Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months

Anastasilakis, Athanasios D.; Polyzos, Stergios A.; Makras, Polyzois; Gkiomisi, Athina; Bisbinas, Ilias; Κατσαρού, Αλεξάνδρα; Filippaios, Andreas; Mantzoros, Christos S.

doi:10.1007/s00198-014-2673-x

Cited by 116 publications

(105 citation statements)

References 17 publications

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“…Furthermore, and interestingly, serum irisin levels in people are inversely correlated with serum sclerostin levels independently of age or sex (44). There is also an inverse correlation between serum irisin levels and vertebral fragility fractures in postmenopausal women (45,46). In contrast, irisin levels in athletes positively correlate with BMD (47).…”

Section: Discussionmentioning

confidence: 99%

The myokine irisin increases cortical bone mass

Colaianni

Cuscito

Mongelli

et al. 2015

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

392

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: Discussionmentioning

confidence: 99%

The myokine irisin increases cortical bone mass

Colaianni

Cuscito

Mongelli

et al. 2015

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

392

399

View full text Add to dashboard Cite

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“…43 Likewise, post-menopausal women showed inverse correlation between Irisin levels and vertebral fragility fractures. 44,45 Conversely, Irisin measured in athletes was positively associated with bone density and strength, 46 supporting the idea that Irisin could have a protective role on bone health. Unfortunately these studies, as many other human studies in which Irisin levels were measured by ELISA assays, have been debated because of poor antibody specificity that may have given artifacts.…”

Section: Irisin Synthesis Beyond the Muscle And Its Autocrine Actionmentioning

confidence: 86%

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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“…Some studies have reported inverse associations of irisin with age [22], [33], and several fold higher irisin levels in young adult men compared with middle aged women [22].…”

Section: Discussionmentioning

confidence: 99%

Irisin Levels Are Lower in Young Amenorrheic Athletes Compared with Eumenorrheic Athletes and Non-Athletes and Are Associated with Bone Density and Strength Estimates

et al. 2014

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Irisin and FGF21 are novel hormones implicated in the “browning” of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14–21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.

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Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months

Abstract: Circulating irisin levels were associated with previous osteoporotic fracture(s); whether this association is independent or is due to confounding by lower muscle mass, potentially reflected by lower creatinine levels, remains to be fully clarified.

Cited by 116 publications

References 17 publications

The myokine irisin increases cortical bone mass

The myokine irisin increases cortical bone mass

Role of Irisin on the bone–muscle functional unit

Irisin Levels Are Lower in Young Amenorrheic Athletes Compared with Eumenorrheic Athletes and Non-Athletes and Are Associated with Bone Density and Strength Estimates

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