ECTS Abstracts (2015) 1 OC2.4

Mitochondrial DNA point mutation is associated with lower bone mineral density and altered bone structure in a matched case-control study

Jakob H Langdahl1,2, Stinus J Hansen3, Knud B Yderstræde4, Per H Andersen2, John Vissing5, Morten Dunø6, Anja L Frederiksen7 & Morten F Nielsen3


1Clinical Genetic Research Unit/Clinical Institute University of Southern Denmark, Odense, Denmark; 2Department of Endocrinology/Hospital of Southwest Jutland, Esbjerg, Denmark; 3Endocrine Research Unit/Clinical Institute University of Southern Denmark, Odense, Denmark; 4Department of Endocrinology/Odense University Hospital, Odense, Denmark; 5Department of Neurology/Rigshospitalet, Copenhagen, Denmark; 6Department of Clinical Genetics/Rigshospitalet, Copenhagen, Denmark; 7Department of Clinical Genetics/Odense University Hospital, Odense, Denmark.


Background: Mitochondrial dysfunction is associated with several clinical outcomes including diabetes, myopathy, hearing loss and is implicated in the human ageing process. Mitochondrial mutations cause osteoporosis in mouse models. The effect of mitochondrial dysfunction on bone has not been studied in humans.

Methods: We recruited 38 patients (24 female, 14 male) with the mtDNA3243A>G mutation aged 45.8±14.9 years. Twenty-three of the cases had diabetes mellitus. Cases were matched with respect to sex, age, height and menopausal status with healthy controls. All participants underwent DXA and HR-pQCT scans. Finite element analysis was used to assess bone strength.

Results: Cases and controls were matched with regard to age, sex and height, but cases had a lower body weight (63.3 vs 75.7 kg) and higher calcium and vitamin D supplements. Based on DXA, cases had a lower total hip aBMD (0.82 vs 0.95 g/cm2, P<0.01), femoral neck aBMD (0.65 vs 0.80 g/cm2, P<0.01) and spine aBMD (0.91 vs 0.98 g/cm2, P=0.02). Compared to controls, cases had smaller cortical area (radius: 56.0 vs 64.2 mm2, P<0.01, tibia: 98.4 vs 134.6 mm2, P<0.01), thinner cortices (radius: 0.80 vs 0.92 mm, P<0.01, tibia: 1.06 vs 1.29 mm, P<0.01) and lower total bone vBMD (radius: 312.6 vs 370.8 mg/cm3, P<0.01, tibia: 275.8 vs 316.2 mg/cm3, P<0.01). In cases, cortical density was lower at the radius (888.8 vs 913.9 mg/cm3, P=0.02) and trabecular density was lower in tibia (154.1 vs 176.8 mg/cm3, P=0.02). In tibia, but not radius, estimated bone stiffness (165.8 vs 209.4 kN/mm, P<0.01) and failure load (8.5 vs 10.7 kN, P<0.01) was lower in cases. Hip BMD remained lower in cases after adjusting for weight.

Conclusion: Bone mass, microarchitecture and strength were compromised in patients with mitochondrial dysfunction. Further studies are needed to describe the effects of mitochondrial dysfunction on bone remodelling.

Disclosure: The authors declared no competing interests. Region of Southern Denmark; The A.P. Møller Foundation for the Advancement of Medical Science; Institute of Regional Health Services Research / University of Southern Denmark.

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