-
1.
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.
-
2.
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.
-
3.
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.
-
4.
Mineral and bone physiology in the foetus, preterm and full-term neonates.
Sethi, A, Priyadarshi, M, Agarwal, R
Seminars in fetal & neonatal medicine. 2020;(1):101076
Abstract
Mother is the major source of minerals in foetal life with placenta actively transporting against a concentration and electrochemical gradient. The foetal serum mineral concentration is thereby higher as compared to maternal values, which possibly help in its rapid accretion in developing bones and for counteracting postnatal fall in calcium levels at birth. Parathyroid hormone related peptide (PTHrP) and parathyroid hormone (PTH) play a major role in mineral physiology during foetal life with hormones like calcitriol, calcitonin, FGF-23 and sex steroids having minimal role. PTHrP and PTH also play a major role in endochondral bone formation and mineralization of skeleton. At the birth, as the cord is clamped, there is loss of active transport of minerals through placenta and the neonate has to rely on enteral intake of minerals to meet the demands of growing bones and metabolisms. The calcium levels fall after birth, reaching a nadir at 24-48 h and gradually rise to adult values over several days, probably resulting from a fall in PTHrP levels and hyporesponsiveness of parathyroid glands. As PTH and calcitriol levels increase postnatally, there is a rise in calcium levels with maturation in functioning of kidneys and intestines. However, there may be significant delay in intestinal maturation in preterm infants along with an increased demand for mineral accretion, which predispose them to osteopenia of prematurity.
-
5.
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.
-
6.
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.
-
7.
Perlecan, a modular instructive proteoglycan with diverse functional properties.
Melrose, J
The international journal of biochemistry & cell biology. 2020;:105849
Abstract
This study reviewed some new aspects of the modular proteoglycan perlecan, a colossal proteoglycan with a 467 kDa core protein and five distinct functional domains. Perlecan is a heparan sulphate proteoglycan that transiently displays native CS sulphation motifs 4-C-3 and 7-D-4 during tissue morphogenesis these are expressed by progenitor cell populations during tissue development. Perlecan is susceptible to fragmentation by proteases during tissue development and in pathological tissues particularly in domains IV and V. The fragmentation pattern of domain IV has been suggested as a means of grading prostate cancer. Domain V of perlecan is of interest due to its interactive properties with integrin α5β1 that promotes pericyte migration enhancing PDGF-BB-induced phosphorylation of PDGFRβ, Src homology region 2 domain-containing phosphatase-2, and focal adhesion kinase supporting the repair of the blood brain barrier following ischaemic stroke. Fragments of domain V can also interact with α2β1 integrin disrupting tube formation by endothelial cells. LG1-LG2, LG3 fragments can antagonise VEGFR2, and α2β1 integrin interactions preventing angiogenesis by endothelial cells. These domain V fragments are of interest as potential anti-tumour agents. Perlecan attached to the luminal surfaces of endothelial cells in blood vessels acts as a flow sensor that signals back to endothelial and smooth muscle cells to regulate vascular tone and blood pressure. Perlecan also acts as a flow sensor in the lacuno-canalicular space regulating osteocytes and bone homeostasis. Along with its biomechanical regulatory properties in cartilaginous tissues this further extends the functional repertoire of this amazingly diverse functional proteoglycan.
-
8.
RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling.
Tobeiha, M, Moghadasian, MH, Amin, N, Jafarnejad, S
BioMed research international. 2020;:6910312
Abstract
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.
-
9.
Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors.
Altieri, B, Di Dato, C, Modica, R, Bottiglieri, F, Di Sarno, A, Pittaway, JFH, Martini, C, Faggiano, A, Colao, A
Nutrients. 2020;(4)
Abstract
Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.
-
10.
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.