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Sample records for metabolic bone diseases

  1. [Metabolic bone diseases].

    PubMed

    Jakob, F

    2007-10-01

    Osteomalacia is caused by impaired vitamin D receptor (VDR) signaling, calcium deficiency, and altered bone mineralization. This can be due to insufficient sunlight exposure, malabsorption, reduced D hormone activation in chronic kidney disease, and rare alterations of VDR signaling and phosphate metabolism. Leading symptoms are bone pain, muscular cramps, and increased incidence of falls in the elderly. The adequate respective countermeasures are to optimize the daily intake of calcium and vitamin D3 and to replace active D hormone and phosphate if deficient. Osteoporosis is characterized by bone fragility fractures upon minor physical impact. Indications for diagnosis and treatment can be established by estimating the absolute fracture risk, taking into account bone mineral density, age, gender, and individual risk factors. Exercise, intervention programs to avoid falls, and specific drugs are capable of substantially reducing fracture risk even in the elderly. Secondary osteoporosis primarily requires both bone-altering medications and effective treatment of underlying diseases.

  2. Bone scan in metabolic bone diseases. Review.

    PubMed

    Abdelrazek, Saeid; Szumowski, Piotr; Rogowski, Franciszek; Kociura-Sawicka, Agnieszka; Mojsak, Małgorzata; Szorc, Małgorzata

    2012-08-25

    Metabolic bone disease encompasses a number of disorders that tend to present a generalized involvement of the whole skeleton. The disorders are mostly related to increased bone turnover and increased uptake of radiolabelled diphosphonate. Skeletal uptake of 99mTc-labelled diphosphonate depends primarily upon osteoblastic activity, and to a lesser extent, skeletal vascularity. A bone scan image therefore presents a functional display of total skeletal metabolism and has valuable role to play in the assessment of patients with metabolic bone disorders. However, the bone scan appearances in metabolic bone disease are often non-specific, and their recognition depends on increased tracer uptake throughout the whole skeleton. It is the presence of local lesions, as in metastatic disease, that makes a bone scan appearance obviously abnormal. In the early stages, there will be difficulty in evaluating the bone scans from many patients with metabolic bone disease. However, in the more severe cases scan appearances can be quite striking and virtually diagnostic.

  3. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  4. [Metabolic bone and joint diseases].

    PubMed

    Endo, Itsuro

    2014-10-01

    Metabolic bone and joint diseases in adults include osteomalacia, rheumatoid arthritis, gouty arthritis. Recently, the newest molecular biology procedures and the clinical observation studies can produce good results for understanding of these diseases. From this perspective, the author introduced updated information of the pathophysiology, the latest diagnostic criteria and the therapy of these diseases.

  5. [Hearing and balance in metabolic bone diseases].

    PubMed

    Zatoński, Tomasz; Temporale, Hanna; Krecicki, Tomasz

    2012-03-01

    There are reports that hearing loss is one of the clinical manifestations of metabolic bone diseases. Demineralization can lead to a reduction in ossicular mass. Paget's disease can reveal loss of mineral density of the cochlear bone. Ear bone remodeling in osteoporosis is similar to the changes in otosclerosis. Moreover, osteoporosis, osteogenesis imperfecta and otosclerosis have a similar genetic mechanism. According to some researchers osteopenia and osteoporosis may well be associated with idiopathic benign positional vertigo (BPV). Dysfunction of the organ of hearing and balance in patients with renal insufficiency may be due to disturbances in calcium phosphate balance and renal osteodystrophy in the course of the disease. Proving the presence of hearing loss in patients with metabolic bone diseases may lead to determining the new indications for bone densitometry in some patients with hearing impairment. Furthermore, audiological examination in patients with osteoporosis may be important because of the impact of hearing loss on prognosis for patients with metabolic bone diseases.

  6. [Serum sclerostin levels and metabolic bone diseases].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2013-06-01

    Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

  7. Mesenchymal stem cells for bone repair and metabolic bone diseases.

    PubMed

    Undale, Anita H; Westendorf, Jennifer J; Yaszemski, Michael J; Khosla, Sundeep

    2009-10-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.

  8. Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases

    PubMed Central

    Undale, Anita H.; Westendorf, Jennifer J.; Yaszemski, Michael J.; Khosla, Sundeep

    2009-01-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases. PMID:19797778

  9. [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Non- invasive assessment of bone turn over markers could define the cause of metabolic bone diseases].

    PubMed

    Suzuki, Atsushi

    2011-09-01

    Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.

  10. Roles of leptin in bone metabolism and bone diseases.

    PubMed

    Chen, Xu Xu; Yang, Tianfu

    2015-09-01

    Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

  11. Oral manifestations of metabolic bone disease: vitamin D and osteoporosis.

    PubMed

    Zachariasen, R

    1990-10-01

    Metabolic bone diseases are disorders of bone remodeling and characteristically involve the entire bony skeleton. Metabolic bone diseases exhibit their effects throughout all skeletal tissue, and very often are first diagnosed from abnormalities appearing in the oral cavity or on dental radiographs. This article presents major metabolic bone diseases that are often manifested in the oral cavity. It discusses the physiology of vitamin D and the major bone disorders associated with abnormal levels of this hormone. Osteoporosis, the most common metabolic bone disease in elderly patients, also will be discussed. With the expanding older population, osteoporosis has become a major health problem and poses special concerns for the dental practitioner.

  12. Recent developments in metabolic bone diseases: a gnathic perspective.

    PubMed

    Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

    2014-12-01

    Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

  13. [Bone and calcium metabolism in life-style related diseases].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2016-03-01

    Accumulating evidence shows that life-style related diseases such as diabetes mellitus, hypertension, dyslipidemia are associated with bone and calcium metabolism. Patients with diabetes mellitus have increased fracture risks, independently of bone mineral density, with abnormality of parathyroid hormone secretion and impaired osteoblastic function. On the other hand, osteocalcin secreted from bone is reported to regulate glucose metabolism. Thus, bone, calcium and glucose metabolism may be deeply associated with each other. In this review, we describe the association between life-style related diseases, especially diabetes mellitus, and metabolism of bone and calcium.

  14. [Magnesium disorder in metabolic bone diseases].

    PubMed

    Ishii, Akira; Imanishi, Yasuo

    2012-08-01

    Magnesium is abundantly distributed among the body. The half of the magnesium exists in the bone. In addition, magnesium is the second most abundant intracellular cation in vertebrates and essential for maintaining physiological function of the cells. Epidemiologic studies have demonstrated that magnesium deficiency is a risk factor for osteoporosis. The mechanism of bone fragility caused by magnesium deficiency has been intensely studied using animal models of magnesium deficiency. Magnesium deficiency causes decreased osteoblastic function and increased number of osteoclasts. Magnesium deficiency also accelerates mineralization in bone. These observations suggest that disturbed bone metabolic turnover and mineralization causes bone fragility.

  15. [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Necessity of bone biopsy].

    PubMed

    Ito, Akemi; Yajima, Aiji

    2011-09-01

    Histological analysis of undecalcified bone biopsy specimens is a valuable clinical and research tool for studying the etiology, pathogenesis and treatment of metabolic bone diseases. In case of osteoporosis, bone biopsy is not usually required for the diagnosis ; however, bone histomorphometry may be useful in rare cases with unusual skeletal fragility. Bone histomorphometry also provides valuable information on the mechanism of action, safety and efficacy of new anti-osteoporosis drugs. Bone histomorphometry is useful for the diagnosis and the assessment of treatment response in rickets/osteomalacia and in CKD-MBD (chronic kidney disease-mineral and bone disorders) . In Japan, bone biopsy is often performed to establish the diagnosis of Paget's disease of bone, especially to differentiate it from metastatic bone disease.

  16. Diabetes mellitus related bone metabolism and periodontal disease

    PubMed Central

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

  17. Diabetes mellitus related bone metabolism and periodontal disease.

    PubMed

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-06-26

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  18. Algorithm for employing physical forces in metabolic bone diseases.

    PubMed

    Massari, Leo

    2011-04-01

    Metabolic bone diseases, especially osteoporosis, demand a multidisciplinary approach. The physical forces find a rationale in the treatment of local alterations in bone-cartilage metabolism. In integrated treatment of vertebral fractures caused by fragility, stimulation with electrical fields has been observed to be effective in reducing pain and improving patients' quality of life.

  19. [Non-corticosteroid drug-induced metabolic bone disease].

    PubMed

    Briot, Karine

    2006-10-01

    After osteoporotic fracture or low bone mineral density measurements, it is necessary to look for secondary causes of osteoporosis, such as drugs. Corticosteroids are the most common cause of drug-induced metabolic bone disease. Other drugs responsible for bone disease include: aromatase inhibitors, GnRH agonists, anticonvulsants, heparin, and L thyroxin at TSH-suppressive doses. Confirmation is required of data about neuroleptics and antivitamin K.

  20. Gamma images in benign and metabolic bone diseases: volume 1

    SciTech Connect

    Sy, W.M.

    1981-01-01

    Volume 1 of ''Gamma images in benign and metabolic bone diseases'' comprises chapters devoted to: general remarks and considerations, radiopharmaceuticals, Paget disease, osteomyelitis, trauma, benign bone tumors, chronic renal dialysis, acute renal failure, osteomalacia and rickets, and osteoporosis. Although published in 1981, the most recent references in the book were 1978 and most are 1977 or earlier. One of the strongest aspects of the volume are tables which categorize diseases, pathophysiology of disease, and image abnormalities. (JMT)

  1. [Updates on Lifestyle-Related Diseases and Bone Metabolism. The metabolic syndrome and bone metabolism].

    PubMed

    Yamaguchi, Toru

    2014-11-01

    The metabolic syndrome is featured by the combination of obesity induced by visceral fat accumulation, dyslipidemia, hyperglycemia, and hypertension. It is well documented that obesity and body weight increase are positively linked to increased bone mineral density (BMD) and reduced fracture risk of weight-bearing bones through mechanical stress. On the other hand, inflammatory cytokines secreted from visceral fat and advanced glycation products induced by hyperglycemia tend to reduce BMD and to increase fracture risk in contrast to obesity. Thus, BMD and fracture risk in patients with the metabolic syndrome may be determined by the balance between the beneficial effect of obesity and detrimental ones of inflammatory cytokines and hyperglycemia on bone.

  2. Metabolic bone diseases during long-term total parenteral nutrition.

    PubMed

    Acca, M; Ragno, A; Francucci, C M; D'Erasmo, E

    2007-01-01

    Long-term total parenteral nutrition (TPN) is a procedure commonly applied to patients with advanced forms of intestinal malabsorption. Among TPN complications, bone metabolic diseases, such as osteoporosis and osteomalacia, are a common finding. Initially considered to be a manifestation of aluminium toxicity which followed massive contamination with the element of the solutions used in TPN, metabolic osteopathy during TPN is currently considered a multiform syndrome, with a multifactorial pathogenesis, which may manifest itself with vague or clear clinical pictures. In this review, we analyse clinical, pathogenetic, and therapeutic aspects of the most common bone metabolic diseases in patients undergoing long-term TPN.

  3. Bone Health and Associated Metabolic Complications in Neuromuscular Diseases

    PubMed Central

    Joyce, Nanette C.; Hache, Lauren P.; Clemens, Paula R.

    2014-01-01

    Synopsis This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Poor bone health with related morbidity is a significant problem for patients with NMD. Although the evidence addressing issues of bone health and osteoporosis have increased as a result of the Bone and Joint Decade, studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy. These problems appear common. Osteomalacia often complicates disease-related baseline osteoporosis and may reduce fracture risk if treated. Future directions are discussed, including the urgent need for studies to both determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD. PMID:23137737

  4. [Bone diseases caused by impaired glucose and lipid metabolism].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

    The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

  5. Bone health and associated metabolic complications in neuromuscular diseases.

    PubMed

    Joyce, Nanette C; Hache, Lauren P; Clemens, Paula R

    2012-11-01

    This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed, focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and spinal muscular atrophy. Future directions are discussed, including the urgent need for studies both to determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD.

  6. Osteopenia (metabolic bone disease) of prematurity

    USDA-ARS?s Scientific Manuscript database

    Osteopenia is defined as postnatal bone mineralization that is inadequate to fully mineralize bones. Osteopenia occurs commonly in very low birth weight (VLBW) infants. Prior to the use of high-mineral containing diets for premature infants, which is the current practice, significant radiographic ch...

  7. Obstructive sleep apnea and metabolic bone disease: Insights in to the relationship between bone and sleep

    PubMed Central

    Swanson, Christine M.; Shea, Steven A.; Stone, Katie L.; Cauley, Jane A.; Rosen, Clifford J.; Redline, Susan; Karsenty, Gerard; Orwoll, Eric S.

    2015-01-01

    Obstructive sleep apnea (OSA) and low bone mass are two prevalent conditions, particularly among older adults, a section of the U.S. population that is expected to grow dramatically over the coming years. OSA, the most common form of sleep disordered breathing, has been linked to multiple cardiovascular, metabolic, hormonal and inflammatory derangements and may have adverse effects on bone. However, little is known about how OSA (including the associated hypoxia and sleep loss) affects bone metabolism. In order to gain insight into the relationship between sleep and bone, we review the growing information on OSA and metabolic bone disease and discuss the pathophysiological mechanisms by which OSA may affect bone metabolism/architecture. PMID:25639209

  8. Metabolic Bone Disease in Viral Cirrhosis: A Prospective Study

    PubMed Central

    Goubraim, Rabia; Kabbaj, Nawal; Salihoun, Mouna; Chaoui, Zakia; Nya, M'Hamed; Amrani, Naima

    2013-01-01

    Background/Aim. Metabolic Bone disorders are well-recognized extrahepatic complications of cirrhosis. The aim was to report their prevalence and the associated factors to their development in patients with viral cirrhosis. Patients and Methods. All consecutive patients with viral cirrhosis were prospectively enrolled. Parathyroid hormone, 25-hydroxyvitamin D, liver function, and phosphocalcic tests were measured in all patients. Bone mineral density was measured at the lumbar spine and total hip by dual-energy X-ray absorptiometry. Data were analyzed using SPSS software. Results. Forty-six cirrhotic patients were included with hepatitis C (87%) and hepatitis B (13%). The Child-Pugh score was grade A in 87% of cases and grade B in 13%. Thirty-seven patients had decreased bone mineral density with osteopenia in 24 patients and osteoporosis in 13 patients. Decreased 25-hydroxyvitamin D was found in 95.6% of cases. Bone disorders were significantly more frequent in old patients with low body mass index, long duration of liver disease, and low 25-hydroxyvitamin D level. None of these factors was an independent factor associated with bone disorders. Conclusion. Our study revealed a high prevalence of metabolic bone disorders among viral cirrhotic patients. Consequently, bone mineral density assessment should be performed systematically in all cirrhotic patients. PMID:27398385

  9. Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

    PubMed

    Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

    2010-01-01

    The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

  10. [Pathological and metabolic bone diseases: Clinical importance for fracture treatment].

    PubMed

    Oheim, R

    2015-12-01

    Pathological and metabolic bone diseases are common and relevant occurrences in orthopedics and trauma surgery; however, fractures are often treated as being the illness itself and not seen as the symptom of an underlying bone disease. This is why further diagnostics and systemic treatment options are often insufficiently considered in the routine treatment of fractures. This review focuses on osteoporosis, osteopetrosis, hypophosphatasia and Paget's disease of bone.In patients with osteoporotic vertebral or proximal femur fractures, pharmaceutical treatment to prevent subsequent fractures is an integral part of fracture therapy together with surgical treatment. Osteopetrosis is caused by compromised osteoclastic bone resorption; therefore, even in the face of an elevated bone mass, vitamin D3 supplementation is crucial to avoid clinically relevant hypocalcemia. Unspecific symptoms of the musculoskeletal system, especially together with stress fractures, are typically found in patients suffering from hypophosphatasia. In these patients measurement of alkaline phosphatase shows reduced enzyme activity. Elevated levels of alkaline phosphatase are found in Paget's disease of bone where bisphosphonates are still the treatment of choice.

  11. Generalized metabolic bone disease in Neurofibromatosis type I

    USDA-ARS?s Scientific Manuscript database

    Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

  12. Metabolic bone disease in juvenile koalas (Phascolartcos cinereus).

    PubMed

    Pye, Geoffrey W; Gait, Sarah Catherine; Mulot, Baptiste; de Asua, Maria Delclaux Real; Martinez-Nevado, Eva; Bonar, Christopher J; Baines, Stephen J; Baines, Elizabeth A

    2013-06-01

    Due to climate restrictions in parts of North America and Europe, koalas (Phascolarctos cinereus) are housed indoors. Koala young (joeys) raised indoors are susceptible to the development of metabolic bone disease (MBD) due to a lack of exposure to natural ultraviolet light to themselves and their female parents (dams). In this retrospective study, radiographs from 27 koala joeys born at four zoos in North America and two zoos in Europe were evaluated for signs of MBD. Eight of the joeys were radiographically diagnosed with MBD and four additional joeys were considered suspect MBD cases; in two joeys absence or presence of MBD could not be determined. All joeys had mild to severe hip and shoulder dysplasia. There were significant associations between a lack of exposure to UV light and MBD development and between MBD and the degree of severity of hip and shoulder dysplasia. It is recommended to house breeding female koalas and their joeys outdoors whenever possible.

  13. [Morphological analysis of bone dynamics and metabolic bone disease. Renal Osteodystrophy and New KDIGO CKD-MBD classification].

    PubMed

    Tsukamoto, Yusuke

    2011-04-01

    Global Kidney Disease Guideline Organization ; KDIGO has decided to express the abnormality in bone and mineral metabolism associated with chronic kidney disease (CKD) as CKD-Mineral Bone Disorder (CKD-MBD) . The term "renal osteodystrophy" is now only used for expressing bone pathological abnormality diagnosed by biopsy. The classical classification of bone pathology in CKD is superseded by new T (Turnover) M (mineralization) V (Volume) classification.

  14. Metabolic bone disease and bone mineral density in very preterm infants.

    PubMed

    Figueras-Aloy, Josep; Álvarez-Domínguez, Enriqueta; Pérez-Fernández, José M; Moretones-Suñol, Gloria; Vidal-Sicart, Sergi; Botet-Mussons, Francesc

    2014-03-01

    To evaluate bone mineral density (BMD) in preterm neonates at discharge and identify the optimum cutoff values for serum alkaline phosphatase (ALP) and phosphorus (P) concentrations to diagnose the severity of metabolic bone disease of prematurity. A total of 336 preterm neonates (≤ 31 weeks' gestation and birth weight ≤ 1500 g) were prospectively evaluated for BMD before discharge using dual-energy X-ray absorptiometry. BMD reference values (at ALP ≤ 500 IU/L) were measured in 279 patients. BMD was classified as poor (<10th percentile) at <0.068 g/cm(2), fair (10th-25th percentile) at 0.068-0.081 g/cm(2), good (25th-75th percentile) at 0.081-0.112 g/cm(2), and very good (>75th percentile) at >0.112 g/cm(2). Increased BMD was associated with a higher birth weight, short duration of parenteral nutrition, and the absence of small for gestational age status, patent ductus arteriosus, intraventricular hemorrhage, and other clinical variables. Metabolic bone disease of prematurity was absent (ALP ≤ 500 IU/L) in 279 cases (83.0%), mild (ALP >500 IU/L and P ≥ 4.5 mg/dL) in 46 cases (13.7%), and severe (ALP >500 IU/L and P <4.5 mg/dL) in 11 cases (3.3%). A BMD >0.068 g/cm(2) at discharge indicated a 90.3% probability of not developing metabolic bone disease of prematurity. The factors independently associated with increased BMD included higher birth weight, short duration of parenteral nutrition, absence of intraventricular hemorrhage, exclusive feeding of fortified breast milk, and older age at discharge. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  15. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  16. [Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers].

    PubMed

    Chu, B; Lu, M Q; Wu, M Q; Shi, L; Fu, L N; Gao, S; Fang, L J; Xiang, Q Q; Bao, L

    2016-05-17

    To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers. The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and β C-terminal telopeptide of type Ⅰ collagen (β-CTX) were monitored regularly in the two years following treatment in 66 cases. (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78±29.93)vs (108.84±29.30) g/L], and higher blood calcium level[(2.47±0.40)vs (2.30±0.29) mmol/L], serum β2-microglobuin level[(6.04±4.84)vs (4.12±3.97)mg/L], and bone marrow plasma cells percentage(33.30%±24.87% vs 23.51%±22.67%)(all P<0.05). (3) Before treatment, the levels of β-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 μg/L, 60.95 vs 43.47 μg/L, both P<0.05). The ratio of β-CTX /tPINP in group B was higher than that

  17. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Bisphosphonates for lifestyle-related disease].

    PubMed

    Okada, Yosuke; Tanaka, Yoshiya

    2014-11-01

    A lifestyle-related disease and osteoporosis are diseases to increase with aging and a lifestyle-related disease has an influence on the bone metabolism. Because the number of patients with lifestyle-related disease is getting larger, it is necessary to prevent fracture in those. Unfortunately, substantial randomized control studies are yet to be done in patients with lifestyle-related disease to clarify if anti-osteoporotic drugs are effective to prevent fractures. It is suggested by the subanalysis in the existing clinical study with usefulness of bisphosphonates with evidence as an osteoporotic therapeutic drug in life-related disease. Here I will review about the effective and problem with bisphosphonate for the lifestyle-related disease with arteriosclerosis.

