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Bone Abstracts (2013) 1 OC2.4 | DOI: 10.1530/boneabs.01.OC2.4

ECTS2013 Oral Communications Bone quality and fracture repair - animal models (6 abstracts)

PPARβ deficiency induces muscle and bone loss with aging but does not impair the bone biomechanical response to loading: a sarco-osteopenic mouse model

Nicolas Bonnet 1 , Béatrice Desvergne 2 & Serge Ferrari 1


1Division of Bone Diseases, Geneva University Hospital and Faculty of Medicine, Switzerland, Geneva, Switzerland; 2Faculty of Biology and Medicine, Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.


Pparβ is crucial for muscle fatty acid oxidation. Pparβ−/− mice have reduced muscle strength, exercise performance, and also a decreased skeletal response to exercise. Here we investigate the influence of Pparβ on muscle and bone loss with aging, and its role on the bone biomechanical response to loading. Pparβ/ and Pparβ+/+ mice were monitored at 1, 3 and 18 months of age. Muscle function was evaluated by handgrip and locomotors activity. Six months-old Pparβ/ and Pparβ+/+male were subjected to in-vivo axial compression of the tibia for 2 weeks. At 1-month of age, lean mass, skeletal muscle function, and bone parameters did not differ between Pparβ/ and Pparβ+/+. From 1 to 3-months of age, Pparβ/ had lesser gain in lean mass (+64 vs +88% in Pparβ+/+, P<0.01) and TB (total body) BMD (+66 vs +73% in Pparβ+/+, P<0.05). Mean force and running distance were significantly lower in Pparβ/. CtTV, CtBV, and strength were also reduced in Pparβ/ (0.56±0.02 mm3, 0.34±0.01 mm3, 19.7±1.3N vs 0.62±0.02 mm3, 0.38±0.02 mm3, 25.1±1.4N respectively in Pparβ+/+, P<0.05). From 3- to 18-months, differences between genotypes in TB lean and bone mass, mean force and running distance further increased. At 18 months of age, Pparβ/ had lower BV/TV, CtTV, CtBV, Ec-PsBFR and Ec-PsMP/BPm, and strength compared to Pparβ+/+. Circulating myostatin increased more with age in Pparβ/ than Pparβ+/+(4.4- vs 2.9-fold, P<0.05). However, following axial compression, the increase in BMD, CtTV, PsBFR and PsMP/BP was similar in both genotypes.

These results indicate that Pparβ plays an important role on the acquisition and maintenance of muscle and bone mass. Hence, in absence of Pparβ, sarcopenia and osteoporosis develop with aging, paralleling an increase in myostatin. However the skeletal response to direct loading is maintained, suggesting that bone alterations are due to the loss of muscle functions and partly reversible.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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