Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 19, Issue 6, 2019

Background: Type 2 Diabetes Mellitus (T2DM) is a worldwide disorder as the most important challenges of health-care systems. Controlling the normal glycaemia greatly profit long-term prognosis and gives explanation for early, effective, constant, and safe intervention. Material and Methods: Finding the main genetic and epigenetic profile of T2DM and the exact molecular targets of T2DM medications can shed light on its personalized management. The comprehensive information of T2DM was earned through the genome-wide association study (GWAS) studies. In the current review, we represent the most important candidate genes of T2DM like CAPN10, TCF7L2, PPAR-γ, IRSs, KCNJ11, WFS1, and HNF homeoboxes. Different genetic variations of a candidate gene can predict the efficacy of T2DM personalized strategy medication. Results: SLCs and AMPK variations are considered for metformin, CYP2C9, KATP channel, CDKAL1, CDKN2A/2B and KCNQ1 for sulphonylureas, OATP1B, and KCNQ1 for repaglinide and the last but not the least ADIPOQ, PPAR-γ, SLC, CYP2C8, and SLCO1B1 for thiazolidinediones response prediction. Conclusion: Taken everything into consideration, there is an extreme need to determine the genetic status of T2DM patients in some known genetic region before planning the medication strategies.

Background: Diabetes Mellitus (DM) is a multisystemic disease involving the homeostasis of insulin secretion by the pancreatic islet beta cells (β-cells). It is associated with hypertension, renal disease, and arterial and arteriolar vascular diseases. Discussion: The classification of diabetes is identified as type 1 (gene linked β-cell destruction in childhood) and type 2 (late onset associated with β-cell overload and insulin resistance in peripheral tissues. Type 1 diabetes is characterized by insulin deficiency, type 2 diabetes by both insulin deficiency and insulin resistance. The former is a genetically programmed loss of insulin secretion whereas the latter constitutes a disruption of the homeostatic relationship between the opposing activity of β- cell insulin and alpha cell (α-cell) glucagon of the Islets of Langerhans. The condition could also occur in pregnancy, as a prenatal occurring event, possibly triggered by the hormonal changes of pregnancy combined with β-cell overload. This review discusses the molecular basis of the biomolecular changes that occur with respect to glucose homeostasis and related diseases in DM. The underlying link between pancreatic, renal, and microvascular diseases in DM is based on oxidative stress and the Unfolded Protein Response (UPR). Conclusion: Studying proteome changes in diabetes can deepen our understanding of the biomolecular basis of disease and help us acquire more efficient therapies.

Background: Diabetes mellitus is a metabolic disorder that is characterized by impaired glucose tolerance resulting from defects in insulin secretion, insulin action, or both. Epigenetic modifications, which are defined as inherited changes in gene expression that occur without changes in gene sequence, are involved in the etiology of diabetes. Methods: In this review, we focused on the role of DNA methylation and protein misfolding and their contribution to the development of both type 1 and type 2 diabetes mellitus. Results: Changes in DNA methylation in particular are highly associated with the development of diabetes. Protein function is dependent on their proper folding in the endoplasmic reticulum. Defective protein folding and consequently their functions have also been reported to play a role. Early treatment of diabetes has proven to be of great benefit, as even transient hyperglycemia may lead to pathological effects and complications later on. This has been explained by the theory of the development of a metabolic memory in diabetes. The basis for this metabolic memory was attributed to oxidative stress, chronic inflammation, non-enzymatic glycation of proteins and importantly, epigenetic changes. This highlights the importance of linking new therapeutics targeting epigenetic mechanisms with traditional antidiabetic drugs. Conclusion: Although new data is evolving on the relation between DNA methylation, protein misfolding, and the etiology of diabetes, more studies are required for developing new relevant diagnostics and therapeutics.