  18. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    PubMed

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities. Copyright © 2015 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  19. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    PubMed Central

    Tejwani, Vickram; Qian, Qi

    2013-01-01

    The elderly chronic kidney disease (CKD) population is growing. Both aging and CKD can disrupt calcium (Ca2+) homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD). CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD. PMID:23760058

  20. New mouse models for metabolic bone diseases generated by genome-wide ENU mutagenesis.

    PubMed

    Sabrautzki, Sibylle; Rubio-Aliaga, Isabel; Hans, Wolfgang; Fuchs, Helmut; Rathkolb, Birgit; Calzada-Wack, Julia; Cohrs, Christian M; Klaften, Matthias; Seedorf, Hartwig; Eck, Sebastian; Benet-Pagès, Ana; Favor, Jack; Esposito, Irene; Strom, Tim M; Wolf, Eckhard; Lorenz-Depiereux, Bettina; Hrabě de Angelis, Martin

    2012-08-01

    Metabolic bone disorders arise as primary diseases or may be secondary due to a multitude of organ malfunctions. Animal models are required to understand the molecular mechanisms responsible for the imbalances of bone metabolism in disturbed bone mineralization diseases. Here we present the isolation of mutant mouse models for metabolic bone diseases by phenotyping blood parameters that target bone turnover within the large-scale genome-wide Munich ENU Mutagenesis Project. A screening panel of three clinical parameters, also commonly used as biochemical markers in patients with metabolic bone diseases, was chosen. Total alkaline phosphatase activity and total calcium and inorganic phosphate levels in plasma samples of F1 offspring produced from ENU-mutagenized C3HeB/FeJ male mice were measured. Screening of 9,540 mice led to the identification of 257 phenodeviants of which 190 were tested by genetic confirmation crosses. Seventy-one new dominant mutant lines showing alterations of at least one of the biochemical parameters of interest were confirmed. Fifteen mutations among three genes (Phex, Casr, and Alpl) have been identified by positional-candidate gene approaches and one mutation of the Asgr1 gene, which was identified by next-generation sequencing. All new mutant mouse lines are offered as a resource for the scientific community.

  1. Generalized metabolic bone disease and fracture risk in Rothmund-Thomson syndrome.

    PubMed

    Cao, Felicia; Lu, Linchao; Abrams, Steven A; Hawthorne, Keli M; Tam, Allison; Jin, Weidong; Dawson, Brian; Shypailo, Roman; Liu, Hao; Lee, Brendan; Nagamani, Sandesh C S; Wang, Lisa L

    2017-08-15

    Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone disease in RTS. Furthermore, the mechanisms that result in this phenotype are largely unknown. In this report, we provide a detailed evaluation of 29 individuals with RTS with respect to their metabolic bone status including bone mineral density, calcium kinetics studies, and markers of bone remodeling. We show that individuals with RTS have decreased areal bone mineral density. Additionally, we demonstrate that the presence of pathogenic variants in RECQL4 and low bone mineral density correlate with the history of increased risk of fractures. Using a RECQL4-deficient mouse model that recapitulates skeletal abnormalities seen in individuals with RTS, we demonstrate that generalized skeletal involvement is likely due to decreased osteogenesis. Our findings are clinically relevant as they may help in the risk stratification of patients with RTS and also in the identification of individuals who may benefit from additional surveillance and management of metabolic bone disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease.

    PubMed

    Delmas, P D

    1990-03-01

    There is not yet an ideal marker of bone formation, but circulating BGP is the most satisfactory at present. New developments include the use of sheep BGP64 and human BGP85 as an immunogen and monoclonal antibodies, which may recognize fragments of BGP released during resorption. The specific measurement of bone alkaline phosphatase and the assay of procollagen fragments and of other noncollagenous bone-related proteins will allow a more precise assessment of the complex osteoblastic functions in normal and pathologic conditions. Finding a sensitive and specific marker of resorption is a challenge because all constituents of bone matrix are likely to be degraded into minute peptides during osteoclastic bone resorption. The measurement of pyridinium crosslinks and possibly of tartrate-resistant acid phosphate by a bone-specific monoclonal antibody are the most tangible improvements in this area. These markers need to be validated by comparison with data obtained by direct measurement of bone turnover on iliac crest biopsy. It should be remembered, however, that circulating markers reflect the overall activity of the whole skeleton, including the cortical, subcortical, and trabecular envelopes, which have different remodeling rates in normal and abnormal states. A circulating marker will not detect a specific defect of the cellular activity of one compartment of bone if the summated turnover of the skeleton is unchanged. Conversely, bone histomorphometry is limited to a small area of the trabecular envelope but allows detection of a specific defect at the cellular level. These differences should be kept in mind, as there is growing evidence that, for example, bone mass and bone turnover of osteoporotic patients before and during treatment vary in different appendicular/axial and cortical/trabecular compartments. Finally, a single marker might be valuable in some diseases and not in others (such as serum BGP in Paget's disease of bone). Despite these difficulties

  3. [Disorders of carbohydrate metabolism, dyslipidemia, and bone metabolic disease after hematopoietic stem cell transplantation].

    PubMed

    Wędrychowicz, Anna; Starzykk, Jerzy

    2013-01-01

    Among long-term survivors after hematopoietic stem cell transplantation (HSCT) late endocrine complications are observed in 20-50%. Very often these complications influence significantly the patient´s life and have to be treated till the end of life. Their proper prevention and monitoring are extremely important in patients who underwent HSCT during childhood. Since the 90s of the last millennium/century, thyroid dysfunction, disorders of somatic and sexual development, and disturbances of fertility have been presented in several publications. In the paper, less known endocrine complications after HSCT published in the last years are discussed. Disorders of carbohydrate metabolism, post-transplant diabetes and insulin resistance are presented. Moreover, dyslipidemia, hypertension, and post-transplant bone metabolic disease are demonstrated/shown. The paper describes the etiopathogenesis, methods of prevention as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover, actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

  4. A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

    PubMed Central

    Pawlak, Krystyna; Oksztulska-Kolanek, Ewa; Domaniewski, Tomasz; Znorko, Beata; Karbowska, Malgorzata; Citkowska, Aleksandra; Rogalska, Joanna; Roszczenko, Alicja; Brzoska, Malgorzata M.; Pawlak, Dariusz

    2017-01-01

    Background Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD. Methods Thirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites. Results Subtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry. Discussion In addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone

  5. Effects of bioactive fatty acid amide derivatives in zebrafish scale model of bone metabolism and disease.

    PubMed

    Carnovali, M; Ottria, R; Pasqualetti, S; Banfi, G; Ciuffreda, P; Mariotti, M

    2016-02-01

    The endocannabinoid system (which includes fatty acid derivatives, receptors, and metabolizing enzymes) is involved in a variety of physiological processes, including bone metabolism in which it regulates the function of osteoblasts and osteoclasts, as well as differentiation of their precursors. The zebrafish (Danio rerio) provides a useful animal model for bone research since zebrafish bones develop rapidly and are anatomically similar to mammalian bones. Putative orthologues and paralogs of endocannabinoid genes have recently been identified in zebrafish, demonstrating the presence of cannabinoid type 1 (CB1) and type 2 (CB2) receptors with affinity to endocannabinoid ligands. To identify therapeutic molecules potentially useful in bone-related diseases, we evaluated the in vivo effects of exposure to long-chain fatty acid amides in adult zebrafish. Using a well-established zebrafish scale model, we found that anandamide and N-linoleoylethanolamine are able to stimulate bone formation by increasing alkaline phosphatase activity in physiological conditions. In addition, they prevent the alteration of bone markers in a prednisolone-induced osteoporosis model in adult zebrafish scales, whereas their esterified forms do not. These data suggest that long-chain fatty acid amides are involved in regulating bone metabolism in zebrafish scales and that the CB2 receptor is a key mediator in this process.

  6. Seasonal variability of vitamin D and bone metabolism in infliximab-treated paediatric Crohn's disease.

    PubMed

    Szabó, Dolóresz; Hosszú, Éva; Arató, András; Müller, Katalin Eszter; Béres, Nóra; Lakatos, Péter László; Papp, Mária; Dezsőfi, Antal; Szabó, Attila J; Szűcs, Dániel; Veres, Gabor

    2015-08-01

    Paediatric Crohn's disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D. The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed. Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohn's disease. Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment. Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Assessment of metabolic bone diseases by quantitative computed tomography

    NASA Technical Reports Server (NTRS)

    Richardson, M. L.; Genant, H. K.; Cann, C. E.; Ettinger, B.; Gordan, G. S.; Kolb, F. O.; Reiser, U. J.

    1985-01-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

  8. Assessment of metabolic bone diseases by quantitative computed tomography

    NASA Technical Reports Server (NTRS)

    Richardson, M. L.; Genant, H. K.; Cann, C. E.; Ettinger, B.; Gordan, G. S.; Kolb, F. O.; Reiser, U. J.

    1985-01-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

  9. Bone and mineral metabolism in adult celiac disease

    SciTech Connect

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  10. The role of extracellular modulators of canonical Wnt signaling in bone metabolism and diseases.

    PubMed

    Boudin, Eveline; Fijalkowski, Igor; Piters, Elke; Van Hul, Wim

    2013-10-01

    The Wnt signaling pathway is a key pathway in various processes, including bone metabolism. In this review, current knowledge of all extracellular modulators of the canonical Wnt signaling in bone metabolism is summarized and discussed. The PubMed database was searched using the following keywords: canonical Wnt signaling, β-catenin bone metabolism, BMD, osteoblast, osteoporosis, Wnt, LRPs, Frizzleds, sFRPs, sclerostin or SOST, dickkopfs, Wif1, R-spondins, glypicans, SOST-dc1 and kremen, all separately as well as in different combinations. Canonical Wnt signaling is considered to be one of the major pathways regulating bone formation. Consequently, a large number of studies were performed to elucidate the role of numerous proteins in canonical Wnt signaling and bone metabolism. These studies led to the identification of novel modulators of the pathway like the R-spondin and glypican protein families. Furthermore novel insights are gained in the regulatory role of the different Wnt proteins. Finally, due to its function in bone formation, the pathway is an interesting target for the development of therapeutics for osteoporosis and other bone diseases. In this review, we discuss the promising results of the Wnt modulators sclerostin, Dkk1 and sFRP1 as targets for osteoporosis treatment. The increasing number of studies into the exact function of all proteins in the canonical Wnt pathway in general and in bone metabolism already led to novel insights in the regulation of the canonical Wnt pathway. In this review we covered the current knowledge of all extracellular modulators of canonical Wnt signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Proceedings of the 2016 Santa Fe Bone Symposium: New Concepts in the Management of Osteoporosis and Metabolic Bone Diseases.

    PubMed

    Lewiecki, E Michael; Bilezikian, John P; Bukata, Susan V; Camacho, Pauline; Clarke, Bart L; McClung, Michael R; Miller, Paul D; Shepherd, John

    The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters. Copyright © 2017. Published by Elsevier Inc.

  12. Fractures Related to Metabolic Bone Disease in Children with Congenital Heart Disease.

    PubMed

    Cheng, Henry H; Carmona, Fabio; McDavitt, Erica; Wigmore, Daniel; Perez-Rossello, Jeannette M; Gordon, Catherine M; Pigula, Frank A; Laussen, Peter C; Rajagopal, Satish K

    2016-01-01

    Critically ill children with congenital heart disease (CHD) are at risk for metabolic bone disease (MBD) and bone fractures. Our objective was to characterize a cohort of CHD patients with fractures and describe a Fragile Bone Protocol (FBP) developed to reduce fractures. Patients who developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement and radiology databases. The FBP (initiated July 2011) systematically identifies patients at risk for MBD and prescribes special handling precautions. Twenty-three fractures were identified in 15 children. Median age at fracture identification was 6.2 months, with a median duration of hospitalization before fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD. Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of those tested, respectively. Compared with patients not diagnosed with fractures, fracture patients had increased exposure to possible risk factors for MBD and had elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not survive to hospital discharge, compared with an overall CICU mortality rate of 2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6 cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04). Critically ill CHD patients are at risk for fractures. They represent a complex group who frequently has hyperparathyroidism and decreased calcitriol levels, and each may predispose to fractures. FBPs consisting of identification and careful patient handling should be considered in at-risk patients. © 2015 Wiley Periodicals, Inc.

  13. The consequences of chronic kidney disease on bone metabolism and growth in children

    PubMed Central

    Bacchetta, Justine; Harambat, Jérôme; Cochat, Pierre; Salusky, Isidro B.; Wesseling-Perry, Katherine

    2012-01-01

    Growth retardation, decreased final height and renal osteodystrophy (ROD) are common complications of childhood chronic kidney disease (CKD), resulting from a combination of abnormalities in the growth hormone (GH) axis, vitamin D deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD–MBD) may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor growth, ROD, fractures, vascular calcifications, increased morbidity and mortality). In 2012, the clinical management of CKD–MBD in children needs to focus on three main objectives: (i) to provide an optimal growth in order to maximize the final height with an early management with recombinant GH therapy when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain acceptable bone quality and cardiovascular status and (iii) to correct all metabolic and clinical abnormalities that can worsen bone disease, growth and cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and 25(OH)vitamin D deficiency. The aim of this review is to provide an overview of the mineral, bone and vascular abnormalities associated with CKD in children in terms of pathophysiology, diagnosis and clinical management. PMID:22851629

  14. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

    PubMed Central

    Ghishan, Fayez K.

    2011-01-01

    Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1β, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammation-associated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD. PMID:21088237

  15. Assessment of metabolic bone diseases by quantitative computed tomography

    SciTech Connect

    Richardson, M.L.; Genant, H.K.; Cann, C.E.; Ettinger, B.; Gordan, G.S.; Kolb, F.O.; Reiser, U.J.

    1985-05-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid- induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements.

  16. Gaucher disease: the role of the specialist on metabolic bone diseases

    PubMed Central

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    Summary According to European legislation, a disease can be considered rare or “orphan” when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

  17. Gaucher disease: the role of the specialist on metabolic bone diseases.

    PubMed

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible.

  18. Leptin in chronic kidney disease: a link between hematopoiesis, bone metabolism, and nutrition.

    PubMed

    Zhang, Jingjing; Wang, Ningning

    2014-06-01

    Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

  19. A fresh look at metabolic bone diseases in reptiles and amphibians.

    PubMed

    Klaphake, Eric

    2010-09-01

    Metabolic bone diseases (MBDs) are a common presenting complaint in reptiles and amphibians to veterinarians; however, understanding of the causes and diagnostic and treatment options is often extrapolated from human or other mammalian medicine models. Although the roles of UV-B, calcium, phosphorus, and cholecalciferol are better understood in some MBDs, there remain many X factors that are not. Likewise, quantitative diagnosis of MBDs has been difficult not only in terms of staging a disease but also regarding whether or not a condition is present. Treatment options also present challenges in corrective husbandry and diet modifications, medication/modality selection, and dosing/regimen parameters.

  20. Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease

    SciTech Connect

    Garnero, P.; Delmas, P.D.

    1993-10-01

    The authors measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenyzmes, they determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 [+-] 4.8 ng/mL for women; 11.0 [+-] 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P<0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2[+-] 1.8 for B-ALP and 0.9 [+-] 1.3 for T-ALP (P<0.001 between the two).

  1. [Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients].

    PubMed

    Martínez, Esteban; Jódar Gimeno, Esteban; Reyes García, Rebeca; Carpintero, Pedro; Casado, José Luis; Del Pino Montes, Javier; Domingo Pedrol, Pere; Estrada, Vicente; Maalouf, Jorge; Negredo, Eugenia; Ocampo, Antonio; Muñoz-Torres, Manuel

    2014-04-01

    To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. [Bone diseases].

    PubMed

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.

  3. Duodenal histopathology and laboratory deficiencies related to bone metabolism in coeliac disease.

    PubMed

    Posthumus, Lotte; Al-Toma, Abdul

    2017-08-01

    Coeliac disease (CD) is a chronic immune-mediated small intestine enteropathy precipitated by gluten in genetically predisposed individuals. Adult presentation is often atypical and malabsorption of vitamins and minerals is common, with a consequent disturbance of bone metabolism. We aim to evaluate laboratory deficiencies related to bone metabolism and the relationship between severity of histological damage and degree of bone mass loss at diagnosis of CD. A retrospective cross-sectional study of 176 adult coeliac patients was carried out. All patients fulfilled the histopathological criteria for CD. Biochemical data were analysed (calcium/phosphate/alkaline-phosphatase/vitamin D/parathormone). Duodenal histology was classified according to the Marsh classification. Bone mass density (BMD) at the lumbar and femoral regions measured by dual X-ray absorptiometry. A P-value of less than 0.05 was considered significant. No correlation was found between the presence of gastrointestinal symptoms and the Marsh histopathological stage (P>0.05). Vitamin D deficiency was most common (44.5%), whereas only 5.7% had hypocalcaemia. Calcium was lower (P<0.05) and parathormone was higher (P=0.01) in patients with Marsh III. These patients had lower lumbar T-score (P<0.05). Although low BMD occurred in all age groups, most osteoporotic patients were aged 45-49 years (81.8%). A multiple regression analysis showed that the Marsh histopathological stage could be a predictor of lower lumbar BMD (r=0.322, B=-1.146, P<0.05). Laboratory deficiencies and decreased BMD could be severe and unrelated to the presence of gastrointestinal symptoms. At diagnosis, the Marsh histopathological stage could predict the occurrence of low BMD, which carries a risk of developing into osteoporosis. In coeliac patients older than 30 years, evaluation of bone biomarkers and dual X-ray absorptiometry examination should be considered.

  4. The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases

    PubMed Central

    Krela-Kaźmierczak, Iwona; Szymczak, Aleksandra; Łykowska-Szuber, Liliana; Stawczyk-Eder, Kamila; Klimczak, Katarzyna; Linke, Krzysztof; Horst-Sikorska, Wanda

    2015-01-01

    Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D. PMID:26528347

  5. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Effects of sclerostin on bone metabolism in patients with diabetes].

    PubMed

    Yamamoto, Masahiro

    2014-11-01

    Sclerostin, a glycoprotein encoded by SOST gene and secreted from osteocyte, is known as an antagonist for bone formation induced in canonical Wnt/β-catenin signaling pathway by inhibiting receptor complex formation through binding to LDL receptor-related protein 5/6 (LRP 5/6) . From clinical symptoms observed in the patients with a loss-of-function mutation in LRP 6, disorder of that signal transduction pathway is considered as one of candidate molecular mechanism for the simultaneous occurrence of diabetes mellitus and osteoporosis. The serum sclerostin levels of diabetic patients as well as non-diabetic subjects are significantly and positively correlated with bone mineral density, which is the strongest determinant factor especially for diabetic patients. In addition, sclerostin concentrations are associated with prevalent vertebral fractures independent of bone mineral density as well as bone turnover, suggesting that elevated sclerostin levels reflect poor bone quality.

  6. Bone metabolism status and associated risk factors in elderly patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Xiaomei, Wang; Hang, Xiao; Lingling, Liu; Xuejun, Li

    2014-09-01

    The prevalence of osteoporosis in older patients with chronic obstructive pulmonary disease (COPD) is higher than in the age-matched elderly patients, but the exact cause in relation to COPD is not clear. We hypothesized that the underlying causes for this difference are related to bone metabolism with the possible risk factors that include the duration of COPD, GOLD grade, cor pulmonale, the frequencies of acute exacerbations within the past year, smoking and inhaled corticosteroid therapy. We conducted a matched-pair study of 100 patients aged older than 65 years at the Southwest Hospital from May to November 2012. The enrolled patients with COPD were matched to controls for age and gender. Clinical characteristics of cohorts were recorded. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and osteoporosis was diagnosed according to the definition of WHO. All cohorts accepted bone metabolism marker measurement, including Procollagen type 1 aminoterminal propeptide (P1NP), β-C-telopeptides of type I collagen (βCTX), and N-terminal midmolecule fragment osteocalcin (N-MID OC). Statistical analysis was calculated using the student's t test, ANOVA and multiple regression analysis at a significance level set at a p < 0.05. Circulating biochemical markers of bone formation (P1NP), resorption (βCTX) and turnover (N-MID OC) were significantly lower in the COPD group than control group, while mean 25-OH Vitamin D was similar in two groups. The P1NP, βCTX, and N-MID OC were still lower in men with COPD, but only P1NP was lower in women with COPD compared to that of controls. Multiple regression analysis in COPD group suggests that age, the frequency of acute exacerbation, and BMD are independent risk factors for P1NP. The frequency of acute exacerbation within the past one year and 25-OH D level are independent risk factors for βCTX; the frequency of acute exacerbation is the only independent risk factor for N-MID OC. These were significant

  7. Stem cell bone marrow transplantation in patients with metabolic storage diseases.

    PubMed

    Krivit, William

    2002-01-01

    In 1984, an initial report was published on the use of BMT for inborn errors of metabolism. Our first BMT patient had a diagnosis of Maroteaux-Lamy syndrome. She had end-stage cardiopulmonary disease at the time of the transplant and was considered likely to die within months. (69) She is still alive 2 decades later, albeit with limited pulmonary function. In 1992, experimental data demonstrated the prevention of CNS deterioration in fucosidase-deficient dogs after BMT.70 These findings have been noted in many other similar studies. (46) Ample data indicate that BMT can reconstitute the CNS in several of these diseases. Progress is continuing in reducing the morbidity and mortality. In the near future, additional advances may allow for no loss of life and no illness during the bone marrow transplantation process. There is hope that by using neonatal screening techniques, infants at risk can have metabolic storage diseases diagnosed before the diseases progress so that effective treatment can be provided. The combination of all of these advances should result in a logarithmic improvement within the next 2 decades. The plan will be to avoid any mortality or morbidity and to always provide complete engraftment that is permanent and enters all tissues completely.

  8. A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

    PubMed

    Fernández, María C; Parisi, Muriel S; Díaz, Sergio P; Mastaglia, Silvina R; Deferrari, Juan M; Seijo, Mariana; Bagur, Alicia; Micheli, Federico; Oliveri, Beatriz

    2007-08-01

    The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

  9. Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease.

