title: 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: In vitro data suggest that myokine irisin may affect bone metabolism by promoting osteoblast differentiation while inhibiting osteoclast differentiation. In this study, circulating irisin levels were associated with previous osteoporotic fractures but not with bone mass and were not affected by denosumab or teriparatide treatment for 3 months.
  
  
  BACKGROUND
  This study aimed to evaluate predictors of circulating irisin in postmenopausal women with low bone mass and to assess a potential effect of denosumab or teriparatide treatment for 3 months.
  
  
  METHODS
  Serum samples for irisin measurement were obtained from (a) postmenopausal women with low bone mass (lumbar spinal [LS] or femoral neck [FN] bone mineral density [BMD] T-score ≤-2.0) and their age-matched controls at baseline and 3 months after denosumab (Dmab) injection (Dmab group, n = 50; Dmab control group, n = 25) and (b) women with more severe disease (LS or FN BMD T-score ≤-2.8) and their age-matched controls at the above-mentioned time points after teriparatide (TPTD) initiation (TPTD group, n = 25; TPTD control group, n = 25).
  
  
  RESULTS
  At baseline, irisin levels were inversely correlated with age (partial coefficient (r p ) = -0.24; p = 0.009), parathyroid hormone (PTH) (r p  = -0.30; p = 0.001), and creatinine (r p  = -0.23; p = 0.016) in univariate analysis, and were lower in women with (n = 26; 41.6 ± 2.7 ng/dL) than without previous osteoporotic fracture(s) (n = 99; 51.0 ± 1.6 ng/dL; p = 0.007). In multiple linear regression, previous osteoporotic fracture(s) and PTH were independently negatively associated with irisin [p = 0.04, CI -16.1 to -0.4 and p = 0.002, CI -0.3 to -0.07, respectively], but only the association with PTH remained after controlling for creatinine levels. Serum irisin levels were not different between women with or without low bone mass and were not affected by either Dmab or TPTD treatment for 3 months.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, Ring Road, 564 29 N. Efkarpia, Thessaloniki, Greece, anastath@endo.gr.
authors.forename: A D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: S A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: P
authors.initials: P
authors.lastname: Makras
authors.forename: A
authors.initials: A
authors.lastname: Gkiomisi
authors.forename: I
authors.initials: I
authors.lastname: Bisbinas
authors.forename: A
authors.initials: A
authors.lastname: Katsarou
authors.forename: A
authors.initials: A
authors.lastname: Filippaios
authors.forename: C S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015519:Bone Density / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D000069448:Denosumab; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000097:blood* / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D010281:Parathyroid Hormone / Q000097:blood; D019379:Teriparatide / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; C577593:FNDC5 protein, human; D005353:Fibronectins; D010281:Parathyroid Hormone; D019379:Teriparatide; D000069448:Denosumab; D003404:Creatinine