The Association Between Bone Remodeling Markers, genes polymorphisms with Incidence of Osteopenia Among Young Saudi Female.

Osteopenia and osteoporosis, are prevalent skeletal systemic conditions, cause weaker bones and an increased risk of fragility fractures. This work is aimed to evaluate the relation between bone-remolding markers and genotypes of four single nucleotide polymorphisms in young Saudi females (rs2297480 of farnesyl diphosphate synthase (FDPS), rs3736228 of Low-density lipoprotein receptor-related protein 5 (LRP5), rs1234612 of sclerostin (SOST), and rs9934438 of Vitamin K epoxide reductase complex subunit 1  (VKORC1) ). For this purpose, 750 premenopausal females aged 18 to 40 years old, either university students, postgraduates, or university employees were recruited and divided into three groups according to bone mineral density BMD (g/cm2) divided by T score into osteoporosis (n = 12), osteopenia (n = 147), and normal (n = 591). Serum SOST, BALP, calcium, phosphate, ALP, albumin, beta-CTXs and human VDR levels were determined. TaqMan SNP Genotyping assays were used to genotype four polymorphisms using real-time PCR (applied biosystem). Results showed that BALP, CTX-1 and SOST were significantly higher in the osteoporosis and osteopenia groups than in the normal group. Bone mineral density readings were considerably lower in females with the GG genotype in FDPS rs2297480 and TT genotype in LRP5 rs3736228, which increase the risk for osteopenia by 3. 6-fold and 3. 06-fold than control respectively. Also, females with the TT genotype in LRP5 rs3736228 have decreased average values for Bone Mineral Density. In conclusion, the GG genotype of FDPS rs2297480 and the TT genotype of LRP5 rs3736228 was shown to be strongly associated with osteopenia in young Saudi females with low bone mineral density and SOST levels.

Expression of toll-like receptor 4 and its connection with type 2 diabetes mellitus.

Toll-like receptor 4 (TLR4) plays an important role in modulating innate immunity. Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired insulin resistance and abnormal immune response. Genetic background and consequently genetic factors might have a key role in both onset and progression of T2DM-related complications.  The aim of this work was to study the role of toll-like receptor 4 (TLR4) in the development of type 2 diabetes mellitus (T2DM). This study was carried out on 90 subjects, 30 type 2 diabetic patients, 30 patients with impaired glucose tolerance and 30 age and gender matched healthy controls. mRNA expression of (TLR4) was assessed by reverse transcriptase PCR (RT-PCR) using real time PCR.. Results showed significant statistical difference between the three studied groups  regarding BMI, serum FBG, HDL, TGs, TC, LDL, HOMA -IR and mRNA expression of TLR4 with highest level of TLR4 mRNA expression in T2DM patients. From this study, it might be concluded that high expression of (TLR4) is associated with T2DM.

Transforming Growth Factor-ß1 gene polymorphism and osteoporosis in postmenopausal egyptian women.

Transforming growth factor-ß1 (TGF-ß1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-ß1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group. There was a significant statistical difference in the CC, CT and TT (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.001). There was a non-significant statistical difference in the CC, CT and TT (T-509C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.082). There was a significant statistical difference between TT,CT and CC of (T869C) and T score, Z score and calcium of osteopenia/osteoporosis group (p value <0.001). There was a non-significant statistical difference between TT, CT and CC of (T-509C) and T score, Z score of osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically significant difference between the three genotyping and serum calcium and creatinine (p value 0.04). Multivariate regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57, 95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-ß1 gene has an impact on bone mineral density and enhancement of the susceptibility to osteopenia/osteoporosis in Egyptian women.

Association of vitamin D receptor gene BsmI (A>G) and FokI (C>T) polymorphism in gestational diabetes among Saudi Women.

OBJECTIVE: Vitamin D receptor (VDR) gene polymorphism have a role in diabetes mellitus pathogenesis. Present study was conducted to determine VDR gene variants among Saudi gestational diabetics (GDM) in Madina, KSA. METHODS: This cross sectional study was conducted on 112 GDM patients and 218 normal healthy control. Age, body mass index and blood pressure levels were recorded. Serum triglycerides (mg/dl), total cholesterol, HDL-cholesterol, LDL-cholesterol, fasting blood glucose FBG and post-prandial blood glucose PPBG were estimated. Extracted DNA template was amplified by PCR reaction and genotyped for single nucleotide polymorphism of BsmI and FokI by restriction fragment length polymorphism-PCR (RFLP-PCR) analysis. RESULTS: FBG and PPBG levels in GDM patients were significantly elevated by +48.6% and +50%, respectively (P=0.005). Serum triglycerides, total cholesterol and LDL-cholesterol (mg/dl) levels in GDM patients were elevated significantly by +40.5% (P=0.005), +16% (P=0.01) and +30.8% (P=0.005), respectively. Serum HDL-cholesterol (mg/dl) showed significant decline by -10.5%. FokI VDR genotypes showed association with PPBG (P=0.05) among GDM patients. The Ff, FF and ff genotype percentage among GDM patients was 48.2%, 30.4% and 21.4%, respectively. FokI (F and f) and BsmI (B and b) alleles frequency showed no significant difference between GDM patients and control. Percentage BsmI and FokI total homozygous and heterozygous variants among GDM was 45.5% and 81.4%, respectively. CONCLUSION: VDR BsmI and FokI polymorphic marker not associated with Saudi GDM.

