RESUMO
INTRODUCTION: Optimising bone health might reduce the burden of both fractures in childhood and fragility fractures in later life. A number of maternal dietary and non-dietary factors have been identified that might influence offspring bone health and represent targets for intervention. AREAS COVERED: This article will outline the accrual of bone mineral throughout the life course and how observational and intervention studies have shown that maternal diet, in particular maternal calcium and 25-hydroxyvitamin D [25(OH)D] status, and lifestyle are associated with offspring bone mineralization. Studies examining the effects of maternal micronutrient supplementation on offspring bone mineral density (BMD) will also be discussed. EXPERT COMMENTARY: There is a wealth of observational evidence relating maternal diet to offspring BMD. However, high quality randomized controlled trials, such as the ongoing MAVIDOS study, are needed before these findings can be definitively translated into public health advice.
Assuntos
Doenças do Desenvolvimento Ósseo/prevenção & controle , Calcificação Fisiológica , Fenômenos Fisiológicos da Nutrição Materna , Lesões Pré-Natais/prevenção & controle , Densidade Óssea , Doenças do Desenvolvimento Ósseo/dietoterapia , Cálcio da Dieta/metabolismo , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Feminino , Humanos , Saúde Materna , Estudos Observacionais como Assunto , Gravidez , Lesões Pré-Natais/dietoterapia , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/prevenção & controleAssuntos
Fator 4 Ativador da Transcrição/genética , Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças do Desenvolvimento Ósseo/metabolismo , Proteínas Alimentares/uso terapêutico , Suplementos Nutricionais , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Animais , Doenças do Desenvolvimento Ósseo/genética , Matriz Óssea/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Calcificação Fisiológica/genética , Diferenciação Celular/genética , Proteínas Alimentares/efeitos adversos , Proteínas Alimentares/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos/genética , Alimentos Formulados/efeitos adversos , Regulação da Expressão Gênica no Desenvolvimento/genética , Camundongos , Camundongos Knockout , Neurofibromatose 1/dietoterapia , Neurofibromatose 1/genética , Neurofibromatose 1/metabolismo , Osteoblastos/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Transdução de Sinais/genéticaRESUMO
Bone formation is controlled by a network of transcription factors and signaling molecules. In this issue, , studying the role of the transcription factor ATF4 in a new mouse model of neurofibromatosis type I skeletal defects, demonstrate striking effects of changing dietary protein on bone formation abnormalities.
Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças do Desenvolvimento Ósseo/metabolismo , Proteínas Alimentares/uso terapêutico , Neurofibromina 1/metabolismo , Osteoblastos/metabolismo , Aminoácidos/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Transporte Biológico Ativo/genética , Doenças do Desenvolvimento Ósseo/congênito , Doenças do Desenvolvimento Ósseo/patologia , Reabsorção Óssea/dietoterapia , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Síndrome de Coffin-Lowry/genética , Síndrome de Coffin-Lowry/metabolismo , Síndrome de Coffin-Lowry/patologia , Colágeno/biossíntese , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Camundongos , Camundongos Knockout , Neurofibromina 1/deficiência , Osteoblastos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/genética , Ligante RANK/biossíntese , Ligante RANK/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/deficiência , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismoRESUMO
The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1(ob)(-/-) mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1(ob)(-/-) mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1(ob)(-/-) mice without affecting other organ weight, while a high-protein diet overcame Atf4(-/-) and Rsk2(-/-) mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development.
Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças do Desenvolvimento Ósseo/metabolismo , Proteínas Alimentares/uso terapêutico , Neurofibromina 1/metabolismo , Osteoblastos/metabolismo , Aminoácidos/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Transporte Biológico Ativo/genética , Doenças do Desenvolvimento Ósseo/congênito , Doenças do Desenvolvimento Ósseo/patologia , Reabsorção Óssea/dietoterapia , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Síndrome de Coffin-Lowry/genética , Síndrome de Coffin-Lowry/metabolismo , Síndrome de Coffin-Lowry/patologia , Colágeno/biossíntese , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Camundongos , Camundongos Knockout , Neurofibromina 1/deficiência , Osteoblastos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/genética , Ligante RANK/biossíntese , Ligante RANK/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/deficiência , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismoRESUMO
The fortuitous discovery of bone mineralization abnormalities in premature babies fed a medium chain triglyceride supplemented formula and exhibiting satisfactory weight gains prompted us to perform calcium and phosphorus balance studies. The infants studied had no major neonatal disorders and were not vitamin D-deficient. Urine assays detected no phosphorus and demonstrated an increase in calcium excretion, suggesting an inadequate phosphorus intake. This hypothesis was confirmed by the appearance of urinary phosphates with a decrease in calcium losses following supplementation of the formula with phosphorus.