    PubMed

    Nakajima, Sachiko; Iijima, Hideki; Egawa, Satoshi; Shinzaki, Shinichiro; Kondo, Jumpei; Inoue, Takahiro; Hayashi, Yoshito; Ying, Jin; Mukai, Akira; Akasaka, Tomofumi; Nishida, Tsutomu; Kanto, Tatsuya; Tsujii, Masahiko; Hayashi, Norio

    2011-10-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory process in the digestive tract and patients with IBD develop osteopenia. Although vitamins K and D are important for maintaining bone health and inhibiting inflammation, their roles in patients with IBD are not clear. We investigated the roles of vitamins K and D in the bone health and inflammation in patients with IBD. Bone mineral density (BMD) of patients with IBD (Crohn's disease [CD], n = 47, and ulcerative colitis [UC], n = 40) was measured with dual-energy X-ray absorptiometry. Vitamin K and D levels of patients with IBD and healthy volunteers (n = 41) were evaluated by measuring serum undercarboxylated osteocalcin and 1,25 dihydroxyvitamin D, respectively. Clinical activity index was evaluated in patients with CD and UC. BMD was low in patients with CD and UC. Serum undercarboxylated osteocalcin levels were significantly higher in patients with CD, but not with UC, compared with healthy subjects, indicating that bone vitamin K is insufficient in patients with CD. The levels of undercarboxylated osteocalcin were significantly correlated with the clinical activity index of CD, although they were not correlated with BMD. The levels of 1,25 dihydroxyvitamin D were significantly lower in patients with CD and UC than in healthy subjects. The levels of 1,25 dihydroxyvitamin D were inversely correlated with BMD in patients with UC and were not correlated with the clinical activity index of CD. Vitamins K and D are insufficient in patients with IBD. Insufficiency of vitamin K is suggested to be associated with inflammatory processes of CD. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Paget's Disease of Bone

    MedlinePlus

    ... page please turn Javascript on. Paget's Disease of Bone What is Paget's Disease of Bone? Click for more information Enlarged and Misshapen Bones Paget's disease of bone causes affected bones to ...

  11. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice

    PubMed Central

    Ohshima, Toshio; Schiffmann, Raphael; Murray, Gary J.; Kopp, Jeffrey; Quirk, Jane M.; Stahl, Stefanie; Chan, Chi-Chao; Zerfas, Patricia; Tao-Cheng, Jung-Hwa; Ward, J. M.; Brady, Roscoe O.; Kulkarni, Ashok B.

    1999-01-01

    Fabry disease is an X-linked metabolic disorder caused by a deficiency of α-galactosidase A (α-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with α-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated α-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of α-Gal A −/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of α-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease. PMID:10339603

  12. Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort (CMC) study.

    PubMed

    Park, Se Eun; Oh, Ki Won; Lee, Won Young; Baek, Ki Hyun; Yoon, Kun Ho; Son, Ho Young; Lee, Won Chul; Kang, Moo Il

    2014-01-01

    In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

  13. Vitamin D levels and bone metabolism in Chinese adult patients with inflammatory bowel disease.

    PubMed

    Tan, Bei; Li, Pan; Lv, Hong; Li, Yue; Wang, Ou; Xing, Xiao Ping; Qian, Jia Ming

    2014-03-01

    We aimed to investigate the serum 25-hydroxyvitamin D3 (25[OH]D3 ) levels and bone metabolism in adult Chinese patients with inflammatory bowel disease (IBD) and to evaluate the correlation between vitamin D levels and the disease activity as well as the potential risk factors. Age- and gender-matched cohort of IBD patients (124 with ulcerative colitis [UC] and 107 with Crohn's disease [CD]) and 122 healthy controls were enrolled in this study. Serum levels of 25(OH)D3 and bone mineral density (BMD) were measured, and the correlation between the two parameters and the severity of the disease as well as the clinical risk factors were analyzed. Serum 25(OH)D3 levels were lower in UC (10.32 ± 4.46 ng/mL, P < 0.001) and CD patients (11.57 ± 5.02 ng/mL, P = 0.029) than that in healthy controls (12.87 ± 4.40 ng/mL). 25(OH)D3 levels were negatively correlated with the disease severity of both UC (r = -0.371, P < 0.001) and CD (r = -0.285, P = 0.030). The incidences of osteopenia and osteoporosis were high in the IBD patients (37.9% and 3.2% in UC and 30.8% and 4.7% in CD, respectively). Cumulative quantity of glucocorticoids use was significantly associated with osteopenia and osteoporosis in both UC (odds ratio [OR] 1.219, 95% confidence interval [CI] 1.054-1.410, P = 0.008) and CD patients (OR 1.288, 95% CI 1.033-1.606, P = 0.025). Vitamin D deficiency is likely to occur in Chinese patients with IBD and is closely associated with the severity of the disease. Glucocorticoids accumulation is a risk factor for osteopenia and osteoporosis. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  14. A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients.

    PubMed

    Veerappan, Sundaram G; Healy, Martin; Walsh, Bernard; O'Morain, Colm A; Daly, Jacqueline S; Ryan, Barbara M

    2016-11-01

    Infliximab (IFX) treatment has shown potentially beneficial effects on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to prospectively evaluate the impact of IFX treatment on bone metabolism in antitumour necrosis factor (TNF)-α-naive IBD patients using established bone metabolism markers and an in-vitro osteoblast model. A total of 37 anti-TNFα-naive IBD patients and 20 healthy controls were included. All measurements were performed at baseline and repeated in IBD patients following IFX therapy. Bone mineral density was measured by dual-energy X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble receptor activator of nuclear factor B ligand and proinflammatory and anti-inflammatory cytokines were measured. Bone formation was measured using osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was measured using serum type 1 collage c-telopeptide. The effect of control and IBD patient sera on human osteoblast viability and differentiation was analysed. OC level was higher in controls than IBD patients (P=0.018). After IFX, OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011) and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX therapy, proinflammatory cytokines TNF-α, interleukin-6 and interleukin-13 decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6), respectively. Sera from IBD patients before IFX showed increased osteoblast viability compared with the controls (P=0.003 to P<0.005), but induced reduced osteoblast differentiation. After IFX, viability reduced to control levels, but osteoblast differentiation increased (P=0.041). IFX treatment induced beneficial effects on bone metabolism. Osteoblast culture results suggest that IBD patients may have increased osteoblast viability, but reduced differentiation, which has implications

  15. [Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease].

    PubMed

    Fekih, Monia; Sahli, Hela; Ben Mustapha, Nadia; Mestiri, Imen; Fekih, Moncef; Boubaker, Jalel; Kaabachi, Naziha; Sellami, Mohamed; Kallel, Lamia; Filali, Azza

    2013-01-01

    Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight <50 kg, a level of ALP phosphates alkaline > 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

  16. [Chronic Kidney Disease and Bone].

    PubMed

    James, Junichiro

    2016-08-01

    Both bone and kidney are members of the physiological network sharing a purpose of systemic mineral metabolism. In patients with chronic kidney disease whose kidney function is lost, the organ functions of other mineral metabolism network member including bone fail into uncontrollable due to dysregulated feedback system. This is the concept of Chronic Kidney Disease(related)- Mineral and Bone Disorder(CKD-MBD). However, the bone metabolic abnormalities in patients with chronic kidney disease cannot be explained merely by the framework of this mineral metabolism network. Although dialysis patients show several times higher hip fracture risk than general population, the main pathogenesis seems not to be their disordered mineral metabolism. We need to consider "uremic osteoporosis" characterized by deteriorated bone material properties due to uremic condition.

  17. Relationship of Bone Metabolism Biomarkers and Periodontal Disease: The Osteoporotic Fractures in Men (MrOS) Study

    PubMed Central

    Turner, Ryan; Wang, Ying; Chao, Raylien; Schulze, P. Christian; Phipps, Kathy; Orwoll, Eric; Dam, Thuy-Tien

    2015-01-01

    Context: Periodontitis is an inflammatory disease of tooth-supporting tissue leading to bone destruction and tooth loss. Periodontitis affects almost 50% of adults greater than 30 years of age. Objective: This study evaluated the association between biomarkers linked to bone formation and resorption with the occurrence and progression of periodontal disease in older men (≥65 y). Design: The Osteoporotic Fractures in Men (MrOS) study is a prospective, observational study among men 65 years of age and older. Setting: This ancillary study, Oral and Skeletal Bone Loss in Older Men, was conducted at two of the six MrOS study sites (Birmingham, AL and Portland, OR). Patients: Patients underwent medical and dental evaluation. Diagnoses of periodontitis were based on clinical attachment loss, pocket depth, calculus, plaque, and bleeding on a random half-mouth. Bone metabolism biomarkers included serum levels of calcium, phosphate (Pi), alkaline phosphatase, albumin, carboxy-terminal collagen crosslinks (CTX), N-terminal propeptides of type I procollagen, isoform 5b of tartrate-resistant acid phosphatase, and urine alpha- carboxy-terminal collagen crosslinks (alpha-CTX) and beta-CTX and serum levels of calciotropic hormones vitamin D (25(OH)D) and PTH. Main Outcome Measures: The aim of this study is to correlate bone metabolism biomarkers with prevalence and progression of periodontal disease in older men. Results: Patients with more severe periodontitis had significantly higher levels of PTH (P trend = .0004), whereas 25(OH)D was lower (P trend = .001). In a subset of men reevaluated at a second dental visit, improvement of periodontitis was associated with lower alpha-CTX, beta-CTX, and CTX levels at baseline after adjusting for age, site, and body mass index. Conclusion: This study suggests that a distinct set of biomarkers of bone metabolism are associated with more severe periodontal disease (PTH, 25(OH)D) and periodontal progression (alpha-CTX, beta-CTX, and CTX

  18. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

    PubMed

    Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

    2009-01-01

    Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.

  19. Magnetic resonance imaging and computerized tomography of a gravid leopard tortoise (Geochelone pardalis pardalis) with metabolic bone disease.

    PubMed

    Raiti, P; Haramati, N

    1997-06-01

    Secondary nutritional metabolic bone disease was diagnosed in a gravid leopard tortoise (Geochelone pardalis pardalis). Diagnosis was based upon history, physical examination, hematology, plasma biochemistry, and radiography. Despite induced oviposition and treatment of metabolic bone disease for 8 wk, the tortoise's condition deteriorated. Repeat radiographs demonstrated gaseous intestinal distention. Oral administration of metoclopramide and mineral oil failed to stimulate defecation. Persistence of the ileus pattern prompted utilization of magnetic resonance imaging (MRI) and computerized tomography (CT). MRI demonstrated brightly enhanced loops of mineral oil-filled small bowel and preovulatory follicles. CT demonstrated dystrophic calcification of the left hepatic lobe and preovulatory follicles and the typical reticular pattern of chelonian lung. The interstitial septa were caused by pulmonary vasculature or bands of smooth muscle.

  20. Hypercalciuric Bone Disease

    NASA Astrophysics Data System (ADS)

    Favus, Murray J.

    2008-09-01

    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

  1. Nutritional and metabolic correlates of cardiovascular and bone disease in HIV-infected patients.

    PubMed

    Fitch, Kathleen; Grinspoon, Steven

    2011-12-01

    The treatment of HIV infection has dramatically reduced the incidence of AIDS-related illnesses. At the same time, non-AIDS-related illnesses such as cardiovascular and bone disease are becoming more prevalent in this population. The mechanisms of these illnesses are complex and are related in part to the HIV virus, antiretroviral medications prescribed for HIV infection, traditional risk factors exacerbated by HIV, and lifestyle and nutritional factors. Further prospective research is needed to clarify the mechanisms by which HIV, antiretroviral medications, and nutritional abnormalities contribute to bone and cardiovascular disease in the HIV population. Increasingly, it is being recognized that optimizing the treatment of HIV infection to improve immune function and reduce viral load may also benefit the development of non-AIDS-related illnesses such as cardiovascular and bone disease.

  2. Periodontitis and bone metabolism

    PubMed Central

    Barbato, Luigi; Francioni, Edoardo; Bianchi, Massimiliano; Mascitelli, Eleonora; Marco, Leila Brancato; Tonelli, Duvina Paolo

    2015-01-01

    Summary Periodontitis is a plaque induced disease characterized by tissue destruction. The extent of the alveolar bone loss depends on the host response stimulated by bacterial infection. Recently researchers have focused on the role of the immune system, of RANK/RANKL/OPG pathway and of cytokines network. Another recent field of interest is osteoimmunology that try to explain the relationship between immune and bone cells in activating bone resorption. Advances in the understanding of the pathogenic mechanisms allowed a better understanding of the relationship with other diseases like osteoporosis and also to hypothesize new therapies based on modulation of host response (host modulatory therapy - HMT). The purpose of this mini-review is to briefly discuss these topics. PMID:26604945

  3. Bone Mass and Mineral Metabolism Alterations in Adult Celiac Disease: Pathophysiology and Clinical Approach

    PubMed Central

    Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto

    2013-01-01

    Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition. PMID:24284619

  4. [Risk factors and biochemical markers in metabolic bone disease of premature newborns].

    PubMed

    Montaner Ramón, Alicia; Fernández Espuelas, Cristina; Calmarza Calmarza, Pilar; Rite Gracia, Segundo; Oliván Del Cacho, María Jesús

    2017-01-01

    Metabolic bone disease (MBD) of prematurity is a complication of multifactorial aetiology, which has been increasing, due to progressive decrease in mortality of preterm newborns. The aim of the study was to analyze risk factors of severe MBD and its analytical markers. Retrospective study involving preterm infants less than 32 weeks gestational age and/or weight less tan 1,500 g born between january 2012 and december 2014. Comparison was made according to the presence of severe MBD. 139 patients were recruited. Mean value of 25(OH)D3 was 70.68 ± 25.20 nmol/L, being higher in patients born in spring-summer than in autumn-winter (80.94 ± 25.33 vs 61.13 ± 21.07; p = 0.000). Levels of 25(OH)D3 were similar in patients with severe MBD compared with the rest of patients (65.61 ± 26.49 vs 72.07 ± 24.89, P = 0.283). Higher levels of alkaline phosphatase (AP, IU/L ) (1314.19 ± 506.67 vs 476.56 ± 188.85; p = 0.000) were found in these patients. Cutoff point of AP 796.5 IU/L (S 95.2%, specificity 92.4%) was calculated by ROC curve. The risk factors most associated to severe EMO were restricted fetal growth, birth weight, duration of ventilation therapy and parenteral nutrition. AP levels were the best marker of severe MBD development. EMO risk increases with the number of risk factors and lower levels of 25(OH)D3. Levels of 25(OH)D3 higher than 70nmol/L appear to protect from the development of severe MBD, even in patients with multiple risk factors.

  5. From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

    PubMed

    Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  6. Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

    PubMed

    Yang, Chao; Kwak, Lucia; Ballew, Shoshana H; Garimella, Pranav S; Jaar, Bernard G; Folsom, Aaron R; Heiss, Gerardo; Selvin, Elizabeth; Lutsey, Pamela L; Coresh, Josef; Matsushita, Kunihiro

    2017-09-22

    Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m(2)). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD. Copyright © 2017

  7. Taxonomy of rare genetic metabolic bone disorders.

    PubMed

    Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

    2015-10-01

    This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

  8. [Updates on Lifestyle-Related Diseases and Bone Metabolism. CKD-related osteoporosis].

    PubMed

    Yamada, Shinsuke; Inaba, Masaaki

    2014-11-01

    Chronic kidney disease (CKD) has a high mortality rate of cardiovascular disease (CVD) . As CKD-mineral and bone disorder (CKD-MBD) is the one of the major risk factors in CVD, it is necessary that CKD patients are controlled CKD-MBD appropriately as early as possible. However, it is difficulty that CKD-MBD condition is exactly diagnosed and controlled, because it presents various conditions according to the difference of patient's background such as having diabetes or stage of CKD. We will give an outline of the mechanism in CKD-MBD according to patient's condition and the association between CKD-MBD and vascular calcification.

  9. Bone disease after renal transplantation

    PubMed Central

    Malluche, Hartmut H.; Monier-Faugere, Marie-Claude; Herberth, Johann

    2015-01-01

    In light of greatly improved long-term patient and graft survival after renal transplantation, improving other clinical outcomes such as risk of fracture and cardiovascular disease is of paramount importance. After renal transplantation, a large percentage of patients lose bone. This loss of bone results from a combination of factors that include pre-existing renal osteodystrophy, immunosuppressive therapy, and the effects of chronically reduced renal function after transplantation. In addition to low bone volume, histological abnormalities include decreased bone turnover and defective mineralization. Low bone volume and low bone turnover were recently shown to be associated with cardiovascular calcifications, highlighting specific challenges for medical therapy and the need to prevent low bone turnover in the pretransplant patient. This Review discusses changes in bone histology and mineral metabolism that are associated with renal transplantation and the effects of these changes on clinical outcomes such as fractures and cardiovascular calcifications. Therapeutic modalities are evaluated based on our understanding of bone histology. PMID:19918255

  10. Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing's disease.

    PubMed

    Guo, Weihong; Li, Fengao; Zhu, Chonggui; Wang, Baoping; Wang, Kunling; Dai, Chenlin; Jia, Hongwei; Wei, Hongyan; He, Qing; Cui, Jin; Yuan, Menghua; Tang, Shaofang; Liu, Wei; Zhu, Tiehong; Gao, Zhihong; Zheng, Fangqiu; Ma, Zhongshu; Qu, Huiqi; Zhu, Mei

    2017-01-01

    Objective To investigate the effects of Cushing's disease (CD) and adrenal-dependent Cushing's syndrome (ACS) on bone mineral density (BMD) and bone metabolism. Methods Data were retrospectively collected for 55 patients with hypercortisolism (CD, n = 34; ACS n = 21) from January 1997 to June 2014. BMD was examined in all patients, and bone turnover markers were tested in some patients. Healthy controls (n = 18) were also recruited. Results The lumbar spine and femoral neck BMD were significantly lower in the ACS and CD groups than in the control group. Lumbar BMD was significantly lower in the ACS than CD group. The collagen breakdown product (CTX) concentrations were significantly higher while the osteocalcin and procollagen type I N-terminal propeptide (PINP) concentrations were significantly lower in the ACS and CD groups than in the control group. The PINP concentration was significantly lower while the CTX concentration was significantly higher in the ACS than CD group. In the CD group only, lumbar BMD and serum adrenocorticotropic hormone had a significant positive correlation. Conclusions Bone turnover markers indicated suppressed osteoblast and enhanced osteoclast activities. PINP and CTX changes might indicate bone mass deterioration. Adrenocorticotropic hormone might be protective for lumbar BMD in patients with CD.

  11. Reduced bone mineral density in glycogen storage disease type III: evidence for a possible connection between metabolic imbalance and bone homeostasis.

    PubMed

    Melis, Daniela; Rossi, Alessandro; Pivonello, Rosario; Del Puente, Antonio; Pivonello, Claudia; Cangemi, Giuliana; Negri, Mariarosaria; Colao, Annamaria; Andria, Generoso; Parenti, Giancarlo

    2016-05-01

    Glycogen storage disease type III (GSDIII) is an inborn error of carbohydrate metabolism caused by deficient activity of glycogen debranching enzyme (GDE). It is characterized by liver, cardiac muscle and skeletal muscle involvement. The presence of systemic complications such as growth retardation, ovarian polycystosis, diabetes mellitus and osteopenia/osteoporosis has been reported. The pathogenesis of osteopenia/osteoporosis is still unclear. The aim of the current study was to evaluate the bone mineral density (BMD) in GSDIII patients and the role of metabolic and endocrine factors and physical activity on bone status. Nine GSDIII patients were enrolled (age 2-20years) and compared to eighteen age and sex matched controls. BMD was evaluated by Dual-emission-X-ray absorptiometry (DXA) and Quantitative ultrasound (QUS). Clinical and biochemical parameters of endocrine system function and bone metabolism were analyzed. Serum levels of the metabolic control markers were evaluated. Physical activity was evaluated by administering the International Physical Activity Questionnaire (IPAQ). GSDIII patients showed reduced BMD detected at both DXA and QUS, decreased serum levels of IGF-1, free IGF-1, insulin, calcitonin, osteocalcin (OC) and increased serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX). IGF-1 serum levels inversely correlated with AST and ALT serum levels. DXA Z-score inversely correlated with cholesterol and triglycerides serum levels and directly correlated with IGF-1/IGFBP3 molar ratio. No difference in physical activity was observed between GSDIII patients and controls. Our data confirm the presence of reduced BMD in GSDIII. On the basis of the results, we hypothesized that metabolic imbalance could be the key factor leading to osteopenia, acting through different mechanisms: chronic hyperlipidemia, reduced IGF-1, Insulin and OC serum levels. Thus, the mechanism of osteopenia/osteoporosis in GSDIII is probably multifactorial

  12. [Nutrition and bone metabolism (author's transl)].

    PubMed

    Goedegebuure, S A; Hazewinkel, H A

    1981-03-01

    Calcium and phosphate metabolism as well as those substances which are essential in regulating this metabolism (parathyroid hormone, thyrocalcitonin and cholecalciferol) are briefly discussed. Of three known forms of bone disease (nutritional secondary hyperparathyroidism, rickets and hypervitaminosis A), the clinical symptoms, radiological changes, (histo)pathological findings, therapeutic procedures as well as the aetiological, pathogenic and pathophysiological features will be reviewed.

  13. From bone abnormalities to mineral metabolism dysregulation in autosomal dominant polycystic kidney disease.

    PubMed

    Mekahli, Djalila; Bacchetta, Justine

    2013-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure. It is a systemic disorder, not only affecting the kidneys, but also associated with cyst formation in other organs such as the liver, spleen, pancreas, and seminal vesicles. Other extra-renal symptoms may consist of intracranial arterial aneurysms, cardiac valvular defects, abdominal and inguinal hernias and colonic diverticulosis. Very little is known regarding bone involvement in ADPKD; however, recent evidence has revealed the potential role of fibroblast growth factor 23 (FGF23). FGF23 is an endocrine fibroblast growth factor acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D with key effects on the bone/kidney/parathyroid axis, and has been shown to increase in patients with ADPKD, even with normal renal function. The aim of this review is to provide an overview of bone and mineral abnormalities found in experimental models and in patients with ADPKD, and to discuss the possible role of FGF23 in this disease.

