Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research

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ergocalciferol 1 endocrinologydiseasesdrugs
glucose intolerance 1 endocrinologydiseases
metabolic bone disease 1 endocrinologydiseases
obesity 2 endocrinologydiseases
osteoporosis 113 endocrinologydiseases
cholecalciferol 1 endocrinologydiseasesdrugs
dexamethasone 1 endocrinologydiseasesdrugs
diabetes mellitus 1 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
cholecalciferol 54549 acid metabolism[[37]]OVX SD ratsLC/MS↑ arachidonic acid ↓ eicosapentaenoic acid, ergocalciferol, cholecalciferol Lipid and fatty acid metabolism[[48]]OVX SD rats (6 weeks post-surgery)GC/MS↑ cholesterol, glycerol,
dexamethasone 11232 directly suppresses the formation of new bone matrix [[28]]. Prednisolone induced Wistar and SD rats and dexamethasone induced Wistar rats were chosen as the glucocorticoid induced osteoporotic animal models (seven animals
ergocalciferol 54533 cycles, amino acid metabolism[[37]]OVX SD ratsLC/MS↑ arachidonic acid ↓ eicosapentaenoic acid, ergocalciferol , cholecalciferolLipid and fatty acid metabolism[[48]]OVX SD rats (6 weeks post-surgery)GC/MS↑ cholesterol,
Select Disease Character Offset Disease Term Instance
diabetes mellitus 30344 removal of the ovaries in premenopausal women. Some women even develop glucose intolerance or type II diabetes mellitus [[77]]. Ma et al. found that the level of glucose was significantly elevated in rats six weeks after
glucose intolerance 30313 glucose level after the surgical removal of the ovaries in premenopausal women. Some women even develop glucose intolerance or type II diabetes mellitus [[77]]. Ma et al. found that the level of glucose was significantly elevated
metabolic bone disease 4602 [[6],[7],[8],[9]]. However, the application of metabolomics in osteoporosis has just begun.Osteoporosis is a metabolic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, which results in
obesity 30704 that ovariectomy can affect the energy metabolism and utilization [[51]]. Estrogen-deficiency induced obesity is associated with fat accumulation and excessive intake of energy that break down the balance of energy
obesity 30955 demonstrated that bone is the source of hormone that affects energy metabolism, insulin resistance, obesity and development of diabetes. Thus, energy metabolism and bone metabolism have a somewhat mutual feedback
osteoporosis 1597 mass and increased risk of fracture in later life. The incidence and costs associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral
osteoporosis 1673 associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral density and bone turnover markers. However, these indexes are not sensitive
osteoporosis 1828 bone turnover markers. However, these indexes are not sensitive and accurate enough to reflect the osteoporosis progression. Metabolomics offers the potential for a holistic approach for clinical diagnoses and treatment,
osteoporosis 2008 approach for clinical diagnoses and treatment, as well as understanding of the pathological mechanism of osteoporosis . In this review, we firstly describe the study subjects of osteoporosis and bio-sample preparation procedures
osteoporosis 2080 the pathological mechanism of osteoporosis. In this review, we firstly describe the study subjects of osteoporosis and bio-sample preparation procedures for different analytic purposes, followed by illustrating the
osteoporosis 2285 illustrating the biomarkers with potentially predictive, diagnosis and pharmaceutical values when applied in osteoporosis research. Then, we summarize the published metabolic pathways related to osteoporosis. Furthermore,
osteoporosis 2371 when applied in osteoporosis research. Then, we summarize the published metabolic pathways related to osteoporosis . Furthermore, we discuss the importance of chronological data and combination of multi-omics in fully
osteoporosis 2500 discuss the importance of chronological data and combination of multi-omics in fully understanding osteoporosis . The application of metabolomics in osteoporosis could provide researchers the opportunity to gain new
