Mid-Thigh Cortical Bone Structural Parameters, Muscle Mass and Strength, and Association with Lower Limb Fractures in Older Men and Women (AGES-Reykjavik Study)

Jóhannesdóttir, Fjóla; Aspelund, Thor; Siggeirsdóttir, Kristín; Jönsson, B; Mogensen, Brynjólfur; Sigurðsson, Sigurður; Harris, Tamara B.; Gudnason, Vilmundur; Lang, Thomas; Sigurðsson, Gunnar

doi:10.1007/s00223-012-9585-6

Cited by 39 publications

(42 citation statements)

References 43 publications

(56 reference statements)

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“…There was no change in thickness, number, and separation of trabeculae in r-irisin-treated compared with control mice. Although it remains unclear why osteoblasts at cortical surfaces will behave differently from those synthesizing trabecular bone, our observation is in line with data indicating greater sensitivity of cortical bone to anabolic factors released by muscle (26,27,35). The selective action of r-irisin on cortical bone is likely to be related to the different functionalities of cortical and trabecular bone.…”

Section: Discussionsupporting

confidence: 89%

“…Specifically, by distributing bone mass away from the center, enlarged bone perimeter and cross-sectional area both contribute to increased pMOI and resistance to bending. The effect of r-irisin, essentially mimicking the effect of mechanotransduction (25)(26)(27), thus allows bone to become structurally more efficient for bending and torsion. Indeed, both mouse (28)(29)(30) and rat (31-34) models have collectively shown positive associations between exercise and increased bone size and bone mass.…”

Section: Discussionmentioning

confidence: 99%

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The myokine irisin increases cortical bone mass

Colaianni

Cuscito

Mongelli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

404

399

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It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg(-1). We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg(-1) per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin-injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle-bone connectivity

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The myokine irisin increases cortical bone mass

Colaianni

Cuscito

Mongelli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

404

399

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“…However, this is also in line with previous literature data reporting that cortical bone is more sensitive to myokines or other anabolic factors released by muscle. [25][26][27] Notably, change in the expression myostatin, also released from skeletal muscle, undergoes opposite direction to Irisin release following exercise, as it has been shown that myostatin signaling is inhibited by acute resistance exercise. 28 In addition, myostatin knock out mice displayed BATexpansion, an effect mediated by the AMPK-PGC1a-FNDC5 pathway in skeletal muscle.…”

Section: Irisin the Messenger Of Healthy Bone-muscle Unitmentioning

confidence: 99%

Role of Irisin on the bone–muscle functional unit

Colaianni

Grano

2015

BoneKEy Reports

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Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action.

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“…5,7,26,27 Þetta hlutfall kvenna er þó heldur laegra ef borið er saman við eldri íslenska rannsókn þar sem hlutfallið var 72% 28 og rannsóknir frá Noregi og Danmörku þar sem hlutfallið var 71% 7 og 72% 5 , en sambaerilegt við tölur frá Svíþjóð, eða 67%. 29 Meðalaldur sjúklingahópsins var 82 ár sem er sambaerilegt við erlendar rannsóknir.…”

Section: Umraeðaunclassified

“…24 Þetta er þó nokkru haerra en í nokkrum nýleg-um erlendum rannsóknum þar sem dánartíðnin var 16-21% (tafla I). 3,26,27 Það var ekki marktaekur munur á dánartíðni milli kvenna og karla eins og sést í erlendum rannsóknum þar sem dánartíðni er haerri hjá körlum. ójafnvaegi í lengd sjúkrahúsdvalar milli sjúklingahópa sem koma að heiman og frá hjúkrunarheimilum og gaeti það hugsanlega haft áhrif á dánartíðni hér á landi ári eftir mjaðmarbrot.…”

Section: Umraeðaunclassified