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Genetic Study Links Blood Protein RSPO3 to Bone Density Loss

A large genetic analysis identifies nine blood proteins linked to osteoporosis risk and connects body weight and blood sugar to one of them.

By Dr. Josh Axe · November 15, 2026 · 1 source · Watch

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At a glance

What they found: Genetically predicted higher body mass index was linked to higher RSPO3 levels, while genetically predicted type 2 diabetes was linked to lower RSPO3 levels.
Who was studied: Older adults.

A genetic analysis published November 3, 2026 in the Journals of Gerontology: Series A identified nine blood proteins linked to osteoporosis risk, with one protein called RSPO3 standing out as the strongest candidate.

Researchers combined two large genetic protein databases, deCODE with 4,907 proteins and the UK Biobank Pharma Proteomics Project with 2,923 proteins, against osteoporosis case data from the FinnGen study covering 10,461 cases. Using a method called Mendelian randomization, which uses genetic variation to estimate cause-and-effect relationships, the primary analysis flagged 31 candidate proteins in the deCODE data and 24 in the UK Biobank data. Cross-checking both datasets narrowed the list to nine proteins linked to osteoporosis risk. One of them, RSPO3, showed moderate evidence of sharing the same genetic signal as osteoporosis risk in a technique called colocalization analysis, which checks whether two traits are driven by the same spot in the genome.

A follow-up genetic analysis found that genetically predicted higher body mass index was linked to higher RSPO3 levels, while genetically predicted type 2 diabetes was linked to lower RSPO3 levels.

In general, signaling proteins like RSPO3 can influence a cellular pathway involved in how bone-building cells form and function; this study did not test that mechanism directly. The authors concluded these nine proteins offer new insight into how bone disease develops and suggest metabolic traits may influence bone health through specific protein pathways.

95%

TSMR analysis suggested that genetically predicted higher body mass index (BMI) was associated with increased RSPO3 levels (β = 0.08, 95% CI 0.02 to 0.14, p = 0.001), whereas type 2 diabetes (T2DM) was associated with lower RSPO3 levels (β = -5.71, 95% CI -11.16 to -0.26, p = 0.045).

The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2026-11-03T00:00:00.000Z

This is a genetic association study, a link rather than proof that any of these proteins are behind bone loss in people. The osteoporosis case data came from a single population registry, body weight and diabetes status were studied through genetic proxies rather than direct measurement, and no diet, exercise or supplement intervention was tested.

Dr. Axe’s Take

Bone density tracks closely with metabolic health, and this gives one more genetic thread connecting body weight, blood sugar and a bone-regulating protein. I would not wait on a drug aimed at RSPO3. I would act on what supports bone strength through mechanisms already well established: steady blood sugar and a healthy body weight through whole foods, protein at each meal and regular strength training. Pair that with weight-bearing exercise and vitamin D from sunlight and foods like wild-caught salmon or egg yolks. This is gene-level evidence, so I treat it as a reason to focus on basic bone-protective habits now.

— Dr. Axe

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Study summary

Who: Genetic data from deCODE (4,907 proteins) and UK Biobank-PPP (2,923 proteins) cohorts; osteoporosis case data from FinnGen (10,461 cases).
Design: Summary-data-based Mendelian randomization and colocalization analysis of plasma proteins and osteoporosis, plus two-sample Mendelian randomization of lifestyle factors on OP-linked proteins.
Dose: Not applicable; genetic/observational analysis, no intervention administered.
Primary result: 9 proteins linked to osteoporosis risk across both cohorts; RSPO3 showed the strongest evidence (colocalization probability 0.643).
Secondary: Higher genetically predicted BMI was linked to higher RSPO3 levels (beta 0.08, 95% CI 0.02 to 0.14). Genetically predicted type 2 diabetes was linked to lower RSPO3 levels (beta -5.71, 95% CI -11.16 to -0.26).
Funding / conflicts: Funding and conflicts not reported in the abstract.
Date: Nov 3, 2026