osteoporosis 2549 combination of multi-omics in fully understanding osteoporosis. The application of metabolomics in osteoporosis could provide researchers the opportunity to gain new insight into the metabolic profiling and pathophysiological
osteoporosis 2800 there is still much to be done to validate the potential biomarkers responsible for the progression of osteoporosis and there are still many details needed to be further elucidated.1. IntroductionMetabolomics is an emerging
osteoporosis 4480 orthopedic field, including osteonecrosis, osteoarthritis, ankylosing spondylitis, bone tumors and osteoporosis [[6],[7],[8],[9]]. However, the application of metabolomics in osteoporosis has just begun.Osteoporosis
osteoporosis 4556 spondylitis, bone tumors and osteoporosis [[6],[7],[8],[9]]. However, the application of metabolomics in osteoporosis has just begun.Osteoporosis is a metabolic bone disease characterized by low bone mass and microarchitectural
osteoporosis 4802 tissue, which results in increased bone fragility and susceptibility to fracture [[10]]. The risk of osteoporosis depends both on how much bone is acquired during skeletal growth and development until peak bone mass
osteoporosis 5159 particularly occurs in postmenopausal women [[12]]. With a worldwide increase in aging populations, osteoporosis is becoming a highly prevalent disease, and brings a great deal of physical and mental pain and massive
osteoporosis 5446 diagnose but difficult to treat, and, although it can be prevented, people at high risk of developing osteoporosis are difficult to identify [[14]]. Given the enormous health and economic impacts of fracture, there
osteoporosis 5646 fracture, there is an imperative to develop strategies to reduce this burden and relieve the pain from osteoporosis .Bone mineral density (BMD) and biochemical indicators of bone turnover are golden standards for evaluating
osteoporosis 5936 the fracture and also serves as a surrogate marker for evaluating the effectiveness of treatment for osteoporosis . However, the determinants of bone quality go beyond measurements of BMD to include the structural and
osteoporosis 6286 postmenopausal women, occur in patients with BMD scores that do not meet the diagnostic criteria of osteoporosis [[15]]. Besides, monitoring acute changes in bone is difficult with BMD compared with the small changes.
osteoporosis 7075 the clinical detection [[18]]. The main reason is that some bone biochemical markers, which are not osteoporosis -specific, only reflect certain degree of bone turnover and may be influenced by some non-skeletal process
osteoporosis 7266 by some non-skeletal process [[21]]. These biomarkers are not suitable for the full investigation of osteoporosis . Metabolomics is a discipline of systematic, qualitative and quantitative analysis of metabolites in
osteoporosis 7953 markers [[22]].This review presents an overview of the developments in the field of metabolomics-based osteoporosis research. It includes the study subjects and sample preparation procedure, and follows by illustrating
osteoporosis 8166 illustrating the metabolic biomarkers with the potentially predictive, diagnosis and pharmaceutical values in osteoporosis research, and then concludes the related metabolic signal pathway. Furthermore, we discuss the importance
osteoporosis 8395 chronological metabolomics data and the combination of multi-omics in fully understanding the mechanism of osteoporosis development.2. Study SubjectsMetabolomics studies for pharmaceutical purpose generally use biological
osteoporosis 9231 osteoporotic animal model group [[23]]. In summary, the biological samples in regard to the metabolomics-based osteoporosis studies were mainly collected at three biological levels, namely cells, animals and clinical human.2.1.
osteoporosis 10517 osteoporotic studies. After hormonal deprivation, accelerated bone turnover and bone loss can result in osteoporosis . The bilateral OVX rat is a classic animal model used to mimics postmenopausal osteoporosis because
osteoporosis 10609 result in osteoporosis. The bilateral OVX rat is a classic animal model used to mimics postmenopausal osteoporosis because the removal of ovaries presents decreased levels of estrogen and progestrogen in humans [[27]].
