Treatment Of Osteoporosis Research Articles

Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis.

Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night. This circadian rhythm of the skeleton is regulated by gut hormones. Until now, gut hormones that have been found to affect skeletal homeostasis include glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which exerts its effects by binding to its cognate receptors (GLP-1R, GLP-2R, GIPR, and Y1R). Several studies have shown that GLP-1, GLP-2, and GIP all inhibit bone resorption, while GIP also promotes bone formation. Notably, PYY has a strong bone resorption-promoting effect. In addition, gut microbiota (GM) plays an important role in maintaining bone homeostasis. This review outlines the roles of GLP-1, GLP-2, GIP, and PYY in bone metabolism and discusses the roles of gut hormones and the GM in regulating bone homeostasis and their potential mechanisms.

Osteoporosis treatment for fracture prevention in elderly

Fracture prevention in the elderly is an urgent issue at all levels: individual, family, and societal. Osteoporosis is the underlying cause of fractures in the elderly, and it is important to understand its pathogenesis and treatment. Diet, exercise, and pharmacotherapy are all important for fracture prevention. Particularly with regard to pharmacotherapy, it is important to understand the mechanism of action of each drug and its characteristics and problems from a clinical point of view. Appropriate treatment of osteoporosis has been proven to reduce fractures in the elderly, and its widespread implementation is desirable.

P002 A comparison between radiologically reported osteopenia and the FRAX score as an indication for bone densitometry

Abstract Background/Aims Osteopenia is defined as a bone mineral density score between -1 and -2.5 standard deviations compared to a young adult reference mean (T-score) based on dual energy x-ray absorptiometry (DXA). Radiologists continue to use the term in a generic and qualitative manner to mean decreased bone mineral density, but they cannot distinguish between osteopenia and osteoporosis which means patients then go on to have a DXA. We would like to see if a FRAX (fracture risk assessment tool) can safely replace osteopenia as an indication for a DXA. Methods We retrospectively identified 2276 patients to have had a DXA scan from October 2022 to March 2023 according to the departmental database. Their referral forms were obtained from the Electronic Medical Record (EMR). Out of these, 150 patients were referred with a sole indication being radiologically reported osteopenia. Out of 150 patients, 22 were excluded as they were found to have other indications not reported on their referral from and seven more were excluded as three had bilateral hip replacement, three were below 40 and one was undergoing gender reassignment and was on oestrogen. The remaining 121 patients were included in the study and their post BMD ( bone mineral density) FRAX score was obtained from patient EMR. Pre BMD FRAX was also calculated using clinical information available on patient’s EMR retrospectively. NOGG ( National Osteoporosis Guideline Group) recommendation of treatment based on the fracture risk as per the FRAX were then compared between pre and post BMD retrospectively to see if there would be any change in treatment plan. Results Of total 121 patients included, 94 were female. Mean age was 68 years. Retrospective review of the case notes revealed that using a FRAX with BMD, total 34 (28.1%) patients needed treatment for osteoporosis while 87 (71.9%) did not. Of 87 patients not requiring treatment, 55 would not have received DXA scan if FRAX assessment was done without BMD. Of the 34 who did need treatment, 32 would still be recommended for a DXA while only two patients wouldn’t. However, these two patients had other clinical indications for osteoporosis assessment and would still have required a specialist referral such that a decision can be made about DXA. Conclusion If radiologically reported osteopenia as an indication for a DXA is replaced by FRAX, DXA would not be needed in nearly half of the patients. This will have potential to save scarce DXA resource without compromising patient safety, treatment plan, and will reduce waiting times. Disclosure S. Srinivas: None. K. Hood: None. H. Sapkota: None.