  14. FGF23 associated bone diseases.

    PubMed

    Liao, Eryuan

    2013-03-01

    Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

  15. Hypothalamic control of bone metabolism.

    PubMed

    Sharan, Kunal; Yadav, Vijay K

    2014-10-01

    Bones are structures in vertebrates that provide support to organs, protect soft organs, and give them shape and defined features, functions that are essential for their survival. To perform these functions, bones are constantly renewed throughout life. The process through which bones are renewed is known as bone remodeling, an energy demanding process sensitive to changes in energy homeostasis of the organism. A close interplay takes place between the diversity of nutritional cues and metabolic signals with different elements of the hypothalamic circuits to co-ordinate energy metabolism with the regulation of bone mass. In this review, we focus on how mouse and human genetics have elucidated the roles of hormonal signals and neural circuits that originate in, or impinge on, the hypothalamus in the regulation of bone mass. This will help to understand the mechanisms whereby regulation of bone is gated and dynamically regulated by the hypothalamus.

  16. Regulation of Bone Metabolism

    PubMed Central

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi

    2017-01-01

    Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation, and bone homeostasis are controlled by various markers and signaling pathways. Bone needs to be remodeled to maintain integrity with osteoblasts, which are bone-forming cells, and osteoclasts, which are bone-degrading cells.In this review we considered the major factors and signaling pathways in bone formation; these include fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), wingless-type (Wnt) genes, runt-related transcription factor 2 (RUNX2) and osteoblast-specific transcription factor (osterix or OSX). PMID:28367467

  17. Regulation of Bone Metabolism.

    PubMed

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi

    2017-04-01

    Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation, and bone homeostasis are controlled by various markers and signaling pathways. Bone needs to be remodeled to maintain integrity with osteoblasts, which are bone-forming cells, and osteoclasts, which are bone-degrading cells.In this review we considered the major factors and signaling pathways in bone formation; these include fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), wingless-type (Wnt) genes, runt-related transcription factor 2 (RUNX2) and osteoblast-specific transcription factor (osterix or OSX).

  18. Bone Marrow Diseases

    MedlinePlus

    ... that help with blood clotting. With bone marrow disease, there are problems with the stem cells or ... marrow makes too many white blood cells Other diseases, such as lymphoma, can spread into the bone ...

  19. [Nutrition-related bone disease].

    PubMed

    Hirota, Kenji; Hirota, Takako

    2006-09-01

    Bone disorders clearly related to nutrition are osteomalacia and osteoporosis. Osteomalacia is caused by a deficiency of vitamin D or a disturbance of its metabolism. Dietary deficiency of phosphate or excess of aluminum or cadmium will also cause osteomalacia. Osteoporosis is associated with low intake of calcium and other nutrients. Dietary copper deficiency might stimulate bone metabolism and increase in hip fractures. Excess vitamin A intake was also associated with lower bone mineral density and higher risk of hip fractures. Excess vitamin D sometimes causes mental simplicity, congenital heart disease and calcification of soft tissue. Therefore not only diet but also drugs and supplements of nutrients should be carefully observed in older women.

  20. Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin.

    PubMed

    Levinger, I; Brennan-Speranza, T C; Zulli, A; Parker, L; Lin, X; Lewis, J R; Yeap, B B

    2017-03-13

    Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e.g. exercise or diet) interventions are often associated with increased circulating levels of OC and/or ucOC. There is also a relationship between lower circulating OC and ucOC and increased measures of vascular calcification and cardiovascular disease. However, not all studies have reported such relationship, some with contradictory findings. Equivocal findings may arise because of the observational nature of the studies and the inability to directly assess the relationship between OC and ucOC on glycaemic control and cardiovascular health in humans. Studying OC and ucOC in humans is further complicated due to numerous confounding factors such as sex differences, menopausal status, vitamin K status, physical activity level, body mass index, insulin sensitivity (normal/insulin resistance/T2DM), tissue-specific effects and renal function among others. Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism. Further mechanistic studies are required to (a) clarify causality, (b) explore mechanisms involved and

  1. Comparing the Effects of Two Feeding Methods on Metabolic Bone Disease in Newborns With Very Low Birth Weights

    PubMed Central

    Lotfi, Asghar; Shiasi, Kobra; Amini, Razieh; Jahangiri, Mohammad; Sharif, Mohammad Reza; Akbari, Hossein; Talari, Hamidreza; Hajmobini, Zahra; Hami, Kamran; Kashani, Hamed Haddad

    2016-01-01

    Introduction: Bone metabolic disease is an important issue in newborns with very low birth weight. The 80 percent of the transport of calcium (Ca) and phosphor (P) from mother to fetus takes place in the third trimester of pregnancy. This transport process is impaired with the preterm delivery of the newborn. On the other side, breast milk and formula are not competent resources to supply sufficient amounts of Ca and P to meet the requirements of the preterm newborn, thereby a greater reduction in the storage of these minerals. The current study has been done with the purpose of comparing the effects of two feeding methods on the indices of metabolic bone disease in newborns with very low birth weights (VLBW). Materials and Methods: The study design was cohort and the study was done on a total of 58 newborns with very low birth weights in Kashan Shahid Beheshti Hospital. The newborns were divided into two groups with 29 placed in the group of alternate feeding on preterm formula (preNan) and the other 29 placed in the group of breast milk and preterm formula (preNan). Eventually, the indices of bone metabolic disease were measured in both groups and were statistically analyzed. Results: The difference between the mean serum levels of Ca in different weeks and also between the two groups were significant (p=0.001). However, the changes in mean serum level of P in the two groups were not significant (P=0.151). The comparison of serum levels of alkaline phosphatase between the two groups indicated that their difference was significant and that they had been influenced by the feeding method (P=0.001). The serum level of bicarbonate, when compared between the two groups, was found to make a significant difference (P=0.001). The difference between the two feeding methods in precipitating rickets and osteopenia was not significant. Conclusion: According to the findings of current study, feeding on preterm formula (preNan) is associated with better and more desirable

  2. Relationships between Bone Turnover and Energy Metabolism

    PubMed Central

    2017-01-01

    It is well established that diabetes can be detrimental to bone health, and its chronic complications have been associated with an increased risk of osteoporotic fracture. However, there is growing evidence that the skeleton plays a key role in a whole-organism approach to physiology. The hypothesis that bone may be involved in the regulation of physiological functions, such as insulin sensitivity and energy metabolism, has been suggested. Given the roles of insulin, adipokines, and osteocalcin in these pathways, the need for a more integrative conceptual approach to physiology is emphasized. Recent findings suggest that bone plays an important role in regulating intermediary metabolism, being possibly both a target of diabetic complications and a potential pathophysiologic factor in the disease itself. Understanding the relationships between bone turnover and glucose metabolism is important in order to develop treatments that might reestablish energy metabolism and bone health. This review describes new insights relating bone turnover and energy metabolism that have been reported in the literature. PMID:28695134

  3. Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

    PubMed Central

    Fisher, A; Srikusalanukul, W; Davis, M; Smith, P

    2013-01-01

    Background Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures. Aims and methods To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured. Results CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death. Conclusion SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets. PMID:23460043

  4. [Bone and calcium update; diagnosis and therapy of metabolic bone disease update. Advances in clinical trials for osteoporosis in Japan].

    PubMed

    Nakamura, Toshitaka

    2011-12-01

    Microdensitometry of the metacarpal bone on radiograph was first set up as the endpoint of the treatment in clinical trials in Japan in 1980s. Then, radial bone mineral content obtained by single photon absorptiometry was used. In 1990s, lumbar spine BMD measured by DXA became the major endpoint of the study which was designed as prospective, randomized, double-blind, controlled trial. In 2000s, assessments on the incidences of the vertebral fractures have become mandatory as the primary endpoint of the placebo-controlled trial. The numbers of the subjects required in the study are getting larger and the subtleties in the study including adverse events more important along the progress of evidence-based medicine.

  5. Effect of Aerobic Exercise on Markers of Bone Metabolism of Overweight and Obese Patients With Chronic Kidney Disease.

    PubMed

    Gomes, Tarcisio Santana; Aoike, Danilo Takashi; Baria, Flavia; Graciolli, Fabiana G; Moyses, Rosa M A; Cuppari, Lilian

    2017-09-01

    The aim of the study was to investigate the effect of aerobic exercise on markers of bone metabolism in overweight and obese nondialysis-dependent patients with chronic kidney disease. This is a post-hoc study with 39 sedentary patients (55.5 ± 8.3 years, body mass index 31.2 ± 4.4 kg/m(2), estimated glomerular filtration rate 26.9 ± 11.7 mL/minute) who were randomly assigned to the aerobic exercise group (n = 24) or the control group (n = 15). The aerobic training (walking) was prescribed according to ventilatory threshold and was performed 3 times per week during 24 weeks. Carboxylated and undercarboxylated osteocalcin (GLA and GLU), sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b), parathyroid hormone, total alkaline phosphatase (AP), body composition, cardiorespiratory, and functional capacity tests were measured at baseline and after the follow-up. At baseline, carboxylated osteocalcin (GLA) and undercarboxylated osteocalcin (GLU) were inversely correlated with estimated glomerular filtration rate (r = -0.64; r = -0.38, respectively). Both osteocalcin fragments were positively correlated with total AP (GLA: r = 0.36; GLU: r = 0.53). An inverse correlation was found between GLA and sclerostin with body fat (r = -0.36; r = -0.46, respectively). GLU was negatively correlated with markers of muscle mass (r = -0.34). TRAP-5b and sclerostin were inversely correlated with 6-minute walk test and time up and go test, respectively (r = -0.34; r = -0.35, respectively). After 24 weeks, all physical capacity parameters increased in the exercise group (P < .001). Except for total AP that increased after 24 weeks in the exercise group (P < .05), no other changes were observed in both groups in relation to the bone metabolism biomarkers investigated. In this post-hoc study, the aerobic training used did not promote relevant changes in the bone metabolism markers investigated. Copyright © 2017 National Kidney

  6. HIV infection, bone metabolism, and fractures.

    PubMed

    Güerri-Fernández, Robert; Villar-García, Judit; Díez-Pérez, Adolfo; Prieto-Alhambra, Daniel

    2014-07-01

    With the advent of high active antiretroviral therapy there was a significant improvement on HIV subjects survival. Thus, bone changes related to HIV became an important aspect of these individuals. HIV affects bone remodeling causing bone fragility. In addition, antiretroviral therapy may also negatively affect bone metabolism. Several studies describe an increased incidence of fractures in these patients when compared with controls without the disease. The European Society of AIDS (EACS), and other societies, have included guidance on management of osteoporosis in HIV-infected patients emphasizing the identification of patients with low bone mass. Supplementation of calcium and vitamin D and the use of alendronate in these individuals should be recommended on a case base.

  7. Bone Disease after Kidney Transplantation

    PubMed Central

    Bouquegneau, Antoine; Salam, Syrazah; Delanaye, Pierre; Eastell, Richard

    2016-01-01

    Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients. PMID:26912549

  8. Effects of obesity on bone metabolism.

    PubMed

    Cao, Jay J

    2011-06-15

    obesity rates have doubled since 1980 and as of 2007, 33% of men and 35% of women in the US are obese. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year.Bone mass and strength decrease during adulthood, especially in women after menopause. These changes can culminate in osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration resulting in increased bone fracture risk. It is estimated that there are about 10 million Americans over the age of 50 who have osteoporosis while another 34 million people are at risk of developing the disease. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure. Several lines of evidence suggest that obesity and bone metabolism are interrelated. First, both osteoblasts (bone forming cells) and adipocytes (energy storing cells) are derived from a common mesenchymal stem cell and agents inhibiting adipogenesis stimulated osteoblast differentiation and vice versa, those inhibiting osteoblastogenesis increased adipogenesis. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.

  9. Multitracer Molecular Imaging of Paget Disease Targeting Bone Remodeling, Fatty Acid Metabolism, and PSMA Expression on PET/CT.

    PubMed

    Derlin, Thorsten; Weiberg, Desiree; Sohns, Jan M

    2016-12-01

    Paget disease is a chronic disorder resulting in enlarged and misshapen bones, and is caused by disorganized bone remodeling. We present the case of an 85-year-old man with prostatic adenocarcinoma and known Paget disease of the right iliac bone who underwent Ga-prostate-specific membrane antigen ligand, C-acetate, and F-fluoride PET/CT for restaging of cancer. On all PET scans, increased tracer accumulation was observed in Paget disease of bone. Besides that Paget disease may mimic metastases on PET/CT using various radiotracers, including Ga-prostate-specific membrane antigen ligands and C-acetate, this case highlights the potential of multiparametric disease characterization on PET.

  10. Autoinflammatory bone diseases.

    PubMed

    Stern, Sara M; Ferguson, Polly J

    2013-11-01

    Autoinflammatory bone disease is a new branch of autoinflammatory diseases caused by seemingly unprovoked activation of the innate immune system leading to an osseous inflammatory process. The inflammatory bone lesions in these disorders are characterized by chronic inflammation that is typically culture negative with no demonstrable organism on histopathology. The most common autoinflammatory bone diseases in childhood include chronic nonbacterial osteomyelitis (CNO), synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, Majeed syndrome, deficiency of interleukin-1 receptor antagonist, and cherubism. In this article, the authors focus on CNO and summarize the distinct genetic autoinflammatory bone syndromes.

  11. The role of leptin in regulating bone metabolism

    PubMed Central

    Upadhyay, Jagriti; Farr, Olivia M.; Mantzoros, Christos S.

    2015-01-01

    Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature on indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk – benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals. PMID:25497343

  12. Generalized metabolic bone disease and fracture risk in Rothmund-Thomson syndrome

    USDA-ARS?s Scientific Manuscript database

    Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of me...

  13. Metabolic bone diseases in patients after allogeneic hematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease.

    PubMed

    Hautmann, Anke Heidewig; Elad, Sharon; Lawitschka, Anita; Greinix, Hildegard; Bertz, Hartmut; Halter, Joerg; Faraci, Maura; Hofbauer, Lorenz Christian; Lee, Stephanie; Wolff, Daniel; Holler, Ernst

    2011-09-01

    With improved outcome of allogeneic stem cell transplantation (allo-SCT) for hematologic malignancies, long-term complications gain greater importance. Skeletal complications such as osteoporosis or avascular necrosis (AVN) occur frequently in allogeneic recipients with a cumulative incidence of diminished bone mineral density of 24-50% between 2 and 12 months after allo-SCT and a cumulative incidence of AVN in as many as 19% of patients 3 years after allo-SCT. Here, we present a review as part of the German, Austrian, and Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease, held 2009 in Regensburg. The Consensus Conference aimed to achieve a consensus on the current evidence of diagnosis, prevention, and therapeutic options of late complications after allo-SCT summarizing and discussing the literature on these topics. In this report, we provide recommendations for metabolic bone diseases agreed upon by the working party. This includes guidelines for diagnosis, prevention, and therapeutic options in patients with low bone mass or AVN.

  14. Metabolic bone disease in the preterm infant: Current state and future directions

    PubMed Central

    Rehman, Moghis Ur; Narchi, Hassib

    2015-01-01

    Neonatal osteopenia is an important area of interest for neonatologists due to continuing increased survival of preterm infants. It can occur in high-risk infants such as preterm infants, infants on long-term diuretics or corticosteroids, and those with neuromuscular disorders. Complications such as rickets, pathological fractures, impaired respiratory function and poor growth in childhood can develop and may be the first clinical evidence of the condition. It is important for neonatologists managing such high-risk patients to regularly monitor biochemical markers for evidence of abnormal bone turnover and inadequate mineral intake in order to detect the early phases of impaired bone mineralization. Dual-energy X-ray absorptiometry has become an increasingly used research tool for assessing bone mineral density in children and neonates, but more studies are still needed before it can be used as a useful clinical tool. Prevention and early detection of osteopenia are key to the successful management of this condition and oral phosphate supplements should be started as soon as is feasible. PMID:26413483

  15. [Bone and calcium update; diagnosis and therapy of bone metabolism disease update. Molecular mechanism in cardiac valve calcification].

    PubMed

    Furukawa, Ken-Ichi; Motomura, Shigeru

    2011-12-01

    When cardiac valve stenosis is accompanied by calcification, symptoms and prognosis become much worse and may cause sudden cardiac death. The prevalence of this disease has increased with the rapidly aging in Japanese society. It has recently been revealed that several genes which relate to physiological ossification and calcification play important roles in this process. To find a suitable target for medical treatment, the molecular mechanism for calcification of cardiac valves should be elucidated in detail. In this review, we summarize the current knowledge on the pathology and molecular mechanism for ectopic calcification of the cardiac valve.

  16. Bone Metabolism after Bariatric Surgery

    PubMed Central

    Yu, Elaine W.

    2014-01-01

    Bariatric surgery is a popular and effective treatment for severe obesity, but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically-induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery. PMID:24677277

  17. Impact of obesity on bone metabolism.

    PubMed

    López-Gómez, Juan J; Pérez Castrillón, José L; de Luis Román, Daniel A

    2016-12-01

    High weight is a protective factor against osteoporosis and risk of fracture. In obesity, however, where overweight is associated to excess fat, this relationship does not appear to be so clear, excess weight has sometimes been associated to decreased bone mass. Obesity interferes with bone metabolism through mechanical, hormonal, and inflammatory factors. These factors are closely related to weight, body composition, and dietary patterns of these patients. The net beneficial or harmful effect on bone mass or risk of fracture of the different components of this condition is not well known. We need to recognize patients at a greater risk of bone disease related to obesity to start an adequate intervention. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  18. [Cytokines in bone diseases. Wnt signal and excessive bone formation].

    PubMed

    Hosoi, Takayuki

    2010-10-01

    Wnt signal has been known to play various roles in many organ from the beginning of embryogensis. Its role in bone metabolism has also been investigated and established. Lipoprotein receptor-related protein 5 (LRP5) is one of the important molecules in wnt signal pathway whose point mutations are related to both bone loss and excessive bone formation. Wnt signal is involved in the action of sclerostin which was found as a gene for osteosclerosis, one of the diseases of excessive bone formation. Wnt signal is keeping the position as an important research target for normal and pathological bone formation.

  19. The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease.

    PubMed

    Pawlak, Dariusz; Domaniewski, Tomasz; Znorko, Beata; Oksztulska-Kolanek, Ewa; Lipowicz, Paweł; Doroszko, Michał; Karbowska, Malgorzata; Pawlak, Krystyna

    2017-08-07

    Chronic kidney disease (CKD) results in decreased bone strength. Serotonin (5-HT) is one of the critical regulators of bone health, fulfilling distinct functions depending on its synthesis site: brain-derived serotonin (BDS) favors osteoblast proliferation, whereas gut-derived serotonin (GDS) inhibits it. We assessed the role of BDS and peripheral leptin in the regulation of bone metabolism and strength in young rats with 5/6 nephrectomy. BDS synthesis was accelerated during CKD progression. Decreased peripheral leptin in CKD rats was inversely related to BDS content in the hypothalamus, brainstem and frontal cortex. Serotonin in these brain regions affected bone strength and metabolism in the studied animals. The direct effect of circulating leptin on bone was not shown in uremia. At the molecular level, there was an inverse association between elevated GDS and the expression of cAMP responsive element-binding protein (Creb) gene in bone of CKD animals. In contrast, increased expression of activating transcription factor 4 (Atf4) was shown, which was associated with GDS-dependent transcription factor 1 (Foxo1), clock gene - Cry-1, cell cycle genes: c-Myc, cyclins, and osteoblast differentiation genes. These results identified a previously unknown molecular pathway, by which elevated GDS can shift in Foxo1 target genes from Creb to Atf4-dependent response, disrupting the leptin-BDS - dependent gene pathway in the bone of uremic rats. Thus, in the condition of CKD the effect of BDS and GDS on bone metabolism and strength can't be distinguished. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. [Bone disease in Gaucher's disease].

    PubMed

    Roca Espiau, Mercedes

    2011-09-01

    The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

  1. Clinical utility of a wheat-germ precipitation assay for determination of bone alkaline phosphatase concentrations in patients with different metabolic bone diseases.

    PubMed

    Braga, V; Dorizzi, R; Brocco, G; Rossini, M; Zamberlan, N; Gatti, D; Adami, S

    1995-07-01

    Bone alkaline phosphatase was evaluated by wheat-germ lectin precipitation in several clinical conditions. The study included 33 premenopausal healthy women, 46 postmenopausal apparently healthy women, 19 growing children, 24 patients with Paget's disease, 31 patients with primary hyperparathyroidism and 66 patients with hepatobiliary diseases. In postmenopausal women the mean T score (i.e.: the number of SD below or above the mean for premenopausal women) was 2.6 +/- 1.3 (SD) for bone alkaline phosphatase and 1.61 +/- 1.21 for total alkaline phosphatase (p < 0.001). The T score for bone alkaline phosphatase provided a better discrimination from normals for both Paget's disease (22.1 +/- 27.8 versus 12.8 +/- 16 p < 0.001) and primary hyperparathyroidism (8.2 +/- 4.3 versus 4.6 +/- 3.7 p < 0.005 for bone alkaline phosphatase and total alkaline phosphatase respectively). After treatment with intravenous bisphosphonate the percent decrease of bone alkaline phosphatase was larger than that of total alkaline phosphatase both in patients with Paget's disease (-46% versus -72% p < 0.01) and in patients with primary hyperparathyroidism (-21% versus -47% p < 0.02) and an estimate of the precision (delta mean/SD of the delta mean) for bone alkaline phosphatase was 1.9-3.7 times higher than that of total alkaline phosphatase. In twelve osteoporotic patients treated for six months with oral alendronate the decrease in bone turnover was detected with significantly higher precision with bone alkaline phosphatase than with total alkaline phosphatase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Bone Diseases - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Diseases URL of this page: https://medlineplus.gov/languages/bonediseases.html Other topics A-Z Expand Section ...

  3. Bone and Celiac Disease.

    PubMed

    Zanchetta, María Belén; Longobardi, Vanesa; Bai, Julio César

    2016-04-01

    More than 50% of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.

  4. Denosumab for bone diseases: translating bone biology into targeted therapy.

    PubMed

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  5. Impaired bone metabolism in glycogen storage disease type 1 is associated with poor metabolic control in type 1a and with granulocyte colony-stimulating factor therapy in type 1b.

