Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a “poor” quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.

Download Full-text

Effect of Antidiabetic Treatment on Bone

Physiological Research ◽

10.33549/physiolres.934297 ◽

2019 ◽

pp. S107-S120 ◽

Cited By ~ 1

Author(s):

J. JACKULIAK ◽

M. KUŽMA ◽

J. PAYER

Keyword(s):

Diabetes Mellitus ◽

Bone Fractures ◽

Negative Impact ◽

Osteoporotic Fractures ◽

Antidiabetic Drugs ◽

Mineral Density ◽

Skeletal Health ◽

Antidiabetic Treatment ◽

Increased Risk ◽

Patients With Diabetes

Patients with diabetes mellitus are at an increased risk of bone fractures. Several groups of effective antidiabetic drugs are available, which are very often given in combination. The effects of these medications on bone metabolism and fracture risk must not be neglected. Commonly used antidiabetic drugs might have a positive, neutral or negative impact on skeletal health. Increased risk of fracture has been identified with use of thiazolidinediones, most definitively in women. Also treatment with sulfonylureas can have adverse effects on bone. One consequence of these findings has been greater attention to fracture outcomes in trails of new diabetes medication (incretins and SGLT-2 inhibitors). The effect of insulin on bone is discussed and the risk of fractures in patients using insulin seems to be unrelated to insulin as itself. The aim of the review is to summarize effects of antidiabetic treatment on bone – bone mineral density, fractures and bone turnover markers. The authors also try to recommend a strategy how to treat patients with diabetes mellitus regarding the risk of osteoporotic fractures. In this review the problem of how to treat osteoporosis in patient with diabetes is also discussed.

Download Full-text

Maternal Diet, Nutritional Status, and Birth-Related Factors Influencing Offspring’s Bone Mineral Density: A Narrative Review of Observational, Cohort, and Randomized Controlled Trials

Nutrients ◽

10.3390/nu13072302 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2302

Author(s):

Daria Masztalerz-Kozubek ◽

Monika A. Zielinska-Pukos ◽

Jadwiga Hamulka

Keyword(s):

Bone Mineral Density ◽

Nutritional Status ◽

Bone Mineral ◽

Bone Health ◽

Maternal Diet ◽

Narrative Review ◽

Cochrane Library ◽

Mineral Density ◽

Eligibility Criteria ◽

Related Factors

There is growing evidence that bone health may be programmed in the first years of life. Factors during the prenatal period, especially maternal nutrition, may have an influence on offspring’s skeletal development and thus the risk of osteoporosis in further life, which is an increasing societal, health and economic burden. However, it is still inconclusive which early life factors are the most important and to what extent they may affect bone health. We searched through three databases (PubMed, Google Scholar, Cochrane Library) and after eligibility criteria were met, the results of 49 articles were analyzed. This narrative review is an overall summary of up-to-date studies on maternal diet, nutritional status, and birth-related factors that may affect offspring bone development, particularly bone mineral density (BMD). Maternal vitamin D status and diet in pregnancy, anthropometry and birth weight seem to influence BMD, however other factors such as subsequent growth may mediate these associations. Due to the ambiguity of the results in the analyzed studies, future, well-designed studies are needed to address the limitations of the present study.

Download Full-text

The Connection Between Vitamin K and Bone Health

Journal of Student Science and Technology ◽

10.13034/jsst.v8i2.64 ◽

2015 ◽

Vol 8 (2) ◽

Author(s):