Treatment patterns in women with postmenopausal osteoporosis using abaloparatide: a real-world observational study

SummaryReview of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed.PurposeAbaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history.MethodsData for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six academic and clinical practice settings across the US.ResultsA total of 173 patients were enrolled (mean [SD] age, 69.8 [7.4] years). At the time of abaloparatide treatment initiation, 78.6% had received other osteoporosis medications. Mean (SD) time from discontinuation of osteoporosis medications prior to initiation of abaloparatide was 1.7 (3.2) years. Twenty-four months of follow-up data from the initiation date of abaloparatide was collected from 94.0% of patients and 6.0% of patients had 12–24 months of follow-up. During the follow-up period, 96.0% of patients had at least one visit for osteoporosis management and 55.5% had access to a medication support program. The median duration of therapy was 18.6 months and 105/162 (64.8%) completed abaloparatide treatment as prescribed. The most common reasons for treatment discontinuation were financial (31.2%) and tolerability (22.8%). Following completion of a course of treatment with abaloparatide, 82/162 (50.6%) patients transitioned to another osteoporosis medication. The median time between abaloparatide treatment course completion and the initiation of follow-on medication was 21 days.ConclusionMost patients completed treatment with abaloparatide as prescribed, and over half continued with an antiresorptive agent. This favorable conduct may be the result of regular follow-up visits and accessibility to both medication and patient support services.

Quercetin in Osteoporosis Treatment: A Comprehensive Review of Its Mechanisms and Therapeutic Potential.

This review aims to provide a theoretical basis and insights for quercetin's clinical application in the prevention and treatment of osteoporosis (OP), analyzing its roles in bone formation promotion, bone resorption inhibition, anti-inflammation, antioxidant effects, and potential mechanisms. OP, a prevalent bone disorder, is marked by reduced bone mineral density and impaired bone architecture, elevating the risk of fractures in patients. The primary approach to OP management is pharmacotherapy, with quercetin, a phytochemical compound, emerging as a focus of recent interest. This natural flavonoid exerts regulatory effects on bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts and promotes bone health and metabolic equilibrium via anti-inflammatory and antioxidative pathways. Although quercetin has demonstrated significant potential in regulating bone metabolism, there is a need for further high-quality clinical studies focused on medicinal quercetin.

Identification of osteoporosis ferroptosis-related markers and potential therapeutic compounds based on bioinformatics methods and molecular docking technology

Research background and purposeOsteoporosis (OP) is one of the most common bone diseases worldwide, characterized by low bone mineral density and susceptibility to pathological fractures, especially in postmenopausal women and elderly men. Ferroptosis is one of the newly discovered forms of cell death regulated by genes in recent years. Many studies have shown that ferroptosis is closely related to many diseases. However, there are few studies on ferroptosis in osteoporosis, and the mechanism of ferroptosis in osteoporosis is still unclear. This study aims to identify biomarkers related to osteoporosis ferroptosis from the GEO (Gene Expression Omnibus) database through bioinformatics technology, and to mine potential therapeutic small molecule compounds through molecular docking technology, trying to provide a basis for the diagnosis and treatment of osteoporosis in the future.Materials and methodsWe downloaded the ferroptosis-related gene set from the FerrDb database (http://www.zhounan.org/ferrdb/index.html), downloaded the data sets GSE56815 and GSE7429 from the GEO database, and used the R software “limma” package to screen differentially expressed genes (DEGs) from GSE56815, and intersected with the ferroptosis gene set to obtain ferroptosis-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the R software “clusterProfiler” package. The random forest model was further screened to obtain essential ferroptosis genes. R software “corrplot” package was used for correlation analysis of essential ferroptosis genes, and the Wilcox test was used for significance analysis. The lncRNA-miRNA-mRNA-TF regulatory network was constructed using Cytoscape software. The least absolute shrinkage and selection operator (LASSO) was used to construct a disease diagnosis model, and a Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic performance, and then GSE7429 was used to verify the reliability of the diagnosis model. Molecular docking technology was used to screen potential small molecule compounds from the Drugbank database. Finally, a rat osteoporosis model was constructed, and peripheral blood mononuclear cells were extracted for qRT-PCR detection to verify the mRNA expression levels of crucial ferroptosis genes.ResultSix DEGs related to ferroptosis were initially screened out. GO function and KEGG pathway enrichment analysis showed that ferroptosis-related DEGs were mainly enriched in signaling pathways such as maintenance of iron ion homeostasis, copper ion binding function, and ferroptosis. The random forest model identified five key ferroptosis genes, including CP, FLT3, HAMP, HMOX1, and SLC2A3. Gene correlation analysis found a relatively low correlation between these five key ferroptosis genes. The lncRNA-miRNA-mRNA-TF regulatory network shows that BAZ1B and STAT3 may also be potential molecules. The ROC curve of the disease diagnosis model shows that the model has a good diagnostic performance. Molecular docking technology screened out three small molecule compounds, including NADH, Midostaurin, and Nintedanib small molecule compounds. qRT-PCR detection confirmed the differential expression of CP, FLT3, HAMP, HMOX1 and SLC2A3 between OP and normal control group.ConclusionThis study identified five key ferroptosis genes (CP, FLT3, HAMP, HMOX1, and SLC2A3), they were most likely related to OP ferroptosis. In addition, we found that the small molecule compounds of NADH, Midostaurin, and Nintedanib had good docking scores with these five key ferroptosis genes. These findings may provide new clues for the early diagnosis and treatment of osteoporosis in the future.

