Osteoporosis Genes and Prevention Strategies

Osteoporosis Genotype Report:

There are quite a few genetic variants that add a little to the risk of osteoporosis. If you have osteoporosis, it is likely that you will have multiple genetic variants that play a role in it. Not all variants are covered by 23andMe or AncestryDNA, so this is only giving you a partial picture of your osteoporosis genes.

How can you use this information? Hopefully, understanding where your genetic susceptibility lies can help you figure out ways of preventing (further) bone loss.

TNFSF11 gene:

One of the newer pharmaceutical options for osteoporosis is a drug known as a RANKL inhibitor. RANKL is the pathway for bone resorption, so blocking the resorption is thought to build stronger bones. TNFSF11 is the gene that encodes the RANKL protein. In addition to bone resorption, RANKL plays an immune system role in other tissues such as the thymus, liver, colon, and more. Disruption of this gene in mouse models leads to severe osteoporosis as well as immune system problems.

The genetic variants below cause lower bone mineral density through increased RANKL.

Check out the natural RANKL inhibitors listed in the Lifehacks section below.

OPG gene:

The OPG gene codes for a protein that inhibits osteoclast, thus increasing bone formation.

LRP5 gene:

The LRP5 gene codes for a protein involved in skeletal homeostasis. Several polymorphisms in LRP5 have been associated with lower bone mineral density. There are rare loss-of-function mutations causing severe osteoporosis and other, also rare, gain-of-function mutations that cause very dense bones.[ref]

SQRDL (sulfide quinone reductase-like) gene:

Sulfide quinone reductase is an enzyme that regulates the hydrogen sulfide levels in the cell. This is important in bone health because the bone marrow mesenchymal stem cells regulate their osteogenic differentiation by producing hydrogen sulfide. Researchers have created mice with low hydrogen sulfide and found that they have osteoporosis — and that giving the mice hydrogen sulfide can reverse bone loss.[ref] Notably, several other recent studies also point to hydrogen sulfide as a regulator of bone formation.[ref]

VDR – Vitamin D Receptor gene:

Vitamin D is important in both calcium absorption and in regulating bone cell functions. There are several significant genetic variants in the VDR gene that have been studied for their association with osteoporosis.

The VDR Fok-I polymorphism is also well-studied. A July 2014 study looked at the effect on osteoporosis based on Fok-I presence and serum 25(OH) D levels.[ref] The study found that for people carrying the normal genotype, there was a good correlation between vitamin D levels and osteoporosis risk. In contrast, for those carrying the less common genotype, vitamin D levels did not reflect osteoporosis risk.

Other studies have shown more of a link to osteoporosis for those with multiple VDR polymorphisms.[ref]

ESR2 gene:

Estrogen deficiency is also a risk factor for osteoporosis. A polymorphism in the estrogen receptor 2 gene has also been associated with osteoporosis in postmenopausal women.

TGFB1 (transforming growth factor-beta 1) gene:

The TGFB1 gene codes for a protein that regulates cell growth, maturation, and cell death. A 2015 meta-analysis looked at the association between the TGFB1 polymorphisms and postmenopausal osteoporosis risk. The results showed an increased risk, but only for Asian women and not for Caucasian women.

Collagen Type 1 Alpha 1 polymorphisms:

The COL1A1 gene is involved in making collagen, which is part of the extracellular matrix of bones as well as in tendons, cartilage, skin, etc.[ref]