...and, since that question being asked seemed to generate a great deal more interest than many I thoujght that addressing it sooner rather than later would be a better idea.
Is there any link between Osteogenesis and having High Cholesteral?
Recently a Question was asked about any connection between HIGH Cholesterol and OI.
At that time I hadn't heard of any studies that demonstrated any connection between the two, but with as much research as is being published and new research publications as there are today, I'll never say never. So here is what “we found” going through the research as of October 2026:
Short answer: no study shows a direct link between OI and high cholesterol (elevated total or LDL)
But there is a real lipid signal in the literature, and it points somewhere slightly different: low HDL (“good”) cholesterol, alongside obesity and insulin resistance.
If you went through the long version on the Chinese Research from 2025 that we published, we talk about a GREAT term that has popped up, called an “Invalid Inference.” When I was in school we used to call this “straight line Logic” where ONE of the steps is not like the others.
These are the kinds of ideas that allow some Physicians to disregard Anecdotal evidence. We, as “civilians” obviously dont have the biological training to consistently put 2++2 together and ALWAYS come up with 4. In my time researching OI, I have come across this often enough to understand the truth behind it.
In our case here's how that might work:
Theory about OI Patients and High blood pressure ( you dont need to raise your hands, I dont need anyone passing out on my dime), is that YES their IS a link between OI and HIGH blood pressure, they just dont know what it is, or how it may operate. This puts many physicians on the defensive or they just dismiss the idea altogether. In my house, if 98% of any group have agreement, thats nota coincidence.
One of the proposed theories works in two directions, so its harder for them to determine which it may be: A. In many OI patients it APPEARS as tough some of the blood pathways are less flexible than average, and therefore the body must build more pressure to get the circulation correct.. The opposite side of THAT discussion falls into the mechanical evidence that states that the base of the Aorta in the heart is actually MORE flexible than normal and prone to tearing. While there is nothing saying that both things can not be true at the same time, if they are, its believed that there is no connection between the two.
Then there is the almost contrary evidence presented at the end of the statement that suggests, that” a real lipid signal in the literature, and it points somewhere slightly different: low HDL (“good”) cholesterol, alongside obesity and insulin resistance.” In this case the belief is stronger that these two things can NOT be present in the same body. One pointing to 'good' cholesteral and one stimulating 'bad cholesteral.' At the moment there are not enough research studies to demonstrate how these two tings can both be accurate in the same patient.
STUDIES AVAILABLE:
The strongest human data (two pediatric cohorts, Peking Union Medical College Hospital)
Zheng et al., 2022, Frontiers in Endocrinology. This comped 225 children with OI to 80 age- and gender-matched healthy controls, measuring triglycerides, total cholesterol, LDL-C and HDL-C. Children with OI had significantly higher fasting glucose and HOMA-IR, but lower HDL-C, than controls.
This causes confusion because when you have a HIGHER fasting glucose level it means the amount of sugar (glucose) in your blood is elevated after you have gone without food or drink (except water) for at least 8 hours,which doesnt lend itself to this issue.
The authors noted that because osteocalcin levels didn’t correlate with any lipid measures, something other than osteocalcin may be driving the lipid changes in OI, which they flagged as worth further study. These children had no previous bisphosphonate treatment, so drugs can’t explain the finding.
Frontiers in Endocrinology (Aug 2022) +3 Zheng et al., 2023, Journal of Endocrinological Investigation. This study had 204 children with OI and 66 matched healthy children. It showed the same pattern. Total cholesterol was essentially the same in both groups (4.21 vs 4.28 mmol/L), and so was LDL (2.23 vs 2.25). HDL-C was lower in the OI group (1.04 vs 1.43 mmol/L, P < 0.001). Lipid values didn’t differ between OI types I, III and IV, or between COL1A1, COL1A2, IFITM5 and recessive genotypes. That suggests the low HDL is not just a feature of severe forms.
Population and claims data
An Ultragenyx-funded analysis of US claims data (ISPOR 2024 abstract) included 2,095 people with OI and found 26.0% had a hyperlipidemia diagnosis. This is the closest thing to a “high cholesterol in OI” figure. Be careful with it, though. The abstract I found doesn’t give the matched control group’s rate, and “hyperlipidemia” codes don’t tell you which lipid fraction was abnormal. It’s worth getting the full poster before citing it.
isporispor An Italian adult cohort (68 adults on long-term neridronate) assessed metabolic and cardiovascular risk factors and found therapy did not change them. This addresses bisphosphonate safety rather than OI-versus-control comparisons.
perpusnas
Mechanistic leads you might find interesting
Bone as an endocrine organ. In the Col1a1Jrt/+ OI mouse, knocking out osteocalcin restored glucose tolerance to normal, supporting osteocalcin as a driver of the altered glucose metabolism. This is about glucose rather than cholesterol, and the human data above suggest lipids may follow a separate path.
bone-abstracts MBTPS2 (X-linked OI). This one connects directly to cholesterol biology. MBTPS2 encodes site-2 protease, which activates transcription factors involved in bone, ER stress, and lipid metabolism (SREBP). SREBP is the master regulator of cholesterol synthesis. However, in patient fibroblasts, fatty acid profiles were altered but no consistent sterol changes were seen.
uni-heidelberguni-heidelberg Bisphosphonates and the cholesterol pathway. This is general pharmacology, not an OI study. Nitrogen-containing bisphosphonates work by blocking an enzyme in the mevalonate pathway, the same pathway statins target. I haven’t found OI-specific evidence that this meaningfully lowers or raises blood lipids. It’s a plausible thread, not a finding.
“OI is not known to cause high LDL cholesterol. Pediatric cohort data show lower HDL along with higher rates of obesity and insulin resistance, independent of bisphosphonate exposure. Adults with OI should get standard lipid screening as part of cardiovascular risk assessment.” That last point fits the 2024 JBMR Delphi consensus, which says cardiovascular disease is a major cause of illness and death in OI, as in the general population. nih
The biggest gap is that there’s no controlled adult lipid study. Every rigorous comparison I found involves children.
Sources: