Context The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (±calcium) for fracture prevention has led to contradictory guidelines. This umbrella review aims to assess the quality and explore the reasons for discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults. Evidence Acquisition We searched 4 databases (2010-2020), Epistemonikos, and references of included SR/MAs, and we contacted experts in the field. We used AMSTAR-2 for quality assessment. We compared results and investigated reasons for discordance using matrices and sub-group analyses (PROSPERO registration: CRD42019129540). Evidence Synthesis We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. Only 2 from 10 SR/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8/12 SR/MAs (relative risk (RR) 0.61-0.84), and any fractures in 7/11 SR/MAs (RR 0.74-0.95). No risk reduction was noted in SR/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SR/MAs stems from inclusion of different trials, related to search periods and eligibility criteria, and varying methodology (using intention to treat, per-protocol, or complete case analysis from individual trials). Vitamin D alone has no protective effect on fracture risk. Conclusions Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized subjects. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up period, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.

Purpose To investigate the impact of two vitamin D doses, bracketed between the IOM recommended dietary allowance (RDA) and the upper tolerable limit, on vitamin D nutritional status in elderly individuals. Methods This is a post-hoc analysis on data collected from a 12-month, double-blinded, randomized control trial. 221 ambulatory participants (≥ 65 years), with a mean BMI of 30.2 kg/m 2, and a mean baseline serum 25-hydroxyvitamin D [25(OH)D] level of 20.4 ± 7.4 ng/ml, were recruited from 3 out-patient centers in Lebanon. They all received 1,000 mg of elemental calcium from calcium citrate daily, and the daily equivalent of 600 IU or 3,750 IU, of vitamin D3. Results Mean 25-hydroxyvitamin D [25(OH)D] level at 12 months was 26.0 ng/ml with low dose and 36.0 ng/ml with high dose, of vitamin D3. The proportion of participants reaching a value ≥ 20 ng/ml was 86% in the low dose, and 99% in the high-dose arms, with no differences between genders. The increment of 25(OH)D per 100 IU/day was 1ng/ml with the low dose, and 0.41 ng/ml with the high dose. Serum 25 (OH)D levels at 1 year were highly variable in both treatment arms. Baseline 25(OH)D level and vitamin D dose, but not age, BMI, gender, nor season, were significant predictors of serum 25(OH)D level post-intervention. Conclusion The IOM RDA of 600 IU/day does not bring 97.5% of ambulatory elderly individuals above the desirable threshold of 20 ng/ml. Country-specific RDAs are best derived taking into account the observed variability and predictors of achieved 25(OH)D levels.

Middle East region experiences a high prevalence of hypovitaminosis D, yet most genetic studies on Vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting the elderly population, who are more susceptible to health burden. We investigated the genetic determinants of 25-hydroxyvitamin D levels in elderly Lebanese individuals (n=199) through a whole exome-based genome-wide association study. We identified new loci with suggestive evidence of an association with Vitamin D levels, including rs141064014 in the MGAM gene (P-value of 4.40 × 10−06) and rs7036592 in PHF2 (P-value of 8.43 × 10−06). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistence replication of numerous variants, including rs2725405 in SLC38A10 (P-value of 3.73 x 10-08). Despite the lower performance of European-derived polygenic risk scores compared to the European estimations, it still effectively predicted Vitamin D deficiency among elderly Lebanese individuals. Our findings provide novel insights into the genetic mechanisms of Vitamin D deficiency in Middle Eastern elderly populations, facilitating the development of personalized approaches for more effective management of hypovitaminosis D. Additionally, we demonstrated that whole exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

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<b><i>Introduction:</i></b> The study aimed to construct and validate a risk prediction model for incidence of postoperative renal failure (PORF) following radical nephrectomy and nephroureterectomy. <b><i>Methods:</i></b> The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2005–2014 were used for the derivation cohort. A stepwise multivariate logistic regression analysis was conducted, and the final model was validated with an independent cohort from the ACS-NSQIP database years 2015–2017. <b><i>Results:</i></b> In cohort of 14,519 patients, 296 (2.0%) developed PORF. The final 9-factor model included age, gender, diabetes, hypertension, BMI, preoperative creatinine, hematocrit, platelet count, and surgical approach. Model receiver-operator curve analysis provided a C-statistic of 0.79 (0.77, 0.82; <i>p</i> &#x3c; 0.001), and overall calibration testing <i>R</i>² was 0.99. Model performance in the validation cohort provided a C-statistic of 0.79 (0.76, 0.81; <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> PORF is a known risk factor for chronic kidney disease and cardiovascular morbidity, and is a common occurrence after unilateral kidney removal. The authors propose a robust and validated risk prediction model to aid in identification of high-risk patients and optimization of perioperative care.