    PubMed

    Melis, D; Pivonello, R; Cozzolino, M; Della Casa, R; Balivo, F; Del Puente, A; Dionisi-Vici, C; Cotugno, G; Zuppaldi, C; Rigoldi, M; Parini, R; Colao, A; Andria, G; Parenti, G

    2014-01-01

    Glycogen storage disease type 1 (GSD1) is a rare and genetically heterogeneous metabolic defect of gluconeogenesis due to mutations of either the G6PC gene (GSD1a) or the SLC37A4 gene (GSD1b). Osteopenia is a known complication of GSD1. The aim of this study was to investigate the effects of poor metabolic control and/or use of GSD1-specific treatments on bone mineral density (BMD) and metabolism in GSD1 patients. In a multicenter, cross-sectional case-control study, we studied 38 GSD1 (29 GSD1a and 9 GSD1b) patients. Clinical, biochemical and instrumental parameters indicative of bone metabolism were analyzed; BMD was evaluated by dual-emission X-ray absorptiometry and quantitative ultrasound. Both GSD1a and GSD1b patients showed reduced BMD compared with age-matched controls. In GSD1a patients, these abnormalities correlated with compliance to diet and biochemical indicators of metabolic control. In GSD1b patients, BMD correlated with the age at first administration and the duration of granulocyte colony-stimulating factor (G-CSF) therapy. Our data indicate that good metabolic control and compliance with diet are highly recommended to improve bone metabolism in GSD1a patients. GSD1b patients on G-CSF treatment should be carefully monitored for the risk of osteopenia/osteoporosis.

  6. Paget Disease of Bone.

    PubMed

    Al-Rashid, Mamun; Ramkumar, Dipak B; Raskin, Kevin; Schwab, Joseph; Hornicek, Francis J; Lozano-Calderón, Santiago A

    2015-10-01

    The current understanding of Paget disease of bone (PDB) has vastly changed since Paget described the first case in 1877. Medical management of this condition remains the mainstay of treatment. Surgical intervention is usually only used in fractures through pagetic bone, need for realignment to correct deformity in major long bones, prophylactic treatment of impending fractures, joint arthroplasty in severe arthritis, or spinal decompression in cases of bony compression of neural elements. Advances in surgical technique have allowed early return to function and mobilization. Despite medical and surgical intervention, a small subset of patients with PDB develops Paget sarcoma.

  7. Bone structure, metabolism, and physiology: its impact on dental implantology.

    PubMed

    Marx, R E; Garg, A K

    1998-01-01

    When placing implants in the mandible or maxilla, it is important for clinicians to understand the process of bone remodeling, the different types of bone, and how these factors can affect the integration of osseous dental implants. Approximately 0.7% of a human skeleton is resorbed daily and replaced by new healthy bone. With aging and metabolic disease states, the normal turnover process may be reduced, resulting in an increase in the mean age of the present bone. This increase can affect the placement and integration of implants. Herein follows a discussion of different types of bone cells, the metabolism of bone, the microscopic, macroscopic, and molecular structure of bone, and the process of bone modeling and remodeling.

  8. The role of serum osteoprotegerin and receptor-activator of nuclear factor-κB ligand in metabolic bone disease of women after obesity surgery.

    PubMed

    Balsa, José A; Lafuente, Christian; Gómez-Martín, Jesús M; Galindo, Julio; Peromingo, Roberto; García-Moreno, Francisca; Rodriguez-Velasco, Gloria; Martínez-Botas, Javier; Gómez-Coronado, Diego; Escobar-Morreale, Héctor F; Botella-Carretero, José I

    2016-11-01

    Metabolic bone disease may appear as a complication of obesity surgery. Because an imbalance in the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system may underlie osteoporosis, we aimed to study this system in humans in the metabolic bone disease occurring after obesity surgery. In this study we included sixty women with a mean age of 47 ± 10 years studied 7 ± 2 years after bariatric surgery. The variables studied were bone mineral density, β-isomer of C-terminal telopeptide of type I collagen cross-links (a bone resorption marker), the bone formation markers osteocalcin and N-terminal propeptide of procollagen 1, serum osteoprotegerin and receptor-activator of nuclear factor-κB ligand. Serum osteoprotegerin inversely correlated with the bone remodeling markers osteocalcin, β-isomer of C-terminal telopeptide of type I collagen cross-links and N-terminal propeptide of procollagen 1. The osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio also correlated inversely with serum parathormone and osteocalcin. Bone mineral density at the lumbar spine was associated with age (β = -0.235, P = 0.046), percentage of weight loss (β = 0.421, P = 0.001) and osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio (β = 0.259, P = 0.029) in stepwise multivariate analysis (R (2) = 0.29, F = 7.49, P < 0.001). Bone mineral density at the hip site was associated only with percentage of weight loss (β = 0.464, P < 0.001) in stepwise multivariate regression (R (2) = 0.21, F = 15.1, P < 0.001). These data show that the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system is associated with bone markers and bone mineral density at the lumbar spine after obesity surgery.

  9. Bone-immune cell crosstalk: bone diseases.

    PubMed

    Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

    2015-01-01

    Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

  10. Phosphate Metabolism in Cardiorenal Metabolic Disease

    PubMed Central

    Gupta, Deepashree; Brietzke, Stephen; Hayden, M.R.; Kurukulasuriya, L. Romayne; Sowers, James R.

    2011-01-01

    Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the ‘normal laboratory range’ by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease. PMID:22096458

  11. From “Kidneys Govern Bones” to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science

    PubMed Central

    Zou, Xin-Rong

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of “Kidneys Govern Bones.” Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes. PMID:27668003

  12. [Infectious bone diseases].

    PubMed

    Tiemann, A H; Krenn, V; Krukemeyer, M G; Seyfert, C; Jakobs, M; Baumhoer, D; Hofmann, G O

    2011-05-01

    Bacterial infection of the bone is a severe disease with complications, potentially including long-term physical disability. The diagnosis and therapy of osteomyelitis include several elements: histopathology, microbiology, radiologic imagining, as well as antibiotic and surgical therapy. Histopathologists differentiate between acute osteomyelitis (infiltration of cancellous bone with neutrophil granulocytes); specific osteomyelitis (epithelioid-like granulomatous inflammation, tuberculosis, mycotic infections); primary/secondary chronic osteomyelitis (lymphocytic infiltration); and special forms of chronic osteomyelitis (varying histomorphology, Brodie abscess, SAPHO syndrome). Another important task in the histopathological diagnosis of inflammatory bone diseases is to differentiate osteomyelitis from malignant entities (sarcoma, lymphoma). Therefore, biopsy samples should be of sufficient size for safe diagnosis. Clinical information and imaging as well as interdisciplinary teamwork between radiologists, microbiologists, orthopedic surgeons and pathologists is mandatory to verify these diagnoses.

  13. [Hypertension, CKD and bone metabolism].

    PubMed

    Nakagami, Hironori; Morishita, Ryuichi

    2011-05-01

    The patients with "Hypertension" and "Chronic Kidney Disease (CKD) " are accompanied with an osteoporosis. In hypertension patients, excess urinary calcium secretion induces secondary parathyroidsim to increase serum calcium (Ca) level, which may lead to Ca release from bone. In this aspect, there are several reports that anti-hypertensive drugs, especially thiazides, increase bone mineral density and decrease the incidence of bone fracture. In addition, we demonstrated that renin-angiotensin system can be involved in the process of osteoporosis. Angiotensin II significantly induced the expression of RANKL (receptor activator of NF-κB ligand) in osteoblasts, leading to the activation of osteoclasts, while these effects were completely blocked by an Ang II type 1 receptor blockade. As for CKD, excess phosphorus (P) due to renal dysfunction induces secondary parathyroidism to decrease serum P level, which similarly leads to osteoporosis. Moreover, excess P can increase FGF23 expression and decrease activated vitamin D, which also resulted in progression of osteoporosis. Both "Hypertension" and "Chronic Kidney Disease (CKD) " are inducible factor to osteoporosis.

  14. [Secondary osteoporosis or secondary contributors to bone loss in fracture. Effects of oxidative stress on bone metabolism].

    PubMed

    Notsu, Masakazu; Yamaguchi, Toru

    2013-09-01

    Recent years, many reports showed that patients with diabetes mellitus, arteriosclerotic diseases and life style diseases have a higher fracture risk, and one of the reasons about it is an oxidative stress on bone metabolism. Oxidative stress, which is induced by life style diseases, aging and menopause, increases active oxygen production and fracture risk by affecting bone metabolism related cells and bone matrix proteins. Since there are few treatments against oxidative stress, so it is important to search further therapeutic agents. This report gives an outline of the effect of oxidative stress on bone metabolism in some conditions, such as diabetes mellitus, arteriosclerotic diseases, chronic kidney diseases and menopause.

  15. Seeing the light in bone metabolism imaging.

    PubMed

    Souris, Jeffrey S

    2002-09-01

    Conventional in vivo imaging of bone metabolism is dominated by gamma-ray bone scintigraphy: a technique in which gamma-ray emissions from radioactively labeled regions of metabolically active bone are mapped. More recently, however, near-infrared fluorescent probes have been developed that optically emulate these radionuclides. Although still in their infancy, techniques based on the use of such functionally targeted fluorophores might one-day offer improved resolution, sensitivity and speed in bone metabolism imaging -- without any of the health risks posed by the internalization of radioactive sources.

  16. Effects of thirty elements on bone metabolism.

    PubMed

    Dermience, Michael; Lognay, Georges; Mathieu, Françoise; Goyens, Philippe

    2015-10-01

    The human skeleton, made of 206 bones, plays vital roles including supporting the body, protecting organs, enabling movement, and storing minerals. Bones are made of organic structures, intimately connected with an inorganic matrix produced by bone cells. Many elements are ubiquitous in our environment, and many impact bone metabolism. Most elements have antagonistic actions depending on concentration. Indeed, some elements are essential, others are deleterious, and many can be both. Several pathways mediate effects of element deficiencies or excesses on bone metabolism. This paper aims to identify all elements that impact bone health and explore the mechanisms by which they act. To date, this is the first time that the effects of thirty minerals on bone metabolism have been summarized.

  17. Paget disease of the bone

    MedlinePlus

    ... ency/article/000414.htm Paget disease of the bone To use the sharing features on this page, ... Paget disease is a disorder that involves abnormal bone destruction and regrowth. This results in deformity of ...

  18. Therapeutic approaches to bone diseases.

    PubMed

    Rodan, G A; Martin, T J

    2000-09-01

    The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. As we age or as a result of disease, this delicate balancing act becomes tipped in favor of osteoclasts so that bone resorption exceeds bone formation, rendering bones brittle and prone to fracture. A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone. Drugs that inhibit the formation or activity of osteoclasts are valuable for treating osteoporosis, Paget's disease, and inflammation of bone associated with rheumatoid arthritis or periodontal disease. Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.

  19. [Vitamin D metabolism of the bone].

    PubMed

    Barvencik, F; Amling, M

    2015-09-01

    Bone health is a crucial requirement for individual mobility. Preventive, diagnostic, and therapeutic actions to preserve or restore bone health are major tasks for orthopedic surgeons and health practitioners in musculoskeletal medicine. In the context of the widespread vitamin D deficiency in Germany, it is relevant to keep in mind thatserum calcitriol levels above > 30 µg/l are necessary for optimal bone metabolism and bone health. In particular, because vitamin D deficiency not only increases the amount of non-mineralized bone matrix (osteoid), but it can also cause negative changes in the mineralized bone tissue. Widening of the osteons and osteocyte lacunae, together with increased bone aging under the osteoid layer, can lead to reduced fracture resistance. Integration of bone metabolism into the orthopedic strategy is an important concept for optimizing treatment in modern musculoskeletal medicine.

  20. [Bone and Nutrition. Sclerostin and bone metabolism].

    PubMed

    Tatsumi, Sawako; Nagamoto, Kenta; Ogata, Mao; Miyamoto, Ken-ichi

    2015-07-01

    Osteocytes orchestrate bone resorption and bone formation by controlling osteoclast and osteoblast activity. On the other hand, osteocytes secret FGF23 (fibroblast growth factor 23), FGF23 acts on the kidney to control phosphate homeostasis. Sclerostin is also released from osteocytes and it regulated osteoblast activity through Wnt/β-catenin pathway. Therefore, an antibody that targets sclerostin is currently in phase- III clinical trials for the treatment of osteoporosis and it is expected as new therapeutics.

  1. The Association between Elevated Levels of Peripheral Serotonin and Its Metabolite – 5-Hydroxyindoleacetic Acid and Bone Strength and Metabolism in Growing Rats with Mild Experimental Chronic Kidney Disease

    PubMed Central

    Oksztulska-Kolanek, Ewa; Znorko, Beata; Domaniewski, Tomasz; Rogalska, Joanna; Roszczenko, Alicja; Brzóska, Małgorzata Michalina; Pryczynicz, Anna; Kemona, Andrzej

    2016-01-01

    Chronic kidney disease (CKD) is associated with disturbances in bone strength and metabolism. The alterations of the serotonergic system are also observed in CKD. We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral serotonin and its metabolite– 5-hydroxyindoleacetic acid on bone biomechanical properties and metabolism in growing rats. The animals were sacrificed one and three months after nephrectomy. Biomechanical properties were determined on two different bone types: the cortical bone of the femoral diaphysis using three-point bending test and the mixed cortico-trabecular bone by the bending test of the femoral neck. Biomechanical tests revealed preserved cortical bone strength, whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone were significantly lower in CKD compared to controls. Serum activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and controls. ALP was associated with lower femoral stiffness and strength, and higher displacements and W. TRACP 5b was inversely associated with cortical Fu and W. The elevated peripheral serotonergic system in CKD was: inversely associated with stiffness but positively related to the displacements and W; inversely associated with cortical Fy but positively correlated with this parameter in cortico-trabecular bone; inversely associated with ALP in controls but positively correlated with this biomarker in CKD animals. In conclusion, this study demonstrates the distinct effect of mild degree of CKD on bone strength in rapidly growing rats. The impaired renal function affects the peripheral serotonin metabolism, which in turn may influence the strength and metabolism of bones in these rats. This relationship seems to be beneficial on the biomechanical properties of the cortico-trabecular bone, whereas the cortical bone strength can be potentially reduced. PMID

  2. Marble Bone Disease: A Rare Bone Disorder

    PubMed Central

    Harinathbabu, Maheswari; Thillaigovindan, Ranjani; Prabhu, Geetha

    2015-01-01

    Osteopetrosis, or marble bone disease, is a rare skeletal disorder due to a defective function of the osteoclasts. This defect renders bones more susceptible to osteomyelitis due to decreased vascularity. This disorder is inherited as autosomal dominant and autosomal recessive. Healthcare professionals should urge these patients to maintain their oral health as well as general health, as this condition makes these patients more susceptible to frequent infections and fractures. This case report emphasizes the signs and symptoms of marble bone disease and presents clinical and radiographic findings.  PMID:26594603

  3. The relationship between intact PTH and biointact PTH (1-84) with bone and mineral metabolism in pre-dialysis chronic kidney disease (CKD).

    PubMed

    O'Flaherty, D; Sankaralingam, A; Scully, P; Manghat, P; Goldsmith, D; Hampson, G

    2013-10-01

    Abnormalities in PTH are implicated in the pathogenesis of bone abnormalities in chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD). PTH concentrations are important in clinical decision and management. This emphasises the importance of providing an assay which measures biologically active PTH. We compared concentrations of intact PTH with biointact PTH (1-84) in CKD and end stage renal disease (ESRD) and investigated the relationship between the 2 PTH assays with bone and mineral laboratory parameters and bone mineral density (BMD) in CKD. We assessed 140 patients (61 in ESRD and 79 with CKD stages 1-4) in this cross-sectional study. We measured biointact PTH (1-84) as well as routine biochemical parameters on all subjects. In the CKD cohort, bone turnover markers; bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase (TRACP)-5b and bone mineral density (BMD) were also determined. In ESRD, intact PTH concentration was significantly higher compared to biointact PTH (1-84) (422 [443] v/s 266 [251] pg/mL, (p<0.001) with an average bias of 60%. In CKD, intact PTH concentration was also higher compared to biointact PTH (1-84) (79[55] v/s 68[49] pg/mL p<0.001) with an average bias of 18%. Only the biointact PTH (1-84) assay showed any significant correlation with serum calcium concentrations (r=-0.26, p<0.05) and phosphate (r=0.25, p<0.05) in CKD. Following multilinear regression analysis and adjustment for all significant co-variables, only eGFR, BAP and 25 (OH)vitamin remained significantly associated with intact PTH and biointact PTH (1-84). The strength of association was stronger between BAP and biointact PTH (1-84) (biointact PTH (1-84): p=0.007, intact PTH: p=0.01). In adjusted analyses, only biointact PTH (1-84) was significantly associated with BMD at the fore-arm (FARM) (p=0.049). The study confirms the differences between intact PTH and biointact PTH (1-84) in ESRD. Whilst there may be similarities in the diagnostic ability of both

  4. [Bone and tooth in calcium and phosphate metabolism].

    PubMed

    Tamamura, Yoshihiro; Yamaguchi, Akira

    2012-01-01

    Tight regulation of serum concentrations of calcium and phosphate is indispensable for maintaining normal physiological condition. Imbalance of this regulation leads to pathophysiological disorders including heart disease, chronic kidney disease, and ectopic calcification. Formation and mineralization of bone and tooth are greatly influenced by calcium and phosphate metabolism since both organs are mainly consist of calcium-phosphate. Calcium and phosphate homeostasis is under hormonal control on its target organs such as kidney, bone and intestine. Calcium and phosphate are absorbed in intestine and reabsorbed and excreted in kidney. Bone store and release them in response to changing physiological demand by osteoblastic bone formation and osteoclastic bone resorption. Bone is also important as an endocrine organ that releases FGF23 from osteocytes, a novel hormone that targets the kidney to inhibit phosphate reabsorption and 1α, 25 (OH) (2)D(3) production.

  5. Genetics Home Reference: Paget disease of bone

    MedlinePlus

    ... Conditions Paget disease of bone Paget disease of bone Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Paget disease of bone is a disorder that causes bones to grow ...

  6. Metabolic activity of sodium, measured by neutron activation, in the hands of patients suffering from bone diseases: concise communication

    SciTech Connect

    Spinks, T.J.; Bewley, D.K.; Paolillo, M.; Vlotides, J.; Joplin, G.F.; Ranicar, A.S.O.

    1980-01-01

    Turnover of sodium in the human hand was studied by neutron activation. Patients suffering from various metabolic abnormalities affecting the skeleton, who were undergoing routine neutron activation for the measurement of calcium, were investigated along with a group of healthy volunteers. Neutron activation labels the sodium atoms simultaneously and with equal probability regardless of the turnover time of individual body compartments. The loss of sodium can be described either by a sum of two exponentials or by a single power function. Distinctions between patients and normal subjects were not apparent from the exponential model but were brought out by the power function. The exponent of time in the latter is a measure of clearance rate. The mean values of this parameter in (a) a group of patients suffering from acromegaly; (b) a group including Paget's disease, osteoporosis, Cushing's disease, and hyperparathyroidism; and (c) a group of healthy subjects, were found to be significantly different from each other.

  7. Calcium and bone metabolism during space flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Heer, Martina

    2002-01-01

    Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

  8. Interaction between bone and glucose metabolism [Review].

    PubMed

    Kanazawa, Ippei

    2017-09-30

    Accumulating evidence has shown that bone and glucose metabolism are closely associated with each other. Since the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM), osteoporosis is recently recognized as one of diabetic complications, called DM-induced bone fragility. Previous studies showed that collagen cross-links of advanced glycation end products (AGEs) and dysfunctions of osteoblast and osteocyte are involved in DM-induced bone fragility. Circulating levels of AGEs and homocysteine are increased in patients with DM, and they directly impair the functions of osteoblast and osteocyte, resulting in decreased bone formation and bone remodeling. On the other hand, bone is recently recognized as an endocrine organ. Previous studies based on in vitro and animal studies showed that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, may regulate glucose homeostasis. Although several clinical studies reported the relationship between osteocalcin and glucose metabolism, further large-scale and intervention studies are necessary to confirm the beneficial effects of osteocalcin on glucose metabolism in human. It has been shown that adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor, is involved in bone metabolism. Adiponectin and metformin stimulate osteocalcin expression and the differentiation of osteoblasts via AMPK activation. Also, AMPK activation protects against oxidative stress-induced apoptosis of osteocytes. These findings suggest that AMPK in osteoblasts and osteocytes may be a therapeutic target for DM-induced bone fragility.

  9. Bone Metabolism in Anorexia Nervosa

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  10. Bone Metabolism on ISS Missions

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

    2014-01-01

    Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those

  11. Anorexia Nervosa, Obesity and Bone Metabolism

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa and obesity are conditions at the extreme ends of the nutritional spectrum, associated with marked reductions versus increases respectively in body fat content. Both conditions are also associated with an increased risk for fractures. In anorexia nervosa, body composition and hormones secreted or regulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, anorexia nervosa is characterized by increases in marrow adiposity and decreases in cold activated brown adipose tissue, both of which are related to low bone density. In obese individuals, greater visceral adiposity is associated with greater marrow fat, lower bone density and impaired bone structure. In this review, we discuss bone metabolism in anorexia nervosa and obesity in relation to adipose tissue distribution and hormones secreted or regulated by body fat content. PMID:24079076

  12. Cancer-associated bone disease.

    PubMed

    Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

    2013-12-01

    Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

  13. Cancer-associated bone disease

    PubMed Central

    Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

    2016-01-01

    Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

  14. Bone Remodeling and Energy Metabolism: New Perspectives

    PubMed Central

    de Paula, Francisco J. A.; Rosen, Clifford J.

    2013-01-01

    Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications. PMID:26273493

  15. Bone Metabolism and the c.-223C > T Polymorphism in the 5'UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease.

