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Fractures are not a function of vitamin D genes – Aug 2018

Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3225 (Published 29 August 2018)
Katerina Trajanoska, PhD student1 2, John A Morris, PhD student3 4, Ling Oei, assistant professor1 2, Hou-Feng Zheng, professor5 6, David M Evans, professor7 8, Douglas P Kiel, professor9 10, Claes Ohlsson, professor11, J Brent Richards, professor3 4, Fernando Rivadeneira, associate professor1 2 on behalf of the GEFOS/GENOMOS consortium and the 23andMe research team
F Rivadeneira f.rivadeneira at erasmusmc.nl, and J B Richards brent.richards at mcgill.ca


Poor vitamin D genes are associated with many health problems.
Osteoporosis does not appear to be one of the problems
Osteoporosis (poor bone strenth) is, however, related to
low Vitamin D and poor gut (which decreases Vit D),
low protein
low Magnesium
low Boron
low Silica
low Exercise
low Vitamin K
low Calcium (but too much is bad)

Pages in BOTH the categories Osteoporosis and Meta-analysis

Overview Osteoporosis and vitamin D contains the following summary

  • FACT: Bones need Calcium (this has been known for a very long time)
  • FACT: Vitamin D improves Calcium bioavailability (3X ?)
  • FACT: Should not take > 750 mg of Calcium if taking lots of vitamin D (Calcium becomes too bio-available)
  • FACT: Adding vitamin D via Sun, UV, or supplements increased vitamin D in the blood
  • FACT: Vitamin D supplements are very low cost
  • FACT: Many trials, studies. reviews, and meta-analysis agree: adding vitamin D reduces osteoporosis
  • FACT: Toxic level of vitamin D is about 4X higher than the amount needed to reduce osteoporosis
  • FACT: Co-factors help build bones.
  • FACT: Vitamin D Receptor can restrict Vitamin D from getting to many tissues, such as bones
  • It appears that to TREAT Osteoporosis:
  •        Calcium OR vitamin D is ok
  •        Calcium + vitamin D is good
  •        Calcium + vitamin D + other co-factors is great
  •        Low-cost Vitamin D Receptor activators sometimes may be helpful
  • CONCLUSION: To PREVENT many diseases, including Osteoporosis, as well as TREAT Osteoporosis
  • Category Osteoporosis has 214 items
  • Category Bone Health has 304 items

Note: Osteoporosis causes bones to become fragile and prone to fracture
  Osteoarthritis is a disease where damage occurs to the joints at the end of the bones
Osteoporosis category includes the following

 Download the PDF from VitaminDWiki

Objectives To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk.

Design Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach.

Setting 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data.

Participants A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor.

Results Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10−68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture.

Conclusions This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.

Created by admin. Last Modification: Tuesday September 4, 2018 20:39:45 GMT-0000 by admin. (Version 4)

Attached files

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10483 Osteo meta.pdf admin 04 Sep, 2018 601.37 Kb 833