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TYPE Review
PUBLISHED 15 December 2023
DOI 10.3389/fped.2023.1226524

Musculoskeletal health in children

and adolescents
EDITED BY
Rashmi Ranjan Das,
Maria Felicia Faienza1*, Flavia Urbano2, Mariangela Chiarito1,
All India Institute of Medical Sciences
Bhubaneswar, India Giuseppe Lassandro2 and Paola Giordano3
1
REVIEWED BY Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari
Nirmal Kumar Mohakud, “Aldo Moro”, Bari, Italy, 2Giovanni XXIII Pediatric Hospital, Bari, Italy, 3Department of Interdisciplinary
KIIT University, India Medicine, University of Bari “Aldo Moro”, Bari, Italy
Joseph John,
All India Institute of Medical Sciences
Bhubaneswar, India
The purpose of this narrative review was to investigate the key determinants of
Eero Haapala, musculoskeletal health in childhood and adolescence, with particular attention
University of Jyvaskyla, Finland to the role of physical activity. First, we examined the importance of bone
Vedran Hadzic, modeling and remodeling in maintaining the bone health and the integrity and
University of Ljubljana, Slovenia
mechanical characteristic of the skeleton. In addition, we reported the evidence
*CORRESPONDENCE on an appropriate calcium and vitamin D intake, as well as local load variation in
Maria Felicia Faienza
achieving proper peak bone mass. Proteomic and transcriptomic studies
[Link]@[Link]
identified the skeletal muscle “secretoma”, consisting of several myokines
RECEIVED 21 May 2023
involved in endocrine and paracrine functions. Among these, we explored the
ACCEPTED 24 November 2023
PUBLISHED 15 December 2023
role of irisin, a myokine involved in the muscle-bone crosstalk, and in the
regulation of metabolic pathways. It is known that physical activity during
CITATION
Faienza MF, Urbano F, Chiarito M, Lassandro G
growing positively impacts on skeleton and can protect by bone loss in
and Giordano P (2023) Musculoskeletal health adulthood. However, there are still concerns about the optimal interval duration
in children and adolescents. and exercise intensity, particularly at the pubertal growth spurt which represents
Front. Pediatr. 11:1226524. a window of opportunity to increase skeletal strength. We reported data from
doi: 10.3389/fped.2023.1226524
clinical trials performed in the last 5 years analyzing the impact of the type and
COPYRIGHT timing of physical activity during childhood on skeletal development. Finally, we
© 2023 Faienza, Urbano, Chiarito, Lassandro
and Giordano. This is an open-access article
reported recent data on the significance of physical activity in some rare diseases.
distributed under the terms of the Creative
Commons Attribution License (CC BY). The use, KEYWORDS
distribution or reproduction in other forums is
permitted, provided the original author(s) and musculoskeletal health, children, adolescents, irisin, physical activity, sports, rare diseases
the copyright owner(s) are credited and that the
original publication in this journal is cited, in
accordance with accepted academic practice.
No use, distribution or reproduction is Introduction
permitted which does not comply with these
terms.