Osteoporosis Management in Patients with Hip Fracture post Fall

Introduction: Osteoporosis increases the risk of fragility fracture. Hip fractures are associated with poor outcomes. Men are under-screened and under-treated for osteoporosis, which tends to be secondary, and men have higher mortality and worse outcomes after hip fracture than do women. This study aimed to describe patients admitted with hip fracture following minimal trauma and to explore any gender differences in calcium and vitamin D deficiency and use of osteoporosis medication before admission. Methods: A retrospective cross-sectional study included all patients admitted to Bankstown-Lidcombe Hospital with a fracture of the hip post fall, with or without surgery, from January 1, 2019, to December 31, 2019. Each patient's electronic medical record was reviewed to collect data. The data were extracted and analysed using GraphPad Prism 9.5.1. Unpaired Student's t-tests and Fisher's exact test were used in the analysis. Results: A total of 203 patients were included with a mean age of 83.5 ± 8.8 years and a range of 40 to 103 years, with over half (51.2%) aged 81 to 90 years. Fifty-nine (29.1%) were male. Of 196 patients with vitamin D levels available, 78 (39.8%) had a deficiency, including 30 of 57 (52.6%) males and 48 of 139 (34.5%) females. Males were twice as likely to be vitamin D deficient as were females on admission (OR 2.106; 95% CI 1.143 to 3.939; p = 0.0243). Of 203 patients, 39 (19.2%) were on osteoporosis treatment before admission, including 6 of 59 (10.2%) male and 33 of 144 (22.9%) female patients. Males were 2.6 times more likely to have had no osteoporosis treatment before admission than were females (OR 2.626; 95% CI 1.059 to 6.340; p = 0.0486). Conclusions: Males were more likely to have vitamin D deficiency and not be prescribed osteoporosis medication before admission in a cohort of patients admitted to the hospital with hip fracture post minimal trauma. To prevent hip fracture and resultant hospitalization, increased awareness is needed in diagnosing and managing osteoporosis in men, ideally occurring in the community.

New molecular aspects of the pathogenesis of osteoporosis – perspectives for early diagnosis and treatment

Osteoporosis (OP) is a common disease leading to low-trauma fractures and is a serious medical and social problem. Often a fracture is the first clinical manifestation of OP that has been asymptomatic for a long time, necessitating the development of methods for early detection and risk assessment of this disease. OP is a multifactorial disease with a strong hereditary component. However, as the data from the study of genetic factors show, only 15% of the heritability of this trait can be explained. In this context, the focus of research is shifting to the area of epigenetic regulation, which controls gene activity without altering the primary structure of the DNA. One of the most promising mechanisms of epigenetic control is methylation, which affects DNA as well as RNA and histones. The characteristics of these mechanisms and the possibilities of their use for the diagnosis and treatment of OP are presented in this review.