Association Between Vitamin D Level and Z-Score Changes of Bone Density in College-Age Saudi Girls: A Cross-Sectional Study.

Objective: Vitamin D (VD) deficiency is a worldwide health problem. VD plays a crucial role in calcium homeostasis, phosphorus metabolism and bone health. Still much remain to understand the effect of VD deficiency on bone mass. This study aimed to evaluate the relationship between VD levels and bone mass density (BMD) among college-age Saudi females. Methods: In a cross-sectional study, 460 females with a median age of 21 years, were enrolled, completed a comprehensive, structured questionnaire which was validated by experienced endocrinologist, a dietician, and a statistician. Body mass indexes (BMI) were calculated, and BMD was estimated through quantitative ultrasound to ankle. Serum VD, calcium, phosphate, parathyroid hormone, and alkaline phosphatase were measured using chemiluminescent immunoassay technique. Results: VD deficiency reached up to 83.3% (66.9% insufficiency and 16.4% deficiency). Lower than normal BMD was detected in 18.3% of subjects, with only 1.1% having a non-age-matched high risk for osteoporosis. The significant independent predictors of Z-score were age of menarche, menstrual irregularities, dairy products consumption, physical activity, BMI, alkaline phosphatase, and history of previous VD supplementation. Conclusion: VD deficiency and low BMD are highly prevalent among college-age Saudi females. Low BMD is not linked to serum level of VD but to its previous use as a supplementation. Early lifestyle changes, attention to gynecological problems, and prevention of VD deficiency are all needed to support BMD among these girls.

Determinants of Z-Score of Bone Mineral Density among Premenopausal Saudi Females in Different Age Groups: A Cross Sectional Study.

This is a comparative multicenter cross-sectional study that evaluated the potential determinants of Z-scores among premenopausal Saudi women before and after the age of peak bone density. The Study concluded that for better BMD among premenopausal women, attention should be paid to early physical activity and healthy nutrition, especially vitamin D, during the childbearing period. OBJECTIVE: To explore the potential determinants of Z-scores among premenopausal Saudi females in different age groups before and after the expected age of peak bone density (PBD). METHODS: This multicenter comparative cross-sectional study was conducted in Madinah and Jeddah, Saudi Arabia, between August 2021 and March 2022. We recruited 886 premenopausal females (605 (68.3%) below and 281 (31.7%) at or above the age of 30). The structured pre-coded Arabic questionnaire included sociodemographic data, a BMD questionnaire, menstrual history, an Arab Teen Lifestyle Study questionnaire, and food frequency data. Metabolic Equivalents (METs) were calculated from physical activity. Analysis of serum PTH, 25(OH) vitamin D (VD) was performed with chemiluminescent immunoassay. BMD was measured with a calcaneal qualitative ultrasound. RESULTS: Most women had age-matched Z-scores, with very few (24 (2.7%)) being non-age-matched with no identified secondary causes. Significant Z-score determinants before PBD were BMI (OR: 0.167, p = 0.003) and total METs (OR: 0.160, p < 0.005). After the age of PBD, significant predictors were parity (OR: 0.340, p = 0.042), history of vitamin D deficiency (OR: 0.352, p = 0.048), and BMI (OR: 0.497, p = 0.019). CONCLUSIONS: Early determinants of Z-scores among premenopausal women were the nutritional status and physical activity. After the age of PBD, parity and vitamin D status offer additional determinants. For better BMD, attention should be paid to early physical activity and healthy nutrition, especially for vitamin D, with intensification of efforts during the childbearing period.

Utilization of Antibiotics for Hospitalized Patients with Severe Coronavirus Disease 2019 in Al-Madinah Al-Munawara, Saudi Arabia: A Retrospective Study.