The coordinated action of osteoblasts, osteoclasts and osteocytes directs bone modelling
and remodeling (1). The former process promotes longitudinal growth of the bones and
adaption of the skeleton to mechanical stress, while the latter removes old or damaged
bone. Thus, bone remodeling maintains the strength of the skeleton over the course of
life. During bone modeling, osteoclasts and osteoblasts work individually, while when
bone remodeling occurs, bone resorption and bone formation are coupled into bone
remodeling units (1). With ageing, the skeleton undergoes substantial architectural and
metabolic modifications, possibly predisposing to osteoporosis and increased risk of
fractures. Although osteoporosis is typically associated with ageing, the contributing
factors can act already during growth. Hence, the impairment of bone health occurs
during the developmental age, when over a third of bone mass is accumulated, reaching a
peak around the second decade of life (2). The conjunction of this critical period of bone
growing with bone loading and physical activity represents a “window of opportunity” to
develop a healthy skeleton (3). Environmental factors, such as diet and exercise, impact
20%–40% of peak bone mass in adulthood. Physical activity is recognized as a means of
health promotion and disease prevention throughout the life (4), although there are few
specific recommendations in infancy and childhood, which represent periods of life

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wherein healthy behaviors can have lasting metabolic and Bone is also a living tissue as old and damaged bone is removed
behavioral consequences (5, 6). An adequate development of and replaced with newly formed bone. This process of bone renewal
skeletal muscles during these two periods may have long-term and repair is called “bone remodeling”, and it is due to the action of
consequences on body composition and inclination to engage in osteoclasts and the osteoblasts (19). In healthy bones, the osteoclast
physical activity throughout life (7). Moreover, although muscle and osteoblast activity are balanced. When this process becomes
fiber composition is genetically determined (8), early physical unbalanced, so that the bone reabsorbing happens faster than bone
training can play an important role in “fiber reprogramming” replacing, bones can become thin and fragile. Bone remodeling is
(9). Bone mineral content (BMC) and bone mineral density determinant to maintaining the integrity and the mechanical
(BMD) increase in response to repetitive and variable loading properties of the skeleton (20). This balance is controlled by
activities through increased force and strain. Moderate or intense the RANK/RANKL/osteoprotegerin (OPG) and Wnt/β-catenin
physical activity and several sports inducing greater than normal pathways which regulate osteoclastogenesis and osteoblastogenesis,
bone load are critical for the achievement of bone strength (10). respectively (21). Bone remodeling’s alterations have been observed
Considering this, the implementation of exercise interventions in several congenital and acquired pediatric disorders (22).
during childhood and adolescence could maximize peak bone Particularly, in subjects with obesity, the condition of low-grade
mass and consequently slow down the onset of osteoporosis. inflammation activates osteoclasts by up regulating the production
In this narrative review, we focused on the key determinants of of RANKL and other inflammatory cytokines, and inhibiting
musculoskeletal health in pediatric age, and we reported the most osteoblastogenesis, thus accelerating bone resorption (23).
recent studies on the impact of physical activity on bone strength
during childhood and adolescence. Furthermore, we reported the
effects of physical activity in some rare diseases in which has Key determinants of bone health in
been demonstrated an improving of bone health. pediatric age
According to the National Osteoporosis Foundation, bone
The concept of bone health: bone health is the consequence of both genetic and environmental factors
modeling, bone remodeling and peak (16). Genetic factors impact skeletal development for approximately
bone mass 60%–80% (16, 24). Numerous loci linked with low bone mass and
osteoporosis have been recognized by Genome Wide Association
Bone contains an organic component represented by (GWA) studies (25), although few studies have been conducted in
collagenous and non-collagenous proteins and cells, and a children. Environmental factors, such as diet and physical activity
mineral part of hydroxyapatite (11). are responsible for 20%–40% of the peak bone mass (16).
Bone cells include osteoblasts, the bone forming cells, which
originate from mesenchymal stem cells; osteocytes, differentiated
from osteoblasts and inserted in the bone matrix; and osteoclasts, Calcium and vitamin D intake
the bone reabsorbing cells, differentiated from hematopoietic
progenitors. Skeletal growth is the result of the bone expansion of Adequate calcium and vitamin D intake, in association with
cortical bone, and bone growing through endochondral ossification physical activity, maximizes peak bone mass and reduces the risk
(12). This process called “bone modeling”, which starts during fetal of osteoporosis and fractures in childhood and adulthood (26).
life and proceeds until epiphyseal fusion, is particularly sensitive to The National Institutes of Health provided the recommendations
mechanical load, supporting the significance of physical activity for calcium intake and calcium content of foods (27). The
during growth (13). The acquisition of bone mass occurs slowly recommended dietary allowance (RDA) for calcium is 1,300 mg
throughout childhood, while it proceeds quickly with the onset of for subjects aged 9–18 years (24). Calcium intakes <600 mg/day,
puberty and at the time of growth spurt. Peak bone mass occurs at may expose to substantial risks of inadequate mineralization (28).