Irisin and Its Role in Postmenopausal Osteoporosis and Sarcopenia.

Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia.

Osteogenic Effects of the Diospyros lotus L. Leaf Extract on MC3T3-E1 Pre-Osteoblasts and Ovariectomized Mice via BMP2/4 and TGF β Pathways.

Osteoporosis, a disease defined by the primary bone strength due to a low bone mineral density, is a bone disorder associated with increased mortality in the older adult population. Osteoporosis is mainly treated via hormone replacement therapy, bisphosphates, and anti-bone resorption agents. However, these agents exert severe side effects, necessitating the development of novel therapeutic agents. Many studies are focusing on osteogenic agents as they increase the bone density, which is essential for osteoporosis treatment. Here, we aimed to investigate the effects of Diospyros lotus L. leaf extract (DLE) and its components on osteoporosis in MC3T3-E1 pre-osteoblasts and ovariectomized mice and to elucidate the underlying related pathways. DLE enhanced the differentiation of MC3T3-E1 pre-osteoblasts, with a 1.5-fold elevation in ALP activity, and increased the levels of osteogenic molecules, RUNX family transcription factor 2, and osterix. This alteration resulted from the activation of bone morphogenic protein 2/4 (BMP2/4) and transformation of growth factor β (TGF β) pathways. In ovariectomized mice, DLE suppressed the decrease in bone mineral density by 50% and improved the expression of other bone markers, which was confirmed by the 3~40-fold increase in osteogenic proteins and mRNA expression levels in bone marrow cells. The three major compounds identified in DLE exhibited osteogenic and estrogenic activities with their aglycones, as previously reported. Among the major compounds, myricitrin alone was not as strong as whole DLE with all its constituents. The osteogenic activity of DLE was partially suppressed by the inhibitor of estrogen signaling, indicating that the estrogenic activity of DLE participated in its osteogenic activity. Overall, DLE suppresses osteoporosis by inducing osteoblast differentiation.

Efficacy of Xianling Gubao capsule vs. its combination therapy in the treatment of primary osteoporosis: A network meta-analysis of randomized controlled trials

ObjectiveThis study aimed to evaluate the efficacy of the Xianling Gubao (XLGB) capsule alone and its combination therapy in primary osteoporosis (POP). MethodsDatabases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and SinoMed were searched from their inception to January 16, 2024, for randomized controlled trials (RCTs) investigating the XLGB treatment for POP. A network meta-analysis (NMA) was performed to evaluate the efficacy and safety of multiple interventions in the treatment of POP. The Cochrane risk-of-bias tool was used to assess the quality of RCTs included in the meta-analysis. Software Stata (version 15.0) was used for statistical analysis. The surface under the cumulative ranking curve (SUCRA) method was used to present the findings from this NMA numerically and graphically by ranking multiple interventions. ResultsA total of 107 RCTs were included in the meta-analysis, involving 10,032 participants and 21 interventions. Meta-analysis showed that XLGB + calcium (Ca) + calcitonin (99.9 %) was the most desirable treatment option for improving clinical efficacy. XLGB + Ca + bisphosphonate (BP) was most effective for improving bone mineral density (BMD) at the lumbar spine, femoral neck BMD, and serum bone Gla protein (BGP). SUCRA values for improving these three outcome measures by XLGB + Ca + BP were 87.4 %, 77.2 %, and 84.3 %, respectively. XLGB + calcitonin was the optimal option in terms of safety evaluation and improving visual analogue scale (VAS), with the SUCRA values being 89.6 % and 94.9 %, respectively. ConclusionsThe XLGB combination therapy is a desirable option for treating POP as it can effectively improve the therapeutic effects, BMD, and serum BGP, as well as relieve pain in patients with POP.

