Drugs For Postmenopausal Osteoporosis Research Articles

Drugs for postmenopausal osteoporosis.

Drugs for postmenopausal osteoporosis.

Comparison table: Some drugs for postmenopausal osteoporosis.

Comparison table: Some drugs for postmenopausal osteoporosis.

Mechanistic PK-PD model of alendronate treatment of postmenopausal osteoporosis predicts bone site-specific response.

Alendronate is the most widely used drug for postmenopausal osteoporosis (PMO). It inhibits bone resorption, affecting osteoclasts. Pharmacokinetics (PK) and pharmacodynamics (PD) of alendronate have been widely studied, but few mathematical models exist to simulate its effect. In this work, we have developed a PK model for alendronate, valid for short- and long-term treatments, and a mechanistic PK-PD model for the treatment of PMO to predict bone density gain (BDG) at the hip and lumbar spine. According to our results, at least three compartments are required in the PK model to predict the effect of alendronate in both the short and long terms. Clinical data of a 2-year treatment of alendronate, reproduced by our PK-PD model, demonstrate that bone response is site specific (hip: 7% BDG, lumbar spine: 4% BDG). We identified that this BDG is mainly due to an increase in tissue mineralization and a decrease in porosity. The difference in BDG between sites is linked to the different loading and dependence of the released alendronate on the bone-specific surface and porosity. Osteoclast population diminishes quickly within the first month of alendronate treatment. Osteoblast population lags behind but also falls due to coupling of resorption and formation. Two dosing regimens were studied (70 mg weekly and 10 mg daily), and both showed very similar BDG evolution, indicating that alendronate accumulates quickly in bone and saturates. The proposed PK-PD model could provide a valuable tool to analyze the effect of alendronate and to design patient-specific treatments, including drug combinations.

Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination

Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K–AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53–Nedd4–Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

Systematic review and quality appraisal of cost-effectiveness analyses of drugs for postmenopausal osteoporosis

Systematic review and quality appraisal of cost-effectiveness analyses of drugs for postmenopausal osteoporosis

Preliminary standardization of lashuna A potential drug for postmenopausal osteoporosis.

Osteoporosis is a major international health problem, accentuated by increasing longevity. Osteoporosis as “a systemic skeletal disease characterized by low bone mass and bone architectural leading to increased risk”. Menopause is the normal process but now a day it becoming the major health problem in developing countries like India. In Ayurveda Menopause deals with jarapakvaavasta of the body Jara and Rajonivritti are manifested due to the progressive reduction in the functional ability of Agnis, which results in an inadequate tissue nutrition. This nutritional imbalance triggers the irreversible degenerative changes in „Sapta Dhatus‟. The disease Osteoporosis is somewhat similar to the description of Asthi Kshaya in which metabolism of Asthi Dhatu is disturbed. Rasayana therapy has proved efficacious in managing and preventing many chronic conditions till date. As Postmenopausal Osteoporosis is a disease related to aging, Rasayana can provide the better alternative to increasing quality of life. Here, the drug Lashuna also one of the Rasayana guna dravya.

MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

Postmenopausal osteoporosis (OPM) is a common type of osteoporosis in females. It is a systemic, chronic bone disease that presents as microstructure degradation of osseous tissue, decreased bone mineral density and increased osteopsathyrosis caused by hypoovarianism and reduced estrogen levels in the body following menopause. In the present study, the role of microRNA (miR)-214-5p in the regulation of the expression of bone marrow stem cells (BMSCs) was investigated, and its molecular mechanism of osteogenic induction in vitro was assessed. When dexamethasone-induced adipogenic differentiation was performed, miR-214-5p expression was increased compared with the control group, as determined by RT-qPCR. Furthermore, oil red O staining, RT-qPCR and western blot analysis demonstrated that overexpression of miR-214-5p promoted adipogenic differentiation, inhibited alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OC) and collagen α-1 (I) chain (COL1A1) mRNA expression, and suppressed transforming growth factor (TGF)-β, phosphorylated (p)-Smad2 and collagen type IV α1 chain (COL4A1) protein expression in BMSCs. Additionally, downregulation of miR-214-5p increased the ALP, Runx2, OC and COL1 mRNA expression and increased TGF-β, Smad2 and COL4A1 protein expression in BMSCs. Furthermore, a TGF-β inhibitor was employed to inhibit TGF-β expression in BMSCs following miR-214-5p downregulation, which led to reduced Smad2, TGF-β and COL4A1 protein expression, and ALP, Runx2, OC and COL1 mRNA expression was also reduced, compared with the miR-214-5p downregulation only group. It was demonstrated that miR-214-5p may weaken osteogenic differentiation of BMSCs through regulating COL4A1. In conclusion, the results of the present study indicated that miR-214-5p may promote the adipogenic differentiation of BMSCs through regulation of the TGF-β/Smad2/COL4A1 signaling pathway, and potentially may be used to develop a novel drug for postmenopausal osteoporosis.