12.5 ± 0.90 years in girls and 14.1 ± 0.95 years in boys (13). Intakes <400 mg/day, especially when combined with low
The changes of bone sizes and thickness occur more rapidly vitamin D levels, represent a risk of rickets and fractures.
after epiphyseal fusion and continue until the attainment of peak A systematic review evaluated the methods and quality of
bone mass during the second decade of life (13). However, the guidelines on calcium and vitamin D supplementation in healthy
changes of bone shape and bone composition occurring during children (29). The authors observed significant variations on
pubertal development, influence the bone strength (14). Thus, calcium and vitamin D recommendations across 24 guidelines
the “bone bank” is built in the first two decades of life, and most and consensus among countries around the world. The
of the risk of osteoporosis depends on what occurs in this recommended calcium intake for children ranged from 400 to
period. Peak bone mass represents a key determinant of bone 1,150 mg/day. Additionally, data on vitamin D supplementation
health and risk of osteoporosis in adulthood (15). Indeed, it is at different ages, vitamin D type, and sunlight exposure were
strictly related to bone strength that in turn is determined by conflicting across studies (29).
bone mass, bone density, microarchitecture, micro repairs and In a previous study, the supplementation of 800 mg of calcium
bone geometry. The attainment of a suitable peak bone mass can and 400 IU of vitamin D daily for 6 months resulted in increases in
prevent fractures both in childhood and adulthood (16–18). cortical and trabecular bone (30). In contrast, a meta-analysis

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demonstrated that rising dairy products in the diet significantly These conformational changes activate a signaling cascade which
improved bone mineral content only in children with low baseline determines bone accretion at the site of deformation (34). To obtain
calcium intake (31). Thus, calcium and vitamin D supplementation an osteogenic response, the bones must undergo such a deformation
would appear to have little influence on bone health. that exceeds the usual deformation threshold. The threshold varies
between individuals and bone sites according to physical activity
habits, age, hormone levels, and other metabolic factors (35). Thus,
Physical activity and musculoskeletal health children and adolescents may have a different response to
comparable mechanical loads: inactive children may improve bone
Muscle and bone interact through both anatomically and mass in response to low-impact loads, while active children will
mechanically, as well as through paracrine and endocrine signals need a greater mechanical load (36). The response is regional,
(32). As regards the mechanical interaction, bones represent a site allowing specific bone to meet increasing loading requirements.
of attachment for muscles and, in turn, skeletal muscles facilitate Indeed, a greater bone density has been observed in the dominant
locomotion by giving strength to the bone; hence, muscles are the arms of baseball, tennis, and squash players with side-to-side
primary source of tension for bones. This is testified by the fact variations ranging from 8% to 22% (37). It has also been
that astronauts experience bone loss and muscle atrophy as they demonstrated that the magnitude of loading and deviations from
are exposed to an environment that lacks gravity, such as space; as normal loading patterns are more important for bone modeling
they return to the ground, the speed of recovery that they than stimulus duration. Mechanical loading induced by physical
experience in their muscle mass exceeds that of bone, suggesting activity is necessary to stimulate bone modeling as it provides the
muscle contraction is essential for bone recovery. Thus, stimulus required to develop a robust skeleton (38). Mechanical
immobility, aging and other diseases can cause changes in both loads of 3.5 g-force for 3 days/week with 100 loads per session and 7
bone and muscle mass. In addition, skeletal muscles produce months of intervention determine an osteogenic effect. Furthermore,
factors which regulate bone metabolism. These muscle-secreted the mechanical loading stimulates the Wnt/-catenin signaling
factors named “myokines”, include myostatin, interleukin (IL)-6, pathway, which in turn downregulates osteoclastogenesis and
IL-7, IL-15, IGF-1, FGF-2, irisin, and BAIBA (33). osteoclast activity, thus influencing bone remodeling (39).
Physical activity has a positive impact on musculoskeletal health. Regarding the muscle response to exercise, the increased load
The skeleton responds to physical stress quickly and bone contributes to muscle size and strength, primarily as a result of
remodeling starts. Exercise leads to bone adaptation by cellular muscle cell hypertrophy rather than hyperplasia (40). The
mechano transduction (34). Quickly, upon exercise, the increase in muscle mass results in an inhibition of myostatin
mechanosensors located through the cells, such as stretch-activated which hence regulates muscle mass. Nonetheless, it is not yet
ion channels and integrins, modify their conformation (Figure 1). clear why only the muscles under load increases muscle mass,

FIGURE 1
Bone adaptation to exercise. MSC, mesenchimal stem cells; RANKL, receptor activator of nuclear factor kappa-Β ligand; RANK, RANKL/OPG receptor;
DKK1, dickkopf-1; OPG, osteoprotegerin; TNFα, tumor necrosis factor alpha.

