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argument is often, if not acrimonious, at least heated. It gives an impression of the fluidity of opinion on many fundamental ideas under discussion and of the urgency with which cardiac cyanosis in the newborn is regarded. When Dr. William Muscott says that the earliest he has operated for pulmonary stenosis is on an infant 3 days old, and Sir Russell Brock agrees that the earlier in the first month that operation is undertaken the better, and when Dr. Varco asks Dr. Senning 'so far as I know they have never yet catheterized any child intrauterine in Sweden, but they have done it through the delivery canal sometimes-would you tell us the indications of the Scandinavian group for catheterization in the immediate newborn period?', one is indeed being kept up with the times. But that was two years ago and already some of the questions then debated have since been answered. This beautifully printed and well-illustrated stiff paperbacked volume is, and will for a few years yet remain, an invaluable companion to a full-scale textbook on congenital heart disease.

Growth at Adolescence.

Bone and skeletal muscle are integrated organs and their coupling has been considered mainly a mechanical one in which bone serves as attachment site to muscle while muscle applies load to bone and regulates bone metabolism. However, skeletal muscle can affect bone homeostasis also in a non-mechanical fashion, i.e., through its endocrine activity. Being recognized as an endocrine organ itself, skeletal muscle secretes a panel of cytokines and proteins named myokines, synthesized and secreted by myocytes in response to muscle contraction. Myokines exert an autocrine function in regulating muscle metabolism as well as a paracrine/endocrine regulatory function on distant organs and tissues, such as bone, adipose tissue, brain and liver. Physical activity is the primary physiological stimulus for bone anabolism (and/or catabolism) through the production and secretion of myokines, such as IL-6, irisin, IGF-1, FGF2, beside the direct effect of loading. Importantly, exercise-induced myokine can exert an anti-inflammatory action that is able to counteract not only acute inflammation due to an infection, but also a condition of chronic low-grade inflammation raised as consequence of physical inactivity, aging or metabolic disorders (i.e., obesity, type 2 diabetes mellitus). In this review article, we will discuss the effects that some of the most studied exercise-induced myokines exert on bone formation and bone resorption, as well as a brief overview of the anti-inflammatory effects of myokines during the onset pathological conditions characterized by the development a systemic low-grade inflammation, such as sarcopenia, obesity and aging.

Myokines: The endocrine coupling of skeletal muscle and bone.

Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.

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RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling.

Physical inactivity has been recognized, by the World Health Organization as the fourth cause of death (5.5 % worldwide). On the contrary, physical activity (PA) has been associated with improved quality of life and decreased risk of several diseases (i.e., stroke, hypertension, myocardial infarction, obesity, malignancies). Bone turnover is profoundly affected from PA both directly (load degree is the key determinant for BMD) and indirectly through the activation of several endocrine axes. Several molecules, secreted by muscle (myokines) and adipose tissues (adipokines) in response to exercise, are involved in the fine regulation of bone metabolism in response to the energy availability. Furthermore, bone regulates energy metabolism by communicating its energetic needs thanks to osteocalcin which acts on pancreatic β-cells and adipocytes. The beneficial effects of exercise on bone metabolism depends on the intermittent exposure to myokines (i.e., irisin, IL-6, LIF, IGF-I) which, instead, act as inflammatory/pro-resorptive mediators when chronically elevated; on the other hand, the reduction in the circulating levels of adipokines (i.e., leptin, visfatin, adiponectin, resistin) sustains these effects as well as improves the whole-body metabolic status. The aim of this review is to highlight the newest findings about the exercise-dependent regulation of these molecules and their role in the fine regulation of bone metabolism.

Implications of exercise-induced adipo-myokines in bone metabolism.

IntroductionLow-impact, high-intensity interval exercise (HIE) was used to investigate the postexercise response in bone turnover markers and cytokines.MethodsTwenty-three recreationally active males (21.8 ± 2.4 yr) performed one HIE bout on a cycle ergometer at 90% maximum workload. The tot

Response of Bone Turnover Markers and Cytokines to High-Intensity Low-Impact Exercise.

