Is the plate to rod transition in trabecular bone loss a real phenomenon or a spurious result of a misused metric?

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A latticework of bony trabeculae stiffens the internal spaces of many bones. Trabeculae transmit forces between joint surfaces and bone shafts and maintain the integrity of vertebrae. Bone loss is a normal physiological response to reduced mechanical load, occurring during bed rest, in sedentary lifestyles, and during the weightlessness of spaceflight. Bone loss is also a normal, undesirable, part of ageing which occurs particularly rapidly in women after menopause. Reduced bone mass is strongly associated with increased fracture risk. Peak bone mass is obtained in humans in early adulthood. Strategies to increase peak bone mass and to slow its physiological loss are of great interest to ensure healthy ageing.In addition to bone mass (bone volume fraction, BV/TV), bone architecture is thought to play a crucial role in trabecular bone's force transmission and fracture resistance. Bone architecture is defined by standard measurements such as trabecular thickness (Tb.Th), spacing (Tb.Sp), interconnectedness (Conn.D), anisotropy (DA) and rod-plate geometry (structure model index, SMI). The bulk behaviour of trabecular bone in physiological loading is almost entirely determined by BV/TV: this is intuitive because the more bone matrix there is per unit volume, the greater the overall volume can resist applied load. Once a higher failure load has been reached, however, the behaviour of trabecular elements dominates collapse of the overall structure. Each trabecula might fail by buckling, shear or crumpling. Bone biologists believe that plate-like trabeculae resist higher loads than rod-like trabeculae and that plate-like trabeculae convert to rod-like trabeculae during bone loss, creating a 'double-whammy': reduced bulk resistance to load due to decreased BV/TV and reduced resistance to trabecular element failure due to rod-like geometry.Whether a plate-to-rod transition actually occurs in bone loss is now in serious doubt, because the paradigm is based on flawed SMI measurements. I recently showed that variation in SMI during bone loss is dominated by increasing amounts of concave portions of the bone surface, which the SMI theory assumes are not there or have a negligible contribution. There is a high correlation between SMI and BV/TV even when the underlying architecture has not changed. SMI is a fundamentally broken measurement that does not do what bone bioscientists use it for. Over 850 papers have cited SMI and a common interpretation when seeing BV/TV and SMI results together is that bone loss is associated with a plate-to-rod transition, however, this is merely an artefact of SMI's design that obscures any true relationship. Statements linking bone loss and plate-rod transition have been repeated often enough to have become an accepted dogma in the bone field.This project aims to overturn the dogma there is a plate to rod transition in bone loss using 3D X-ray microtomography (XMT) image data sets archived from previous experiments. To measure rods and plates independent of BV/TV, the PDRA will validate a new method, ellipsoid factor (EF), that defines rods and plates by the shape of the biggest ellipsoid that fits within each bony region. Rods can fit long, javelin-shaped ellipsoids, while plates can fit flat, discus-shaped ellipsoids. The PDRA will use image data collected on RVC's XMT instrument, images from my project partner Phil Salmon at Bruker microCT, and from other collaborators worldwide, and aim to increase our current pool of ~150 images from 3 studies to ~1000 images from ~20 studies. Having identified rods and plates in bone samples, the PDRA will correlate rods and plates with mechanical behaviour using finite elements analysis in the physiological load range for bulk behaviour and overload range for trabecular element failure behaviour. The primary benefit of the work is improved understanding of true geometric and mechanical changes in bone loss, along with the new EF method and free software.