title: Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures.
abstract: Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both p<0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to fracture.
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Shigdel
authors.affiliation: Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Osima
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway; Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Luai A
authors.initials: LA
authors.lastname: Ahmed
authors.affiliation: Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Department of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ragnar M
authors.initials: RM
authors.lastname: Joakimsen
authors.affiliation: Department of Clinical Endocrinology, Oslo University Hospital, Oslo, Norway.
authors.forename: Erik F
authors.initials: EF
authors.lastname: Eriksen
authors.affiliation: Endocrine Centre, Austin Health, University of Melbourne, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Zebaze
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway. Electronic address: ashild.bjornerem@uit.no.
authors.forename: Åshild
authors.initials: Å
authors.lastname: Bjørnerem
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000503:physiopathology*; D058866:Osteoporotic Fractures / Q000000981:diagnostic imaging / Q000503:physiopathology*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D016062:Porosity; D011347:Procollagen / Q000097:blood; D011857:Radiographic Image Interpretation, Computer-Assisted / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide
keywords: Bone mineral density; Bone turnover markers; Cortical porosity; Non-vertebral fracture