Facile fabrication of phosphazene-quercetin-alendronate composites as pH-responsive bone-targeted nanomedicine for osteoporosis treatment

Osteoporosis, closely related to age, is characterized by impaired bone mass and bone strength, damage of bone microstructure, resulting in a higher risk of fractures with minimal trauma, especially in the hip and spine. Quercetin (Que), a natural compound, has previously demonstrated its potential anti-osteoporosis effects via promoting bone formation and anti-bone resorption. However, Que is poor water solubility, lack of bone targeting, and requires high concentration to exert its therapeutic effects. In this work, a pH-responsive and bone-targeted nanomedicine HCCP-Que-PEG-ALN (HQPA) was developed via using hexachlorocyclotriphosphazene(HCCP) as the cross-linkage, Que, alendronate (ALN), and amino-polyethylene glycol (NH2-PEG) as other building blocks. We demonstrated that HQPA can form spherical nanoparticles in aqueous solution with average size of 158.3 ± 59.8 nm with high drug loading capacity of Que (31.4 w/w%) and obvious bone-targeting capability. in vitro experimental results indicated that HQPA NPs have dual anti-osteoporosis effects of promoting osteoblasts and inhibiting osteoclasts. Furthermore, HQPA NPs can effectively reduce the bone loss in OVX mice with low toxicity to major organs. We believe that this method should be a general and useful route for fabrication of bone-targeted natural-compounds-based nanomedicines for treatment different bone-related diseases.

Enhanced oral bioavailability of levormeloxifene and raloxifene by nanoemulsion: simultaneous bioanalysis using liquid chromatography-tandem mass spectrometry.

Aim & objective: Levormeloxifene (L-ORM) and raloxifene (RAL) are selective estrogen receptor modulators used in the treatment of postmenopausal osteoporosis and breast cancer. Here, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous estimation of both drugs. Materials & methods: A quality-by-design (QbD) approach was used for the optimization of the nanoemulsion, and US FDA guidelines were followed for method validation. Results: Multiple reaction monitoring transitions were used for L-ORM (459.05→98.50), RAL (475.00→112.02) and internal standard (180.10→110.2). Analytes were resolved in a C18 column with 80:20 v/v% acetonitrile (ACN), 0.1% formic acid in triple-distilled water as a mobile phase. The developed method was linear over a concentration range of 1-600ng/ml. Pharmacokinetic results of free L-ORM-RAL and the L-ORM-RAL nanoemulsion showed Cmax of free L-ORM- 70.65±16.64, free RAL13.53±2.72, L-ORM nanoemulsion 65.07±14.0 and RAL-nanoemulsion 59.27±17.44ng/ml. Conclusion: Future findings will contribute to the treatment of postmenopausal osteoporosis and breast cancer using L-ORM and RAL.

Osteoporosis treatments for intervertebral disc degeneration and back pain: a perspective.

Low back pain derived from intervertebral disc (IVD) degeneration is a debilitating spinal condition that, despite its prevalence, does not have any intermediary guidelines for pharmacological treatment between palliative care and invasive surgery. The development of treatments for the IVD is complicated by the variety of resident cell types needed to maintain the regionally distinct structural properties of the IVD that permit the safe, complex motions of the spine. Osteoporosis of the spine increases the risk of vertebral bone fracture that can increase the incidence of back pain. Fortunately, there are a variety of pharmacological treatments for osteoporosis that target osteoblasts, osteoclasts and/or osteocytes to build bone and prevent vertebral fracture. Of particular note, clinical and preclinical studies suggest that commonly prescribed osteoporosis drugs like bisphosphonates, intermittent parathyroid hormone, anti-sclerostin antibody, selective estrogen receptor modulators and anti-receptor activator of nuclear factor-kappa B ligand inhibitor denosumab may also relieve back pain. Here, we cite clinical and preclinical studies and include unpublished data to support the argument that a subset of these therapeutics for osteoporosis may alleviate low back pain by also targeting the IVD.

SIRT1 and ZNF350 as novel biomarkers for osteoporosis: a bioinformatics analysis and experimental validation.