Background: Diabetes, defined as a chronic metabolic syndrome, exhibits global prevalence and phenomenal rise worldwide. The rising incidence accounts for a global health crisis, demonstrating a profound effect on low and middle-income countries, particularly people with limited healthcare facilities. Methods: Highlighting the prevalence of diabetes and its socio-economic implications on the population across the globe, the article aimed to address the emerging significance of computational biology in drug designing and development, pertaining to identification and validation of lead molecules for diabetes treatment. Results: The drug discovery programs have shifted the focus on in silico prediction strategies minimizing prolonged clinical trials and expenses. Despite technological advances and effective drug therapies, the fight against life-threatening, disabling disease has witnessed multiple challenges. The lead optimization resources in computational biology have transformed the research on the identification and optimization of anti-diabetic lead molecules in drug discovery studies. The QSAR approaches and ADMET/Toxicity parameters provide significant evaluation of prospective “drug-like” molecules from natural sources. Conclusion: The science of computational biology has facilitated the drug discovery and development studies and the available data may be utilized in a rational construction of a drug ‘blueprint’ for a particular individual based on the genetic organization. The identification of natural products possessing bioactive properties as well as their scientific validation is an emerging prospective approach in antidiabetic drug discovery.

Background and objective: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder. Pancreatic β-cell dysfunction and insulin resistance are the most common and crucial events of T2DM. Increasing evidence suggests the association of epigenetic modifications with the pathogenesis of T2DM through the changes in important biological processes including pancreatic β- cell differentiation, development and maintenance of normal β-cell function. Insulin sensitivity by the peripheral glucose uptake tissues is also changed by the altered epigenetic mechanisms. In this review, we discussed the major epigenetic alterations and their effects on β-cell function, insulin secretion and insulin resistance in context of T2DM. Methods: We investigated the presently available epigenetic modifications including DNA methylation, posttranslational histone modifications, ATP-dependent chromatin remodeling and non-coding RNAs related to the pathogenesis of T2DM. Published literatures on this topic were searched both on Google Scholar and Pubmed with related keywords and investigated for relevant information. Results: The epigenetic modifications introduce changes in gene expression which are essential for appropriate β-cell development and functions, insulin secretion and sensitivity resulting in the pathogenesis of T2DM. Interestingly, T2DM could also be a prominent reason for the mentioned epigenetic alterations. Conclusion: This review article emphasized on the epigenetic modifications associated with T2DM and discussed the consequences in deterioration of the disease condition.

Background: The 3-Hydroxy-3-MethylGlutaryl-CoA reductase inhibitors, better known as statins, are used extensively in the treatment of dyslipidemia and cardiovascular risk reduction. They have also demonstrated a variety of non-lipid lowering, or pleiotropic effects. Pertaining to the endocrine system the benefits of statins can extend to patients with the polycystic ovarian syndrome and thyroid disease. However, there is also increasing evidence that statin use can lead to deleterious effects in different organs, including worsening glycemia and the development of diabetes mellitus. Objective: The aim of this review is to describe the most relevant and updated evidence regarding the pleiotropic effects of statins in endocrine disorders. Methods: We did a systematic review of scientific articles published in PubMed regarding the effects of statins on the different aspects of the endocrine system up until June 5th of 2018. Results: We identified preliminarily 61 publications, of which 4 were excluded due to having abstract format only, and 5 were excluded for not containing pertinent information to the study. Conclusion: Several aspects of the endocrine system have been shown to be influenced by the pleiotropic effects that statins exert, however, the benefits of statins on cardiovascular morbidity and mortality largely outweigh this deleterious effect, and statin therapy should continue to be recommended.