    PubMed

    Krela-Kaźmierczak, Iwona; Kaczmarek-Ryś, Marta; Szymczak, Aleksandra; Michalak, Michał; Skrzypczak-Zielińska, Marzena; Drwęska-Matelska, Natalia; Marcinkowska, Michalina; Eder, Piotr; Łykowska-Szuber, Lilianna; Wysocka, Ewa; Linke, Krzysztof; Słomski, Ryszard

    2016-12-01

    Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in

  16. Calcium and Bone Metabolism During Spaceflight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2002-01-01

    The ability to understand and counteract weightlessness-induced bone loss will be critical for crew health and safety during and after space station or exploration missions lasting months or years, respectively. Until its deorbit in 2001 , the Mir Space Station provided a valuable platform for long-duration space missions and life sciences research. Long-duration flights are critical for studying bone loss, as the 2- to 3-week Space Shuttle flights are not long enough to detect changes in bone mass. This review will describe human spaceflight data, focusing on biochemical surrogates of bone and calcium metabolism. This subject has been reviewed previously. 1-

  17. Green Tea and Bone Metabolism

    USDA-ARS?s Scientific Manuscript database

    Osteoporosis is a major health problem in elderly men and women. Epidemiological evidence has shown association between tea consumption and age-related bone loss in elderly men and women. The aim of this review is to provide a systemic review of green tea and bone health to cover the following topi...

  18. For whom the bell tolls: distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases.

    PubMed

    Manolagas, Stavros C; Parfitt, A Michael

    2013-06-01

    Osteocytes are long-lived and far more numerous than the short-lived osteoblasts and osteoclasts. Immured within the lacunar-canalicular system and mineralized matrix, osteocytes are ideally located throughout the bone to detect the need for, and accordingly choreograph, the bone regeneration process by independently controlling rate limiting steps of bone resorption and formation. Consistent with this role, emerging evidence indicates that signals arising from apoptotic and old/or dysfunctional osteocytes are seminal culprits in the pathogenesis of involutional, post-menopausal, steroid-, and immobilization-induced osteoporosis. Osteocyte-originated signals may also contribute to the increased bone fragility associated with bone matrix disorders like osteogenesis imperfecta, and perhaps the rapid reversal of bone turnover above baseline following discontinuation of anti-resorptive treatments, like denosumab.

  19. FOR WHOM THE BELL TOLLS: DISTRESS SIGNALS FROM LONG-LIVED OSTEOCYTES AND THE PATHOGENESIS OF METABOLIC BONE DISEASES

    PubMed Central

    Manolagas, Stavros C.; Parfitt, A. Michael

    2012-01-01

    Osteocytes are long-lived and far more numerous than the short-lived osteoblasts and osteoclasts. Immured within the lacunar-canalicular system and mineralized matrix, osteocytes are ideally located throughout bone to detect the need for, and accordingly choreograph, the bone regeneration process by independently controlling rate limiting steps of bone resorption and formation. Consistent with this role, emerging evidence indicates that signals arising from apoptotic and old/or dysfunctional osteocytes are seminal culprits in the pathogenesis of involutional, post-menopausal, steroid-, and immobilization-induced osteoporosis. Osteocyte-originated signals may also contribute to the increased bone fragility associated with bone matrix disorders like osteogenesis imperfecta, and perhaps the rapid reversal of bone turnover above baseline following discontinuation of anti-resorptive treatments, like denosumab. PMID:23010104

  20. Endocrine Regulation of Bone and Energy Metabolism in Hibernating Mammals

    PubMed Central

    Doherty, Alison H.; Florant, Gregory L.; Donahue, Seth W.

    2014-01-01

    Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases. PMID:24556365

  1. Endocrine regulation of bone and energy metabolism in hibernating mammals.

    PubMed

    Doherty, Alison H; Florant, Gregory L; Donahue, Seth W

    2014-09-01

    Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  2. Osteoprotegerin, s-RANKL, and selected interleukins in the pathology of bone metabolism in patients with Crohn's disease

    PubMed Central

    Wysocka, Ewa; Szymczak, Aleksandra; Eder, Piotr; Michalak, Michał; Łykowska-Szuber, Liliana; Stawczyk-Eder, Kamila; Klimczak, Katarzyna; Linke, Krzysztof; Horst-Sikorska, Wanda

    2015-01-01

    Introduction Crohn's disease (CD) promotes the development of osteopaenia/osteoporosis, the cytokine background of which is not fully known. Aim Evaluation of bone mineral density (BMD), the prevalence of osteopaenia and osteoporosis, and the determination of the levels of selected interleukins (IL), osteoprotegerin (OPG), and s-RANKL proteins in patients with CD in relation to a control group and assessment of the relationship between the tested cytokines, OPG, s-RANKL, and BMD. Material and methods Thirty-seven CD patients and 37 healthy volunteers (control group) were enrolled into the study. Densitometry of the lumbar spine (L2–L4) and of the femoral neck using the DXA technique was carried out. Serum levels of: IL-13, IL-4, IL-17, IL-1β, OPG, and s-RANKL were determined using the ELISA method. Progression-of-disease questionnaires were collected. Results The prevalence of osteoporosis and osteopaenia in the CD group was: 18.92% and 32.43% in L2–L4; 13.51% and 35.13% in the neck, respectively. The IL-13 and IL-1β concentrations were significantly higher and OPG was significantly lower in CD patients when compared to controls. In the case of all subjects: IL-13 correlated negatively with the BMD of the neck, IL-17 correlated negatively with the Z-score of L2–L4, and OPG correlated negatively with the IL-13. In the case of CD patients, IL-4 correlated negatively with the BMD of L2–L4. Conclusions The incidence of osteopaenia and osteoporosis in Polish CD patients is high. IL-13, IL-1β, and IL-4 seem to be connected with the pathology of decreased BMD in CD. It can be hypothesised that IL-13 may lower BMD by modulating OPG. PMID:27110308

  3. The prevalence of osteoporosis and the rate of bone loss in Korean adults: the Chungju metabolic disease cohort (CMC) study.

    PubMed

    Lim, Y; Jo, K; Ha, H-S; Yim, H-W; Yoon, K-H; Lee, W-C; Son, H-Y; Baek, K H; Kang, M-I

    2017-04-01

    Because the rate of bone loss is an important risk factor for fracture, we studied longitudinal changes in bone mineral density (BMD). Although the BMD of the hip decreased over time, spine BMD remained largely stable or increased. Therefore, spine BMD may not be appropriate for assessing BMD change.

  4. Interactions between muscle tissues and bone metabolism.

    PubMed

    Kawao, Naoyuki; Kaji, Hiroshi

    2015-05-01

    Sarcopenia and osteoporosis have recently been noted for their relationship with locomotive syndrome and increased number of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which may be associated with frailty. Several clinical data have indicated that increased muscle mass is related to increased bone mass and reduced fracture risk. Genetic, endocrine and mechanical factors as well as inflammatory and nutritional states concurrently affect muscle tissues and bone metabolism. Several genes, including myostatin and α-actinin 3, have been shown in a genome-wide association study (GWAS) to be associated with both sarcopenia and osteoporosis. Vitamin D, growth hormone and testosterone as well as pathological disorders, such as an excess in glucocorticoid and diabetes, affect both muscle and bone. Basic and clinical research of bone metabolism and muscle biology suggests that bone interacts with skeletal muscle via signaling from local and humoral factors in addition to their musculoskeletal function. However, the physiological and pathological mechanisms related to muscle and bone interactions remain unclear. We found that Tmem119 may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage. We also reported that osteoglycin and FAM5C might be muscle-derived humoral osteogenic factors. Other factors, including myostatin, osteonectin, insulin-like growth factor I, irisin and osteocalcin, may be associated with the interactions between muscle tissues and bone metabolism. © 2014 Wiley Periodicals, Inc.

  5. The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn's disease - a phase 1 trial with three doses.

    PubMed

    Dhere, T; Copland, I; Garcia, M; Chiang, K Y; Chinnadurai, R; Prasad, M; Galipeau, J; Kugathasan, S

    2016-09-01

    Mesenchymal stromal cells ability to reset immune functionalities may be useful in Crohn's disease. To perform a first-in-human phase 1 safety clinical trial of metabolically fit autologous bone marrow-derived mesenchymal stromal cells in 12 subjects with Crohn's disease utilising three doses. Autologous mesenchymal stromal cells were derived from marrow aspirate and propagated for 2-3 weeks with fibrinogen depleted human platelet lysate and subsequently administered to subjects without interval cryobanking. Twelve subjects received a single mesenchymal stromal cell intravenous infusion of 2, 5 or 10 million cells/kg BW(n = 4/group). Infused mesenchymal stromal cells were analysed for cell surface marker expression, IDO(indoleamine 2,3-dioxygenase) upregulation by IFNγ stimulation, and inhibition of third party peripheral blood mononuclear cell proliferation in vitro. The primary end point measured was safety and tolerability; clinical response was assessed as a secondary endpoint. All patients tolerated the mesenchymal stromal cell infusion well and no dose limiting toxicity was seen. Seven patients had serious adverse events of which five were hospitalisations for Crohn's disease flare. Two of these serious adverse events were possibly related to the mesenchymal stromal cells infusion. Five subjects showed clinical response 2 weeks after the infusion. Mesenchymal stromal cell phenotype, cytokine responsiveness, and peripheral blood mononuclear cell proliferation blockade were not different among the patients. Single infusion of fresh autologous bone marrow mesenchymal stromal cells propagated ex vivo using human platelet lysate-supplemented media was safe and feasible at intravenous doses of up to 10 million cells/kg BW in patients with Crohn's disease. © 2016 John Wiley & Sons Ltd.

  6. Calcium renal lithiasis and bone mineral density. Importance of bone metabolism in urinary lithiasis.

    PubMed

    Arrabal-Polo, M Á; Sierra Girón-Prieto, M; Orgaz-Molina, J; Zuluaga-Gómez, A; Arias-Santiago, S; Arrabal-Martín, M

    2013-06-01

    Calcium Nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphor-calcium metabolism. To establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites. We performed a PubMed literature review using different MeSH Terms like "Nephrolithiasis", "Bone mineral density", "Urinary stones", "Calcium", Bone resorption" and "Bone formation", with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected. In different studies reviewed have been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and β-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients. We recommend perform markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

  7. Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models.

    PubMed

    Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L; Snyder, Brian D; Rosenberg, Andrew E; Nazarian, Rosalynn M; Hrovat, Mirko I; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang

    2010-06-01

    In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization.

  8. Bone and metabolic complications of urinary diversions.

    PubMed

    Cano Megías, Marta; Muñoz Delgado, Eva Golmayo

    2015-02-01

    Hyperchloremic metabolic acidosis is a complication of urinary diversion using ileum or colon. Its prevalence ranges from 25% and 46% depending on the procedure used and renal function of the patient. It is a consequence of intestinal fluid and electrolyte exchange between intestinal mucosa and urine. The main mechanism is absorption of ammonium and chloride from urine. Long-term chronic metabolic acidosis in these patients may lead to impaired bone metabolism and osteomalacia. Regular monitoring of pH, chlorine, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment.

  9. Bone mass and bone metabolism markers during adolescence: The HELENA Study.

    PubMed

    Gracia-Marco, L; Vicente-Rodríguez, G; Valtueña, J; Rey-López, J P; Díaz Martínez, A E; Mesana, M I; Widhalm, K; Ruiz, J R; González-Gross, M; Castillo, M J; Moreno, L A

    2010-01-01

    The assessment of bone mineral content (BMC) and density (BMD) status in children and adolescents is important for health and the prevention of diseases. Bone metabolic activity could provide early information on bone mass development. Our aim was to describe bone mass and metabolism markers according to age and Tanner stage in adolescents. Spanish adolescents (n = 345; 168 males and 177 females) aged 12.5-17.5 years participated in this cross-sectional study. Body composition variables were measured by dual-energy X-ray absorptiometry. Serum osteocalcin (n = 101), aminoterminal propeptide of type I procollagen (n = 92) and β-isomerized C-telopeptides (β-CTX, n = 65) and urine samples (β-CTX; n = 237) were analyzed by electrochemiluminescence immunoassay. Analysis of covariance showed that females had higher values for BMC and BMD in most of the regions. Both males and females had a significant decrease in bone markers while sexual maturation increases (all p < 0.05). Males had an increased bone turnover compared to females (all p < 0.05, except for urine β-CTX in Tanner ≤IV). Our results support the evidence of dimorphic site-specific bone accretion between sexes and show an increased bone turnover in males, suggesting higher metabolic activity. Copyright © 2010 S. Karger AG, Basel.

  10. Calcium and bone disease

    PubMed Central

    Blair, Harry C.; Robinson, Lisa J.; Huang, Christopher L.-H.; Sun, Li; Friedman, Peter A.; Schlesinger, Paul H.; Zaidi, Mone

    2013-01-01

    Calcium transport and calcium signaling are of basic importance in bone cells. Bone is the major store of calcium and a key regulatory organ for calcium homeostasis. Bone, in major part, responds to calcium-dependent signals from the parathyroids and via vitamin D metabolites, although bone retains direct response to extracellular calcium if parathyroid regulation is lost. Improved understanding of calcium transporters and calcium-regulated cellular processes has resulted from analysis of genetic defects, including several defects with low or high bone mass. Osteoblasts deposit calcium by mechanisms including phosphate and calcium transport with alkalinization to absorb acid created by mineral deposition; cartilage calcium mineralization occurs by passive diffusion and phosphate production. Calcium mobilization by osteoclasts is mediated by acid secretion. Both bone forming and bone resorbing cells use calcium signals as regulators of differentiation and activity. This has been studied in more detail in osteoclasts, where both osteoclast differentiation and motility are regulated by calcium. PMID:21674636

  11. Biological effect of hydrolyzed collagen on bone metabolism.

    PubMed

    Daneault, Audrey; Prawitt, Janne; Fabien Soulé, Véronique; Coxam, Véronique; Wittrant, Yohann

    2017-06-13

    Osteoporosis is a chronic and asymptomatic disease characterized by low bone mass and skeletal microarchitectural deterioration, increased risk of fracture, and associated comorbidities most prevalent in the elderly. Due to an increasingly aging population, osteoporosis has become a major health issue requiring innovative disease management. Proteins are important for bone by providing building blocks and by exerting specific regulatory function. This is why adequate protein intake plays a considerable role in both bone development and bone maintenance. More specifically, since an increase in the overall metabolism of collagen can lead to severe dysfunctions and a more fragile bone matrix and because orally administered collagen can be digested in the gut, cross the intestinal barrier, enter the circulation, and become available for metabolic processes in the target tissues, one may speculate that a collagen-enriched diet provides benefits for the skeleton. Collagen-derived products such as gelatin or hydrolyzed collagen (HC) are well acknowledged for their safety from a nutritional point of view; however, what is their impact on bone biology? In this manuscript, we critically review the evidence from literature for an effect of HC on bone tissues in order to determine whether HC may represent a relevant alternative in the design of future nutritional approaches to manage osteoporosis prevention.

  12. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk. PMID:23874147

  13. Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2004-01-01

    Understanding bone loss during space flight is one of the most critical challenges for maintaining astronaut health on space exploration missions. Flight and ground-based studies have been conducted to better understand the nature and mechanisms of weightlessness-induced bone loss, and to identify a means to counteract the loss. Maintenance of bone health requires a balance between bone formation and bone resorption. Early space research identified bone loss as a critical health issue, but could not provide a distinction between the bone formation and breakdown processes. The recent identification of collagen crosslinks as markers of bone resorption has made possible a clear understanding that a decrease in bone resorption is an important effect of space flight, with bone formation being unchanged or only slightly decreased. Calcium regulatory factors have also been studied, in an attempt to understand their role in bone loss. The lack of ultraviolet light exposure and insufficient dietary sources of vitamin D often lead to reduced vitamin D stores on long-duration flights. Serum parathyroid hormone (PTH) concentrations are decreased during flight compared to before flight, although small subject numbers often make this hard to document statistically. As expected, reduced PTH concentrations are accompanied by reduced 1,25-dihydroxyvitamin D concentrations. Calcium kinetic studies during space flight confirm and extend the information gained from biochemical markers of bone metabolism. Calcium kinetic studies demonstrate that bone resorption is increased, bone formation is unchanged or decreased, and dietary calcium absorption is reduced during space flight. Evaluations have also been conducted of countermeasures, including dietary, exercise, and pharmacological treatments. In recent studies, many potential countermeasures show promise at mitigating bone loss in ground-based analogs of weightlessness (e.g., bed rest), but require further ground and flight testing to

  14. Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2004-01-01

    Understanding bone loss during space flight is one of the most critical challenges for maintaining astronaut health on space exploration missions. Flight and ground-based studies have been conducted to better understand the nature and mechanisms of weightlessness-induced bone loss, and to identify a means to counteract the loss. Maintenance of bone health requires a balance between bone formation and bone resorption. Early space research identified bone loss as a critical health issue, but could not provide a distinction between the bone formation and breakdown processes. The recent identification of collagen crosslinks as markers of bone resorption has made possible a clear understanding that a decrease in bone resorption is an important effect of space flight, with bone formation being unchanged or only slightly decreased. Calcium regulatory factors have also been studied, in an attempt to understand their role in bone loss. The lack of ultraviolet light exposure and insufficient dietary sources of vitamin D often lead to reduced vitamin D stores on long-duration flights. Serum parathyroid hormone (PTH) concentrations are decreased during flight compared to before flight, although small subject numbers often make this hard to document statistically. As expected, reduced PTH concentrations are accompanied by reduced 1,25-dihydroxyvitamin D concentrations. Calcium kinetic studies during space flight confirm and extend the information gained from biochemical markers of bone metabolism. Calcium kinetic studies demonstrate that bone resorption is increased, bone formation is unchanged or decreased, and dietary calcium absorption is reduced during space flight. Evaluations have also been conducted of countermeasures, including dietary, exercise, and pharmacological treatments. In recent studies, many potential countermeasures show promise at mitigating bone loss in ground-based analogs of weightlessness (e.g., bed rest), but require further ground and flight testing to

  15. Bone disease in primary hyperparathyroidism

    PubMed Central

    Bandeira, Francisco; Cusano, Natalie E.; Silva, Barbara C.; Cassibba, Sara; Almeida, Clarissa Beatriz; Machado, Vanessa Caroline Costa; Bilezikian, John P.

    2015-01-01

    Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT. PMID:25166047

  16. Bone Disease and Idiopathic Hypercalciuria

    PubMed Central

    Zerwekh, Joseph E.

    2008-01-01

    Observational and epidemiological studies alike have demonstrated that idiopathic hypercalciuric (IH) stone-forming patients typically demonstrate bone mineral density scores significantly less than those observed for age- and gender-matched normal subjects or those for non-hypercalciuric stone-forming patients. Most of these studies have relied on changes in bone mineral density (BMD) and have not explored the mechanism(s) involved. There have been a small number of studies that have relied on dynamic bone histomorphometry to ascertain the nature of the bone defect in IH patients. When performed, these studies have clearly demonstrated increased bone resorption and high bone turnover in patients with fasting hypercalciuria while suppressed bone formation indices are the most consistent finding in patients with the absorptive variant of IH. The causes of this apparent difference in bone remodeling between the two variants of IH is still uncertain. Available evidence suggests that potential mechanisms may be dependent in large part to genetic, metabolic, and nutritional causes of hypercalciuria and bone loss in patients with IH. PMID:18359394

  17. [Unawareness of the K/DOQI guidelines for bone and mineral metabolism in predialysis chronic kidney disease: results of the OSERCE Spanish multicenter-study survey].

    PubMed

    Bover, J; Górriz, J L; Martín de Francisco, A L; Caravaca, F; Barril, G; Molinero, L M

    2008-01-01

    Since its publication in 2003, the K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease (CKD) have become a worldwide reference. The aim of this study was to analyze the observance to these guidelines in patients with a glomerular filtration rate < 60 ml/min/1,73m2 not yet included in dialysis in a Spanish multicenter cohort. A questionnaire by investigator/centre was completed by 32 different nephrologists participating in the OSERCE study and representing the overall Spanish public health net. We observed that biochemical parameters were measured less frequently than recommended, except in CKD stage 3. The therapeutic goals for intact PTH were not properly reported by 59 % of the consulted nephrologists for stages 3 and 4, whereas only 22% did not report them properly for stage 5. The goals for phosphorus were not adequately reported in 50 % of cases (stages 3 y 4) and 60 % (stage 5). For calcium, these values were 70 %, 73.3 % and 65.5 % for stages 3, 4 and 5, respectively. A corrected plasma calcium between 9.5 and 10.2 mg/dl is still considered adequate for 31%. As much as 87% nephrologists stated that they did not sistematically measure calcidiol plasma levels. In general, these results demonstrate that there is a great degree of unawareness of K/DOQITM predialysis guidelines. Thus, their poor implementation is probably not only due to the lower availability of approved therapeutic agents, the difficult achievement of goals or the disbelief on current recommendations. It would be desirable that forthcoming guidelines such as the KDIGO could also consider the need of educational efforts for CKD-Mineral and Bone Disorder.

  18. Diseases of Phenylalanine Metabolism

    PubMed Central

    Parker, Charles E.

    1979-01-01

    Continuing investigation of the system that hydroxylates phenylalanine to tyrosine has led to new insights into diseases associated with the malfunction of this system. Good evidence has confirmed that phenylketonuria (PKU) is not caused by a simple lack of phenylalanine hydroxylase. Dihydropteridine reductase deficiency as well as defects in biopterin metabolism may also cause the clinical features of phenylketonuria. Furthermore, these diseases do not respond to the standard treatment for phenylketonuria. PMID:388868

  19. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases.

    PubMed

    Ke, Hua Zhu; Richards, William G; Li, Xiaodong; Ominsky, Michael S

    2012-10-01

    The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.

  20. Oral Health and Bone Disease

    MedlinePlus

    ... and ill-fitting or loose dentures. Effects of Osteoporosis Treatments on Oral Health It is not known ... Resources For more information on osteoporosis, visit: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: ...

  1. Bone Marrow Diseases - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Marrow Diseases URL of this page: https://medlineplus.gov/languages/bonemarrowdiseases.html Other topics A-Z Expand Section ...

