Abstract
Higher stature and lower weight are associated with increased risk of fracture. However, the pathophysiology for the associations of height and weight with bone microarchitecture and geometry is unclear. We examined whether these associations were consistent with causation and/or with shared familial factors. In this cross-sectional study of 566 female twins aged 26-76 yr, a regression analysis for twin data, Inference about Causation by Examination of FAmilial CONfounding (ICE FALCON), was used for testing causation. The bone microarchitecture and geometry of the distal tibia was assessed using HR-pQCT and the StrAx1.0 software. Higher stature was associated with larger total bone cross-sectional area (CSA), lower total bone volumetric bone mineral density (vBMD), larger cortical CSA, thinner cortices, higher porosity of the total cortex, compact cortex, outer and inner transitional zone (TZ), lower cortical vBMD, and larger medullary CSA (regression coefficients (β) ranging from -.37 to .60, all p<.05). Using ICE FALCON, the cross-pair cross-trait associations attenuated toward zero after adjusting for the within-individual association (absolute values of β ranging from .05 to .31, all p<.001). Higher weight was associated with higher total bone vBMD, larger cortical CSA and thicker cortices, lower porosity of the total cortex and inner TZ, and higher cortical vBMD (β ranging from -.23 to .34, all p<.001), and thinner trabeculae, higher trabecular number, lower trabecular separation, and higher trabecular vBMD (β ranging from -.31 to .39, all p<.05). Only cortical CSA attenuated toward zero after adjusting for the within-individual association between weight and bone microarchitecture (β = .042, p=.046). Higher stature was associated with a weaker cortical, not trabecular bone traits, whereas higher weight was associated with stronger cortical and trabecular bone traits. The results were consistent with height having a causal effect on weaker cortical bone structure, whereas weight had a casual effect on the larger cortical CSA.