Background The effect of physical exercise on bone metabolism has been thoroughly discussed and a positive correlation between physical exercise and Bone Mineral Density (BMD) has been established. At the one hand many issues have not been entirely clarified: the impact of exercise on biochemical (especially novel like RANK/RANKL/OPG) markers of bone metabolism and mainly the type of exercise (high or low impact exercise, intensity of training). At the other hand, it is interesting to note that the aforementioned pathway is related not only to bone (and musculo-skeletal in general) metabolism, but also to cardiovascular metabolism and it is thought to be one of the possible causative links of the positive correlation between osteoporosis and cardiovascular disease.

Methods The literature search was performed via the internet using the Medline, Scopus and Cochrane database. The key words which were searched in the abstracts were the terms “RANK”, “RANKL”, “OPG”, “physical exercise”, “sports”, “osteoporosis markers”, “bone turnover markers”.

Results Our systematic review of the literature revealed 7 (seven) papers concerning the relationship of RANK/RANKL/OPG pathway with sports and physical exercise. The general trend observed in most papers was that physical exercise and sports activity have a positive impact in the RANK/RANKL/OPG pathway. It is important to note that extremely intense exercise (marathon running and beyond) might have detrimental effect on the pathway thus influencing negatively bone metabolism. Four (4) papers were focused on fit persons and intense training whether the rest three (3) papers were focused on exercise for obese or postmenopausal individuals.

Conclusions The role of RANK/RANKL/OPG pathway in both bone/musculo-skeletal and cardiovascular metabolism has rather recently been studied. The possible positive influence of exercise on this pathway might have valuable positive effect on both metabolical systems. The further clarification of the exact pattern of exercise that might have the most significant impact on the RANK/RANKL/OPG pathway is needed, but our review points out that high impact (but not extremely intense) exercise is more beneficiary.