Jamy (Ning) Fu

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Vitamin K ◽

Bone Health ◽

Bone Fractures ◽

The Body ◽

Mineral Density ◽

Densité Minérale Osseuse ◽

The Impact ◽

Viable Method

Vitamin K is essential to the body because it is known to help blood coagulate and activate osteocalcin, a protein involved in maintaining healthy bones. In this review, one study observing the impact of vitamin K supplementation on patients’ bone mineral densities and three studies focusing on the effects of vitamin K supplementation on the incidence of bone fractures are discussed to determine whether the vitamin may be important for maintaining bone health. While some promising results, such as an increase in bone mineral density of subjects after vitamin K supplementation arose, the conclusions reached by the four studies were not statistically significant enough to justify the importance of vitamin K in maintaining bone health. Well-controlled studies that are unbiased, statistically powerful, and focused on vitamin K’s effects on bone density are required in the future to provide further insight on whether vitamin K supplementation is a viable method of improving bone health. La vitamine K est essentielle pour le corps, car il est connu pour assister dans la coagulation du sang ainsi qu’activer l'ostéocalcine, une protéine impliquée dans le maintien de la santé des os. Ici, une étude dirigé vers les observations de l'impact de la consommation de suppléments de la vitamine K sur la densité minérale osseuse de patients, puis trois autres études portant sur les effets de la consommation de suppléments de la vitamine K sur l'incidence des fractures osseuses sont examinées afin de déterminer si la vitamine soit une facteur important dans le maintien de la santé des os. Tandis que des résultats sont révélés prometteurs, comme ceux montrant une augmentation de la densité minérale osseuse des sujets après la consommation des suppléments de la vitamine K, l’ensemble de conclusions tirées des quatre études ne présente pas suffisamment de données qui pourraient suggérer une corrélation entre la consommation des suppléments de la vitamine K et la santé des os. Des études supplémentaires portant sur les effets de la vitamine K sur la densité osseuse, mené dans des conditions contrôlés, bien conçus, impartiales, qui produiront des résultats persuasifs, sont nécessaires à être effectuer à l'avenir afin de donner un meilleur aperçu de l’effet de la supplémentation en vitamine K comme une méthode viable dans l’entretien de la santé des os.

Download Full-text

Negative impact of polycystic ovary syndrome on bone health: a systematic review and meta-analysis

Human Reproduction Update ◽

10.1093/humupd/dmz020 ◽

2019 ◽

Vol 25 (5) ◽

pp. 634-646 ◽

Cited By ~ 6

Author(s):

Júlia Mottecy Piovezan ◽

Melissa Orlandin Premaor ◽

Fábio Vasconcellos Comim

Keyword(s):

Systematic Review ◽

Polycystic Ovary Syndrome ◽

Bone Health ◽

Bone Markers ◽

Bone Fractures ◽

Polycystic Ovary ◽

Meta Analysis ◽

Mineral Density ◽

Ovary Syndrome ◽

The Impact

Abstract BACKGROUND Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health. OBJECTIVE AND RATIONALE This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk. SEARCH METHODS A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR). OUTCOMES Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle–Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, −0.04; 95% CI, −0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, −0.07; 95% CI, −0.13 to −0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, −0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, −0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, −2.68; 95% CI, −4.70 to −0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls. WIDER IMPLICATIONS On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS.

Download Full-text

Soda intake and osteoporosis risk in postmenopausal American-Indian women

Public Health Nutrition ◽

10.1017/s136898001000337x ◽

2011 ◽

Vol 14 (11) ◽

pp. 1900-1906 ◽

Cited By ~ 8

Author(s):

Joy D Supplee ◽

Glen E Duncan ◽

Barbara Bruemmer ◽

Jack Goldberg ◽

Yang Wen ◽

...

Keyword(s):