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while the decrease in circulating levels of myostatin resulting from biochemical markers of bone formation and irisin increase in
exercise should affect the whole body (41). This suggests that other bone tissue after 2 weeks of free wheel-running exercise (56).
unknown soluble factors produced by skeletal muscles after Exercise-induced irisin, or exogenous administration of irisin, can
exercise may contribute to increases in muscle size and strength. prevent bone loss, as demonstrated in hind-limb suspended mice
On the other hand, during aging and immobility, the (47). However, the true effect of physical activity in promoting
physiological changes caused by skeletal unloading determine the secretion of irisin is still debated. Some studies reported a huge
onset of sarcopenia, characterized by a decrease in the size effect of exercise in promoting irisin release (45–47), while others
(atrophy) and number (hypoplasia) of muscle fibers. Therapeutic did not document any changes in irisin levels after both acute
strategies to treat sarcopenia are currently aimed at targeting the and chronic exercise (57, 58). Probably, this disagreement
myostatin/activin signaling mechanism, on the basis of the depends on the type and duration of exercise, and the type of
principle of “muscle-bone crosstalk”. assay for irisin assessment. Conversely, serum irisin levels has
been identified as a predictive biomarker for sarcopenia (59, 60).
Moreover, irisin can activate the differentiation of osteoblasts
Irisin: a myokine involved in the crosstalk under microgravity conditions by promoting the secretion of β-
between muscle and bone catenin protein and increase OPG levels (61).
Furthermore, body composition is also a relevant factor for
Irisin is a myokine firstly identified for its role in inducing musculoskeletal health, in fact age-related loss of skeletal muscle
browning of white adipose tissue and increasing energy (sarcopenia) is often associated with obesity (“sarcopenic
expenditure (42). Then, both in human and mouse it has been obesity”). Increased myostatin levels have been shown to result in
demonstrated that irisin is also involved in glucose homeostasis low levels of muscle tissue mass and at the same time inhibit
by promoting liver glycogen synthesis and inhibiting insulin signaling, muscle mitochondrial biogenesis, lipid
gluconeogenesis (43, 44). Further role of this myokine in oxidation and energy expenditure, therefore this myokine could
cognitive functions, learning, and memory has been recognized play a key role in sarcopenic obesity (62).
(45). In humans irisin represents a link between physical activity
and metabolic homeostasis, as it mediates the beneficial effects of
exercise on glucose and lipid metabolism, and it provides to The impact of exercise interventions
maintain musculoskeletal homeostasis (46, 47). This evidence on bone strength
strengthens the hypothesis that muscle can be considered an
endocrine organ. Studies of proteomics and transcriptomics Physical exercise and healthy eating habits during growing
identified the composition of the skeletal muscle “secretome” increases the probabilities of accruing bone, and potentially
leading to identification of several myokines (48). Most of the delays osteoporosis in adulthood. Literature data on the
proteins identified in cultures of myotube were predicted as effectiveness of physical activity interventions in childhood and
putative secreted proteins, pointing out that skeletal muscle acts adolescence are heterogeneous.
as an endocrine organ. Functional analysis suggests their role in A meta-analysis of 27 studies found a significant effect of
skeletal muscle as paracrine regulators of oxidation, hypertrophy, weight bearing activity on BMC and BMD (63). Children
angiogenesis, and extracellular matrix (49). These myokines are involved in school-based exercise programs for 9 months showed
also involved in the regulation of body weight, inflammation, higher whole-body, femoral neck and total hip BMC compared
insulin sensitivity, and cognitive function. Thus, muscle derived with their counterparts not involved in exercising (64).
regulatory RNAs could represent a novel frontier for the Furthermore, a persistence of the benefits 3 years after ceasing
treatment of chronic diseases. Exercise as downhill running, the intervention has been observed. Longitudinal studies reached
eccentric exercise, and resistance training determine a systemic different conclusions regarding whether the osteogenic effect
marked cytokine response, with a higher degree of muscle depends on continuing physical activity into adulthood (65–67).
involvement (50). However, a strong elevation of several Subject who practiced sports during childhood showed a greater
cytokines and chemokines in skeletal muscle has been described hip BMC in adulthood than their sedentary counterparts (68). A
after exercise with long duration or high intensity (51), while a cross-sectional cohort study investigated the longstanding effects
less evident or absent response has been observed after moderate of soccer on BMD and fracture risk, demonstrating a higher
intense physical activity (52). The direct involvement of irisin in BMD, and lower risk of fractures in the athletes 30 years after
bone metabolism, by inducing the differentiation of bone retirement (69).
