis in the Russian Federation has not been previously studied. Data on this issue is also limited in foreign literature. However, it is a potential treatment option for hemodialysis patients with chronic hypoparathyroidism and severe bone disorders. In this article, we present 2 clinical cases of substitution and anabolic therapy with teriparatide in this cohort of patients.

Spirocitromycetin, a Fungal Polyketide with an Antiosteoporotic Pharmacophore.

Spirocitromycetin, an antiosteoporotic polyketide bearing a unique spirocycle, was characterized from a human mucus sputum-derived Penicillium velutinum. Its structure and absolute configuration were elucidated spectrally, with its biosynthetic pathway likely mediated via polivione, a reported heptaketide. Spirocitromycetin was shown to be antiosteoporotic at 0.1 μM in the prednisolone-induced osteoporotic zebrafish model. A combination of spirocitromycetin variant synthesis and bioassay has identified 5'-methyl-3'H-spiro[chromane-3,2'-furan]-3',4-dione as an unreported antiosteroporotic pharmacophore. Collectively, this work offers new starting (sub)structures that may be of significance for antiosteoporotic drug discovery.

The potential anti-osteoporotic effect of exercise-induced increased preptin level in ovariectomized rats.

Osteoporosis increases bone fragility and fractures. Preptin hormone is regulated by moderate exercise training and increases bone formation. Therefore, this study was conducted to see how estradiol administration and moderate exercise training affected osteoporotic changes in ovariectomized (OVX) rats. To achieve this aim, 36healthy adult female Wistar albino rats were randomized into Sham, OVX, ovariectomized estradiol-treated (OVX + E) (OVX + E rats were treated using subcutaneous estradiol benzoate 2.5μg/kg body weight/day), ovariectomized practicing moderate exercise training, ovariectomized estradiol-treated and practiced a moderate exercise training, and ovariectomized alendronate-treated (OVX + Alen) (OVX + Alen rats were treated orally with alendronate 3mg/kg body weight/week) groups. Alendronate was used as a standard anti-osteoporotic drug. Moderate exercise training, including therapy with estradiol and alendronate for OVX rats began on the fourth week and lasted for six weeks. Results showed that OVX rats had estrogen and preptin deficiency in serum. These deficiencies were associated with a significant increase in bone resorption biomarkers (urinary deoxypyridinoline and hydroxyproline), and bone formation biomarkers (serum osteocalcin and bone-specific alkaline phosphatase). Also, serum pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) were increased, while bone osteopontin (OPN) expression was decreased. Subsequently, the osteoporotic alterations were verified based on histopathological changes. From the results, estradiol therapy and moderate exercise training significantly improved these findings to the same extent as that of the standard alendronate treatment. Therefore, through their anti-inflammatory properties, increasing bone OPN expression, and regulating serum preptin; estradiol therapy and moderate exercise training can reduce osteoporotic alterations in OVX rats. Thus, combined estradiol therapy and moderate exercise training could be a promising potential therapeutic protocol to reduce postmenopausal osteoporosis. Also, targeting serum preptin and bone osteopontin regulation could have a critical role in the treatment of postmenopausal osteoporosis.

Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

Current prevalence and patterns of anti-osteoporotic drug use based on real-world nation-wide data on 8,641,341 individuals

Current prevalence and patterns of anti-osteoporotic drug use based on real-world nation-wide data on 8,641,341 individuals

Impact of comorbidities on patterns and annual cost of anti-osteoporotic drug treatment based on real-world nation-wide data on 8,641,341 individuals

Impact of comorbidities on patterns and annual cost of anti-osteoporotic drug treatment based on real-world nation-wide data on 8,641,341 individuals

An inconvenient status in anti-osteoporotic treatment process: corticosteroid use.

There are limited studies investigating the comparison of the efficacy of anti-osteoporotic drugs in different conditions resulting in osteoporosis in older adults. This study aimed to compare the effectiveness of anti-osteoporotic agents in older adults with or without glucocorticoid-induced osteoporosis. This retrospective study included 364 patients with osteoporosis, aged 65 years and older. Bone mineral density measurement was performed, and the percent change from baseline was calculated at month 24. Of the 364 patients, 80 were glucocorticoid users. Similar changes in the bone mineral density of the lumbar spine and femoral neck and fracture risk were found in patients with or without glucocorticoid-induced osteoporosis. There was no significant difference in bone mineral density changes between the groups in terms of anti-osteoporotic agents used. This study demonstrated that the response to anti-osteoporotic agents was similar in older adults with glucocorticoid-induced osteoporosis and those without glucocorticoid-induced osteoporosis. The results of our study may guide osteoporosis treatment in older individuals with glucocorticoid-induced osteoporosis.

Possible Repositioning of an Oral Anti-Osteoporotic Drug, Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase.