American Indian ◽

Bone Health ◽

Bone Fractures ◽

Mineral Density ◽

Related Factors ◽

American Indian Women ◽

Indian Women ◽

Increased Risk ◽

Soda Consumption ◽

Osteoporosis Risk

AbstractObjectiveLow bone mass often leads to osteoporosis and increased risk of bone fractures. Soda consumption may contribute to imbalances that lead to decreased bone mineral density (BMD) and general bone health. We examined the relationship between soda consumption and osteoporosis risk in postmenopausal American-Indian women, an at-risk population because of nutritional and other lifestyle-related factors.DesignCross-sectional analysis using logistic regression to examine associations between soda consumption and osteoporosis, and linear regression to examine the association between soda consumption and BMD, with and without adjustment for demographic and lifestyle factors. Quantitative ultrasound of the heel was performed to estimate BMD (g/cm2).SettingAmerican-Indian communities in the Northern Plains and Southwestern USA.SubjectsA total of 438 postmenopausal American-Indian women.ResultsWomen with osteoporosis were significantly older and had lower BMI, average daily soda intakes, BMD levels and use of hormones than women without osteoporosis (P< 0·05). Soda consumption was not associated with increased odds of osteoporosis in either unadjusted or adjusted models (P> 0·05), although age (increased), BMI (decreased) and past hormone use (decreased) were all significantly associated with osteoporosis risk (P< 0·05).ConclusionsAlthough the present study did not find associations between soda consumption and osteoporosis risk in postmenopausal American-Indian women, analyses did confirm confounding between soda consumption and age and BMI. This suggests that any potential effects of soda consumption on bone health are largely mediated through these factors.

Download Full-text

Diabetic Skeletal Health and Potential Benefits of Exercise

Journal of Clinical Exercise Physiology ◽

10.31189/2165-6193-8.3.108 ◽

2019 ◽

Vol 8 (3) ◽

pp. 108-114

Author(s):

Elizabeth O'Neill

Keyword(s):

Diabetes Mellitus ◽

Bone Mineral Density ◽

Bone Tissue ◽

Bone Health ◽

Cellular Activity ◽

Mineral Density ◽

Skeletal Health ◽

Increased Risk ◽

Potential Benefits ◽

Potential Methods

ABSTRACT Bone tissue undergoes continual remodeling through resorption and formation. The balance between these 2 activities is critical to optimizing bone mineral density (BMD) and the biomechanical integrity of the tissue, thereby reducing fractures. There is increasing evidence that diabetes negatively alters the cellular activity of bone tissue and reduces bone quality resulting in an increased risk of fractures. The mechanisms by which diabetes impacts bone are not completely understood; however, insulin, hyperglycemia, and glycation appear to influence skeletal regulation. This review will explore the influence of diabetes mellitus on bone as well as examine the potential methods by which exercise can serve as a nonpharmacological method to optimize bone health in persons with diabetes.

Download Full-text

Vitamin K Nutrition and Bone Health

Nutrients ◽

10.3390/nu12071909 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1909 ◽

Cited By ~ 2

Author(s):

Naoko Tsugawa ◽

Masataka Shiraki

Keyword(s):

Energy Metabolism ◽

Fracture Risk ◽

Vitamin K ◽

Bone Health ◽

Bone Fractures ◽

Vitamin K Deficiency ◽

Protein Levels ◽

K Deficiency ◽

Dependent Protein

Vitamin K is essential for blood coagulation and plays an important role in extrahepatic metabolism, such as in bone and blood vessels, and in energy metabolism. This review discusses the assessment of vitamin K sufficiency and the role of vitamin K in bone health. To elucidate the exact role of vitamin K in other organs, accurate tools for assessing vitamin K deficiency or insufficiency are crucial. Undercarboxylated vitamin K-dependent protein levels can be measured to evaluate tissue-specific vitamin K deficiency/insufficiency. Vitamin K has genomic action through steroid and xenobiotic receptor (SXR); however, the importance of this action requires further study. Recent studies have revealed that the bone-specific, vitamin K-dependent protein osteocalcin has a close relationship with energy metabolism through insulin sensitivity. Among the organs that produce vitamin K-dependent proteins, bone has attracted the most attention, as vitamin K deficiency has been consistently associated with bone fractures. Although vitamin K treatment addresses vitamin K deficiency and is believed to promote bone health, the corresponding findings on fracture risk reduction are conflicting. We also discuss the similarity of other vitamin supplementations on fracture risk. Future clinical studies are needed to further elucidate the effect of vitamin K on fracture risk.