Background: Grape phytochemicals prevent intestine-related and subsequent other inflammatory diseases. Phytochemicals and vitamin D are useful for the regulation of inflammatory responses. Phytochemicals is the generic name for terpenoids, carotenoids, and flavonoids that consist of a variety of chemicals contained in vegetables and fruits. There are a variety of grape cultivars that contain many kinds of phytochemicals in their skin and seeds. Grape phytochemicals including Grape Seed Extracts (GSE) have already been used to maintain healthy condition through manipulating inflammatory responses by decreasing the expression of inflammation-related factors. Discussion: Grape phytochemicals mainly consist of a variety of chemicals that include terpenoid (oleanolic acid), carotenoids (β-carotene, lutein), and flavonoids: flavon-3-ols (quercetin), flavan-3-ols (catechins), anthocyanins, oligomers and polymers (tannins and proanthocyanidins), and resveratrol. Phytochemicals improve the dysbiosis (gut microbiota complication) induced by metabolic syndrome and regulate inflammatory diseases induced by TNF-α production. Once absorbed, flavonoids change into glucuronide-form, move into the bloodstream and reach the inflammatory sites including liver, lung, and sites of arteriosclerosis, where they become active. Furthermore, oleanolic acid acts on TGR5 - the cholic acid receptor, as an agonist of cholic acid. These anti-inflammatory effects of phytochemicals have been proven by the experimental animal studies and the clinical trials. Conclusion: It is expected the new health food products will be created from grape skins and seeds since grape phytochemicals participate in the prevention of inflammatory diseases like intestine-related inflammatory diseases.

Background: Thyroid diseases occur more frequently in people exposed to ionizing radiation, but the relationship between occupational exposure to ionizing radiation and thyroid pathologies still remains unclear. Objective: To evaluate the prevalence of thyroid diseases in healthcare workers exposed to low-level ionizing radiation compared with a control group working at the University Hospital of Bari, Southern Italy, and living in the same geographical area, characterized by mild iodine deficiency. Methods: We ran a cross-sectional study to investigate whether healthcare workers exposed to ionizing radiation had a higher prevalence of thyroid diseases. Four hundred and forty-four exposed healthcare workers (241 more exposed, or “A Category”, and 203 less exposed, or “B Category”) and 614 nonexposed healthcare workers were enrolled during a routine examination at the Occupational Health Unit. They were asked to fill in an anamnestic questionnaire and undergo a physical examination, serum determination of fT3, fT4 and TSH, anti-TPO ab and anti-TG ab and ultrasound neck scan. Thyroid nodules were submitted to fine needle aspiration biopsy when indicated. Results: The prevalence of thyroid diseases was statistically higher in the exposed workers compared to controls (40% vs 29%, adPR 1.65; IC95% 1.34-2.07). In particular, the thyroid nodularity prevalence in the exposed group was approximately twice as high as that in the controls (29% vs 13%; adPR 2.83; IC95% 2.12-3.8). No statistically significant association was found between exposure to ionizing radiation and other thyroid diseases. Conclusion: In our study, mild ionizing radiation-exposed healthcare workers had a statistically higher prevalence of thyroid diseases than the control group. The results are likely due to a closer and more meticulous health surveillance programme carried out in the ionising radiation-exposed workers, allowing them to identify thyroid alterations earlier than non-exposed health staff.

Background: Behcet’s Disease (BD) is a multisystemic inflammatory disorder affecting large vessels, lungs joints, gastrointestinal and neurological systems. The pathogenesis of BD remains poorly understood. Identifying the key signaling pathway is crucial for a complete understanding of the pathogenesis of BD. Objective: The aim of this study was to determine mRNA expression level of Src family kinases (SFKs) members and their involvement in lipopolysaccharide (LPS)-induced mitogen-activated protein kinases (MAPKs) regulation in peripheral blood mononuclear cells (PBMCs) of active BD patients. Methods: Twenty- five active BD patients and twenty-five healthy controls were included in the study. PBMCs were isolated from total blood by density gradient centrifugation. The mRNA expression levels of SFKs members were measured by real-time quantitative PCR (RT-qPCR). The effect of SFKs activity on LPS-induced activation MAPKs (Erk1/2, p38 and JNK) was examined by Western blot. Results: The mRNA expression levels of Hck, Src, Lyn, Yes and Fyn were found to be slightly decreased in active BD patients compared to the control subjects, but a slight change in mRNA level of SFKs members did not impact on protein levels and protein activity. LPS-induced Erk1/2 phosphorylation was significantly increased in the absence of SFKs activity in active BD patients. However, inhibition of SFKs activity had no effect on LPS-induced phosphorylation of p38 and JNK in both controls and active BD patients. Conclusion: SFKs downregulate LPS-induced Erk1/2 phosphorylation in PBMCs of active BD patients.