marrow stromal cells into mature osteoblasts, has been A recent study demonstrated that the age at which children first
demonstrated (53). In healthy children, irisin serum levels start walking might affect their bone strength in later life (70).
positively correlate with bone mineral status and negatively with Ireland et al., examined the association between walking age and
inhibitors of Wnt signaling pathway (54). Furthermore, high bone mineralization by Dual-energy x-ray absorptiometry (DXA)
irisin levels correlate with a better glycemic control and bone and Quantitative Computed Tomography (pQCT) in subjects
health in children affected with type 1 diabetes (55). Zhang et al., aged between the ages of 60 and 64 years (70). Later
confirmed the positive regulatory effect of irisin on bone during independent walking age has been associated with lower BMC,
physical exercise, as they found an increased expression of suggesting that early mechanical loading on the skeleton might

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influence bone strength development. A systematic review of the the peripubertal phase, the period immediately preceding puberty
literature evaluated the changes induced on bone mineralization represents a “window of opportunity” in which the skeleton is
by ball games, dancing, jumping and other physical activities. more sensitive to mechanical stress (35).
The results of this study showed that weight-bearing exercise in
childhood had a positive effect on bone strength, while exercise
performed during prepubertal and peripubertal age caused an The impact of physical activity on
increase in bone mineral accrual (71). These results have been musculoskeletal health
confirmed by other studies which observed that, although
osteogenesis and bone anabolism are more pronounced during In this section we reported the most important clinical trial
conducted in the last 5 years that investigated weight-bearing
physical activities improving musculoskeletal health. Table 1
TABLE 1 Clinical trial investigated weight-bearing physical activities shows the recent data on the effects of sport interventions on
improving musculoskeletal health.
bone mineralization.
Study Participants Exercise Bone The PRO-BONE study explored the effect of 12-months
intervention mineralization involvement in osteogenic (football) and non-osteogenic
details outcomes (swimming and cycling) sports in 116 adolescent male athletes
Vlachopoulos 116 males aged 37 swimmers - Footballers had aged 13.1 years ±1.0 (72). The authors observed that after 12-
et al., 2017 13.1 0.1 years 37 footballers higher
(64) evaluated at 28 cyclists improvement in
months participation, footballers showed significantly higher
baseline and at 14 controls BMC compared to BMC at most skeletal sites than swimmers and cyclists. A
12-month (follow Duration: more cyclists and previous study demonstrated that 8 months of sport-specific
up) than 3 h per week swimmers
- No significant
training improved total body BMD by 2.9% in footballers, but
difference between not in swimmers (73). These results confirm previous studies
swimmers and that reported that swimming and cycling have no effect on bone
cyclists was found
strength, possibly due to the low ground reaction forces
Larsen et al., 295 Danish school 96 small-sided ball - Both training types produced during exercise (74, 75). Therefore, football improves
2016 (68) children aged 8– game group (SSG) resulted in higher
10 years 83 strength training change scores in
bone strength compared to non-osteogenic sports which should
group (CST) postural balance be combined with weight-bearing activities.
- 116 controls - SSG group had The randomized controlled trial FIT FIRST involving 295
Duration: 3 × higher change
40 min/week over scores in leg aBMD
Danish children aged between 8 and 10 years evaluated the effects
10 months compared with on bone mineralization and muscular structure after 10 months of
CST and controls high-intensity school training (3 × 40 min/week) consisting of
team soccer and other ball games or circuit training with weight-
Bielemann 4,106 adolescents Two groups: - Time spent in MPA
et al., 2019 from the 1993 - 150 min/week of at 11 and 15 years bearing exercises (76). The authors observed that both high-impact
(69) Pelotas Birth moderate was not associated school interventions improved musculoskeletal health in children.
Cohort Physical physical activity with aBMD The observations confirmed that in childhood the skeleton adapts
activity assessed at (MPA) improvement
11, 15, and 18 - at least 75 min/ - VPA at all time
to the physiological changes induced by physical training and
years of age by week of vigorous points was suggested that both high-intensity interval program and odd-
self-report and at physical activity positively related impact training may improve musculoskeletal health.
