Does bone resorption stimulate periosteal expansion? A cross sectional analysis of β-C-telopeptides of type I collagen (CTX), genetic markers of the RANKL pathway, and periosteal circumference as measured by pQCT

John P Kemp, Adrian Sayers, Lavinia Paternoster, David M Evans, Kevin Deere, Beate St Pourcain, Nicholas J Timpson, Susan M Ring, Mattias Lorentzon, Terho Lehtimäki, Joel Eriksson, Mika Kähönen, Olli Raitakari, Marika Laaksonen, Harri Sievänen, Jorma Viikari, Leo-Pekka Lyytikäinen, George Davey Smith, William D Fraser, Liesbeth VandenputClaes Ohlsson, Jon H Tobias

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


We hypothesised that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum ß-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodelling such as cortical bone mineral density (BMDC ). CTX and mid-tibial pQCT scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass and height. CTX was positively related to PC [ß= 0.19 (0.13, 0.24)] (coefficient?=?SD change per SD increase in CTX, 95% CI)], but inversely associated with BMDC [ß= -0.46 (-0.52,-0.40)] and cortical thickness [ß= -0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) [ß= 0.09 (0.03, 0.14)]. To examine the causal nature of this relationship, we then analysed whether SNPs within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding RANK, RANKL and OPG were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (P?
Original languageEnglish
Pages (from-to)1015–1024
Number of pages10
JournalJournal of Bone and Mineral Research
Issue number4
Early online date7 Sep 2013
Publication statusPublished - Apr 2014


  • CTX
  • pQCT

Cite this