Relating Bone Strain to Local Changes in Radius Microstructure Following 12 Months of Axial Forearm Loading in Women

Abstract

18Work in animal models suggest that bone structure adapts to local bone strain, but this 19 relationship has not been comprehensively studied in humans. Here, we quantified the 20 influence of strain magnitude and gradient on bone adaptation in the forearm of 21 premenopausal women performing compressive forearm loading (n=11) and non-22 36 normal loads and in response to a novel loading intervention, and represents an 37 important step toward defining exercise interventions to maximize bone strength. 38 40 Osteoporotic fractures represent a significant clinical burden, with 1 in 3 women 41 over age fifty experiencing a fragility fracture in their lifetime [1]. Exercise may have the 42 potential to increase bone mass and offset age-related bone loss. Athletes applying 43 high-intensity mechanical loads over extended periods of time have higher bone density 44 than their peers [2,3], and develop site-specific loading adaptations such as increased 45 cortical thickness in the dominant arms of tennis [4,5] and baseball [6] players. In 46 normal healthy adults, clinical trials have shown that high-impact and resistive exercises 47 consistently elicit a 1-3% increase in bone density at the hip over 6-24 months [7][8][9][10]. 48 However, moving towards a more personalized approach that tunes interventions to 49 deliver the optimal "dose" of loading for an individual requires a detailed understanding 50 of the relationship bone tissue loading and changes in bone structure. 51 Animal models have provided insight into the local relationship between bone 52 loading and adaptation. Early models established a controlling role of mechanical strain 53 magnitude [11,12] and the novelty of strain distribution [13,14] on the amount of new 54 bone formed following a dynamic loading intervention. Focusing on the local 55 relationship between bone strain and adaptation, it has been shown that cortical bone 56 formation is related to local strain magnitude [15] and spatial gradient [16,17]. In 57 murine vertebral loading models focusing on the trabecular bone response, principal 58 stresses, principal strains, strain energy density, and the spatial gradient of strain 59 moderately predict the initiation of trabecular bone formation and resorption [18][19][20][21]. 60 It is generally suggested that these tissue-level deformations drive cellular-level 61 Journal of Biomechanical Engineering 4 mechanical stimuli, such as fluid streaming potentials and membrane shear stresses, 62 which are transduced by osteocytes into biochemical cues regulating osteoblast and 63 osteoclast activity [22,23]. While the mechanisms linking bone strain and cell behavior 64 are likely similar in humans, the strength of the relationship between strain and 65 adaptation may differ due to greater genetic variability and the influence of systemic 66 factors such as hormones, diet, and exercise history. However, due to technical 67 challenges in measuring bone strain and changes in bone microstructure in vivo in 68 humans, data addressing this...

Clinical observation of diminished bone quality and quantity through longitudinal HR-pQCT-derived remodeling and mechanoregulation

“…Consistent with previous studies which found normal physiological activity levels result in significant relationships between bone formation and FE-derived mechanical stimulus 30 , 31 , the mechanoregulation analysis revealed strong relationships between local mechanics and remodeling in all groups. Trends were observed in the magnitude of the difference between the resorption and formation threshold values (i.e.…”

“…However, the regional and tissue-level measures do not fully capitalize on the capabilities of HR-pQCT, which when combined with a longitudinal imaging protocol include microstructural analysis of bone remodeling 29 through dynamic morphometry which allows for the direct quantification of bone formation and resorption and of the association of this remodeling with the mechanical loading of the bone, i.e. mechanoregulation 30,31 . To date, the ability of such longitudinal, extended HR-pQCT analysis tools to detect clinically relevant changes in bone quality and quantity has yet to be thoroughly investigated.…”

Clinical Observation of Diminished Bone Quality and Quantity through Longitudinal HR-pQCT-derived Remodeling and Mechanoregulation

“…Consistent with previous studies which found normal physiological activity levels result in significant relationships between bone formation and FE-derived mechanical stimulus 31,32 , the mechanoregulation analysis revealed strong relationships between local mechanics and remodeling in all groups. Differences were observed in the magnitude of the difference between the resorption and formation threshold values (i.e.…”

“…Further, the ability to track changes in the cortical and trabecular compartments has revealed both age-related 24–26 and disease-specific characteristics 26–29 not previously realized using regional DXA-based measures. However, the regional and tissue-level measures do not fully capitalize on the capabilities of HR-pQCT, which when combined with a longitudinal imaging protocol include microstructural analysis of bone remodeling 30 and mechanoregulation 31,32 . To date, the ability of such longitudinal, extended HR-pQCT analysis tools to detect clinically relevant changes in bone quality and quantity has yet to be thoroughly investigated.…”

Dominant and nondominant distal radius microstructure: Predictors of asymmetry and effects of a unilateral mechanical loading intervention

“…We previously showed that a similar mechanical loading regimen elicited changes in distal radius BMD that were related to local mechanical strain environment ( Bhatia et al, 2015 ). In a subset of this cohort, we showed that local trabecular strain magnitude and gradient were higher near formation versus resorption sites ( Mancuso and Troy, 2020 ). Similarly, local trabecular strain environment has been linked to local formation/resorption in small animals ( Webster et al, 2012 ).…”