Background: Hypothyroidism has been related to low-weight births, abortion and prematurity, which have been associated with changes in the content of glycogen and vascularization of the placenta. Since hypothyroidism can cause dyslipidemia, it may affect the lipid content in the uterus affecting the development of fetuses. Objective: To investigate the effect of hypothyroidism on the lipid levels in serum and uterus during pregnancy and their possible association with the size of fetuses. Method: Adult female rabbits were grouped in control (n = 6) and hypothyroid (n = 6; treated with methimazole for 29 days before and 19 days after copulation). Food intake and body weight were daily registered. At gestational day 19 (GD19), dams were sacrificed under an overdose of anesthesia. Morphometric measures of fetuses were taken. Total cholesterol (TC), triglyceride (TAG), and glucose concentrations were quantified in blood, uterus and ovaries of dams. The expression of uterine 3β- hydroxysteroid dehydrogenase (3β-HSD) was quantified by Western blot. Results: Hypothyroidism reduced food intake and body weight of dams, as well as promoted low abdominal diameters of fetuses. It did not induce dyslipidemia and hyperglycemia at GD19 and did not modify the content of lipids in the ovary. However, it reduced the content of TAG and TC in the uterus, which was associated with uterine hyperplasia and an increased expression of 3β-HSD in the uterus. Conclusion: Hypothyroidism alters the lipid content in the uterus that might subsequently affect the energy production and lipid signaling important to fetal development.

Background: Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet. Objective: In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells. Methods: In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells. Results: Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis. Conclusion: Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

Background: Obesity is associated with lower serum vitamin D (25(OH)D) levels through several mechanisms. The aim of the study was to examine the possibility of a negative association between fat mass and 25(OH)D levels in a cohort of otherwise healthy overweight and obese subjects, independently of age, sex, blood pressure levels and anthropometric and metabolic parameters. Materials and Methods: 147 overweight and obese subjects (106 women and 41 men), aged between 18 and 69 years, were enrolled into the study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, insulin, glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. The season in which the blood samples were collected was autumn. Insulin resistance was assessed by using the Homeostasis Model Assessment (HOMA-IR). Body composition parameters (Fat Mass [FM], Fat Free Mass [FFM], body cell mass [BCM], Total Body Water [TBW]) were measured by electrical Bioimpedance Analysis (BIA). Lastly, demographic, anthropometric and clinical parameters (age, Body Mass Index [BMI], Waist Circumference [WC], Systolic (SBP) and Diastolic (DBP) blood pressure) were also assessed. Results: 25(OH)D levels were significantly and negatively correlated with BMI (P <0.001), WC (P <0.01), DBP (P <0.05), insulin (P <0.001), HOMA-IR (P <0.01), triglycerides (P <0.01), and fat mass (P <0.001). A multivariate regression analysis was performed by considering 25(OH)D levels as the dependent variable and sex, waist circumference, fat mass, DBP, triglycerides, and insulin (or HOMAIR) as the independent ones, and 25(OH)D levels maintained a significant and independent relationship only with fat mass (negative) (P <0.01). Conclusion: This study clearly shows that 25(OH)D circulating levels are progressively lower with the increase of fat mass, independently of sex, body fat distribution, blood pressure and insulin and metabolic parameters. These data strongly show that adipose tissue accumulation per se is absolutely the main factor responsible factor for lower 25(OH)D levels in obese subjects, possibly through sequestration of fat soluble 25(OH)D in fat mass.

