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1.
The Bones of Children With Obesity.
Fintini, D, Cianfarani, S, Cofini, M, Andreoletti, A, Ubertini, GM, Cappa, M, Manco, M
Frontiers in endocrinology. 2020;:200
Abstract
Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers. Both adipocytes and osteoblasts derive from multipotent mesenchymal stem cells (MSCs) and obesity drives the differentiation of MSCs toward adipocytes at the expense of osteoblast differentiation. Furthermore, adipocytes in bone marrow microenvironment release a number of pro-inflammatory and immunomodulatory molecules that up-regulate formation and activation of osteoclasts, thus favoring bone frailty. On the other hand, body adiposity represents a mechanical load, which is beneficial for bone accrual. In this frame, bone quality, and structure result from the balance of inflammatory and mechanical stimuli. Diet, physical activity and the hormonal milieu at puberty play a pivotal role on this balance. In this review, we will address the question whether the bone of obese children and adolescents is unhealthy in comparison with normal-weight peers and discuss mechanisms underlying the differences in bone quality and structure. We anticipate that many biases and confounders affect the clinical studies conducted so far and preclude us from achieving robust conclusions. Sample-size, lack of adequate controls, heterogeneity of study designs are the major drawbacks of the existing reports. Due to the increased body size of children with obesity, dual energy absorptiometry might overestimate bone mineral density in these individuals. Magnetic resonance imaging, peripheral quantitative CT (pQCT) scanning and high-resolution pQCT are promising techniques for the accurate estimate of bone mineral content in obese children. Moreover, no longitudinal study on the risk of incident osteoporosis in early adulthood of children and adolescents with obesity is available. Finally, we will address emerging dietary issues (i.e., the likely benefits for the bone health of polyunsaturated fatty acids and polyphenols) since an healthy diet (i.e., the Mediterranean diet) with balanced intake of certain nutrients associated with physical activity remain the cornerstones for achieving an adequate bone accrual in young individuals regardless of their adiposity degree.
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2.
Muscle, Bone, and Fat Crosstalk: the Biological Role of Myokines, Osteokines, and Adipokines.
Kirk, B, Feehan, J, Lombardi, G, Duque, G
Current osteoporosis reports. 2020;(4):388-400
Abstract
PURPOSE OF REVIEW Skeletal muscle and bone are connected anatomically and physiologically, and play a crucial role in human locomotion and metabolism. Historically, the coupling between muscle and bone has been viewed in light of mechanotransduction, which dictates that the mechanical forces applied to muscle are transmitted to the skeleton to initiate bone formation. However, these organs also communicate through the endocrine system, orchestrated by a family of cytokines namely myokines (derived from myocytes) and osteokines (derived from bone cells). A third player in this biochemical crosstalk is adipose tissue and the secretion of adipokines (derived from adipocytes). In this review, we discuss the bidirectional effects of myokines and osteokines on muscle and bone metabolism, and the impact of adipokines on both of these secretory organs. RECENT FINDINGS Several myokines, notably, IL6, irisin, IGF-1, BDNF, myostatin, and FGF2 exert anabolic/catabolic effects on bone, while the osteokines osteocalcin and sclerostin have shown to induce muscle anabolism and catabolism, respectively. Adipokines, such as leptin, resistin, adiponectin, and TNFα (released from adipose tissue), can also modulate muscle and bone metabolism. Contrarily, exercise-mediated release of lipolytic myokines (IL6, irisin, and LIF) stimulates thermogenesis by promoting the browning of adipocytes. Myokines, osteokines, and adipokines exert autocrine/paracrine effects locally as well as through the endocrine system, to regulate muscle, bone, and fat metabolism. Reductions in physical activity and increases in energy intake, both linked with aging, leads to adipocyte hypertrophy and the recruitment of immunological cells (macrophages). In turn, this releases pro-inflammatory adipokines which induces chronic low-grade inflammation (LGI), a key player in the pathology of several diseases. However, exercise-induced stimulation of bioactive cytokines, through muscle-bone-fat crosstalk, increases muscle anabolism, bone formation, mitochondrial biogenesis, glucose utilization, and fatty acid oxidation, and attenuates chronic LGI.
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3.
Changes in Bone Metabolism After Sleeve Gastrectomy Versus Gastric Bypass: a Meta-Analysis.
