Metabolic Profile of Bone in Professional Athletes

Physical Activity Clinical Trial

— SportMarkers  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03386981
• Other study ID #: SportMarkers
• Status: Recruiting
• Phase: N/A
• First received: December 5, 2017
• Last updated: January 4, 2018
• Start date: February 4, 2016
• Est. completion date: February 4, 2019

Study information

• Verified date: January 2018
• Source: Istituto Ortopedico Galeazzi
• Contact: Giovanni Lombardi, PhD
• Phone: 0039026621
• Email: giovanni.lombardi[@]grupposandonato.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 4, 2019
• Est. primary completion date: February 4, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Disease, Metabolic
• Bone Diseases
• Bone Diseases, Metabolic
• Metabolic Diseases
• Physical Activity

Intervention

Other:
• blood and saliva tests
Blood and saliva will be tested for: bone turnover markers, cytokines, chemokines, adipokines, myokines and hormones regulating bone and energy metabolism

Locations

Country	Name	City	State
Italy	Istituto Ortopedico Galeazzi	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Ortopedico Galeazzi

Country where clinical trial is conducted

Italy, 

References & Publications (18)

Allison RJ, Farooq A, Hamilton B, Close GL, Wilson MG. No association between vitamin D deficiency and markers of bone health in athletes. Med Sci Sports Exerc. 2015 Apr;47(4):782-8. doi: 10.1249/MSS.0000000000000457. — View Citation

Banfi G, Lombardi G, Colombini A, Lippi G. Bone metabolism markers in sports medicine. Sports Med. 2010 Aug 1;40(8):697-714. doi: 10.2165/11533090-000000000-00000. Review. — View Citation

Chilibeck PD, Sale DG, Webber CE. Exercise and bone mineral density. Sports Med. 1995 Feb;19(2):103-22. Review. — View Citation

Corsetti R, Barassi A, Perego S, Sansoni V, Rossi A, Damele CA, Melzi D'Eril G, Banfi G, Lombardi G. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers — View Citation

Fang S, Deng Y, Gu P, Fan X. MicroRNAs regulate bone development and regeneration. Int J Mol Sci. 2015 Apr 13;16(4):8227-53. doi: 10.3390/ijms16048227. Review. — View Citation

Grasso D, Corsetti R, Lanteri P, Di Bernardo C, Colombini A, Graziani R, Banfi G, Lombardi G. Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race. Scand J Med Sci Sports. 2015 Feb;25(1):70-80. doi: 10 — View Citation

Lombardi G, Colombini A, Freschi M, Tavana R, Banfi G. Seasonal variation of bone turnover markers in top-level female skiers. Eur J Appl Physiol. 2011 Mar;111(3):433-40. doi: 10.1007/s00421-010-1664-7. Epub 2010 Sep 29. — View Citation

Lombardi G, Corsetti R, Lanteri P, Grasso D, Vianello E, Marazzi MG, Graziani R, Colombini A, Galliera E, Corsi Romanelli MM, Banfi G. Reciprocal regulation of calcium-/phosphate-regulating hormones in cyclists during the Giro d'Italia 3-week stage race. — View Citation

Lombardi G, Lanteri P, Colombini A, Banfi G. Blood biochemical markers of bone turnover: pre-analytical and technical aspects of sample collection and handling. Clin Chem Lab Med. 2012 Feb 3;50(5):771-89. doi: 10.1515/cclm-2011-0614. Review. — View Citation

Lombardi G, Lanteri P, Colombini A, Mariotti M, Banfi G. Sclerostin concentrations in athletes: role of load and gender. J Biol Regul Homeost Agents. 2012 Jan-Mar;26(1):157-63. — View Citation

Lombardi G, Lanteri P, Graziani R, Colombini A, Banfi G, Corsetti R. Bone and energy metabolism parameters in professional cyclists during the Giro d'Italia 3-weeks stage race. PLoS One. 2012;7(7):e42077. doi: 10.1371/journal.pone.0042077. Epub 2012 Jul 2 — View Citation

Lombardi G, Perego S, Luzi L, Banfi G. A four-season molecule: osteocalcin. Updates in its physiological roles. Endocrine. 2015 Mar;48(2):394-404. doi: 10.1007/s12020-014-0401-0. Epub 2014 Aug 27. Review. — View Citation

Lombardi G, Sanchis-Gomar F, Perego S, Sansoni V, Banfi G. Implications of exercise-induced adipo-myokines in bone metabolism. Endocrine. 2016 Nov;54(2):284-305. Epub 2015 Dec 30. Review. — View Citation

Murphy NM, Carroll P. The effect of physical activity and its interaction with nutrition on bone health. Proc Nutr Soc. 2003 Nov;62(4):829-38. Review. — View Citation

Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005 Nov;26(4):97-122. — View Citation

Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D. Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol (1985). 2004 Jul;97(1):119-29. — View Citation

Snow CM, Williams DP, LaRiviere J, Fuchs RK, Robinson TL. Bone gains and losses follow seasonal training and detraining in gymnasts. Calcif Tissue Int. 2001 Jul;69(1):7-12. Epub 2001 Jun 5. — View Citation

Walsh MC, Choi Y. Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. Front Immunol. 2014 Oct 20;5:511. doi: 10.3389/fimmu.2014.00511. eCollection 2014. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	myokines, adipokines, cytokines, chemokines, hormones regulating bone and energy metabolism	different markers will be assayed depending on the group of subjects	0-36 Months