  2. Bone disease and HIV infection.

    PubMed

    Amorosa, Valerianna; Tebas, Pablo

    2006-01-01

    The high prevalence of bone demineralization among human immunodeficiency virus (HIV)-infected patients in the current therapeutic era has been described in multiple studies, sounding the alarm that we may expect an epidemic of fragility fractures in the future. However, despite noting high overall prevalences of osteopenia and osteoporosis, recent longitudinal studies that we review here have generally not observed accelerated bone loss during antiretroviral therapy beyond the initial period after treatment initiation. We discuss the continued progress toward understanding the mechanisms of HIV-associated bone loss, particularly the effects of HIV infection, antiretroviral therapy, and host immune factors on bone turnover. We summarize results of clinical trials published in the past year that studied the safety and efficacy of treatment of bone loss in HIV-infected patients and provide provisional opinions about who should be considered for bone disease screening and treatment.

  3. [Bone and Calcium Research Update 2015. Metabolic crosstalk bone and other organs].

    PubMed

    Ochi, Hiroki; Takeda, Shu

    2015-01-01

    Bone homeostasis is maintained by bone formation and bone resorption. The identification that nervous system controls bone metabolism through leptin deficient mice studies opened a new field in bone biology. Notably, sympathetic and parasympathetic nerve system regulate bone metabolism. In addition, sensory nerve system also has been shown to be involved in the regulation of bone homeostasis. On the other hand, recent studies reported that bone derived hormones, such as osteocalcin or fibroblast growth factor 23, regulate systemic metabolism. Based on these findings, currently the bone-organ crosstalk has been noted.

  4. Small molecules for bone diseases.

    PubMed

    Masuya, Keiichi; Teno, Naoki

    2010-04-01

    Bones play many roles in the body, providing structure, protecting organs, anchoring muscles and storing calcium. Over 100 million people worldwide suffer from bone diseases, mainly osteoporosis, cancer-related bone loss, osteoarthritis and inflammatory arthritis. Osteoporosis itself has no specific symptoms, and the main consequence is the increased risk of bone fractures. Therefore, the prevention of bone diseases is important to maintain the quality of life in the human society. However, treatment options are still insufficient. This review article gives a summary of the low molecular mass modulators of bone diseases targets disclosed in patent applications and articles, mainly during the last 5 years. Readers will rapidly gain an overview of these modulators not only for historical targets, but also of emerging and re-visited targets. Readers will also be able to see the current research trend and the main players in this field. Drug discovery for bone diseases has made progress in the last years. The research area has dynamically shifted from historical targets (bisphosphonate, parathyroid hormone and calcitonin) to newly confirmed targets or targets re-visited which were biologically validated in the past. Cathepsin K inhibitors should be very close to launching in the market.

  5. Bone and mineral metabolism in African Americans.

    PubMed

    Bell, N H

    1997-08-01

    Important differences exist in the metabolism of bone and mineral and the vitamin D endocrine system between whites and African Americans and include rate o f skeletal remodeling, bone mass, and vitamin D metabolism. A higher bone mineral density (BMD) in African Americans is associated with a diminished incidence o f osteoporosis and fractures. Serum 17beta-estradiol and the rate of GH secretion are higher in black than in white men, but there is no racial difference in women in this regard. The mechanisms for reduced rate o f skeletal remodeling and for greater BMD in blacks are not known, but diminished rate of skeletal remodeling could be a contributing factor for greater bone mass. Reduction in serum 25-hydroxyvitamin D in blacks is attributed to increased skin pigment and to diminished dermal production of vitamin D(3) and consequent decreased hepatic synthesis o f the metabolite. There is no evidence that alteration of the vitamin D endocrine system contributes to or is responsible for racial differences in skeletal remodeling and bone mass. Black infants, however, are at risk for developing vitamin D-deficient rickets, particularly when breast-fed.

  6. Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET–CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion

    PubMed Central

    Ranade, Rohit; Basu, Sandip

    2017-01-01

    Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET. PMID:28217023

  7. Bone scintigraphy elucidates different metabolic stages of melorheostosis

    PubMed Central

    Izadyar, Sina; Gholamrezanezhad, Ali

    2012-01-01

    Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3rd and 4th metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4th metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3rd left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints. PMID:22514755

  8. Bone scintigraphy elucidates different metabolic stages of melorheostosis.

    PubMed

    Izadyar, Sina; Gholamrezanezhad, Ali

    2012-01-01

    Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3(rd) and 4(th) metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4(th) metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3(rd) left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints.

  9. Restoration of the GM2 ganglioside metabolism in bone marrow-derived stromal cells from Tay-Sachs disease animal model.

    PubMed

    Martino, S; Cavalieri, C; Emiliani, C; Dolcetta, D; Cusella De Angelis, M G; Chigorno, V; Severini, G M; Sandhoff, K; Bordignon, C; Sonnino, S; Orlacchio, A

    2002-08-01

    The therapeutic potential of bone marrow-derived stromal cells for the therapy of Tay-Sachs disease is primarily related to the restoration of their own GM2 ganglioside storage. With this aim, we produced bone marrow-derived stromal cells from the adult Tay-Sachs animal model and transduced them with a retroviral vector encoding for the alpha-subunit of the lysosomal enzyme beta-hexosaminidase A (E.C. 3.2.1.52). Our results demonstrate that transduced Tay-Sachs bone marrow-derived stromal cells have beta-hexosaminidase A comparable to that of bone marrow-derived stromal cells from wild-type mice. Moreover, beta-hexosaminidase A in transduced Tay-Sachs bone marrow-derived stromal cells was able to hydrolyze the GM2 ganglioside in a feeding experiment, thus demonstrating the correction of the altered phenotype.

  10. Hyponatremia and bone disease.

    PubMed

    Negri, Armando Luis; Ayus, Juan Carlos

    2016-09-24

    Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement

  11. Bone Disease in Multiple Myeloma.

    PubMed

    Eda, Homare; Santo, Loredana; David Roodman, G; Raje, Noopur

    2016-01-01

    Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristics of multiple myeloma (MM). Nearly 90 % of patients with MM develop osteolytic bone lesions, frequently complicated by skeletal-related events (SRE) such as severe bone pain, pathological fractures, vertebral collapse, hypercalcemia, and spinal cord compression. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. OBD is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Inhibition of osteolysis and stimulation of OB differentiation leads to reduced tumor growth in vivo. Therefore, novel agents targeting OBD are promising therapeutic strategies not only for the treatment of MM OBD but also for the treatment of MM. Several novel agents in addition to bisphosphonates are currently under investigation for their positive effect on bone remodeling via OC inhibition or OB stimulation. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from MM OBD but also capitalizing on the resultant antitumor activity.

  12. Taking a toll on the bones: regulation of bone metabolism by innate immune regulators.

    PubMed

    Bar-Shavit, Zvi

    2008-04-01

    The interplay between the immune system and bone metabolism has been recognized as important for both of these systems. Various factors produced and released during immune responses markedly affect bone cells and bone metabolism. Meanwhile, niches for lymphocytes in bone also play an important role in the biology of these cells. Osteoimmunology, a new area of research focusing on associations between the immune and bone systems, is based on the concept that deeper investigation of the relationships between these systems will enhance our understanding of their biology and contribute to the discovery of novel therapeutic approaches for diseases of the two systems. Toll-like receptors (TLRs), the focus of this review, sense pathogen-derived molecules and initiate the inflammatory reactions of innate immune cells. TLRs are also expressed in bone cells, and their activation affects osteoclast differentiation and activity in a complex manner: TLR activation in early osteoclast precursors blocks the differentiation of those cells, while in cells that have already started their osteoclastic differentiation, it stimulates this process and increases the survival rates of mature osteoclasts (OCs). Activation of TLRs in osteoblasts (OBs) induces the production of osteoclastogenic cytokines, such as RANKL and TNF-alpha, thereby contributing to TLR ligand-induced osteoclastogenesis. These processes are the reason for the bone loss observed in variety of infectious diseases. The inhibition of osteoclastogenesis by TLR activation in early precursor cells may play a role in reducing the excessive bone loss caused by pathogenic infection and shifting the balance between the bone and immune systems during infection to recruit immune cells.

  13. Vitamin D and bone disease.

    PubMed

    Christodoulou, S; Goula, T; Ververidis, A; Drosos, G

    2013-01-01

    Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a "good bone health" guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.

  14. Metabolic bone disease in juvenile Humboldt penguins (Spheniscus humboldti): investigation of ionized calcium, parathyroid hormone, and vitamin D3 as diagnostic parameters.

    PubMed

    Adkesson, Michael J; Langan, Jennifer N

    2007-03-01

    Three cases of metabolic bone disease (MBD) were identified in juvenile Humboldt penguins (Spheniscus humboldti) in a zoological collection. Diagnosis, monitoring, and treatment were challenging, in part because radiographs and traditional serum biochemistries did not provide adequate information to guide appropriate clinical management. Normal values for ionized calcium (iCa), 25-hydroxyvitamin D3 [25-(OH) D3], and parathyroid hormone (PTH) have not been reported for any species in the order Sphenisciformes. This study aimed to establish reference ranges for these parameters to provide a method for assessing clinical cases of MBD and other disease processes. iCa was measured in 33 healthy adult birds from two zoological collections by using a portable clinical analyzer. iCa also was measured from 14 of these birds at a commercial laboratory. Mean and standard deviation were determined to be 1.21 +/- 0.09 and 1.29 +/- 0.10 mmol/L, respectively. Limited data exist on iCa in avian species, but these results are consistent with other reports and provide a useful clinical parameter. Analysis of PTH and 25-(OH) D3 was performed at a commercial laboratory on samples from 14 healthy adult penguins in one collection. Means and standard deviations for PTH and 25-(OH) D3 were 0.8 +/- 0.3 pmol/L and 3.7 +/- 2.4 nmol/L, respectively. These results are near the minimal functional detectable limits of the assays; raising uncertainty about the validity and usefulness of currently available PTH and 25-(OH) D3 tests in this species.

  15. Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone.

    PubMed

    Prisby, Rhonda D

    2017-12-01

    Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair and provides O2, nutrients, waste elimination, systemic hormones and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow. It is becoming increasingly clear that the vascular and skeletal systems are intimately linked in metabolic regulation and physiological and pathological processes. This review examines how agents such as mechanical loading, parathyroid hormone, estrogen, vitamin D and calcitonin, all considered anabolic for bone, have tremendous impacts on the bone vasculature. In fact, these agents influence bone blood vessels prior to influencing bone. Further, data reveal strong associations between vasodilator capacity of bone blood vessels and trabecular bone volume, and poor associations between estrogen status and uterine mass and trabecular bone volume. Additionally, this review highlights the importance of the bone microcirculation, particularly the vascular endothelium and NO-mediated signaling, in the regulation of bone blood flow, bone interstitial fluid flow and pressure and the paracrine signaling of bone cells. Finally, the vascular endothelium as a mediator of bone health and disease is considered. © 2017 Society for Endocrinology.

  16. What Is Paget's Disease of Bone?

    MedlinePlus

    ... About Paget’s Disease and Other Related Conditions: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ... org) in the preparation of this publication. NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ...

  17. Kinetic measurements of bone mineral metabolism: The use of Na-22 as a tracer for long-term bone mineral turnover studies

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1978-01-01

    Sodium-22 was studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with (22)Na which is released through the metabolic turnover of the bone. The (22)Na which is not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high but nontoxic levels of NaCl. The (22)Na tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

  18. [Overview: derangement of bone metabolism in diabetes mellitus].

    PubMed

    Takeuchi, Yasuhiro

    2009-09-01

    Since it is well known that insulin actions have direct and indirect effects on bone metabolism, bone metabolism and bone fragility in patients with diabetes mellitus is a clinically important issue to be addressed. As in glucose metabolism, an involvement of insulin deficiency and insulin resistance should be discussed independently in bone metabolism. Impaired bone formation is primarily involved in bone loss in patients with type 1 diabetes who are lack in insulin secretion. In contrast, bone fragility due to poor bone quality is a major problem in patients with type 2 diabetes who are resistant to insulin actions. Through clinical investigations, it has been established that elderly women with diabetes are at high risk in fracture. Taken together, one should be aware of bone integrity in patients with diabetes, especially in elderly women.

  19. Metabolic and Clinical Consequences of Hyperthyroidism on Bone Density

    PubMed Central

    Gorka, Jagoda; Taylor-Gjevre, Regina M.

    2013-01-01

    In 1891, Von Recklinghausen first established the association between the development of osteoporosis in the presence of overt hyperthyroidism. Subsequent reports have demonstrated that BMD loss is common in frank hyperthyroidism, and, to a lesser extent, in subclinical presentations. With the introduction of antithyroid medication in the 1940s to control biochemical hyperthyroidism, the accompanying bone disease became less clinically apparent as hyperthyroidism was more successfully treated medically. Consequently, the impact of the above normal thyroid hormones in the pathogenesis of osteoporosis may be presently underrecognized due to the widespread effective treatments. This review aims to present the current knowledge of the consequences of hyperthyroidism on bone metabolism. The vast number of recent papers touching on this topic highlights the recognized impact of this common medical condition on bone health. Our focus in this review was to search for answers to the following questions. What is the mechanisms of action of thyroid hormones on bone metabolism? What are the clinical consequences of hyperthyroidism on BMD and fracture risk? What differences are there between men and women with thyroid disease and how does menopause change the clinical outcomes? Lastly, we report how different treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis. PMID:23970897

  20. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Efficacy of selective estrogen receptor modulators (SERMs) in lifestyle-related osteoporosis].

    PubMed

    Ohta, Hiroaki

    2014-11-01

    Most of the evidence for osteoporosis treatment comes from that in primary osteoporosis, with very little evidence available for that in secondary osteoporosis including lifestyle-related osteoporosis as a lifestyle-related disease despite the fact that secondary osteoporosis affects more patients than primary osteoporosis. This is in contrast to osteoporosis associated with type 2 diabetes and chronic kidney disease, where accumulating evidence demonstrates that osteoporosis is accounted for by decreases in bone strength associated with deterioration of bone quality due to accumulation of advanced glycation end products (AGEs) in collagen that results from elevated homocysteine and pentosidine levels. In this regard, given the ample evidence for their efficacy against deterioration of bone quality, selective estrogen receptor modulators (SERMs) are currently thought to represent the most efficacious of all available therapeutic agents for lifestyle-related osteoporosis.

  1. Heritability of markers of bone metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Zwart, S. R.; Hargens, A. R.

    2005-01-01

    Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

  2. Heritability of markers of bone metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Zwart, S. R.; Hargens, A. R.

    2005-01-01

    Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

  3. [Control of bone remodeling by nervous system. Regulation of bone metabolism by appetite regulating neuropeptides].

    PubMed

    Fukuda, Toru; Takeda, Shu

    2010-12-01

    The traditional view of bone metabolism as a primarily endocrine activity has been expanded in recent years following the identification of nervous system controlling bone metabolism by leptin studies. Especially, hypothalamic appetite regulating-peptides, such as NPY, CART and NMU have been demonstrated to be bone-regulating neuropeptides. Recently, other neuropeptides, such as serotonin and oxytocin, are reported to be associated with bone metabolism.

  4. [Dehydroepiandrosterone(DHEA)and bone metabolism].

    PubMed

    Ohnaka, Keizo

    2016-07-01

    Dehydroepiandrosterone(DHEA), an adrenal androgen, has attracted much attention as an anti-aging hormone as well as a marker for senescence because of its unique change along with aging. DHEA is reported to have beneficial effects such as anti-diabetes, anti-obesity, and anti-atherosclerosis. It is also shown that DHEA has anti-osteoporosis effects to increase bone mineral density in randomized controlled trials(RCTs). As osteoblasts express aromatase which will convert androgen to estrogen, DHEA may act protectively against osteoporosis through its metabolites. Because there is no report on fracture risk by DHEA administration, further studies are required to clarify DHEA effects on human bone metabolism.

  5. Characteristics of bone mineral metabolism in patients with stage 3-5 chronic kidney disease not on dialysis: results of the OSERCE study.

    PubMed

    Górriz, José L; Molina, Pablo; Bover, Jordi; Barril, Guillermina; Martín-de Francisco, Angel L; Caravaca, Francisco; Hervás, José; Piñera, Celestino; Escudero, Verónica; Molinero, Luis M

    2013-01-18

    OSERCE is a multi-centre and cross-sectional study with the aim of analysing the biochemical, clinical, and management characteristics of bone mineral metabolism alterations and the level of compliance with K/DOQI guideline recommendations in patients with chronic kidney disease (CKD) not on dialysis. The study included a total of 634 patients from 32 different Spanish nephrology units, all with CKD, estimated glomerular filtration rates <60 ml/min/1.73 m(2), and not on dialysis (K/DOQI stage: 33% stage 3, 46% stage 4, and 21% stage 5). In 409 of these patients, laboratory parameters were also measured in a centralised laboratory, including creatinine, calcium, phosphorous, intact parathyroid hormone (PTH), 25-OH-vitamin D, and 1,25-OH2-Vitamin D levels. The rates of non-compliance with the K/DOQI objectives for calcium, phosphorous, intact PTH, and calcium x phosphate product among these patients were 45%, 22%, 70%, and 4%, respectively. Of the 70% of patients with intact PTH levels outside of the target range established by the K/DOQI guidelines, 55.5% had values above the upper limit and 14.5% had values below the lower limit. Of the 45% of patients with calcium levels outside of the target range, 40% had values above the upper limit and 5% had values below the lower limit. Of the 22% of patients with phosphorous levels outside of the target range, 19% had values above the upper limit, and 3% had values below the lower limit. Finally, 4% of patients also had values for the calcium x phosphate product that were outside of the recommended range. Only 1.8% of patients complied with all four K/DOQI objectives. The values detected in centralised laboratory analyses were not significantly different from those measured in the laboratories at each institution. In addition, 81.5% of patients had a deficiency of calcidiol (25-OH-D3) (<30 ng/ml); of these, 35% had moderate-severe deficiency (<15 ng/ml) and 47% had mild deficiency (15-30 ng/ml). Calcitriol (1,25-OH2-D3

  6. Leptin in joint and bone diseases: new insights.

    PubMed

    Scotece, M; Conde, J; Lopez, V; Lago, F; Pino, J; Gomez-Reino, J J; Gualillo, O

    2013-01-01

    Leptin is an adipokine with pleiotropic actions that regulates food intake, energy metabolism, inflammation and immunity, and also participates in the complex mechanism that regulates skeleton biology, both at bone and cartilage level. Leptin is increased in obesity and contributes to the "low-grade inflammatory state" of obese subjects causing a cluster of metabolic aberrations that affects joints and bone. In this review, we report the most recent research advances about the role of leptin in bone and cartilage function and its implication in inflammatory and degenerative joint diseases, such as osteoarthritis, rheumatoid arthritis and osteoporosis.

  7. The pleiotropic effects of paricalcitol: Beyond bone-mineral metabolism.

    PubMed

    Egido, Jesús; Martínez-Castelao, Alberto; Bover, Jordi; Praga, Manuel; Torregrosa, José Vicente; Fernández-Giráldez, Elvira; Solozábal, Carlos

    2016-01-01

    Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD.

  8. Vascular calcification, bone and mineral metabolism after kidney transplantation

    PubMed Central

    D’Marco, Luis; Bellasi, Antonio; Mazzaferro, Sandro; Raggi, Paolo

    2015-01-01

    The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article. PMID:26722649

  9. Effects of food enriched with egg yolk hydrolysate (bone peptide) on bone metabolism in orchidectomized dogs.

    PubMed

    Kobayashi, Toyokazu; Koie, Hiroshi; Watanabe, Arisa; Ino, Arisa; Watabe, Kazuya; Kim, Mujo; Kanayama, Kiichi; Otsuji, Kazuya

    2015-04-01

    We examined the effects of chicken egg hydrolysate (also known as "bone peptide" or BP) on bone metabolism in 5- to 8-month-old orchidectomized dogs. The bone formation marker serum bone alkaline phosphatase (BAP) and the bone resorption marker urine deoxypyridinoline (DPD) were used as indicators to measure changes in bone metabolism. The following results were observed that Serum BAP was higher in dogs fed BP-enriched food throughout the clinical investigation. Serum BAP was statistically significantly higher in dogs fed BP-enriched food than in dogs fed non-BP-enriched food at 2 months after orchidectomy. This suggests that BP promoted bone formation immediately after orchidectomy.

  10. Nuclear Receptors: Decoding Metabolic Disease

    PubMed Central

    Sonoda, Junichiro; Pei, Liming; Evans, Ronald M.

    2008-01-01

    Nuclear receptors (NR) are a superfamily of ligand-activated transcription factors that regulate development, reproduction, and metabolism of lipids, drugs and energy. The importance of this family of proteins in metabolic disease is exemplified by NR ligands used in the clinic or under exploratory development for the treatment of diabetes mellitus, dyslipidemia, hypercholesterolemia, or other metabolic abnormalities. Genetic studies in humans and rodents support the notion that NRs control a wide variety of metabolic processes by regulating the expression of genes encoding key enzymes, transporters and other proteins involved in metabolic homeostasis. Current knowledge of complex NR metabolic networks is summarized here. PMID:18023286

  11. [Bone metabolism and cardiovascular function update. Role of vitamin D in the bone and vascular intercommunication].

    PubMed

    Okano, Toshio

    2014-07-01

    Vascular calcification, hypertension and cardiac hypertrophy have been often complicated in osteoporotic patients with low bone mass. Since there are many similarities among the processes of bone formation and vascular calcification, vitamin D insufficiency has been thought to be deeply involved in the pathogenesis of these diseases. Indeed, in animal studies, vitamin D receptor gene knockout mice have been shown to display severe vascular calcification, high blood pressure, and left ventricular hypertrophy. On the other hand, in clinical studies, active vitamin D restores vascular calcification and improves heart function in dialysis patients. Whether 1,25 (OH) ₂D₃ acts directly on vascular smooth muscle cells and cardiomyocytes or acts indirectly on them via regulating calcium metabolism remains unclear. The elucidation of the role of vitamin D in the bone and vascular intercommunication and its application toward drug development could be an important step forward in the realization of health and longevity society.

  12. Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs.

    PubMed

    Hamed, Sherifa A

    2016-01-01

    Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.