Osteoporosis (OP) is characterized by bone mass decrease and bone tissue microarchitectural deterioration in bone tissue. This study identified potential biomarkers for early diagnosis of OP and elucidated the mechanism of OP. Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) for the GSE56814 dataset. A gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to identify key modules associated with healthy and OP samples. Functional enrichment analysis was conducted using the R clusterProfiler package for modules to construct the transcriptional regulatory factor networks. We used the "ggpubr" package in R to screen for differentially expressed genes between the two samples. Gene set variation analysis (GSVA) was employed to further validate hub gene expression levels between normal and OP samples using RT-PCR and immunofluorescence to evaluate the potential biological changes in various samples. There was a distinction between the normal and OP conditions based on the preserved significant module. A total of 100 genes with the highest MM scores were considered key genes. Functional enrichment analysis suggested that the top 10 biological processes, cellular component and molecular functions were enriched. The Toll-like receptor signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, osteoclast differentiation, JAK-STAT signaling pathway, and chemokine signaling pathway were identified by Kyoto Encyclopedia of Genes and Genomes pathway analysis. SIRT1 and ZNF350 were identified by Wilcoxon algorithm as hub differentially expressed transcriptional regulatory factors that promote OP progression by affecting oxidative phosphorylation, apoptosis, PI3K-Akt-mTOR signaling, and p53 pathway. According to RT-PCR and immunostaining results, SIRT1 and ZNF350 levels were significantly higher in OP samples than in normal samples. SIRT1 and ZNF350 are important transcriptional regulatory factors for the pathogenesis of OP and may be novel biomarkers for OP treatment.

Surrogate markers in assessment of bisphosphonate effectiveness in osteoporosis treatment (bone mineral density, bone turnover markers)

A review of the literature which summarizes our knowledge on the use of surrogate markers of the osteoporosis treatment effectiveness when on bisphosphonate (BP) therapy. Bone mineral density (BMD) and markers of bone turnover, which have been shown to be associated with the clinical fracture end point, have been used as surrogate criteria for the effectiveness of treatment of osteoporosis in randomized controlled trials. When prescribing BP for the treatment of osteoporosis, BMD measurement every 12 months by dual-energy x-ray absorptiometry (DXA) is the well-described surrogate marker of BP efficacy. At the same time, stabilization of BMD is also a criterion for the treatment effectiveness since changes in BMD determined only 16% of the anti-fracture effectiveness of BP. Markers of bone remodeling can be used as surrogate markers after 3 (bone resorption) or 6 (bone formation) months from the start of BP therapy. A decrease of 30% or more is considered to be prognostically effective for both antifracture and BMD gain. There is a direct relationship between the degree of bone remodeling markers decrease and the antifracture effectiveness of BP therapy. The decrease in markers persists throughout the entire period of therapy and, accordingly, they can be used as surrogate markers of effectiveness and adherence to BP therapy throughout the entire treatment period. However, the presence of pathological fractures is a key clinical manifestation of osteoporosis and should be considered first in every decision making compared to any surrogate marker.Thus, when prescribing BP treatment, surrogate markers of changes in BMD and/or markers of bone remodeling can be used to monitor the effectiveness of treatment throughout the entire period of treatment and patients’ monitoring.

Review of recommendations for bisphosphonate treatment interruption-discontinuation

