Feeding intervention potentiates the effect of mechanical loading to induce new bone formation in mice

Samvelyan, Hasmik Jasmine; Mathers, John C.; Skerry, Timothy M.

doi:10.1096/fj.202100334rr

Cited by 4 publications

(9 citation statements)

References 50 publications

(83 reference statements)

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“…Findings from Borer and colleagues ( 79 ) indicated that only meals before exercise induced anabolic responses, whereas meals following the exercise did not, providing a sufficient exercise impulse was provided within circadian constraints. The importance of sufficient nutrients was also confirmed within a recent animal model ( 89 ). The findings showed that reintroduction of food after a 16-h fast markedly increased new cortical bone in tibia and further increased the response of the bone to mechanical stimuli.…”

Section: Exercise and Bone Remodelingmentioning

confidence: 57%

Idiosyncratic bone responses to blood flow restriction exercise: new insights and future directions

Hughes,

Centner

2024

Journal of Applied Physiology

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Applying blood flow restriction (BFR) during low load exercise induces beneficial adaptations of the myotendinous and neuromuscular system. Despite the low mechanical tension, BFR exercise facilitates a localized hypoxic environment and increase in metabolic stress, widely regarded as the primary stimulus for tissue adaptations. First evidence indicates that low load BFR exercise is effective in promoting an osteogenic response in bone, although this has previously been postulated to adapt primarily during high-impact weight-bearing exercise. Besides studies investigating the acute response of bone biomarkers following BFR exercise, first long-term trials demonstrate beneficial adaptations in bone in both healthy and clinical populations. Despite the increasing number of studies, the physiological mechanisms are largely unknown. Moreover, heterogeneity in methodological approaches such as biomarkers of bone metabolism measured, participant and study characteristics, and time-course of measurement render it difficult to formulate accurate conclusions. Furthermore, incongruity in the methods of BFR application (e.g., cuff pressure) limits the comparability of datasets and thus hinders generalizability of study findings. Appropriate use of biomarkers, effective BFR application and befitting study design has the potential to progress knowledge on the acute and chronic response of bone to BFR exercise and contribute toward the development of a novel strategy to protect or enhance bone health. Therefore, the purpose of the present synthesis review is to: i) evaluate current mechanistic evidence; ii) discuss and offer explanations for similar and contrasting data findings; and iii) create a methodological framework for future mechanistic and applied research.

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Section: Exercise and Bone Remodelingmentioning

confidence: 57%

Idiosyncratic bone responses to blood flow restriction exercise: new insights and future directions

Hughes,

Centner

2024

Journal of Applied Physiology

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“…The right knee joints of 16-week-old wild type C57BL/6 male mice ( n = 6) were subjected to non-invasive, dynamic axial mechanical loading under the isoflurane-induced anaesthesia (liquid isoflurane was vaporised to a concentration of 4% and maintained at a concentration of 2% with oxygen) for 7 min/day, 3 alternate days a week for 2 weeks according to the protocols described in the previous studies ( 13 , 14 ). The left knee joints were non-loaded internal controls in these animals.…”

Section: Methodsmentioning

confidence: 99%

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

et al. 2021

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The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM (p=0.002 and p<0.0001, respectively) and loaded (both p<0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.

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“…The prevailing view in the field of bone research is that a substantial supra-threshold mechanical stimulus is a necessary condition for any anabolic bone remodeling [ 35 , 36 ]. Yet in several protocols that manipulate the timing of nutrients and exercise, anabolic changes in bone can be triggered at sub-threshold mechanical loading either by a meal in the absence of the second mechanical stimulus [ 27 ], or after delayed access to food [ 37 ], and by timed blood-flow restriction (BFR) [ 38 ].…”

Section: Can Timing Of Nutrients and Exercise Increase Bone Sensitivi...mentioning

confidence: 99%

“…The capacity of bone to respond to subthreshold mechanical stimulation was also demonstrated after substantial nutrient deprivation. In study [ 37 ], tibiae of 17-week old mice received 40 cycles of loading, ranging between 1100 and 2200 microstrain in the type of apparatus shown in Figure 1 A. The anabolic bone response was examined after mechanical stimulation during two hours of refeeding that followed a 16-h fast.…”

Section: Can Timing Of Nutrients and Exercise Increase Bone Sensitivi...mentioning

confidence: 99%

“… Table legend: AL = ad libitum feeding in mice; BFR = blood-flow restriction; DS = necessary distance to be walked in km (miles); DT = downhill treadmill exercise at −6°; IMP = impulse or duration of effective exercise in minutes of walking, EAM = exercise 1 to 2 h after eating a substantial meal; EBM = exercise 1 h before a substantial meal; EB = exercise bout(s); l = left; LP = Lower panel(s); LS = walking on level surface; PRF = post-refeeding in the mouse study (not done in humans) r = right; RI = Insertion of rest in chronological hours; SP = speed of effective exercise in km/h (miles/h); ST = exercise starting time in military time; TPTD = teriparatide, synthetic parathyroid hormone; UP = upper panel(s); UT = uphill treadmill at +6°; # teriparatide (TPTD) injection to postmenopausal women with osteoporosis; * mouse study [ 37 ], not tried in humans. …”

Section: Figurementioning

confidence: 99%

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How to Suppress Mineral Loss and Stimulate Anabolism in Postmenopausal Bones with Appropriate Timing of Exercise and Nutrients

Borer

2024

Nutrients

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Background. Bone Health and Osteoporosis Foundation (BHOF) reports that as of 2023, approximately 10 million of older Americans have osteoporosis and another 44 million have low bone density. Osteoporosis is a serious handicap for the elderly and, in particular, for estrogen-deficient postmenopausal women, as it increases the risk of debilitating bone weakness and fractures. The BHOF recommendations for prevention of osteopenia, osteoporosis and bone fractures are to perform weight-bearing and muscle-strengthening exercises and to take recommended amounts of daily calcium and vitamin D. Methods. The purpose of this review is to describe and discuss recent evidence-based research on how to effectively utilize timing of exercise and calorie intake for stimulation of postmenopausal bone anabolism, and to provide this new information in the form of specific and actionable recommendations. Results. The five evidence-based recommendations are as follows: 1. Select an appropriate circadian time of day for exercise; 2. Increase walking speed to raise the movement momentum; 3. Eat a weight-maintenance meal one or two hours before the exercise bout; 4. Sustain the duration of walking activity (impulse) for 40 to 45 min; and 5. Repeat effective exercise stimulus 7 to 8 h after the first one to double the anabolic effect. Osteogenesis can also be increased with subthreshold mechanical loading, where needed, under several special circumstances. Conclusions. This review should provide pragmatic actionable pointers on how to utilize the idiosyncratic bone responsiveness to timing of movement and meals to prevent osteoporosis and encourage research toward a better understanding of how bone detects adequacy of a mechanical stimulus and determines duration of necessary rest to recover its sensitivity to mechanical stimulation and nutrients.

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Feeding intervention potentiates the effect of mechanical loading to induce new bone formation in mice

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 4 publications

References 50 publications

Idiosyncratic bone responses to blood flow restriction exercise: new insights and future directions

Idiosyncratic bone responses to blood flow restriction exercise: new insights and future directions

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

How to Suppress Mineral Loss and Stimulate Anabolism in Postmenopausal Bones with Appropriate Timing of Exercise and Nutrients

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