18 years by (VPA) to aBMD
accelerometry improvement in
Bieleman et al., examined the relations between physical
boys activity and areal BMD (aBMD) according to intensity of
- VPA was related to exercise in several sports: outdoor soccer, indoor football,
higher a BMD at 18
athletics, basketball, volleyball, tennis, handball, dance,
years of age in girls
gymnastics, martial arts, swimming, trapper, and playing bat
Zribi et al., 39 adolescents 20 prepubescent At follow-up,
2022 (74) aged 11 ± 1 years boys, volleyball volleyball players
(77). Vigorous physical activity improved aBMD more than
at baseline and at players 19 controls gained more BMD in moderate physical activity, especially in boys. In particular, the
12-month (follow Duration: for whole body than involvement in vigorous activities from the middle to the end of
up) volleyball players 4– controls; a close
6 h of training plus correlation was
adolescence seems to be related to higher aBMD. Other studies
one competition observed between the described differences induced by physical activities on aBMD
game a week for at increment of whole between boys and girls (78–80). The better impact of vigorous-
least 18 months in body lean mass and
intensity physical activity on bone density in boys than in girls
addition to 2 weekly increased BMD and
physical education BMC in whole body may be explained by the increased sensitivity to mechanical
sessions at school (of loading in boys during adolescence and exposure to testosterone
50 min each)
which increases bone and muscle mass (81).
Controls: physical
education session at Zribi et al. evaluated longitudinally the consequences of 1-year
school (50 min of volleyball on BMD and BMC, assessed by DXA (82). Volleyball
each)
is a team sport which includes different movements such as

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accelerations and decelerations, rapid changes of direction and prophylaxis. The National Hemophilia Foundation (NHF) has
repetitive jumps. All actions generate high stresses on the upper suggested guidelines for athletic participation of patients with
and lower limbs from the reaction forces produced by the jumps, bleeding disorders (90). For hemophilic patients, a minimum of
which measure three to six times the body weight. 60 min of exercise per day, with adequate supervision, is
This study demonstrated that playing volleyball 4–6 h per week recommended after receiving prophylaxis.
for approximately 1 year resulted in higher BMD and BMC at all To overcome the problem and allow physical activity for every
skeletal sites analyzed in prepubertal boys compared with non- child with hemophilia, the Italian study group has drawn up some
physically active controls. In volleyball the mechanical forces recommendations which invite gradual training before accessing
acting on the bones derive both by the high reaction forces intense physical activity. Gradual training allows the individual
produced by the impact with the ground in the jump, and by the subject to understand which and what physical activity practice
muscular contractions which pull their bone attachment. and favors the possibility of daily moderate physical activity to
limit the chronic evolution of arthropathy (91).
Prader-Willi syndrome (PWS) is the most frequent form of
Physical activity in rare diseases genetic obesity. It is characterized by severe hypotonia and
feeding problems in early infancy, followed by excessive eating
Physical activity has a key role in the care of patients affected and gradual development of severe obesity (92). In adulthood,
with rare diseases, as it exerts both physic and psychological PWS patients develop cardio-respiratory diseases, psychiatric
effects, pointing to increase quality of life. In addition, there is disorders as well as various comorbidities such as muscle
evidence that physical activity can improve bone health in some weakness and scoliosis. Encouraging physical activity is an
skeletal and extra-skeletal rare diseases. essential objective of the management of PWS both in children
Rheumatic and musculoskeletal diseases include a group of and adults. In the last years, several studies have considered
systemic diseases such as osteoarthritis, rheumatoid arthritis, physical activity in PWS patients (93–95). Although most studies
systemic lupus erythematosus, axial spondyloarthritis, psoriatic have described a low exercise in patients with PWS, it is not
arthritis, systemic sclerosis, characterized by pain, disability, and clear whether the decreased physical activity in these patients is
low quality of life. Patients with rheumatic and musculoskeletal related to obesity per se, or to the physical and intellectual
disorders experience loss of mobility, loss of autonomy, and disabilities related to this syndrome. A recent systematic review
higher mortality rates. Consequently, these disorders have a high which considered controlled trials, single-group interventions,
impact on the social and health system. observational, and qualitative studies reported that only 5%–8%
The recent recommendations of the European League Against of PWS children (93, 96, 97) and 15%–25% of adults (94, 98)
Rheumatism (EULAR) taskforce suggested that exercise met the WHO physical activity and sedentary behavior
interventions improve pain and functions, although the size of guidelines (99). According with WHO guidelines, 60 min/day of
the effect varied by type of diseases and type of intervention moderate-to-vigorous physical activity is suggested for children,
(83). As weight gain has been associated with worse outcomes and 150–300 min/week (i.e., at least 30 min/day) for adults (98).