osteoporosis 10987 treatments (6–10 animals per group) through metabolomics approaches. In addition, glucocorticoid induced osteoporosis is the most important form of secondary osteoporosis because it can cause bone loss, indirectly aggravates
osteoporosis 11040 approaches. In addition, glucocorticoid induced osteoporosis is the most important form of secondary osteoporosis because it can cause bone loss, indirectly aggravates bone absorption and directly suppresses the formation
osteoporosis 11792 disease progression [[29]]. Thus far, a total of two research papers were about metabolomics studies on osteoporosis with human samples. The advantages of population-based metabolomics study are not only the large sample
osteoporosis 12007 sample size but also the encompassment of people with various statuses in terms of menopausal status and osteoporosis progression. However, the metabolites presented in clinical samples are always affected by many factors,
osteoporosis 12641 to identify specific and sensitive metabolites that would be used in the diagnosis and prognosis of osteoporosis . A study from Qi et al. involved 364 female subjects divided into four groups (premenopausal women with
osteoporosis 12875 postmenopausal women with normal BMD, postmenopausal women with osteopenia and postmenopausal women with osteoporosis ), from Jiangsu Province geriatric hospital, China [[22]]. They studied the connection between osteoporosis
osteoporosis 12982 osteoporosis), from Jiangsu Province geriatric hospital, China [[22]]. They studied the connection between osteoporosis progression and BMD in postmenopausal women and discovered biomarkers that could distinguish low BMD
osteoporosis 13477 biomarkers could indicate low BMD in postmenopausal women and it may be useful for predicting the risk of osteoporosis in postmenopausal women at early age.3. Sample PreparationOver the past ten years, 1H NMR, GC/MS (gas
osteoporosis 14614 detected [[33]].The main sample preparation procedures for 1H NMR, GC/MS and LC/MS analyses of the osteoporosis related biological matrix are listed in Table 1. Urine samples were commonly diluted with pure water
osteoporosis 17466 biomarkers discovery in clinical practice. The identified potential biomarkers in metabolomics-based osteoporosis have been summarized in Table 2.4.1. Potential Application in Prediction of OsteoporosisMetabolic alterations
osteoporosis 17787 dysfunctions [[44]]. Since early intervention programs are likely to be most effective in the progression of osteoporosis , the discovery of highly sensitive biomarkers for the early diagnosis of different pathologies related
osteoporosis 17910 discovery of highly sensitive biomarkers for the early diagnosis of different pathologies related to the osteoporosis process is extremely important. Among the strategies for the management of osteoporosis, nutrition plays
osteoporosis 17998 related to the osteoporosis process is extremely important. Among the strategies for the management of osteoporosis , nutrition plays an important preventive role in contributing to peak bone mass acquisition during childhood
osteoporosis 18236 and in attenuation of bone loss with age, thus potentially prolonging the period before diagnosis of osteoporosis or risk of fracture. Metabolomics provides the opportunity to monitor small changes in metabolites which
osteoporosis 18870 diagnosis is of utmost importance because many of the complications associated with the development of osteoporosis can be decreased through early intervention. In addition, metabolomics can monitor the minor changes
osteoporosis 19040 metabolomics can monitor the minor changes of metabolites from the healthy status to osteopenia to osteoporosis , and assist in the discovery of the biomarkers that are closely associated to such metabolites transformation.
osteoporosis 19205 are closely associated to such metabolites transformation. One of the main challenges in preventing osteoporosis is to accurately identify people who are at risk for subsequent fracture. The changes on the metabolites
osteoporosis 19412 metabolites can give some instructions to adopt earlier interventions for delaying the occurrence of osteoporosis .4.2. Potential Application in Diagnosis of OsteoporosisWhen applying the outcomes of metabolomics in
osteoporosis 21077 PLS-DA analysis [[34]]. In summary, these studies showed that metabolic alterations are associated with osteoporosis , and metabolomics platform can play important roles in investigating osteoporosis. However, some studies
osteoporosis 21159 are associated with osteoporosis, and metabolomics platform can play important roles in investigating osteoporosis . However, some studies showed the different conclusions. These disparities may be due to the differences
osteoporosis 21735 derived from treatments [[46]]. Currently, studies investigating the effects of the treatments for osteoporosis from metabolomics perspective have mainly been conducted in three types of drug origin, including estrogen
osteoporosis 21964 derivatives, diphosphate and Traditional Chinese Medicine (TCM) extracts. Metabolomics can be applied in the osteoporosis studies for evaluations of the side effect, therapeutic effect, and dosage effect of certain treatments.
