Metabolic Profile of Bone in Professional Athletes

Study Overview
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Brief Summary
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Physical activity is a key stimulus for bone metabolism through both direct mechanisms (e.g., as a result of the applied load and/or impact) and indirect mechanisms (e.g., the activation of several metabolic pathways and the production of several mediators and effectors that have systemic effects). However, different kinds of physical activity exert different effects on bone and endocrine system. Aim of the study is to investigate the effects of different kinds of physical activity on bone metabolism and on the relationships existing between bone metabolism, energy metabolism, hormone profile, and organ functionality.

Detailed Description
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Genetics explain about 70% of the inter-individual variance of bone mineral density (BMD) but maintenance and acquisition of bone mass strikingly depend on environmental factors as diet, calcium intake (in both quantitative and qualitative terms), and physical activity (PA). Among these, the biomechanical load generated by different kinds of PA represents the most important physiological stimulus able to increase bone mass and density. Bone is a metabolically active tissue that undergoes to continuous remodeling throughout the coupling of resorption (operated by osteoclasts) and formation (operated by osteoblasts). Osteocytes, the quiescent form of osteoblasts, regulate the activity of the other two cell types and directly respond to load. Under normal conditions, resorption and formation are strikingly coupled and this guarantees an equilibrium between old bone matrix removal and new matrix deposition. This equilibrium is dependent upon several hormones and local mediators (e.g., cytokines, myokines, adipokines). Physiological (e.g., growth, aging, PA) and pathological conditions (e.g., metabolic diseases, bed rest, drugs) inbalance this equilibrium towards one side and, hence, affect bone mass. Regarding PA, for example, it is known that weight-bearing aerobic activity has positive effects on BMD and, hence, it is considered a preventive strategy against post-menopausal bone loss. Differently from radiological imaging, that gives information about established architectural changes happened at a specific site in bone, biochemical and molecular markers of bone turnover give an instantaneous picture of the metabolic status of bone cells and, possibly, their immediate response to a stimulus. Other than the bony response, PA activates several endocrine responses and particularly, the whole set of responses needed for managing the energy stores and to save the most nobile functions (e.g., brain, hearth). Hence, bone is subjected to the endocrine regulation of energy usage but, as recently discovered, being it the primary mechanosensor of load, it acts itself as an endocrine organ able to signal to other tissues and organs the changing environmental conditions. Although several molecular aspects about the effects of PA on bone metabolism and the bone-energy cross-talk, a number of unresolved questions still exists. The study of different physiological models (i.e., athletes belonging to different disciplines) might allow the identification of common mechanisms regulating the response to PA and, from another side, to understand the physiological response to different stresses applied onto the muscle-skeletal apparatus. The general aim of this study is to investigate the effects of different kinds of professional physical activity on bone metabolism and the relationship between bone metabolism, energy metabolism, hormone profile, and organ functionality. The primary aim is to deepen the knowledge of the molecular mechanisms by which PA modulates bone metabolism. Specifically, this study will evaluate the bony effects of specific kinds of PA, over the time (over an entire season, over consecutive seasons, during different phases of a season), as well as the direct comparison of the bony effects of different kinds of PA and training. Secondary aims are: to contextualize the modification of bone cell metabolism within the whole-body homeostatic profile. Particularly, markers of the energy metabolism and the inflammatory status (hormone, myokines, adipokines, cytokines, chemokines) will be evaluated. focused case-control studies will be conducted by including as little-active control the people belonging to the technical staff of the cooperating teams. This is a perspective monocentric pilot study with different components: longitudinal perspective: repeated evaluations over the time case-control: comparison among different populations of athletes and technical staff Being based on already planned blood drawings (as independently decided by the team physicians), and since the researchers will use only waste material derived from these sample, the overall implant of the study is observational.

Official Title
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Study of the Metabolic Profile of Bone in Professional Athletes as a Function of the Kind of Physical Activity Performed

Conditions
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Bone Disease, Metabolic, Physical Activity

Intervention / Treatment
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* Other: blood and saliva tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >/= 18 yo healthy status caucasians Exclusion Criteria: < 18 yo pregnancy status ongoing or previous (<5 years) neoplasia acute or chronic inflammatory pathologies primary metabolic diseases of bone recent bone fractures (< 6 months) chronic drugs recent drugs administration (< 2 months) for non steroidal anti-inflammatory drugs (NSAIDs) and steroids anxious-depressive conditions inability to understand the information given by the recruiting physician

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Professional athletes: Professional athletes belonging to different discipline | Other: blood and saliva tests<br>* Blood and saliva will be tested for: bone turnover markers, cytokines, chemokines, adipokines, myokines and hormones regulating bone and energy metabolism<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone turnover markers | different markers of bone turnover (osteocalcin, N-terminal type I pro-collagen, beta-crosslaps, osteopontin, bone-alkaline phosphatase, tartrate-resistant acid phosphatase 5b) will be tested depending on the group of subjects considered time-by-time | 0-36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myokines, adipokines, cytokines, chemokines, hormones regulating bone and energy metabolism | different markers will be assayed depending on the group of subjects | 0-36 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Energy metabolism, Homeostasis, Bone turnover markers