Background: Osteoprotegerin (OPG) is a tumor necrosis factor receptor super-family member. It specifically acts on bone by increasing bone mineral density and bone volume. Recent studies have evidenced its close relation to the development of atherosclerosis and plaque destabilization. Elevated OPG level has also been associated with the degree of coronary calcification in the general population and it has been considered to be a marker of coronary atherosclerosis. Objective: The aim of this study was to determine the relation between OPG levels and Coronary Artery Calcification score (CACs) in Type 2 diabetic patients in comparison to healthy controls. Methods: Our study included 45 type 2 diabetic patients (mean age 51.7 years; 51.1% male) without evidence of previous CVD and 45 healthy age and sex matched subjects as control. All participants were subjected to full history, full examination and lab investigations. Serum OPG concentration was measured by an enzyme-linked immunosorbent assay (ELISA) and CAC imaging was performed using non contrast Multi detector CT of the heart. Results: Significant CAC (<10 Agatston units) was seen in 23 patients (51.11 %). OPG was significantly high in diabetic patients in comparison to controls with mean 12.9±5.7 pmol/l in cases, and 8.6±0.5 pmol/l in controls (P value < 0.001). The Coronary Artery Calcification Score (CACS) was positively correlated with age and duration of diabetes. The OPG was positively correlated with age, fasting blood sugar and duration of diabetes. The CACS showed a significantly positive correlation with OPG. Conclusion: Findings suggested that increasing in serum OPG was consistent with CAC and could be used for the early diagnosis of subclinical atherosclerosis.

Background and Objective: Oral cancer is one of the most common malignancies that affect human beings across the world and early detection of oral cancer is believed to reduce the morbidity significantly. Fluorescence diagnosis is emerging as a promising method in the differentiation of cancerous lesions and thus helping in the determination of resolution for the surgical resection of affected area of malignancy very accurately. The aim of this study was to evaluate the usefulness of an autofluorescence hand held device (OralID) to detect oral premalignant lesions. Methods: 98 potentially high-risk oral cancer patients were divided into two groups (n=49/group). Both the groups were first examined by conventional oral examination under white light and oral findings were noted. Subjects under group B were further examined under fluorescence light through hand held device, i.e. OralID. After the examinations, a surgical biopsy sample was taken from the suspected lesions under local anaesthesia from both the groups to confirm the diagnosis through histopathological analysis. Results: The positive potential malignant lesions (PMLs) observed in Group A when compared with biopsy reporting was 89.47% true positive while in Group B was 95.24%. The sensitivity reported of Group A was 89.47% and Group B was 97.56%. We observed 8.09% more sensitivity and 11.36% more specificity when we incorporate adjunctive the fluorescence examination using OralID. Conclusion: Results from this study suggests that OralID is a true adjunct to conventional oral examination in detecting early potential malignant changes in subjects visiting for regular dental check-up.

Introduction: Thyroid hormones are essential for the normal development, differentiation, metabolic balance and physiological function of all tissues. Mean platelet volume (MPV) indicates mean platelet size and reflects platelet production rate and stimulation. Increased platelet size has been observed in association with known cardiovascular risk factors. The neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) are known markers of the systemic inflammatory response. This study aimed to investigate the effect of thyroid hormone changes by comparing platelet count, MPV values, NLR and PLR in thyroid papillary carcinoma. Methods: Forty-nine females and nine males comprising a total of 58 patients were included in the study. Clinical and laboratory parameters of patients were recorded in the following three phases of the disease: euthyroid phase (before thyroid surgery), overt hypothyroid (OH) phase (before radioactive iodine [RAI] treatment) and subclinical hyperthyroid (SCH) phase (six months after RAI treatment). Results: The mean thyroid-stimulating hormone (TSH) values of the patients in the euthyroid, OH and SCH phases were 1.62±1.17, 76.4±37.5 and 0.09±0.07 μIU/mL, respectively. The mean MPV values of the patients in the euthyroid, OH and SCH phases were 9.45±1.33, 9.81±1.35 and 9.96±1.21 fL, respectively. MPV was significantly higher in the SCH phase than in the euthyroid phase (p=0.013). Platelet count, NLR and PLR were not statistically different between the euthyroid, OH and SCH phases. Conclusion: The results of this study demonstrated that the levels of MPV increased significantly in the SCH phase in patients with papillary thyroid carcinoma (PTC), and increased MPV values contributed to increased risk of cardiovascular complications. These findings suggest that MPV can be a valuable, practical parameter for monitoring the haemostatic condition in thyroid disorders. No significant difference was observed in platelet count, NLR and PLR in all stages of PTC.