osteoporosis 22101 of the side effect, therapeutic effect, and dosage effect of certain treatments. The treatments for osteoporosis and menopause-related syndromes evaluated by metabolomics approaches are listed in Table 3.4.3.1. Estrogen
osteoporosis 22352 critical roles in the maintenance of bone density. Estrogen deficiency results in increased incidence of osteoporosis . HRT is currently considered as the most effective treatment to prevent osteoporosis. However, this
osteoporosis 22437 increased incidence of osteoporosis. HRT is currently considered as the most effective treatment to prevent osteoporosis . However, this approach is not very popular among women in view of the unfavorable outcomes. Accordingly,
osteoporosis 23561 Alendronate sodium, a nitrogen-containing bisphosphonate, is widely used for the prevention and treatment of osteoporosis . Chen and coworkers revealed that alendronate had profound effects on the serum metabolites in the OVX
osteoporosis 24794 extracts are popular alternatives for prevention, management and treatment of menopausal syndrome, osteoporosis and other bone related diseases in both experimental studies and clinical trials. Er-Xian decoction,
osteoporosis 25206 Angelica sinensis Diels in a compositional ratio of 9:9:6:6:9:9, has been widely used for treating osteoporosis and relieving menopausal syndrome [[59],[60],[61],[62]]. Xue et al. demonstrated that the administration
osteoporosis 25947 functions of replenishing the kidney, strengthening the bones, promoting the healing fracture, treating osteoporosis and relieving pain [[64]]. The research groups of Huang, Zhang, and Liu, respectively, studied the anti-osteoporotic
osteoporosis 26429 base is used to tonify the kidney and strengthen bones and muscles for the prevention and treatment of osteoporosis in TCM [[65],[66]]. Li et al. investigated the anti-osteoporosis effect of velvet collagen hydrolysate
osteoporosis 26494 for the prevention and treatment of osteoporosis in TCM [[65],[66]]. Li et al. investigated the anti- osteoporosis effect of velvet collagen hydrolysate by metabolomics study [[54]]. Vinegar, which is a rich source
osteoporosis 26703 source of minerals, could enhance intestinal calcium absorption and reduce bone turnover in preventing osteoporosis [[67]]. Lee et al. found that the Rubus coreanus vinegar could be served as a potential dietary supplement
osteoporosis 26853 Rubus coreanus vinegar could be served as a potential dietary supplement to counter the progression of osteoporosis as for the metabolomics results revealed that the metabolites in the plasma returned to a normal level
osteoporosis 27209 vitamin D have proven to be important, modifiable lifestyle factors for the prevention and management of osteoporosis in older people [[68],[69],[70]]. Sheedy et al. used 1H NMR-based metabolomics approach to analyze urine
osteoporosis 29379 amino acid metabolism, gut microbiota and kidney damage may play a certain role in the development of osteoporosis . The possibly involved metabolic pathways deduced from the disturbed concentrations of the potential
osteoporosis 32231 of plasma fatty acids and lipids were considered an important factor for the classification of the osteoporosis progression. Patients with lower BMD and osteoporosis also have higher lipid levels. Qi et al. found
osteoporosis 32285 important factor for the classification of the osteoporosis progression. Patients with lower BMD and osteoporosis also have higher lipid levels. Qi et al. found that postmenopausal women with osteopenia and osteoporosis
osteoporosis 32391 osteoporosis also have higher lipid levels. Qi et al. found that postmenopausal women with osteopenia and osteoporosis had lower concentration of high-density lipoprotein cholesterol (HDL-C) and higher concentrations of