for most of these conditions, maintaining an adequate body Replacing sedentary lifestyle with physical activity has beneficial
weight is also recommended. effects for lifelong health preservation, particularly for individuals
Physical activity is essential for children with hemophilia, a rare with low physical activity levels such as PWS patients (100).
X-linked bleeding disorder caused by a missing or defective clotting Recently, a protocol for a randomized trial on increasing
factor, to maintain joint movement, reduce joint bleeding, develop resistance training in young people with PWS has been started
muscle mass and strength, and prevent secondary chronic disease (101). The purpose of this study is to establish whether
and osteopenia/osteoporosis (84–86). In the past, since there was progressive resistance training is effective in improving muscle
no treatment for hemophilia, the affected children were forbidden strength in PWS subjects, understand participants’ experiences
to exercise because the risk of bleeding. Current therapies not only and identify factors influencing implementation, and determine
treat acute bleeding, but also prevent it. It is sufficient to pre- long-term efficacy in terms of healthcare expenditure.
administer the deficient clotting factor and the risk of bleeding is
temporarily reduced. The availability of effective and safe drugs
drives patients and caregivers to insistently ask doctors to start Conclusion and future directions
physical activity as for their peers (87).
Although for a hemophilic child under pharmacological treatment The skeleton is a structure made up of living tissue that grows,
there are no contraindications for practicing sports, the sport repairs, and renews itself. It plays a supportive role for muscles and
promotion for hemophilic children is yet an obstacle course (88). a protecting role for internal organs. Furthermore, the skeleton
Different guidelines indicated hemophilic subjects’ sports influences energy metabolism through a continuous interaction
participation according with type and severity (89). In addition, with cytokines derived from both adipose and muscle tissue, and
the selection of activities should consider individual preferences, with insulin. There is substantial evidence that skeletal muscle
abilities, and physical conditions. However, high-impact sports secretes factors which act as mediators of endocrine signaling
such as rugby, boxing, soccer and basketball, or sports with a and are also implicated in the favorable effects of exercise.
higher risk of injury are often discouraged despite good Skeletal muscle “secretoma” during exercise has not yet been

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described, but research has developing modified myokines with the Author contributions
aim of supporting the treatment of chronic diseases.
Adequate nutrition and physical activity can influence MF wrote the manuscript. FU, GL and MC performed medline
musculoskeletal health; however how exercise during pediatric age research and selected the literature. PG critically revised the
affects bone health remains to be investigated. Previous studies manuscript. All authors contributed to the article and approved
have demonstrated a cumulative effect of vigorous physical activity the submitted version.
during adolescence on BMD, suggesting that any time in
adolescence is a window of opportunity to increase bone mass.
The mechanical forces acting on the loaded bones are generated Conflict of interest
both by the high reaction forces produced by the impact with the
ground in sports such as high jump, basketball, and volleyball, and The authors declare that the research was conducted in the
by the muscle contractions that pull their attachment on the absence of any commercial or financial relationships that could
skeleton. This agrees with previous studies that have shown that be construed as a potential conflict of interest.
lean mass development is the best predictor of bone mass
accumulation. Osteogenic sports, such as football, result in a
higher BMC than non-osteogenic sports, such as swimming and Publisher’s note
cycling, in which physical activities should be combined with
weight-bearing movements to optimize bone growth. All claims expressed in this article are solely those of the
Studies of larger cohorts of children and adolescents addressing authors and do not necessarily represent those of their affiliated
issues such as the complex interaction between bone, gut, white organizations, or those of the publisher, the editors and the
and brown adipose tissue, nutrition, and physical activity will be reviewers. Any product that may be evaluated in this article, or
needed in the future to provide new insights into this fascinating claim that may be made by its manufacturer, is not guaranteed
field of metabolic endocrinology. or endorsed by the publisher.

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