Diabetes and Bone

Towards more Quality – Deciphering the Sweet Bone Phenomenon


Bone in patients with diabetes breaks easily and heals poorly. Sometimes, it does not heal at all. For the patients, this means immobility over months and as a consequence less life quality. Type 2 diabetes mellitus and osteoporosis may affect half of the aging European population. However, the ‘sweet bone phenomenon’ remains a conundrum, since bone mineral density is paradoxically high or normal. Therefore, we set out to answer the fundamental question “How is bone weakened by diabetes?”

We believe that bone material strength is affected by direct and indirect effects of type 2 diabetes mellitus on bone. In the last four years, our group has found that bone microarchitecture and accumulation of advanced glycosation endproducts (AGE) contribute to poor bone quality in diabetes. In our ongoing studies, we test how microvascular damage and persistent low-grade inflammation may contribute to impaired bone cell function. To tackle these research questions, we use preclinical models and comprehensively assess intact and regenerating bone with a spectrum of high-resolution imaging modalities and advanced cell biology methods.

We expect to uncover the cause of poor bone quality in diabetes by focussing on vascular and inflammatory mechanisms and to deliver better bone therapies for patients with diabetes.

Principal Investigators

Lorenz Hofbauer

Lorenz Hofbauer, MD

«I am trying to find the missing link.»

Juliane Saalbach Hirsch

Juliane Salbach-Hirsch, PhD

«Research is going up all alleys to see if they are blind.»

Martina Rauner, PhD

Martina Rauner, PhD

«It is an important research area as it concerns so many people worldwide.»

Björn Busse, Universitätsklinikum Hamburg-Eppendorf
Pawel Szulc, INSERM Lyon, France
Martin von Bergen, Helmholtz Zentrum für Umweltforschung, Leipzig
Christine Hofbauer, Universitätsklinikum Dresden
Nicola Napoli, University Campus Bio-Medico of Rome, Italy
Anjali Kusumbe, Oxford University, UK

Dragoun Kolibová S, Wölfel EM, Hemmatian H, Milovanovic P, Mushumba H, Wulff B, Neidhardt M, Püschel K, Failla AV, Vlug A, Schlaefer A, Ondruschka B, Amling M, Hofbauer LC, Rauner M, Busse B, Jähn-Rickert K. Osteocyte apoptosis and cellular micropetrosis signify skeletal aging in type 1 diabetes. Acta Biomater. 2023;162:254-265.

Muschitz C, Kautzky-Willer A, Winhofer Y, Rauner M, Haschka J, Cejka D, Wakolbinger-Habel R, Pietschmann P. Common guideline of the Austrian Society for Bone and Mineral Research and the Austrian Diabetes Society. Wien Klin Wochenschr. 2023;135(Suppl 1):207-224. German.

Wölfel EM, Schmidt FN, Vom Scheidt A, Siebels AK, Wulff B, Mushumba H, Ondruschka B, Püschel K, Scheijen J, Schalkwijk CG, Vettorazzi E, Jähn-Rickert K, Gludovatz B, Schaible E, Amling M, Rauner M, Hofbauer LC, Zimmermann EA, Busse B. Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation. J Bone Miner Res. 2022;37:2259-2276.

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;10:207-220.

Carro Vázquez D, Emini L, Rauner M, Hofbauer C, Grillari J, Diendorfer AB, Eastell R, Hofbauer LC, Hackl M. Effect of Anti-Osteoporotic Treatments on Circulating and Bone MicroRNA Patterns in Osteopenic ZDF Rats. Int J Mol Sci. 2022;23:6534.

Daamouch S, Emini L, Rauner M, Hofbauer LC. MicroRNA and Diabetic Bone Disease. Curr Osteoporos Rep. 2022;20:194-201

Anastasilakis AD, Tsourdi E, Tabacco G, Naciu AM, Napoli N, Vescini F, Palermo A. The Impact of Antiosteoporotic Drugs on Glucose Metabolism and Fracture Risk in Diabetes: Good or Bad News? J Clin Med. 2021 2;10:996.

Hildebrandt N, Colditz J, Dutra C, Goes P, Salbach-Hirsch J, Thiele S, Hofbauer LC, Rauner M. Role of osteogenic Dickkopf-1 in bone remodeling and bone healing in mice with type I diabetes mellitus. Sci Rep. 2021 21;11:1920.

Ferrari S, Eastell R, Napoli N, Schwartz A, Hofbauer LC, Chines A, Wang A, Pannacciulli N, Cummings SR. Denosumab in postmenopausal women with osteoporosis and diabetes: Subgroup analysis of FREEDOM and FREEDOM extension. Bone. 2020;134:115268.

Picke AK, Sylow L, Møller LLV, Kjøbsted R, Schmidt FN, Steejn MW, Salbach-Hirsch J, Hofbauer C, Blüher M, Saalbach A, Busse B, Rauner M, Hofbauer LC. Differential effects of high-fat diet and exercise training on bone and energy metabolism. Bone. 2018;116:120-134.

Picke AK, Campbell GM, Blüher M, Krügel U, Schmidt FN, Tsourdi E, Winzer M, Rauner M, Vukicevic V, Busse B, Salbach-Hirsch J, Tuckermann JP, Simon JC, Anderegg U, Hofbauer LC, Saalbach A. Thy-1 (CD90) Promotes bone formation and protects against obesity. Science Transl Med 2018;10(453).

Picke AK, Sylow L, Møller LLV, Kjøbsted R, Schmidt FN, Steejn MW, Salbach-Hirsch J, Hofbauer C, Blüher M, Saalbach A, Busse B, Rauner M, Hofbauer LC. Differential effects of high-fat diet and exercise training on bone and energy metabolism. Bone 2018;116:120-34.

Picke AK, Gordaliza Alaguero I, Campbell GM, Glüer CC, Salbach-Hirsch J, Rauner M, Hofbauer LC, Hofbauer C. Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy. Bone 2016;82:108-15.

Hamann C, Rauner M, Höhna Y, Bernhardt R, Mettelsiefen J, Goettsch C, Günther KP, Stolina M, Han CY, Asuncion FJ, Ominsky MS, Hofbauer LC. Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus. J Bone Miner Res 2013;28:627-38.

Hamann C, Kirschner S, Günther KP, Hofbauer LC. Bone, sweet bone—osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol. 2012;8:297-305.