The acute exercise effects on bone markers in adults are unclear, while in children, there are no such data.
 To investigate the acute response of biochemical markers of bone turnover to a high-impact exercise session consisting of high-mechanical loading in boys and young men. Twelve boys (10.2 ± 0.4 years) and 14 men (22.0 ± 0.8 years) underwent a protocol of plyometric jumping exercises (total 144 jumps). Venous blood samples were collected pre-, 5 min, 1 and 24 h post-exercise, and analyzed for markers of bone formation and resorption: bone-specific alkaline phosphatase (bone ALP), osteoprotegerin (OPG), amino-terminal cross-linking telopeptide (NTx), and receptor activator of nuclear factor kappa beta ligand (RANKL). Boys had higher resting bone ALP (111.9 ± 29.2 vs. 30.6 ± 11.2 µg/L, p < 0.05) and NTx levels (49.8 ± 13.2 vs. 21.7 ± 5.9 nM BCE, p < 0.05) than men but no group differences were observed in resting OPG or RANKL. Following exercise (24 h), bone ALP and NTx increased in both boys and men (bone ALP: 24.1 vs. 9.9 %, respectively; NTx: 23.5 vs. −5 %, respectively), although the group-by-time interaction was not statistically significant. OPG increased significantly (p < 0.05) in both groups (5.7 and 16.1 %, respectively). Even one session of plyometric exercises appear to stimulate bone formation in boys and men, as reflected by the increase in bone ALP and OPG. The boys’ response appears more pronounced than the men’s, suggesting that during growth, cellular bone activities respond with greater magnitude to mechanical stimuli.

Effects of plyometric exercise session on markers of bone turnover in boys and young men.

Summary
Physical exercise benefits bone structure and mineralization, especially in children Immediately following high-impact exercise, PTH increased and returned to resting values within 24 h in both groups, while sclerostin increased in men but not in boys The underlying mechanisms and implication of this age-related differential response are unclear

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Differential sclerostin and parathyroid hormone response to exercise in boys and men

Adolescent idiopathic scoliosis (AIS) is often associated with low bone mineral content and density (BMC, BMD). Bracing, used to manage spine curvature, may interfere with the growth-related BMC accrual, resulting in reduced bone strength into adulthood. The purpose of this study was to assess the effects of brace treatment on BMC in adult women, diagnosed with AIS and braced in early adolescence. Participants included women with AIS who: (i) underwent brace treatment (AIS-B, n = 15, 25.6 ± 5.8 yrs), (ii) underwent no treatment (AIS, n = 15, 24.0 ± 4.0 yrs), and (iii) a healthy comparison group (CON, n = 19, 23.5 ± 3.8 yrs). BMC and body composition were assessed using dual-energy X-ray absorptiometry. Differences between groups were examined using a oneway ANOVA or ANCOVA, as appropriate. AIS-B underwent brace treatment 27.9 ± 21.6 months, for 18.0 ± 5.4 h/d. Femoral neck BMC was lower (p = 0.06) in AIS-B (4.54 ± 0.10 g) compared with AIS (4.89 ± 0.61 g) and CON (5.07 ± 0.58 g). Controlling for lean body mass, calcium and vitamin D daily intake, and strenuous physical activity, femoral neck BMC was statistically different (p = 0.02) between groups. A similar pattern was observed at other lower extremity sites (p < 0.05), but not in the spine or upper extremities. BMC and BMD did not correlate with duration of brace treatment, duration of daily brace wear, or overall physical activity. Young women with AIS, especially those who were treated with a brace, have significantly lower BMC in their lower limbs compared to women without AIS. However, the lack of a relationship between brace treatment duration during adolescence and BMC during young adulthood, suggests that the brace treatment is not the likely mechanism of the low BMC.

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Kimberly Kish

Papers

Response of Bone Turnover Markers and Cytokines to High-Intensity Low-Impact Exercise.

Effects of plyometric exercise session on markers of bone turnover in boys and young men.

Differential sclerostin and parathyroid hormone response to exercise in boys and men

Does bracing affect bone health in women with adolescent idiopathic scoliosis