osteoporosis 32812 (LDL), choline, glycerophosphatide and lipid in mice, which indicated that the biological mechanism of osteoporosis is associated with lipid metabolism [[51]]. In Lee’s study, the levels of lysoPC 14:0, lysoPC 16:0,
osteoporosis 33758 loss in the metabolomics study [[34]].5.3. Amino Acid MetabolismIn the formation of postmenopausal osteoporosis , the amino acid metabolism is disturbed. Glutamine may regulate bone metabolism via osteoclasts and
osteoporosis 34440 insulin-like growth factor-1, and the over-breakdown of muscle, which may be the cause for the developing osteoporosis [[41]]. Liu’s study also showed that tryptophan and phenylalanine were elevated in the plasma of osteoporotic
osteoporosis 35981 microflora [[41]].5.5. Kidney DamageAging is associated with decreases in bone quality and kidney function; osteoporosis and kidney insufficiency are common comorbidities in older people [[86]]. According to TCM theory, the
osteoporosis 36119 are common comorbidities in older people [[86]]. According to TCM theory, the major pathogenesis of osteoporosis is the deficiency of kidney essence, reduction of marrow and flaccidity of bones [[87]]. In the study
osteoporosis 37443 decade, bone mass normally peaks. Subsequently, mass begins to decrease, which can lead to fractures and osteoporosis in later life. It is notable that the postmenopausal fast bone loss makes women more vulnerable to osteoporosis
osteoporosis 37555 in later life. It is notable that the postmenopausal fast bone loss makes women more vulnerable to osteoporosis [[90]]. Although effective treatments can reduce fracture risk, it is probably not possible to fully
osteoporosis 37722 fracture risk, it is probably not possible to fully restore bone strength once the patient has developed osteoporosis because of the irreversible bone microarchitecture [[91]]. It is hard and often disappointing to treat
osteoporosis 37850 irreversible bone microarchitecture [[91]]. It is hard and often disappointing to treat established osteoporosis . The strategies of preventing the disease from developing or treating at the early stage are of much
osteoporosis 38001 disease from developing or treating at the early stage are of much importance. Therefore, prevention of osteoporosis is better than cure. The rate of bone loss importantly contributes to osteoporosis at old age. The early
osteoporosis 38084 Therefore, prevention of osteoporosis is better than cure. The rate of bone loss importantly contributes to osteoporosis at old age. The early identification of people who are at higher risk of undergoing fast bone loss and
osteoporosis 38286 bone loss and taking early intervention would be of great clinical importance to ultimately prevent osteoporosis [[92]].Metabolomics can show which compounds are present, and in what quantities, at given time points
osteoporosis 39529 relationship between the metabolites alteration and bone loss.Most metabolomics data describing menopausal or osteoporosis metabolites alterations have been generated from cross-sectional studies, which are easier to conduct,
osteoporosis 39725 easier to conduct, but do not allow the investigation about the metabolites alterations along with osteoporosis progression [[22],[30]]. The measurement of bone mass with the chronological alteration trend of biomarkers
osteoporosis 39933 of biomarkers may reliably identify the women at perimenopause who are at highest risk of developing osteoporosis later in life. In addition, a study based on large samples of perimenopausal women with a reasonably
osteoporosis 40137 reasonably long duration of follow-up has the ability to define the metabolites difference among the osteoporosis progression, which would not be possible to achieve in smaller or cross-sectional studies [[95]]. The
osteoporosis 40463 better prediction of the women who will suffer the coming event of rapid bone loss and even develop osteoporosis . Chronological metabolomics data will assist women to gain some early interventions to lower the risk
