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Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

ABSTRACT: Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones.

SUBMITTER: Sroga GE

PROVIDER: S-EPMC4309541 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

Sroga Grażyna E GE Wu Ping-Cheng PC Vashishth Deepak D

PloS one 20150128 1

Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent mann ...[more]

PMID: 25629402

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Project description:Background and objectivesTrabecular bone score is a gray-level textural measure obtained from dual energy x-ray absorptiometry lumbar spine images that provides information independent of areal bone mineral density. The association between trabecular bone score and incident fractures in adults with reduced kidney function and whether this association differs from that of adults with normal kidney function are unknown.Design, setting, participants, & measurementsWe included 1426 participants ages ≥40 years old (mean age of 67 years) in the community-based Canadian Multicentre Osteoporosis Study. We stratified participants at cohort entry (2005-2008) by eGFR (eGFR<60 ml/min per 1.73 m2 [n=199; 72.4% stage 3a, 25.1% stage 3b, and 2.5% stage 4] versus ≥60 ml/min per 1.73 m2 [n=1227]). Trabecular bone score was obtained from lumbar spine (L1-L4) dual energy x-ray absorptiometry images, with a lower trabecular bone score representing worse bone structure. Over an average of 4.7 years follow-up (maximum follow-up of 5 years), we documented incident fragility (low-trauma) fracture events (excluding craniofacial, foot, and hand sites). We used a modified Kaplan-Meier estimator to determine the 5-year probability of fracture. Cox proportional hazard regression per SD lower trabecular bone score expressed the gradient of fracture risk.ResultsIndividuals with an eGFR<60 ml/min per 1.73 m2 who had a trabecular bone score value below the median (<1.277) had a significantly higher 5-year fracture probability than those above the median (18.1% versus 6.2%; P=0.01). The association between trabecular bone score and fracture was independent of bone mineral density and other clinical risk factors in adults with reduced and normal kidney function (adjusted hazard ratio per SD lower trabecular bone score: eGFR<60 ml/min per 1.73 m2: adjusted hazard ratio, 1.62; 95% confidence interval, 1.04 to 2.51; eGFR≥60 ml/min per 1.73 m2: adjusted hazard ratio, 1.44; 95% confidence interval, 1.13 to 1.83).ConclusionsLower lumbar spine trabecular bone score is independently associated with a higher fracture risk in adults with reduced kidney function. Additional study is needed to examine the association between trabecular bone score and fractures in individuals with diagnosed CKD-mineral and bone disorder.

Project description:Fractures associated with bone fragility in older adults signal the potential for secondary fracture. Fragility fractures often precipitate further decline in health and loss of mobility, with high associated costs for patients, families, society and the healthcare system. Promptly initiating a coordinated, comprehensive pharmacological bone health and falls prevention program post-fracture may improve osteoporosis treatment compliance; and reduce rates of falls and secondary fractures, and associated morbidity, mortality and costs.This pragmatic, controlled trial at 11 hospital sites in eight regions in Quebec, Canada, will recruit community-dwelling patients over age 50 who have sustained a fragility fracture to an intervention coordinated program or to standard care, according to the site. Site study coordinators will identify and recruit 1,596 participants for each study arm. Coordinators at intervention sites will facilitate continuity of care for bone health, and arrange fall prevention programs including physical exercise. The intervention teams include medical bone specialists, primary care physicians, pharmacists, nurses, rehabilitation clinicians, and community program organizers.The primary outcome of this study is the incidence of secondary fragility fractures within an 18-month follow-up period. Secondary outcomes include initiation and compliance with bone health medication; time to first fall and number of clinically significant falls; fall-related hospitalization and mortality; physical activity; quality of life; fragility fracture-related costs; admission to a long term care facility; participants' perceptions of care integration, expectations and satisfaction with the program; and participants' compliance with the fall prevention program. Finally, professionals at intervention sites will participate in focus groups to identify barriers and facilitating factors for the integrated fragility fracture prevention program.This integrated program will facilitate knowledge translation and dissemination via the following: involvement of various collaborators during the development and set-up of the integrated program; distribution of pamphlets about osteoporosis and fall prevention strategies to primary care physicians in the intervention group and patients in the control group; participation in evaluation activities; and eventual dissemination of study results.

Dataset Information

Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

Publications

Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

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