A Systematic Review of Cost-Effectiveness Analyses of Drugs for Postmenopausal Osteoporosis

Given the limited availability of healthcare resources and the recent introduction of new anti-osteoporosis drugs, the interest in the cost effectiveness of drugs in postmenopausal osteoporosis remains and even increases. This study aims to identify all recent economic evaluations on drugs for postmenopausal osteoporosis, to critically appraise the reporting quality, and to summarize the results. A literature search using Medline, the National Health Service Economic Evaluation database and the Cost-Effectiveness Analysis Registry was undertaken to identify original articles published between January 1, 2008 and December 31, 2013. Studies that assessed cost effectiveness of drugs in postmenopausal osteoporosis were included. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement was used to assess the quality of reporting of these articles. Of 1,794 articles identified, 39 studies fulfilled the inclusion criteria. They were conducted in 14 different countries and nine active interventions were assessed. When compared with no treatment, active osteoporotic drugs were generally cost effective in postmenopausal women aged over 60-65years with low bone mass, especially those with prior vertebral fractures. Key drivers of cost effectiveness included individual fracture risk, medication adherence, selected comparators and country-specific analyses. Quality of reporting varied between studies with an average score of 17.9 out of 24 (range 7-21.5). This review found a substantial number of published cost-effectiveness analyses of drugs in osteoporosis in the last 6years. Results and critical appraisal of these articles can help decision makers when prioritizing health interventions and can inform the development of future economic evaluations.

Secondary osteoporosis or secondary contributors to bone loss in fracture. Therapeutic strategy for glucocorticoid-induced osteoporosis

Glucocorticoid is widely used to treat a variety of diseases and causes a number of significant side effects. Glucocorticoid-induced osteoporosis (GIOP) is known as a serious adverse effect during long-term glucocorticoid therapy. Guideline in Japan recommends bisphosphonates as first-line drugs. Bisphosphonates increase bone mineral density (BMD) and reduce vertebral fracture risk in patient beginning or continuing glucocorticoid treatment. As well as increased bone resorption, GIOP could induce severe suppression of bone formation. Although bisphosphonates are effective for GIOP, anabolic therapeutic strategies should be considered as alternative therapy in GIOP. Teripatratide (PTH (1-34) ) , a bone anabolic drug, is widely used in primary osteoporosis with severe osteoporotic fracture or extremely low bone mass, and has been reported to increase BMD and to reduce the risk of fractures also in GIOP. Denosumab, an anti receptor activator of nuclear factor-κB ligand, recently approved as a drug for postmenopausal osteoporosis was also effective for GIOP in clinical trials, and would be new candidate to treat GIOP.

Asian plants as a promising alternative to classic drugs in postmenopausal osteoporosis: A review of literature from clinical perspective

Osteoporosis is characterised by low bone mineral density (BMD) resulting in fragile bones with increased risk of fracture. According to statistics, 75 million people worldwide suffer from osteoporosis. However, the higher consumption of soy by the Asian population is thought to be one of the contributing factors for the lower incidence of osteoporosis-related fractures in the region. Various side effects were reported to be associated with the use of both estrogen or hormone replacement therapy, and other classical anti-fracture agents. Therefore, alternative approaches, and especially natural therapies to treat osteoporosis are currently under research. In traditional Chinese medicine, osteoporosis is considered to be a disorder caused by the insufficiency of kidney yang, and the herbs perceived to be able to tonify the kidney yang have been used for more than 1000 years as therapy. Within this context, we have systematically researched the specialty literature on the topic, in an attempt to check whether various Asian plants could constitute valid therapies in the prophylaxis and treatment of osteoporosis, especially postmenopausal one. The current evidence suggests that isoflavones as well as other compounds from Asian plants extracts may regulate bone turnover by complex mechanisms and increase BMD, thus, potentially, reducing the fracture rate. Key words: Osteoporosis, traditional Chinese medicine, Asian plants, bone turnover, osteoclast, osteoblast, estrogen, postmenopause.