osteoporosis 40589 Chronological metabolomics data will assist women to gain some early interventions to lower the risk of getting osteoporosis from longitudinal metabolomics studies. Assessment of biomarkers over a longer period of time at multiple
osteoporosis 40759 biomarkers over a longer period of time at multiple occasions can provide more precise outcomes in the osteoporosis research. The long-term goal of these designs is primarily to improve our understanding of osteoporosis
osteoporosis 40863 osteoporosis research. The long-term goal of these designs is primarily to improve our understanding of osteoporosis progression.7. Potential of Multi-Omics Integration in Osteoporosis ResearchIt is difficult to comprehensively
osteoporosis 42969 development program of the new anti-osteoporotic drugs.Numerous candidate genes for the susceptibility of osteoporosis have been identified in the past. These genes, involved in calcium and bone metabolism as well as other
osteoporosis 43148 and bone metabolism as well as other aspects of bone strength and quality, have been implicated in osteoporosis . Together with functional genomics, next approaches and technologies for diagnosis and drug discovery
osteoporosis 43266 Together with functional genomics, next approaches and technologies for diagnosis and drug discovery in osteoporosis might involve RNA silencing and microRNA antagonism. Additional studies applying the massive parallel
osteoporosis 47029 molecular targets that may serve as potential diagnostic biomarkers and monitor in the progression of osteoporosis and promote the development of translational medicine for targeting therapy. Omics can act as an important
osteoporosis 47403 discussed above, multi-omics analyses would facilitate the development of personalized medicine in osteoporosis and emerge as the optimal therapeutic direction for the future of orthopedic science.8. ConclusionsThe
osteoporosis 47551 therapeutic direction for the future of orthopedic science.8. ConclusionsThe applications of metabolomics in osteoporosis studies have mainly had following two purposes: (1) using MS or 1H NMR technique to delineate the metabolic
osteoporosis 47779 and determining the significantly altered metabolites which are responsible for the development of osteoporosis ; and (2) identifying and charactering specific metabolic pathways which may serve as targets for the
osteoporosis 47922 charactering specific metabolic pathways which may serve as targets for the treatment or intervention in osteoporosis . The metabolomics-based osteoporosis studies as reported in the literature were almost all conducted
osteoporosis 47959 which may serve as targets for the treatment or intervention in osteoporosis. The metabolomics-based osteoporosis studies as reported in the literature were almost all conducted using the untargeted metabolomics approaches.
osteoporosis 48476 targeted metabolomics studies with untargeted metabolomics to improve the selectivity and accuracy. As osteoporosis is a kind of progressive systemic skeletal disease, the biomarkers from chronological and longitudinal
osteoporosis 48648 biomarkers from chronological and longitudinal metabolomics data will give a comprehensive view of how osteoporosis develops and assist people to gain some early interventions to lower the risk of getting osteoporosis.
osteoporosis 48750 osteoporosis develops and assist people to gain some early interventions to lower the risk of getting osteoporosis . Furthermore, metabolomics combined with other systems biology datasets will further our understanding
osteoporosis 48887 metabolomics combined with other systems biology datasets will further our understanding of the complexity of osteoporosis and detect personalized response to osteoporosis therapy. By disclosing disease-specific metabolic profiles,
