Thread by @I_mitochondria

Patients with T2DM, CVD, conditions of hyperinsulinaemia, have lower: bone remodelling and osteocalcin levels, and increased rates of fragility fractures.

T2DM “hyperinsulinaemia-osteofragilitas” bone phenotype presents with normal to increased BMD mdpi.com/2227-9059/9/9/…

Hyperinsulinaemia and IR positively associate with increased BMD and fragility fractures

Hyperinsulinaemia enforces glucose fuelling, decreasing NAD+-dependent antioxidant activity:

➡️⬆️ ROS & mt fission,
➡️⬇️ OxPhos ATP production capacity, needed for osteoblasto/cytogenesis.

Osteocytes directly mineralise and resorb bone, & inhibit mineralisation of their lacunocanalicular space via pyrophosphate.

Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability.

Decreased bone remodelling and micropetrosis ensues.

Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport.

Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis.

Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure.

Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics.

Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.

Bone is too often considered just a supporting structure. Bone regulates metabolic, endocrine and neurological health. #osteoporosis #osteofragilitas #hyperinsulinaemia #insulinresistance #T2DM

Thank you to my awesome co-authors! @PharmacistCath @kenbrookler