Mechanisms and therapeutics of glucocorticoid-induced osteoporosis.

Mechanisms of glucocorticoid-induced osteoporosis (GIOP) are categorized into local and systemic effects. In the local mechanisms, direct inhibitory effect of glucocorticoid on bone formation is thought to be one of the important mechanisms of GIOP. In contrast, secondary hyperparathyroidism induced by negative balance of calcium due to inhibition of absorption and increase of excretion is an important systemic mechanism of GIOP. Other mechanisms of GIOP are also shown in this review. From clinical points of view, serum markers for evaluation of GIOP have been discussed. Osteocalcin, procollagen type I N-terminal peptide, and bone-specific alkaline phosphatase as markers of bone formation are decreased in GIOP. Collagen I N-terminal telopeptide and tartrate resistent acid phosphatase isoform 5b as markers of bone resorption are increased in GIOP. Clinical guidelines have recommended that bisphosphonate is the first choice for the treatment of GIOP. Teriparatide is recombinant human parathyroid hormone 1-34, which should be considered as a therapeutic option for those at high risk of bone fracture. Denosumab, an anti receptor activator of nuclear factor-β ligand approved as a drug for postmenopausal osteoporosis was also effective for GIOP in clinical trials.

Emerging drugs for postmenopausal osteoporosis

Postmenopausal osteoporosis (PMO) is a common skeletal disease with serious consequences due to fractures, including increased risk of disability and death. The risk of fractures can be reduced with medications that are currently available; however, these drugs are frequently not prescribed due to failure to recognize that a patient is at high risk for fracture; fear of adverse drug effects; or, sometimes, high cost. When these drugs are prescribed, long-term adherence to therapy is poor. Efforts to improve the clinical effectiveness of pharmacological therapies have included lengthening the interval between doses, simplifying drug administration, and manipulating the molecular structure of drugs in existing therapeutic classes. Recent improvement in understanding the pathophysiology of PMO at the molecular level has fostered the development of new therapeutic agents with novel mechanisms of action. This is a review of the data on the efficacy and safety of emerging drugs for the treatment of PMO, including agents with novel mechanisms of action (denosumab, odanacatib, antibody to sclerostin), new estrogen agonists/antagonists (lasofoxifene, bazedoxifene, arzoxifene), new delivery systems for existing drugs (salmon calcitonin, teriparatide), and drug combinations given concurrently, sequentially, or cyclically. These new therapeutic agents, new delivery systems, and new methods of combining drugs may ultimately reduce the great personal and economic burden of osteoporotic fractures.

Ostéoporose post-ménopausique : traiter aujourd'hui et demain

Currently available drugs in postmenopausal osteoporosis have proven efficacy, based on randomized clinical trials with very high levels of evidence. Decreasing the rates of incident fractures was the primary endpoint in these trials. Antiosteoporotic drugs have distinct mechanisms of action towards bone resorption and bone formation. They are also distinguishable through distinct effects on the various osteoporotic events, that is vertebral, peripheral, and femoral fractures. Only bisphosphonates and strontium ranelate have demonstrated efficacy for all these types of fractures. Furthermore, strontium ranelate is the only agent able to inhibit bone resorption while stimulating bone formation. Further therapeutic advances are expected to occur within years, including the release of biological modulators of osteoclasts and osteoblasts, and the construction of innovative strategies for the optimal use of available drugs.

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline N-telopeptide of type l collagen (NTX ) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGF g 2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX ) as well as bone resorptive cytokines (IL-11,TGF g 2 ). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis. (Pyr), deoxy-pyridinoline (DPyr) and

Registration of drugs for postmenopausal osteoporosis in The Netherlands: Can surrogate clinical endpoints be accepted?

Registration of drugs for postmenopausal osteoporosis in The Netherlands: Can surrogate clinical endpoints be accepted?