KIAA1199 has a strong hyaluronidase activity in inflammatory arthritis. This study aimed to identify a drug that could reduce KIAA1199 activity and clarify its effects on inflammatory arthritis. Rat chondrosarcoma (RCS) cells were strongly stained with Alcian blue (AB). Its stainability was reduced in RCS cells, which were over-expressed with the KIAA1199 gene (RCS-KIAA). We screened the drugs that restore the AB stainability in RCS-KIAA. The effects of the drug were evaluated by particle exclusion assay, HA ELISA, RT-PCR, and Western blotting. We further evaluated the HA accumulation and the MMP1 and three expressions in fibroblast-like synoviocytes (FLS). In vivo, the effects of the drug on symptoms and serum concentration of HA in a collagen-induced arthritis mouse were evaluated. Ipriflavone was identified to restore AB stainability at 23%. Extracellular matrix formation was significantly increased in a dose-dependent manner (p = 0.006). Ipriflavone increased the HA accumulation and suppressed the MMP1 and MMP3 expression on TNF-α stimulated FLS. In vivo, Ipriflavone significantly improved the symptoms and reduced the serum concentrations of HA. Conclusions: We identified Ipriflavone, which has inhibitory effects on KIAA1199 activity. Ipriflavone may be a therapeutic candidate based on its reduction of KIAA1199 activity in inflammatory arthritis.

A 2-year follow-up of a novel Fracture Liaison Service: can we reduce the mortality in elderly hip fracture patients? A prospective cohort study.

SummaryOsteoporosis is an underdiagnosed disease that results in bone fragility and risk of fractures. Fracture Liaison Service (FLS) is a secondary prevention model which identifies patients at risk for fragility fractures. The introduction of a FLS protocol showed an increase of anti-osteoporotic drug prescription and significant reduction of all-cause mortality.Introduction Hip fractures are the most severe osteoporotic fracture due to their associated disability and elevated risk of mortality. FLS programs have enhanced the management of osteoporosis-related fractures. Our objective is to analyze the effect of the FLS model over survival and 2-year mortality rate following a hip fracture.MethodsWe conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture during 3 consecutive years, before and after the implementation of the FLS in our center (i.e., between January 2016 and December 2018). Patients’ information was withdrawn from our local computerized database. Patients were followed for 2 years after the hip fracture. Mortality and re-fracture rates were compared between the two groups using a multivariate Cox proportional hazard model.ResultsA total of 1101 patients were included in this study (i.e., 357 before FLS implementation and 744 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (583 (78.4%) vs 44 (12.3%); p < 0.01). There was an increase of adherence to treatment after FLS implementation (227 (38.9%) vs 12 (3.3%); p = 0.03). A total of 222 (29.8%) patients after FLS implementation and 114 (31.9%) individuals before FLS implementation (p = 0.44) died during the follow-up period. A second fracture occurred in 49 (6.6%) patients after FLS implementation and in 26 (7.3%) individuals before FLS implementation (p = 0.65). Patients who were treated with anti-osteoporotic drugs after the implementation of the FLS protocol had a lower all-cause 1-year and 2-year mortality compared with patients managed before the implementation of the FLS protocol (adjusted hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59–0.96; HR 0.87, 95% CI 0.69–1.09, respectively).ConclusionsThe implementation of a FLS protocol was associated with an increase of anti-osteoporotic treatment, higher adherence, and greater survival in elderly hip fracture patients. There was a significant reduction of all-cause mortality in the FLS patients treated with anti-osteoporotic. However, the application of the FLS did not affect the risk of suffering a second fragility fracture.

Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects.

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis.

Incidence and predictors of fragility fracture in postmenopausal rheumatoid arthritis patients receiving oral bisphosphonates: a longitudinal observational study

BackgroundAlthough many studies have reported the predictors of fractures in patients with rheumatoid arthritis (RA) who are not receiving anti-osteoporotic treatments or who are receiving unspecified treatments, studies focusing on the predictors of fracture in patients with RA who are currently being treated with oral bisphosphonates (BP) are quite scarce. This study aims to investigate the incidence and predictors of fragility fracture in postmenopausal patients with RA receiving oral BP.MethodsThis retrospective longitudinal observational study comprised 98 postmenopausal RA patients receiving oral BP for a minimum of 6 months between April 2015 and December 2020. The cumulative incidence of fragility fractures including vertebral and nonvertebral fractures was investigated using the Kaplan–Meier method. Cox proportional hazards analysis was used to analyze baseline predictors of future fragility fractures. To determine a cutoff value of continuous predictors, the receiver-operating characteristic curve was applied.ResultsTwenty patients developed fractures during the study period, with a cumulative incidence of 6.1% at 12 months, 10.5% at a median follow-up of 28 months, and 14.4% at 36 months. Multivariable Cox hazards analysis showed a history of prior vertebral fracture (hazard ratio [HR] 6.26, 95% confidence interval [CI] 1.99‒19.68, P = 0.001) and dose of methotrexate (HR 0.87, 95% CI 0.76‒0.99, P = 0.041) to be independent predictors. The cutoff value for methotrexate dose was 4 mg/week.ConclusionsWe found a cumulative incidence of any fractures of 10.5% at 28 months in patients with RA currently being treated with oral BP. A history of prior vertebral fractures and methotrexate dose were positive and negative predictors for fractures, respectively. Practitioners should consider selecting another anti-osteoporotic drug in patients with RA who remain at risk despite receiving oral BP.

The Use of Intravenous Zoledronate May Reduce Retear Rate after Rotator Cuff Repair in Older Female Patients with Osteoporosis: A First In-Human Prospective Study.

The objective of this study was to demonstrate the effect of intravenous (IV) zoledronate administration on rotator cuff healing, retear rate, and clinical outcomes in osteoporotic patients who underwent arthroscopic rotator cuff repair (ARCR) compared with patients with normal bone densities. In this prospective nonrandomized comparative study with propensity score matching, 30 patients who were postoperatively administered IV zoledronate (5 mg) were enrolled as the study group. The control group was matched using 1-to-2 propensity score matching. Radiologic and functional outcomes were evaluated 6 months after surgery. The functional scores in both groups exhibited significant improvement 6 months after surgery. Compared with Group 1 (osteoporosis with IV zoledronate injection) Group 2 (normal bone density) showed significant improvement in their University of California, Los Angeles (UCLA) shoulder score and Constant Shoulder Score (CSS) at 6 months postoperatively. The range of motion improved in both groups at 6 months after surgery. The retear rates according to Sugaya’s classification (IV and V) were 13.3% (4 of 30 patients) and 25% (15 of 60 patients) in Groups 1 and 2, respectively, which established a non-inferiority of Group 1 to the control group. The retear pattern according to Rhee’s classification in Group 1 was type I in all cases, whereas eight cases of type I and seven cases of type II patterns were observed in Group 2, which was statistically insignificant between the groups. In conclusion, anti-osteoporotic drug use is beneficial for patients with osteoporosis to reduce the failure rate after an ARCR of length > 2 cm, especially in older female patients. Moreover, thorough scrutiny is required to detect osteoporosis in patients with rotator cuff tears, especially in female patients.

Zoledronic Acid Contraindications Prevalence among Hip-Fractured Patients Aged 75 Years or Over Hospitalized in an Orthogeriatric Unit

Objective: Zoledronic acid (ZA) is an antiosteoporotic drug that has been proven to reduce mortality after a hip fracture (HF). ZA is however underused with older HF patients. One possible cause may be the high prevalence of severe renal failure and hypocalcemia which contraindicate ZA administration. The aim of this study was to assess the prevalence of these 2 contraindications in patients aged 75 years or older admitted into an orthogeriatric (OG) unit after a low-energy HF. The secondary objective was to assess the prevalence of situations in which ZA must be used with caution. Methods: Our retrospective descriptive monocentric study was performed in an OG unit on a cohort of elderly patients hospitalized for HF from August 2015 to August 2017. Prevalence of hypocalcemia lower than 2 mmol/L and Cockcroft creatinine clearance lower than 35 mL/min was recorded. Results: Among the 194 patients admitted for HF, 136 patients (mean age 86 ± 5.6 years; 101 women) were included. The mean length of hospital stay was 15 ± 9 days. 111 (81.5%) had no contraindications to ZA administration. More than 80% presented situations in which ZA had to be used with caution, including 25(OH)D deficiency (20%). Conclusion: The majority of subjects aged 75 years or older admitted to hospital after an HF seem to have no contraindication for ZA administration during their immediate postoperative hospital stay. The hospitalization period after HF repair gives the opportunity to give most of them this treatment to improve their prognosis, taking into account situations in which ZA must be used with caution.

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects.

As cannabinoid CB2 receptors (CB2R) possess various pharmacological effects—including anti-epilepsy, analgesia, anti-inflammation, anti-fibrosis, and regulation of bone metabolism—without the psychoactive side effects induced by cannabinoid CB1R activation, they have become the focus of research and development of new target drugs in recent years. The present study was intended to (1) establish a double luciferase screening system for a CB2R modulator; (2) validate the agonistic activities of the screened compounds on CB2R by determining cAMP accumulation using HEK293 cells that are stably expressing CB2R; (3) predict the binding affinity between ligands and CB2 receptors and characterize the binding modes using molecular docking; (4) analyze the CB2 receptors–ligand complex stability, conformational behavior, and interaction using molecular dynamics; and (5) evaluate the regulatory effects of the screened compounds on bone metabolism in osteoblasts and osteoclasts. The results demonstrated that the screening system had good stability and was able to screen cannabinoid CB2R modulators from botanical compounds. Altogether, nine CB2R agonists were identified by screening from 69 botanical compounds, and these CB2R agonists exhibited remarkable inhibitory effects on cAMP accumulation and good affinity to CB2R, as evidenced by the molecular docking and molecular dynamics. Five of the nine CB2R agonists could stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. All these findings may provide useful clues for the development of novel anti-osteoporotic drugs and help elucidate the mechanism underlying the biological activities of CB2R agonists identified from the botanical materials.

Влияние антиостеопоротических средств на качество костной ткани: обзор литературы и результаты собственных исследований

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