Tian, Z, Fan, XT, Li, SZ, Zhai, T, Dong, J
Obesity surgery. 2020;(1):77-86
Abstract
BACKGROUND Gastric bypass (GB) and sleeve gastrectomy (SG) are two common types of bariatric surgery that carry many potential complications. Among these complications, bone metabolism-related diseases have attracted substantial attention; however, no meta-analysis of them has been performed to date. METHODS We searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before January 2019. The following indicators were evaluated: serum parathyroid hormone (PTH), calcium, phosphorus and 25-hydroxyvitamin D levels, body mass index (BMI), and bone mineral density (BMD). RESULTS Thirteen studies met our inclusion criteria. Overall results showed that patients undergoing GB had lower levels of 25-hydroxyvitamin D (MD = - 1.85, 95% CI (- 3.32, - 0.39) P = 0.01) and calcium (MD = - 0.15, 95% CI (- 0.24, - 0.07) P = 0.0006) as well as higher levels of PTH (MD = 3.58, 95% CI (0.61, 7.09) P = 0.02) and phosphorus (MD = 0.22, 95% CI (0.10, 0.35) P = 0.0005). The results of BMI and BMD were comparable in each group. CONCLUSION Our meta-analysis suggested that obese patients undergoing GB had lower levels of serum calcium and 25-hydroxyvitamin D as well as higher levels of serum phosphorus and PTH. To prevent postoperative bone metabolism-related diseases, appropriate postoperative interventions should be undertaken for particular surgical procedures.
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4.
Bone Mineral Density in Adolescent Boys: Cross-Sectional Observational Study.
Kopiczko, A, Adamczyk, JG, Łopuszańska-Dawid, M
International journal of environmental research and public health. 2020;(1)
Abstract
Physical inactivity of children can be a precursor of reduced bone mineral density, considered to be a typical problem only in old age. The aim of this study was to evaluate bone mineral density in 96 Polish boys aged 14-17 years with varied physical activity (swimmers, track and field athletes, non-athletes) and the effect of bone composition, birth weight and breastfeeding during infancy on bone parameters. Anthropometric and body composition measurements were performed according to the kinanthropometric standards. Bone parameters of the forearm were measured by means of dual-energy X-ray absorptiometry. Data on the infant's birth weight and the length of breastfeeding were collected during direct interviews with mothers. The strongest links with bone parameters were found for the type of physical activity and birth weight. Regardless of birth weight, track and field athletes had the most advantageous bone parameters (mainly sT-score prox values). Swimmers with normal or low birth weight had less favourable sT-score prox values than non-athletes. The type of physical activity proved to be an important determinant of bone parameters. Childhood and adolescence are important periods of bone development and increasing the content of bone mineral components, and the bone status in later years of life depends to a large extent on this period. The perinatal period, especially the correct birth weight of the child, not only has a significant effect on general health, but also on bone status.
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5.
Primary Aldosteronism and Bone Metabolism: A Systematic Review and Meta-Analysis.
Shi, S, Lu, C, Tian, H, Ren, Y, Chen, T
Frontiers in endocrinology. 2020;:574151
Abstract
BACKGROUND Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis. METHODS Pubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient. RESULTS A final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (MD=21.50 pg/ml, 95% CI (15.63, 27.37), P<0.00001) and slightly increased urinary calcium levels (MD = 1.65 mmol/24 h, 95% CI (1.24, 2.06), P < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery. CONCLUSIONS PA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.
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6.
Mineral and nutritional requirements of preterm infant.
Czech-Kowalska, J
Seminars in fetal & neonatal medicine. 2020;(1):101071
Abstract
Preterm infants are at risk of growth failure and metabolic bone disease due to insufficient nutrient supply in postnatal life. An ample provision of protein, energy, calcium and phosphates through parenteral or/and enteral nutrition is crucial for bone growth and mineralization. Additional vitamin D supplementation improves bone mineralization and enhance intestinal absorption of minerals.
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7.
Plant-based diets and bone health: sorting through the evidence.
Hsu, E
Current opinion in endocrinology, diabetes, and obesity. 2020;(4):248-252
Abstract
PURPOSE OF REVIEW An increase in awareness of vegetarian and vegan (plant-based) diets has brought forth numerous studies on their effects on health. The study of nutrition-based factors affecting bone health is difficult, given the length of time before clinical effects are evident. Furthermore, population-based studies must account for strong confounding influences as effects may be because of association, not causality. Yet, it is highly plausible that dietary factors affect bone remodeling in multiple ways. Plant-based diets may alter macronutrient and micronutrient balance, may cause differences in prebiotic and probiotic effects on gut microbiota, and may subtly change the inflammatory and immune response. RECENT FINDINGS Several recent studies have looked at plant-based nutrition and markers of bone health, using measures such as bone turnover markers, bone mineral density, or fracture rates. Although population based and cross-sectional studies can be prone to confounding effects, a majority did not show differences in bone health between vegetarians/vegans and omnivores as long as calcium and vitamin D intake were adequate. A few prospective cohort or longitudinal studies even demonstrate some benefit to a plant-based diet, but this claim remains unproven. SUMMARY There is no evidence that a plant-based diet, when carefully chosen to maintain adequate calcium and vitamin D levels, has any detrimental effects on bone health. Theoretical findings suggest a long-term plant-based diet may reduce the risk of osteoporosis, through mechanisms that are currently speculative.
