Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials.

CONTEXT: The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (±â€…calcium) for fracture prevention has led to contradictory guidelines. OBJECTIVE: This umbrella review aims to assess the quality and explore the reasons for the discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults. METHODS: We searched 4 databases (2010-2020), Epistemonikos, and references of included SRs/MAs, and we contacted experts in the field. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) for quality assessment. We compared results and investigated reasons for discordance using matrices and subgroup analyses (PROSPERO registration: CRD42019129540). We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. RESULTS: Only 2 from 10 SRs/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8 of 12 SRs/MAs (relative risk [RR] 0.61-0.84), and any fractures in 7 of 11 SR/MAs (RR 0.74-0.95). No fracture risk reduction was noted in SRs/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SRs/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). CONCLUSION: Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized individuals. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up periods, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.

Systematic review of major osteoporotic fracture to hip fracture incidence rate ratios worldwide: implications for Fracture Risk Assessment Tool (FRAX)-derived estimates.

The Fracture Risk Assessment Tool (FRAX) is the most widely used tool for fracture prediction. It provides 10-year probabilities for hip and major osteoporotic fracture (MOF). It uses country-specific hip fracture incidence and life expectancy data, and for most countries, MOF/hip fracture incidence rate ratios (IRRs) from Malmo Sweden. However, the risk of MOF varies by age, sex, and geography. The objective is to compare the MOF/hip IRRs across countries, by sex and age. This systematic review targeted observational studies of MOF and hip fractures in individuals >50 years (PROSPERO 2019 CRD42019129259). One reviewer screened potential articles. Two reviewers completed duplicate and independent data abstraction, and assessed study quality based on population representativeness, study design and duration, definition of ethnicity, and fracture characteristics. We calculated the MOF/hip IRRs (95% confidence interval) and Z-values to compare IRRs in various countries to those for Sweden. We included 27 studies, of fair to good quality in the majority, from Europe (15), US and Canada (7), Asia (3), and Australia (2). The IRRs were twofold to 10-fold higher in younger compared to older age categories, and in women compared to men, with few exceptions. Within Europe, and using Sweden as a reference, MOF/Hip IRRs in women 50-54 years from Finland, Italy, Netherlands, Denmark, and UK were significantly lower by 38% to 60%. Findings were similar in men. At older ages, MOF/Hip IRRs were consistently lower in women from European countries compared to Sweden, by 10%-40% and 11%-51%, at 75-79 years and 85-89 years, respectively. Findings were heterogenous in men and in non-European countries. In conclusion, the MOF/hip fracture IRR may vary between countries. The variability at older ages may affect FRAX prediction when country-specific fracture IRRs are not used. Further research is needed to elucidate the implication of our findings to FRAX-derived MOF estimates in various countries. © 2021 American Society for Bone and Mineral Research (ASBMR).

Time trends and predictors of hypovitaminosis D across the life course: 2009-2016.

PURPOSE: We investigated prevalence, determinants, seasonal changes, and time trends in hypovitaminosis D. We derived a desirable serum 25-hydroxy-vitamin D (25OHD) level in adults/elderly by evaluating the 25OHD-parathyroid hormone (PTH) exponential relationship. METHODS: We analyzed serum 25OHD data from a large laboratory database (N = 151,705), from a major academic medical center in Lebanon, from 2009 to 2016. We used cross calibration formulas to convert measured 25OHD levels to LC-MS/MS equivalents based on our external quality assurance protocols. RESULTS: 6% of the population were children (mean age 11 ±â€¯5 years, 56% girls), 68% were adults (44 ±â€¯13 years, 71% women), and 25% were elderly (74 ±â€¯6 years, 59% women). The prevalence of hypovitaminosis D, in the entire population, was 39%, 29% and 23% at 25OHD cutoffs of 20 ng/ml, 15 ng/ml, and 12 ng/ml, respectively, across all years. Using multivariate analysis, predictors of 25OHD levels below 12, 15 and 20 ng/ml were younger age, male sex, winter months, and inpatient status both in adults and elderly. In children, older age, female sex, winter months, and inpatient status, predicted levels below 15 ng/ml and 20 ng/ml, but only older age, female sex, and winter months predicted levels below 12 ng/ml. There was a significant steady annual increase in 25OHD levels between 2009 and 2016 of 0.9 ng/ml/year (95% CI: 0.7, 1.0) in children, 1.2 ng/ml/year (1.2, 1.3) in adults and 2.6 ng/ml/year (2.6, 2.8) in the elderly. Using best fit non-linear regression models, on a subset of adults and elderly in whom concomitant 25OHD and PTH data was available (N = 4025), PTH levels plateaued at a serum 25OHD level of 26.1 ng/ml. CONCLUSION: Secular increase in serum 25OHD levels is observed in Lebanon, but hypovitaminosis D is still prevalent. Our data provides basis for a desirable 25OHD level above 26 ng/ml in adult and elderly Lebanese individuals.