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

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?