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8.
Bone Status in Patients with Phenylketonuria: A Systematic Review.
de Castro, MJ, de Lamas, C, Sánchez-Pintos, P, González-Lamuño, D, Couce, ML
Nutrients. 2020;(7)
Abstract
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in preventing intellectual disability in PKU patients who are treated early, suboptimal outcomes have been reported, including bone mineral disease. In this systematic review, we summarize the available evidence on bone health in PKU patients, including data on bone mineral density (BMD) and bone turnover marker data. Data from cohort and cross-sectional studies of children and adults (up to 40 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, quality assessment was performed applying the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS I) tool. We found that mean BMD was lower in PKU patients than in reference groups, but was within the normal range in most patients when expressed as Z-score values. Furthermore, data revealed a trend towards an imbalance between bone formation and bone resorption, favoring bone removal. Data on serum levels of minerals and hormones involved in bone metabolism were very heterogeneous, and the analyses were inconclusive. Clinical trials that include the analysis of fracture rates, especially in older patients, are needed to gather more evidence on the clinical implications of lower BMD in PKU patients.
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9.
Δ1 -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder.
Marco-Marín, C, Escamilla-Honrubia, JM, Llácer, JL, Seri, M, Panza, E, Rubio, V
Journal of inherited metabolic disease. 2020;(4):657-670
Abstract
The bifunctional homooligomeric enzyme Δ1 -pyrroline-5-carboxylate synthetase (P5CS) and its encoding gene ALDH18A1 were associated with disease in 1998. Two siblings who presented paradoxical hyperammonemia (alleviated by protein), mental disability, short stature, cataracts, cutis laxa, and joint laxity, were found to carry biallelic ALDH18A1 mutations. They showed biochemical indications of decreased ornithine/proline synthesis, agreeing with the role of P5CS in the biosynthesis of these amino acids. Of 32 patients reported with this neurocutaneous syndrome, 21 familial ones hosted homozygous or compound heterozygous ALDH18A1 mutations, while 11 sporadic ones carried de novo heterozygous ALDH18A1 mutations. In 2015 to 2016, an upper motor neuron syndrome (spastic paraparesis/paraplegia SPG9) complicated with some traits of the neurocutaneous syndrome, although without report of cutis laxa, joint laxity, or herniae, was associated with monoallelic or biallelic ALDH18A1 mutations with, respectively, dominant and recessive inheritance. Of 50 SPG9 patients reported, 14 and 36 (34/2 familial/sporadic) carried, respectively, biallelic and monoallelic mutations. Thus, two neurocutaneous syndromes (recessive and dominant cutis laxa 3, abbreviated ARCL3A and ADCL3, respectively) and two SPG9 syndromes (recessive SPG9B and dominant SPG9A) are caused by essentially different spectra of ALDH18A1 mutations. On the bases of the clinical data (including our own prior patients' reports), the ALDH18A1 mutations spectra, and our knowledge on the P5CS protein, we conclude that the four syndromes share the same pathogenic mechanisms based on decreased P5CS function. Thus, these syndromes represent a continuum of increasing severity (SPG9A < SPG9B < ADCL3 ≤ ARCL3A) of the same disease, P5CS deficiency, in which the dominant mutations cause loss-of-function by dominant-negative mechanisms.
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10.
Post-natal bone physiology.
El-Farrash, RA, Ali, RH, Barakat, NM
Seminars in fetal & neonatal medicine. 2020;(1):101077
Abstract
Post-natal bone development is characterized by substantial longitudinal bone growth and changes in skeletal size and shape. Bone is in a dynamic process of continuous remodeling which helps to regulate calcium homeostasis, repair micro-damage to bones from everyday stress, and to shape the skeleton during growth. Bone growth is regulated by systemic hormones and locally generated factors. Understanding their mechanisms of action enables us to obtain a better appreciation of the cellular and molecular basis of bone remodeling and could therefore be valuable in approaches to new therapies. This article will review molecular and cellular control of skeletal growth in the post-natal period, the physiology of each bone cell with their systemic and local regulators, as well as the physiology of bone remodeling.