Assuntos
Doenças do Desenvolvimento Ósseo/dietoterapia , Alimentos Fortificados , Alimentos Infantis , Recém-Nascido Prematuro , Fósforo/uso terapêutico , Doenças do Desenvolvimento Ósseo/etiologia , Doenças do Desenvolvimento Ósseo/metabolismo , Humanos , Lactente , Recém-NascidoAssuntos
Fenômenos Fisiológicos da Nutrição Animal , Doenças do Desenvolvimento Ósseo/veterinária , Doenças Ósseas Metabólicas/veterinária , Doenças das Aves Domésticas/etiologia , Animais , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças Ósseas Metabólicas/dietoterapia , Membro Posterior , Aves Domésticas , Doenças das Aves Domésticas/dietoterapiaRESUMO
Three experiments were conducted with day-old broiler chicks to determine the effects of dietary choline, biotin, and manganese on cartilage hexosamine and hydroxyproline content. The incidence of leg weakness was 75% or higher on all basal diets. The levels of supplementation found to minimize leg weakness were 1540 mg choline chloride/kg diet, .2 mg biotin/kg diet, and 100 mg manganese/kg diet. The levels required to maintain normal epiphyseal cartilage hexosamine content were 385 mg of choline chloride, .05 mg of biotin, and 25 mg of manganese/kg of diet. Substantially higher levels of nutrients were needed to reduce the incidence of leg weakness. Only with manganese supplementation was the incidence of leg weakness significantly reduced at the level of supplementation required for normal hexosamine content. Hydroxyproline content was not affected by varying the levels of supplemental choline, biotin, or manganese.
Assuntos
Biotina/farmacologia , Doenças do Desenvolvimento Ósseo/veterinária , Doenças das Cartilagens/veterinária , Galinhas/metabolismo , Colina/farmacologia , Hexosaminas/análise , Hidroxiprolina/análise , Manganês/farmacologia , Doenças das Aves Domésticas/dietoterapia , Animais , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças do Desenvolvimento Ósseo/metabolismo , Cartilagem/análise , Doenças das Cartilagens/dietoterapia , Doenças das Cartilagens/metabolismo , Epífises , Extremidades , Feminino , Alimentos Fortificados , MasculinoRESUMO
Three experiments were conducted using commercially available broiler chicks to study the influence of high levels of pyridoxine on incidence of twisted legs. Chicks were grown in wire floored battery brooders to two weeks of age when they were weighed and visually scored for twisted legs. Supplementation of a diet containing 2.2 mg synthetic vitamin B6/kg with 10 and 20 mg/kg pyridoxine resulted in a significant decrease (P less than or equal to .05) in incidence of twisted legs in Experiment 1. In Experiment 2, supplementation with 30, 60, or 100 mg/kg numerically reduced incidence, but the differences were not statistically significant. Incidence of twisted legs was significantly increased by injecting chicks with .5 ml physiological saline at 1 and 7 days of age in comparison to noninjected controls. Including 10 mg pyridoxine HCl in the saline reduced the incidence but it was still numerically higher than the noninjected controls. Factors other than vitamin B6 nutrition appear to play a more important role in the etiology of twisted legs in broiler chicks.
Assuntos
Doenças do Desenvolvimento Ósseo/veterinária , Doenças das Cartilagens/veterinária , Galinhas/metabolismo , Doenças das Aves Domésticas/dietoterapia , Piridoxina/uso terapêutico , Animais , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças das Cartilagens/dietoterapia , Extremidades , MasculinoRESUMO
Foreleg lameness caused by the interaction of diet and rapid growth rate is all too frequently encountered in the large and giant breeds of dogs. In this paper, the influence of rapid growth rate and growth hormone on bone formation is briefly considered. The importance causes of this problem are discussed. These are hypertrophic osteodystrophy, osteodystrophy II, retained enchondral cartilage cores, panosteitis an nutritional secondary hyperparathyroidism. Rickets and hypertrophic pulmonary osteoarthropathy are also considered. Emphasis is placed on the aetiology, radiographic diagnosis and rational treatment. A case report of a 6-month-old Great Dane with osteodystrophy II and retained enchondral cartilage cores in the ulnar metaphyses is presented as an example of such a problem.
Assuntos
Doenças do Desenvolvimento Ósseo/veterinária , Doenças do Cão/etiologia , Membro Anterior , Artropatias/veterinária , Coxeadura Animal/etiologia , Animais , Doenças do Desenvolvimento Ósseo/dietoterapia , Doenças do Desenvolvimento Ósseo/etiologia , Doenças do Cão/dietoterapia , Cães , Artropatias/etiologia , Coxeadura Animal/dietoterapia , MasculinoRESUMO
A bent-limb syndrome in lambs raised in total confinement was characterized by curvature of the forelimbs. Radiographic findings included flaring of the affected long bone and thinning of the growth plate. The main histologic change was endochondral dysplasia of the long bone. In feed samples, all trace minerals analyzed were within recommended concentrations except iron, which was much higher (400 ppm dry matter) than the normal requirement of lambs (70 ppm). All mineral concentrations in serum were normal except those of inorganic phosphorus and iron, which were higher. Results of soft tissue and bone mineral analyses were normal. Altering the ratio of calcium and phosphorus did not affect the incidence of disease, but intramuscular administration of massive doses of vitamin D3 and reducing the amount of dietary iron had a prophylactic effect. The increase in serum phosphorus was probably related to the dietary excess of iron, which probably decreased vitamin D metabolite formation in the kidney, which in turn could be prevented by massive doses of vitamin D3.