Faculté de médecine Faculté de médecine

Bone Fragility in Diabetes

Further understanding of the fundamental mechanisms underlying bone fragility in diabetes will ultimately improve therapeutic approaches to prevent fractures in this high-risk population.

RESEARCH AIMS

In our research group, we use biochemistry, cell culture, mouse genetics, and human cohorts to study the pathophysiology of diabetes-induced bone fragility. Osteocytes, the long-lived cells residing within the bone matrix, orchestrate bone modelling and remodelling in response to mechanical loading and hormones. Recent findings suggest that osteocyte functions are defective in type 1 (T1D) and type 2 diabetes (T2D). Therefore, we are currently investigating the roles of insulin signalling in osteocytes in the context of T1D (Akita mice) and T2D (mice subjected to a high-fat diet + streptozotocin regimen). In addition, we are exploring how reduced autophagy, altered mitochondria-associated endoplasmic reticulum membranes, and excessive PDGFRβ signalling in osteocytes contribute to the pathogenesis of T2D-induced bone fragility (HFD + STZ). Finally, we use proteomic analyses of sera obtained from a cohort of patients with metabolic syndrome and T2D to identify novel markers of T2D-induced bone fragility.

CORE EXPERTISE

Mouse models:

  • Akita^mut/mut (T1D)

  • High-fat diet (T2DM)

  • SerpinF1 KO + HFD (Pigment epithelium-derived factor, microvascularisation)

  • High-fat diet + STZ

  • Db/Db (T2DM)

  • Atg7^lox/lox (autophagy)

  • Dmp1-Cre (osteocytes)

  • Igf1rflox/flox; Insrflox/flox (insulin signalling)

Bone investigation techniques:

  • Histology: Calcified tissue histology (methyl methacrylate embedding), immunohistology (cryo-histology, paraffin embedding)

  • Bone imaging: Micro-computed tomography (Viva-CT Scanco)

  • Bone biomechanical resistance testing (Instron)

  • Bone matrix quality properties (nano-indentation)

SELECTED PUBLICATIONS

  1. Ferrari S, Betah D, Feldman RG, Langdahl BL, Oates M, Timoshanko J, Wang Z, Dhaliwal R. Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes. J Clin Endocrinol Metab. 2025 Jan 24;dgae862. doi:10.1210/clinem/dgae862. Online ahead of print. PMID: 39854280.
  2. Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, El-Hajj Fuleihan G, Ferrari S. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. J Clin Endocrinol Metab. 2023 May 8;dgad255. doi:10.1210/clinem/dgad255. PMID: 37155585
  3. Hofbauer LC, Busse B, Eastell R, Ferrari S, Frost M, Müller R, Burden AM, Rivadeneira F, Napoli N, Rauner M. Bone fragility in diabetes: novel concepts and clinical implications. Lancet Diabetes Endocrinol. 2022 Mar;10(3):207–220. doi:10.1016/S2213-8587(21)00302-3. PMID: 35101185
  4. Bonnet N, Bourgoin L, Biver E, Douni E, Ferrari S. RANK Ligand inhibition improves muscle strength and insulin sensitivity concomitant to bone mass restoration. J Clin Invest. 2019 Aug 1;129(8):3214–3223. doi:10.1172/JCI126650. PMID: 31120440
  5. Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, El-Hajj Fuleihan G, Josse R, Kendler DL, Kraenzlin M, Suzuki A, Pierroz DD, Schwartz AV, Leslie WD. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int. 2018 Dec;29(12):2585–2596. doi:10.1007/s00198-018-4701-5. PMID: 30066131​​​​
3 Jul 2025

Type 1 Diabetes