Download Full-text

Combination of Micronutrients for Bone (COMB) Study: Bone Density after Micronutrient Intervention

Journal of Environmental and Public Health ◽

10.1155/2012/354151 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Stephen J. Genuis ◽

Thomas P. Bouchard

Keyword(s):

Bone Density ◽

Bone Health ◽

Positive Impact ◽

Bisphosphonate Therapy ◽

Health Clinic ◽

Osteoporotic Bone ◽

Health Issues ◽

Mineral Density ◽

Skeletal Health ◽

Micronutrient Therapy

Along with other investigations, patients presenting to an environmental health clinic with various chronic conditions were assessed for bone health status. Individuals with compromised bone strength were educated about skeletal health issues and provided with therapeutic options for potential amelioration of their bone health. Patients who declined pharmacotherapy or who previously experienced failure of drug treatment were offered other options including supplemental micronutrients identified in the medical literature as sometimes having a positive impact on bone mineral density (BMD). After 12 months of consecutive supplemental micronutrient therapy with a combination that included vitamin D3, vitamin K2, strontium, magnesium and docosahexaenoic acid (DHA), repeat bone densitometry was performed. The results were analyzed in a group of compliant patients and demonstrate improved BMD in patients classified with normal, osteopenic and osteoporotic bone density. According to the results, this combined micronutrient supplementation regimen appears to be at least as effective as bisphosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micronutrient protocol. This micronutrient regimen also appears to show efficacy in individuals where bisphosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy.

Download Full-text

The impact of diet, body composition, and physical activity on child bone mineral density at five years of age—findings from the ROLO Kids Study

European Journal of Pediatrics ◽

10.1007/s00431-019-03465-x ◽

2019 ◽

Vol 179 (1) ◽

pp. 121-131 ◽

Cited By ~ 3

Author(s):

Marco K. McVey ◽

Aisling A. Geraghty ◽

Eileen C. O’Brien ◽

Malachi J. McKenna ◽

Mark T. Kilbane ◽

...

Keyword(s):

Physical Activity ◽

Bone Mineral Density ◽

Vitamin D ◽

Early Childhood ◽

Body Composition ◽

Bone Mineral ◽

Bone Health ◽

Bone Fractures ◽

Mineral Density ◽

The Impact

Abstract Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD. Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.

Download Full-text

Nutrients, Diet, and Other Factors in Prenatal Life and Bone Health in Young Adults: A Systematic Review of Longitudinal Studies

Nutrients ◽

10.3390/nu12092866 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2866

Author(s):

Karina H. Jensen ◽

Kamilla R. Riis ◽

Bo Abrahamsen ◽

Mina N. Händel

Keyword(s):

Vitamin D ◽

Young Adults ◽

Bone Health ◽

Internal Validity ◽

Dietary Factors ◽

Mineral Density ◽

Skeletal Health ◽

Calcium Phosphorus ◽

High Concentrations ◽

Exposures During Pregnancy

Optimizing skeletal health in early life has potential effects on bone health later in childhood and in adulthood. We aimed to evaluate the existing evidence that maternal exposures during pregnancy have an impact on the subsequent bone health among offspring in young adults aged between 16 and 30 years. The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42019126890). The search was conducted up to 2 April 2019. We included seven observational prospective cohort studies that examined the association between maternal dietary factors, vitamin D concentration, age, preeclampsia, and smoking with any bone indices among offspring. The results indicated that high concentrations of maternal vitamin D; low fat intake; and high intakes of calcium, phosphorus, and magnesium may increase the bone mineral density in offspring at age 16. Evidence also suggests that the offspring of younger mothers may have a higher peak bone mass. It remains inconclusive whether there is an influence of preeclampsia or maternal smoking on bone health among young adults. Our assessment of internal validity warrants a cautious interpretation of these results, as all of the included studies were judged to have serious risks of bias. High-quality studies assessing whether prenatal prognostic factors are associated with bone health in young adults are needed.

Download Full-text