Background: Most patients admitted to intensive care units (ICUs) with severe Corona Virus Disease 2019 (COVID-19) pneumonia receive antibacterial antibiotics with little evidence of bacterial infections. Objective: This study was designed to review the profiles of patients with severe COVID-19 pneumonia requiring intensive care, the rate of bacterial coinfection, the antibiotics used, and their relation to patient outcomes (death or recovery). Methods: This was a retrospective study that reviewed the medical records of all patients with confirmed COVID-19 (n = 120) severe pneumonia admitted directly from the emergency room to the intensive care unit, at a public hospital during the period from May 2020 to April 2021. The data collected included patients' demographic and laboratory data, comorbidities, antibiotic treatment, and their outcome. Descriptive statistics, bivariate inferential analysis tests (chi-square and unpaired T-Tests) and multivariable binary logistic regression were performed. Results: The mean age of the patients was 56.8 ± 16.5 years old, and among them, 74 (62.7%) were males. Of the included patients, 92 (77.0%) had comorbidities, 76 (63.3%) required mechanical ventilation and 30 (25%) died. All patients received empirical antibiotics for suspected bacterial coinfection. The most common antibiotics used were azithromycin (n = 97, 8%) and imipenem (n = 83, 9%). Ninety patients (75%) were on two empirical antibiotics. Early positive cultures for pathogens were found only in four patients (3.3%), whereas 36 (30%) patients had positive cultures 5-10 days after admission. The most frequently isolated pathogens were Acinetobacter baumannii (n = 16) and coagulase-negative Staphylococci (n = 14). In bivariate analysis empirical treatment with azithromycin resulted in a significantly lower mortality rate (p = 0.023), meanwhile mechanical ventilation, days of stay in intensive care unit, morbidities (e.g., lung disease), linezolid and, vancomycin use associated with mortality (p< 0.05). The adjusted logistic regression, controlling for age and gender, revealed that azithromycin antibiotic was more likely protective from mortality (OR= 0.22, 95%CI 0.06-0.85, p=0.028. However, patients with lung diseases and under mechanical ventilation were 35.21 and 19.57 more likely to die (95%CI =2.84-436.70, p=0.006; 95%CI=2.66-143.85, p=0.003, respectively). Conclusion: Bacterial coinfection with severe COVID-19 pneumonia requiring intensive care was unlikely. The benefit of Azithromycin over other antibiotics could be attributed to its anti-inflammatory properties rather than its antibacterial effect.

Association of Vitamin D Gene Polymorphisms and Bone Mineral Density in Healthy young Saudi Females.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by low bone mineral density. Vitamin D metabolism may play a pivotal role in its pathophysiology. OBJECTIVES: To determine the association between Vitamin D receptor gene polymorphisms and bone density, as well as its relation to biochemical markers of bone turnover, in a healthy Saudi female population. METHODS: A cross-sectional study was carried out at Taibah University, Madinah Region, Kingdom of Saudi Arabia. After receiving informed consent, blood samples from 300 subjects were collected to measure calcium, phosphorus, alkaline phosphatase, parathyroid hormone osteocalcin, and 1,25-OHD and perform genetic analysis of SNPs in vitamin D receptors (VDR) rs2228570, rs731236, and rs11568820. RESULTS: There were significant differences between the CC, CT, and TT alleles of VDR rs2228570. Carrying the TT allele was associated with increased risks of decreased bone density and the presence of osteopenia with lower vitamin D3 levels (p≤0.001). The VDR rs731236 gene showed that CC allele carriers had significant risk of osteopenia. The AA genotype of rs11568820 showed lower levels of physical activity, bone mineral density, Z scores, serum osteocalcin, phosphorus, and parathyroid hormones. CONCLUSION: The presence of the TT allele of the SNP rs2228570 of the VDR gene and the SNP rs731236 of the CC genotype was associated with the presence of osteopenia and decreased bone mineral density alongside malfunctions of vitamin D.

Nutritional and health status of medical students at a university in Northwestern Saudi Arabia.

OBJECTIVE: To assess the nutrition and health status, nutrients intake, and physical activity among Saudi medical students. METHODS: A cross-sectional survey using a questionnaire, anthropometric measurements, and laboratory assessments was conducted from January to May 2011 on 194 randomly selected Saudi medical students at Taibah University, Madinah, Kingdom of Saudi Arabia. The adequacy of nutrient intake was compared with the recommended daily intake (RDI) per the National Research Council. RESULTS: Caloric intake was derived from carbohydrates (72.1%), fats (19.4%) and proteins (8.4%). Proteins and fats were obtained from a greater number of animal sources than of plant sources (5.3% versus 3.2% for proteins and 11.6% versus 7.8% for fats). There were low percentages of RDI of fibers (8.5%), most vitamins especially vitamin D (14.2%), and minerals (potassium (31.3%), zinc (40.7%), magnesium (24.5%), and calcium (47%). Overall, 34.5% of the students were overweight, and 10.3% were obese. Dyslipidemia was diagnosed in 24.7%, and 56.2% had high high-sensitivity C-reactive protein (hs-CRP). There was a positive correlation between the median caloric intake and both the BMI (r=0.42, p=0.00) and hs-CRP (r=0.3, p=0.001). Inactivity was prevalent among the students (64.4%). CONCLUSION: This study showed deficiencies in several essential nutrients among medical students, and the prevalence of overweight status, obesity, and inactivity were relatively high. These results indicate the need to improve nutrition and promote healthy lifestyles among the medical students.