Objective: Maternal vitamin D deficiency is an important risk factor that causes infantile rickets in the neonatal and infantile period. The aim of this study was to review the prevalence, clinical characteristics, and treatment of vitamin D deficiency and the follow-ups with infants and their mothers by the neonatal intensive care unit of Afiyet Hospital in Turkey. Methods: Calcium (Ca), phosphorus (P) and 25 (OH) vitamin D were studied and prospectively recorded in infants and their mothers detected to have hypocalcemia during routine biochemistry tests performed on the third postnatal day of the patients follow up and treated with different diagnoses. Results: A total of 2,460 infants were admitted into the neonatal intensive care unit between August 2014 and January 2018. Of the infants included in the study, 324 (66.1%) were male and 166 (33.8%) were female, and 366 (74.6%) of them had been delivered by cesarean section (C/S), 124 (25.3%) of them had been delivered by Normal Spontaneous Delivery (NSD). Hypocalcemia was detected in 490 (19.9%) of the infants. In a total of 190 (38.7%) infants and 86 mothers (17.5%), the levels of 25 (OH) vitamin D were found to be below the laboratory detection limit of <3 ng/ml. When vitamin D deficiency + insufficiency is assessed by season, 151 of them were found to be in summer (30.99%), 118 in spring (24.18%), 117 in the winter season(23.87%), and 93 in autumn(18.97%), respectively. There was a statistically significant positive correlation of 78.7% between the vitamins D values of the mothers and the infants (p: 0.000, p<0.05). Conclusion: This study conducted that a positive correlation of between the vitamin D values of the mothers and the infants. In order to prevent maternal vitamin D deficiency, the appropriate dose of prophylaxis providing optimal levels of vitamin D and should be given by according to the levels of 25 (OH) D vitamin during pregnancy.

Background: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine’s neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients. Methods: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded. Results: The results of the present trial showed that ω-3 fatty acids and nano-curcumin can reinforce each other’s effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). Conclusion: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.

Objective: Mazabraud's syndrome is a rare form of bone fibrous dysplasia associated with intramuscular myxomas. Fibrous dysplasia, is generally localized to pelvis and femur and it results in a fragile bone with deformities, pain, pathological fractures and functional impairment. Intramuscular myxomas, are rare benign mesenchymal neoplasms that exceptionally may evolve to malignant forms. Methods: This case report describes a 66-year-old woman with Mazabraud’s Syndrome (MS), characterized both by monostotic right femur fibrous dysplasia and by a solitary intramuscular myxoma at the right quadriceps muscle, that underwent a long-term treatment (4 years) with intravenous zoledronic acid. Results: Zoledronic acid therapy rapidly lowered bone pain together with a reduction of intramuscular myxoma volume, but did not affect the extension of fibrous dysplasia. No adverse effects have been observed during treatment. Conclusion: Highly active bisphosphonates are commonly used for the treatment of bone metabolic disorders and they are generally well tolerated. Zoledronic acid may represent a promising alternative to surgical intervention in MS, although its use in rare form of bone fibrous dysplasias is still controversial.