Five studies, two of them already covered on this site's femoral neck bone density page, found the genetic loci behind bone density measured at the spine specifically.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Spine (lumbar) bone mineral density is bone density measured at the lower spine, one of the two sites — along with the femoral neck — a clinical DXA scan reports on to diagnose osteoporosis. This site covers it separately from its femoral neck, heel, total-body, and paediatric bone density pages, since each measures a genuinely different skeletal site.
Rivadeneira et al. 2009 meta-analysed 5 GWAS covering 19,195 people of Northern European descent, measuring femoral neck and lumbar spine BMD together, and found 20 loci — 13 new, 7 confirmed — including ZBTB40 and SPTBN1 among the named regions. This page's rs7524102, in ZBTB40, and rs11898505, in SPTBN1, both come directly from this study.
Styrkarsdottir et al. 2008, a year earlier, ran a discovery analysis in 5,861 Icelandic participants, replicated in 7,925 more across Iceland, Denmark, and Australia, and found 5 regions: RANKL, OPG, ESR1, ZBTB40, and the MHC region. This page's rs4870044, in ESR1, is this paper's own finding — the same ZBTB40 locus Rivadeneira's later, larger study also confirmed.
Choi et al. 2016 studied a Korean discovery cohort of 2,729 people, replicated in a Chinese Han cohort and two Caucasian populations, and found a genuinely novel, East-Asian-specific locus at UHMK1 — functionally validated in the lab, where knocking the gene down changed how bone-building and bone-resorbing cells differentiated. The same study found rs9371538, in ESR1, associated with lumbar spine BMD specifically; that variant is on this page too.
Estrada et al. 2012, the largest BMD meta-analysis at the time — 17 GWAS, 32,961 people of European and East Asian ancestry — found 56 loci in total, 32 of them new, with 14 also linked to fracture risk. This page's LEKR1 and MPP7 variants come from that broader 56-locus set.
Two more studies behind this page's remaining variants — Zheng et al. 2015 and Pei et al. 2018 — are already covered in full on this site's femoral neck bone density page, which both studies also measured; see that page for the EN1 mouse-model finding and the MACROD2/OSBPL2 loci in detail rather than repeating it here.
Osteoporosis is diagnosed with a DXA bone density scan, not with genotype. None of the variants here is used clinically to diagnose low bone density or guide treatment decisions.
Bone density screening and osteoporosis treatment decisions follow clinical guidelines based on measured bone density and fracture risk factors — not the variants listed here.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Spine Bone Mineral Density comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 14 of 14 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
It is bone density measured at the lower (lumbar) spine, one of the two sites — along with the femoral neck — a clinical DXA scan uses to diagnose osteoporosis.
Across five studies, the same handful of genes — especially ZBTB40 and ESR1 — were repeatedly confirmed independently, alongside dozens of other loci including a novel East-Asian-specific gene, UHMK1.
No. Osteoporosis is diagnosed with a DXA bone density scan, not genotype. This page describes population-level genetic contributions to bone density at the spine specifically.
Because DXA scans report on both sites separately, and the genetics differ somewhat between them — though two of the five studies behind this page also measured femoral neck BMD and are covered in full on that separate page.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.