Bisphosphonates are the main medications in the treatment of osteoporosis, which are effective in reducing the risk of fractures in patients with osteoporosis. It is known that after treatment with bisphosphonates, bone mineral density remains quite stable for a certain time, as well as markers of bone metabolism remain reduced, which, along with the side effects of long-term bisphosphonate therapy, determines the possibility of “Drug holidays”. At the same time, during a break in bisphosphonate treatment, the risk of fractures begins to increase, which is a reason to resume therapy.Currently, there is no uniform worldwide data of starting a “drug holidays” on bisphosphonates. The duration of the “drug holidays” also differs in clinical recommendations from different countries. When to conduct a risk assessment of fractures during a “drug holidays”? To answer these questions, we assessed existing clinical recommendations for treatment interruption/discontinuation of bisphosphonates. A literature search was conducted using the following resources: PubMed®, the Cochrane Library, websites of major international osteoporosis associations, and other targeted Internet searches. The main search terms were “Clinical Guideline of Osteoporosis”, “Bisphosphonates”, “Drug holidays in osteoporosis”, “Discontinuation of bisphosphonates”. Тhe search was carried out using articles in Russian and English published between January 1, 2016 and September 15, 2023. 17 clinical guidelines from different countries (Russian, American, European, Asian and Australian) were found and analyzed in which was information about the break in the treatment and withdrawal of bisphosphonates.The majority of clinical recommendations have the same opinion on the issue of starting “drug holidays”: with a moderate risk of fractures, you can take a break from treatment with tableted bisphosphonates after 5 years, after zoledronic acid — after 3 years of therapy. At high and very high risk of fractures, the duration of treatment is 10 and 6 years, respectively. The duration of “drug holidays” vary in the recommendations, but in most cases the decision-making is based not on the duration, but on the assessment of the risk of fractures with their regular reassessment, which includes previous and new low-energy fractures, the emergence of new risk factors, a decrease in BMD, the dynamics of bone markers, re-evalua­tion of FRAX®.

Deprescribing bisphosphonates in the osteoporosis treatment in older people

The term deprescribing (de-prescribe) means the abolition of appointments. In the modern researches, deprescribing is presented as a planned and controlled process of dose reduction or drug cessation, which can potentially harm the patient and/or does not benefit the patient. The target population for deprescribing is the older people, as old age and limited life expectancy are themselves reasons to try to reduce and optimize the drug load. Frailty syndrome or dementia, decreased kidney function and comorbidity are expected to coexist with polypragmasy and inconsistent appointments of different specialists. In foreign and domestic scientific studies there are manuals and recommendations on deprescribing of various groups of drugs for the elderly and seniors: proton pump inhibitors, sugary drugs, psychotropic drugs and others. However, with regard to osteoporosis drug therapy, the concept of deprescribing is debated rather sparingly, despite the possible serious side effects of osteoporosis treatment in the older age group.The review presents data from small clinical studies and systematic reviews describing deprescribing antiosteoporotic drugs from the bisphosphonate group, the reasons for their withdrawal and its consequences for the elderly and seniors with osteoporosis, as well as the analysis of tools for optimizing pharmacotherapy in elderly and seniors with respect to deprescribing of bisphosphonates.

The consensus of experts of the russian association for osteoporosis on the long-term treatment of osteoporosis with bisphosphonates

The consensus of experts of the russian association for osteoporosis on the long-term treatment of osteoporosis with bisphosphonates

Changes in Testing and Treatment Methods in Osteoporosis Care.

Osteoporosis treatment plays a crucial role in preventing fractures, particularly in bedridden patients. We conducted a questionnaire survey presenting hypothetical clinical cases in 2015 and 2020 to investigate trends over a 5-year period. The target population included physicians working in clinics and hospitals within our neighbourhood. The cases were presented, and the questionnaire was administered in a confidential format. The orthopaedic surgeons were matched for age and practice, resulting in 74 cases being included in the analysis. Comparing the 2015 and 2020 results, we observed a notable increase in physicians who would perform "bone mineral density measurements of the lumbar spine and hip." Furthermore, there was a significant rise in the percentage of respondents willing to test for bone metabolic markers, such as serum type I collagen cross-linked N-telopeptide (NTX), procollagen I N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Regarding therapeutic agents, bisphosphonates decreased in usage, whereas parathyroid hormone and romosozumab witnessed an increase. In conclusion, the percentage of physicians requesting bone mineral density measurements of the lumbar spine and hip increased over the five-year period. In addition, more physicians chose to utilise bone metabolic markers due to their ease of measurement through blood tests and reduced diurnal variation. Finally, there was a marked trend towards the administration of drugs capable of rapidly and effectively increasing bone mineral density at an early stage of treatment.