osteoporosis 48936 will further our understanding of the complexity of osteoporosis and detect personalized response to osteoporosis therapy. By disclosing disease-specific metabolic profiles, and metabolic trajectories associated with
osteoporosis 49329 much to be done to verify and validate the potential biomarkers responsible for the progression of osteoporosis entailing intensive use of labor and technology and generally requiring a large number of study participants
osteoporosis 49619 1Table 1The sample preparation procedures for GC/MS, 1H NMR, and LC/MS analysis in metabolomics-based osteoporosis studies.Detection MethodBiological SampleSample SourceSample Preparation ProceduresReferencesGC/MSPlasmaOVX
osteoporosis 53096 13,000 rpm for 10 minijms-17-02018-t002_Table 2Table 2The biomarkers and related metabolic pathways in osteoporosis by metabolomics approaches.Biological SampleSample SourceDetective MethodChange Trend in Osteoporosis
osteoporosis 55503 NMR↑ LDL/vLDL, glucose, lactate, lipids, NAc/OAcLipid and energy metabolism[[53]]Postmenopausal with osteoporosis GC/MS↑ linoleic acid, oleic acid, arachidonic acid, 11, 14-eicosadienoic acid, eicosapentaenoic acid,
osteoporosis 57043 up-regulated trend; ↓ represents the down-regulated trend.ijms-17-02018-t003_Table 3Table 3Treatments for osteoporosis evaluated by metabolomics approaches.ClassificationsTreatmentsSample SourcesBiological SamplesPurposesReferencesEstrogen
osteoporosis 57571 ratsSerumImprovement of estrogen deficiency status[[48]]BisphosphonatesFDP-SrOVX SD ratsPlasmaAnti- osteoporosis efficacy[[45]]FosamaxOVX C57BL/6JNarl miceSerumAnti-osteoporosis efficacy[[37]]TCM or herbal formula
osteoporosis 57636 status[[48]]BisphosphonatesFDP-SrOVX SD ratsPlasmaAnti-osteoporosis efficacy[[45]]FosamaxOVX C57BL/6JNarl miceSerumAnti- osteoporosis efficacy[[37]]TCM or herbal formula extractsRhizoma Drynariae extractPrednisolone induced Wistar ratsPlasmaAnti-osteoporosis
osteoporosis 57761 efficacy[[37]]TCM or herbal formula extractsRhizoma Drynariae extractPrednisolone induced Wistar ratsPlasmaAnti- osteoporosis efficacy[[40]]Rhizoma Drynariae extractPrednisolone induced Wistar ratsKidney tissue extractsAnti-osteoporosis
osteoporosis 57872 ratsPlasmaAnti-osteoporosis efficacy[[40]]Rhizoma Drynariae extractPrednisolone induced Wistar ratsKidney tissue extractsAnti- osteoporosis and replenish the kidney[[23]]Rhizoma Drynariae extractPrednisolone induced ratsUrineAnti-osteoporosis
osteoporosis 57975 extractsAnti-osteoporosis and replenish the kidney[[23]]Rhizoma Drynariae extractPrednisolone induced ratsUrineAnti- osteoporosis efficacy[[55]]Gushudan extractPrednisolone induced SD ratsSerum/urineAnti-osteoporosis efficacy[[41]]Er-Xian
osteoporosis 58062 ratsUrineAnti-osteoporosis efficacy[[55]]Gushudan extractPrednisolone induced SD ratsSerum/urineAnti- osteoporosis efficacy[[41]]Er-Xian decoctionOVX SD ratsPlasma/urineAnti-osteoporosis efficacy[[51]]Hypericum perforatum
osteoporosis 58134 induced SD ratsSerum/urineAnti-osteoporosis efficacy[[41]]Er-Xian decoctionOVX SD ratsPlasma/urineAnti- osteoporosis efficacy[[51]]Hypericum perforatum L. extractOVX SD ratsSerum/urineRelieve menopausal syndromes[[38]]Velvet
osteoporosis 58314 ratsSerum/urineRelieve menopausal syndromes[[38]]Velvet collagen hydrolysateDexamethasone induced SD ratsUrineAnti- osteoporosis efficacy[[54]]Rubus coteanus VinegarOVX SD ratsPlasmaAnti-osteoporosis efficacy[[39]]Icariin from Epimedii
osteoporosis 58385 hydrolysateDexamethasone induced SD ratsUrineAnti-osteoporosis efficacy[[54]]Rubus coteanus VinegarOVX SD ratsPlasmaAnti- osteoporosis efficacy[[39]]Icariin from Epimedii FoliumOVX ICR miceSerumAnti-osteoporosis efficacy[[53]
osteoporosis 58462 VinegarOVX SD ratsPlasmaAnti-osteoporosis efficacy[[39]]Icariin from Epimedii FoliumOVX ICR miceSerumAnti- osteoporosis efficacy[[53]

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