  13. MicroRNAs in bone diseases.

    PubMed

    Gennari, L; Bianciardi, S; Merlotti, D

    2017-04-01

    MicroRNAs are small, noncoding single-stranded RNAs that have emerged as important posttranscriptional regulators of gene expression, with an essential role in vertebrate development and different biological processes. This review highlights the recent advances in the function of miRNAs and their roles in bone remodeling and bone diseases. MicroRNAs (miRNAs) are a class of small (∼22 nt), noncoding single-stranded RNAs that have emerged as important posttranscriptional regulators of gene expression. They are essential for vertebrate development and play critical roles in different biological processes related to cell differentiation, activity, metabolism, and apoptosis. A rising number of experimental reports now indicate that miRNAs contribute to every step of osteogenesis and bone homeostasis, from embryonic skeletal development to maintenance of adult bone tissue, by regulating the growth, differentiation, and activity of different cell systems inside and outside the skeleton. Importantly, emerging information from animal studies suggests that targeting miRNAs might become an attractive and new therapeutic approach for osteoporosis or other skeletal diseases, even though there are still major concerns related to potential off target effects and the need of efficient delivery methods in vivo. Moreover, besides their recognized effects at the cellular level, evidence is also gathering that miRNAs are excreted and can circulate in the blood or other body fluids with potential paracrine or endocrine functions. Thus, they could represent suitable candidates for becoming sensitive disease biomarkers in different pathologic conditions, including skeletal disorders. Despite these promising perspectives more work remains to be done until miRNAs can serve as robust therapeutic targets or established diagnostic tools for precision medicine in skeletal disorders.

  14. Metabolic syndrome and eye diseases.

    PubMed

    Poh, Stanley; Mohamed Abdul, Riswana Banu Binte; Lamoureux, Ecosse L; Wong, Tien Y; Sabanayagam, Charumathi

    2016-03-01

    Metabolic syndrome is becoming a worldwide medical and public health challenge as it has been seen increasing in prevalence over the years. Age-related eye diseases, the leading cause of blindness globally and visual impairment in developed countries, are also on the rise due to aging of the population. Many of the individual components of the metabolic syndrome have been shown to be associated with these eye diseases. However, the association of metabolic syndrome with eye diseases is not clear. In this review, we reviewed the evidence for associations between metabolic syndrome and certain ocular diseases in populations. We also reviewed the association of individual metabolic syndrome components with ocular diseases due to a paucity of research in this area. Besides, we also summarised the current understanding of etiological mechanisms of how metabolic syndrome or the individual components lead to these ocular diseases. With increasing evidence of such associations, it may be important to identify patients who are at risk of developing metabolic syndrome as prompt treatment and intervention may potentially decrease the risk of developing certain ocular diseases.

  15. Photodynamic therapy of diseased bone

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support

  16. Pain and Paget's Disease of Bone

    MedlinePlus

    ... Home Paget’s Disease of Bone Paget’s Disease Management Pain and Paget’s Disease of Bone Publication available in: ... focus(); */ } //--> Print-Friendly Page May 2015 Types of Pain Paget’s disease can cause several different kinds of ...

  17. [Metabolic status and bone mineral density in patients with pseudarthrosis of long bones in hyperhomocysteinemia].

    PubMed

    Bezsmertnyĭ, Iu O

    2013-06-01

    In article described research of the metabolic status and bone mineral density in 153 patients with with pseudarthrosis of long bones, in individuals with consolidated fractures and healthy people. The violations of reparative osteogenesis at hyperhomocysteinemia are accompanied by disturbances of the functional state of bone tissue, inhibition of biosynthetic and increased destruction processes, reduced bone mineral density in the formation of osteopenia and osteoporosis. The degree and direction of change of bone depends on the type of violation of reparative osteogenesis.

  18. Analysis of bone metabolism during early stage and clinical benefits of early intervention with alendronate in patients with systemic rheumatic diseases treated with high-dose glucocorticoid: Early DIagnosis and Treatment of OsteopoRosis in Japan (EDITOR-J) study.

    PubMed

    Tanaka, Yoshiya; Mori, Hiroko; Aoki, Takatoshi; Atsumi, Tatsuya; Kawahito, Yutaka; Nakayama, Hisanori; Tohma, Shigeto; Yamanishi, Yuji; Hasegawa, Hitoshi; Tanimura, Kazuhide; Negoro, Nobuo; Ueki, Yukitaka; Kawakami, Atsushi; Eguchi, Katsumi; Saito, Kazuyoshi; Okada, Yosuke

    2016-11-01

    We conducted a prospective multicenter study to assess early changes in the dynamics of bone metabolism in patients with systemic connective tissue diseases following commencement of high-dose glucocorticoid therapy and the benefits of early treatment with bisphosphonate and vitamin D analogue. The subjects of this randomized controlled trial were 106 female patients with systemic connective tissue diseases treated for the first time with glucocorticoids at doses equivalent to prednisolone ≥20 mg/day (age ≥ 18 years). One week after initiation of glucocorticoid therapy, patients were randomly assigned to treatment with alfacalcidol at 1 μg/day (n = 33), alendronate 35 mg/week (n = 37), and alfacalcidol plus alendronate (n = 36). The primary endpoints were changes in lumbar spine bone density at 6 months of treatment and the frequency of bone fracture at 12 months. Commencement of glucocorticoid therapy was associated with a rapid and marked bone resorption within 1 week. The combination of alfacalcidol and alendronate administered after the first week of glucocorticoid therapy halted the pathological processes affecting bone metabolism, increased bone density, and reduced the incidence of bone fracture over a period of 12 months. Taken together, the use of the combination of alfacalcidol and alendronate improved bone metabolism, increased bone density, and significantly reduced the incidence of bone fracture during 1-year high-dose glucocorticoid therapy.

  19. Lysophosphatidylinositol Signalling and Metabolic Diseases

    PubMed Central

    Arifin, Syamsul A.; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  20. Lysophosphatidylinositol Signalling and Metabolic Diseases.

    PubMed

    Arifin, Syamsul A; Falasca, Marco

    2016-01-15

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis.

  1. Mineral metabolism in heart disease.

    PubMed

    Heine, Gunnar H

    2015-07-01

    Strong experimental and clinical evidence points towards a substantial contribution of mineral metabolism disorders to the initiation and progression of cardiovascular disease. Vice versa, recent work suggests that cardiovascular disease may also cause mineral metabolism alterations. Experimental studies suggest that hyperphosphatemia, elevated plasma levels of phosphaturic hormones--parathyroid hormone and fibroblast growth factor-23 (FGF-23)--and hypovitaminosis D exert detrimental effects on vascular tissue and on the myocardium. Accordingly, in longitudinal clinical cohort studies, individuals with high plasma levels of phosphate, parathyroid hormone and FGF-23, and with low vitamin D levels, face worst cardiovascular prognosis.Notably, recent evidence suggests that cardiovascular disease may not only follow but also induce mineral metabolism disorders: severe derangements in mineral metabolism were observed in patients with acute heart failure, who face a tremendous increase in plasma FGF-23. Unfortunately, few prospective studies have been completed hitherto that specifically target components of the mineral metabolism for cardiovascular disease prevention or treatment. A bidirectional interaction exists between mineral metabolism disorders and cardiovascular disease. However, clinical evidence for a cardiovascular benefit of therapeutic interventions into mineral metabolism is outstanding.

  2. Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolism.

    PubMed

    Giaginis, Costas; Tsantili-Kakoulidou, Anna; Theocharis, Stamatios

    2007-06-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that regulate the storage and catabolism of dietary fats. PPARs constitute molecular targets for the treatment of human metabolic disorders, and also play a crucial role in inflammatory-related disease and cancer. Recent evidence has revealed the presence of three different PPAR isotypes (alpha, beta/delta, and gamma) in different cells of the bone tissue, as well as the possible role of PPAR ligands in bone turnover. In the present review, the latest knowledge of the expression of PPARs in bone tissue and the diverse effects of PPAR ligands on bone metabolism is summarized. PPARs, especially of the gamma isotype, could be targets for the treatment of diverse bone diseases such as osteoporosis and osteopenia related to either diabetes or aging.

  3. Bone density in elite judoists and effects of weight cycling on bone metabolic balance.

    PubMed

    Prouteau, Stephanie; Pelle, Anne; Collomp, Katia; Benhamou, Laurent; Courteix, Daniel

    2006-04-01

    Weight cycling has been shown to exert negative effects on bone metabolism and bone mass, whereas weight-bearing activity is positively associated with bone mineral density (BMD). Bone health in judoists and effects of weight cycling on bone metabolism have not previously been investigated. To examine potential disrupter and stimulators of bone integrity, this study analyzed bone parameters at baseline and the effects of the first weight cycle of the season on bone metabolic status in 48 male and female elite judoists. Body composition and lumbar, femoral, and total body BMD were evaluated by dual-energy x-ray absorptiometry. Cortisol, osteocalcin, C-terminal telopeptide of type I collagen (CTx), and bone uncoupling index (UI) were measured in judoists at normal body weight, after weight reduction, and after regaining weight. As a comparison, a control group of moderately active students was included at baseline. Training, menstrual status, and calcium intake were assessed by questionnaires. EUweighted judoists displayed high BMD and an increased rate of bone formation. Precompetitive weight loss averaged 4 +/- 0.3% of body weight and induced an acute rise in cortisol (81%, P < 0.05) and CTx (33%, P < 0.0001), with a metabolic imbalance in favor of bone resorption. A 4 +/- 0.5% weight regain restored a positive UI in favor of bone formation. Metabolic responses were not dependent on gender. BMD was unaltered by weight cycling. Increased bone formation rate pertaining to judo athletes lent protection from alterations in bone metabolic balance associated with weight cycling. This observation suggests that powerful osteogenic stimuli provided by judo's unique biomechanical environment may help prevent bone loss associated with weight loss.

  4. MiRNAs in bone diseases.

    PubMed

    Moore, Benjamin T; Xiao, Peng

    2013-01-01

    MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the 3'UTR (untranslated region) of mRNAs, are known to play various roles in the pathogenesis of many different types of diseases. Specifically, in bone diseases, recent emphasis has been placed on the involvement of miRNAs in the differentiation and proliferation of bone and cartilage cells, particularly with regards to how these mechanisms contribute to bone homeostasis. In this review, we summarize miRNAs that are important in the differentiation and proliferation of bone cells, and specific miRNAs associated with bone diseases, such as osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides the perspective that miRNA studies will identify not only new mechanisms in basic bone research, but also potential novel diagnostic biomarkers and drug targets for bone diseases.

  5. Diabetes mellitus and bone disease in cystic fibrosis.

    PubMed

    Curran, David R; McArdle, John R; Talwalkar, Jaideep S

    2009-10-01

    Patients with cystic fibrosis are frequently affected with pancreatic insufficiency and are predisposed to the development of diabetes mellitus (DM) and bone demineralization. Cystic fibrosis-related diabetes mellitus is a clinical entity distinct from type 1 and type 2 diabetes, with important implications for the nutritional and pulmonary health of cystic fibrosis patients. This form of diabetes owes largely to insulin deficiency, but alterations in insulin sensitivity and hepatic glucose production have also been described. Therapy for cystic fibrosis-related diabetes differs substantially from type 2 DM, with careful attention to prandial glycemic excursions crucial to controlling its metabolic effects. Bone disease, including osteopenia and osteoporosis, also occurs with increased frequency in cystic fibrosis, owing to defects in intestinal absorption, chronic inflammation, lung disease, low body weight, and gonadal dysfunction. The pathogenesis, implications, diagnosis, and therapy of cystic fibrosis-related bone demineralization are discussed, with attention to recommended approaches to prevention of and treatment of established bone disease.

  6. Imaging Sensitivity of Quiescent Cancer Cells to Metabolic Perturbations in Bone Marrow Spheroids

    PubMed Central

    Cavnar, Stephen P.; Xiao, Annie; Gibbons, Anne E.; Rickelmann, Andrew D.; Neely, Taylor; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2016-01-01

    Malignant cells from breast cancer and other common cancers such as prostate and melanoma may persist in bone marrow as quiescent, non-dividing cells that remain viable for years or even decades before resuming proliferation to cause recurrent disease. This phenomenon, referred to clinically as tumor dormancy, poses tremendous challenges to curing patients with breast cancer. Quiescent tumor cells resist chemotherapy drugs that predominantly target proliferating cells, limiting success of neo-adjuvant and adjuvant therapies. We recently developed a 3D spheroid model of quiescent breast cancer cells in bone marrow for mechanistic and drug testing studies. We combined this model with optical imaging methods for label-free detection of cells preferentially utilizing glycolysis versus oxidative metabolism to investigate the metabolic state of co-culture spheroids with different bone marrow stromal and breast cancer cells. Through imaging and biochemical assays, we identified different metabolic states of bone marrow stromal cells that control metabolic status and flexibilities of co-cultured breast cancer cells. We tested metabolic stresses and targeted inhibition of specific metabolic pathways to identify approaches to preferentially eliminate quiescent breast cancer cells from bone marrow environments. These studies establish an integrated imaging approach to analyze metabolism in complex tissue environments to identify new metabolically-targeted cancer therapies. PMID:27478871

  7. Metabolic syndrome in rheumatological diseases.

    PubMed

    Pereira, Rosa Maria Rodrigues; de Carvalho, Jozélio Freire; Bonfá, Eloísa

    2009-03-01

    Metabolic syndrome is characterized by a combination of various cardiovascular risk factors (age, gender, smoking, hypertension and dyslipidemia) that imply additional cardiovascular morbidity that is greater than the sum of the risks associated with each individual component. Herein, the authors review the rheumatological diseases in which metabolic syndrome has been studied: gout, osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ankylosing spondylitis. The prevalence of metabolic syndrome in these disorders varies from 14% to 62.8%. The great majority of these studies demonstrated that this frequency was higher in rheumatological diseases than in the control populations, suggesting that either the presence or the treatment of those diseases seems to influence the risk of developing metabolic syndrome.

  8. Mechanisms influencing bone metabolism in chronic illness.

    PubMed

    Daci, E; van Cromphaut, S; Bouillon, R

    2002-01-01

    Bone is permanently renewed by the coordinated actions of bone-resorbing osteoclasts and bone-forming osteoblasts, which model and remodel bone structure during growth and adult life. The origin of osteoblastic cells (osteoblasts, osteocytes and bone-lining cells) differs from that of osteoclasts, but both cell groups communicate with each other using cytokines and cell-cell contact as to optimally maintain bone homeostasis. This communication in many ways uses the same players as the communication between cells in the immune system. During acute life-threatening illness massive bone resorption is the rule, while bone formation is suppressed. During chronic illness, the balance between bone formation and bone resorption also shifts, frequently resulting in decreased bone mass and density. Several factors may contribute to the osteopenia that accompanies chronic illness, the most important being undernutrition and low body weight, inflammatory cytokines, disorders of the neuroendocrine axis (growth hormone/IGF-1 disturbances, thyroid and gonadal deficiency), immobilization, and the long-term use of glucocorticoids. Their combined effects not only influence the generation and activity of all bone cells involved, but probably also regulate their life span by apoptotic mechanisms. Osteopenia or even osteoporosis and bone fragility, and before puberty also decreased linear growth and lower peak bone mass are therefore frequent consequences of chronic illnesses.

  9. Clinical utility of biochemical markers of bone metabolism for improving the management of patients with advanced multiple myeloma.

    PubMed

    Lipton, Allan; Cook, Richard J; Coleman, Robert E; Smith, Matthew R; Major, Pierre; Terpos, Evangelos; Berenson, James R

    2007-03-01

    Osteolytic bone lesions from advanced multiple myeloma (MM) result in significant skeletal morbidity. Therefore, biochemical markers of bone metabolism, such as the N-terminal and C-terminal telopeptides of type I collagen, bone-specific alkaline phosphatase, and osteocalcin, have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity, and response to antiresorptive treatment. Several studies have shown that the majority of biochemical markers of bone metabolism are increased in patients with MM with osteolytic bone lesions, thus reflecting changes in bone metabolism associated with tumor growth. There is also a growing body of evidence that markers of bone metabolism correlate with the risk of skeletal complications, disease progression, and death. In addition, bone markers could potentially be used as a tool for early diagnosis of bone lesions. The aim of this review is to improve our understanding of bone markers as a clinical tool for the management of malignant bone disease in patients with MM.

  10. Role of RANKL in bone diseases.

    PubMed

    Anandarajah, Allen P

    2009-03-01

    Bone remodeling is a tightly regulated process of osteoclast-mediated bone resorption, balanced by osteoblast-mediated bone formation. Disruption of this balance can lead to increased bone turnover, resulting in excessive bone loss or extra bone formation and consequent skeletal disease. The receptor activator of nuclear factor kappaB ligand (RANKL) (along with its receptor), the receptor activator of nuclear factor kappaB and its natural decoy receptor, osteoprotegerin, are the final effector proteins of osteoclastic bone resorption. Here, I provide an overview of recent studies that highlight the key role of RANKL in the pathophysiology of several bone diseases and discuss the novel therapeutic approaches afforded by the modulation of RANKL.

  11. Fluoride-related bone disease associated with habitual tea consumption.

    PubMed

    Hallanger Johnson, Julie E; Kearns, Ann E; Doran, Patric M; Khoo, Teck Kim; Wermers, Robert A

    2007-06-01

    Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (> 15 micromol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation.

  12. Sympathetic neural influence on bone metabolism in microgravity (Review).

    PubMed

    Mano, Tadaaki; Nishimura, N; Iwase, S

    2010-12-01

    Bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space and also for bedridden elderly people. Recent studies have indicated that the sympathetic nervous system plays a role in bone metabolism. This paper reviews findings concerning with sympathetic influences on bone metabolism to hypothesize the mechanism how sympathetic neural functions are related to bone loss in microgravity. Animal studies have suggested that leptin stimulates hypothalamus increasing sympathetic outflow to bone and enhances bone resorption through noradrenaline and β-adrenoreceptors in bone. In humans, even though there have been some controversial findings, use of β-adrenoblockers has been reported to be beneficial for prevention of osteoporosis and bone fracture. On the other hand, microneurographically-recorded sympathetic nerve activity was enhanced by exposure to microgravity in space as well as dry immersion or long-term bed rest to simulate microgravity. The same sympathetic activity became higher in elderly people whose bone mass becomes generally reduced. Our recent findings indicated a significant correlation between muscle sympathetic nerve activity and urinary deoxypyridinoline as a specific marker measuring bone resorption. Based on these findings we would like to propose a following hypothesis concerning the sympathetic involvement in the mechanism of bone loss in microgravity: An exposure to prolonged microgravity may enhance sympathetic neural traffic not only to muscle but also to bone. This sympathetic enhancement increases plasma noradrenaline level and inhibits osteogenesis and facilitates bone resorption through β-adrenoreceptors in bone to facilitate bone resorption to reduce bone mass. The use of β-adrenoblockers to prevent bone loss in microgravity may be reasonable.

  13. [Bone metabolism and cardiovascular function update. Nerve system and mutual interaction between bone and blood vessel].

    PubMed

    Ochi, Hiroki; Takeda, Shu

    2014-07-01

    The identification that nervous system controls bone metabolism through leptin deficient mice studies opened a new field in bone biology. Notably, sympathetic and parasympathetic nerve system regulate bone metabolism. In addition, sensory nerve system also has been shown to be involved in the regulation of bone homeostasis. On the other hand, traditionally, it is well known that invasion of vessels into cartilage during the skeletal development is important for normal bone formation. And, the decrease of angiogenesis with aging leads to low bone mass and delaying of fracture healing. Although these indicate that blood vessel activity is closely related to bone remodeling, its molecular mechanism is still unknown. Most recently, the mechanism of coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone was reported.

  14. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  15. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  16. Communication of bone cells with hematopoiesis, immunity and energy metabolism

    PubMed Central

    Asada, Noboru; Sato, Mari; Katayama, Yoshio

    2015-01-01

    The bone contains the bone marrow. The functional communication between bone cells and hematopoiesis has been extensively studied in the past decade or so. Osteolineage cells and their modulators, such as the sympathetic nervous system, macrophages and osteoclasts, form a complex unit to maintain the homeostasis of hematopoiesis, called the ‘microenvironment'. Recently, bone-embedded osteocytes, the sensors of gravity and mechanical stress, have joined the microenvironment, and they are demonstrated to contribute to whole body homeostasis through the control of immunity and energy metabolism. The inter-organ communication orchestrated by the bone is summarized in this article. PMID:26512322

  17. The effects of thiazide diuretics on bone mineral metabolism.

    PubMed Central

    Pierce, R. O.; Perry, A.

    1998-01-01

    Thiazide diuretics cause changes in calcium metabolism. Clinically, these changes include a decreased excretion of calcium, and in some instances, this results in a corresponding increase in bone mineral. The study of mineral metabolism in bone is difficult because of the slow turnover rate of bone. For this reason, the rat fracture model was used to study bone mineral metabolism in animals given thiazide diuretics. Fifty rats were divided into four groups: group 1 received a fracture of the right tibia and thiazide diuretics, group 2 received thiazide and no fracture, group 3 received no drugs and a fracture, and group 4 received no drugs and no fracture. At the end of 35 days postinjury, all animals were sacrificed. Biochemical and biomechanical results were analyzed, and revealed that animals that received thiazide diuretics and a fracture had the highest bone mineral content. PMID:9473929

  18. [Diet for lifestyle-related diseases to maintain bone health].

    PubMed

    Hirota, Takako; Hirota, Kenji

    2011-05-01

    Dieting methods for preventing age-related diseases such as cardiovascular disease, hypertension and diabetes, as well as osteoporosis are proposed here. Losing weight to prevent and ameliorate metabolic syndrome can lead to loss of bone and muscle mass. However, when subjects had milk before dinner while dieting, their fat mass was efficiently decreased and their muscle mass increased without any change of bone mass. Increased intake of vitamin D enhanced these effects. Therefore we suggest that people with high risk of metabolic disorders should take more low fat dairy products and fish, together with fruits, vegetables, and soy in order to increase their intake of calcium, vitamin D, n-3 polyunsaturated fatty acids, protein, antioxidants, various vitamins and minerals, and fiber to protect them from the deterioration of arteries and bones.

  19. Influence of physical activity to bone metabolism.

    PubMed

    Drenjančević, Ines; Davidović Cvetko, Erna

    2013-02-01

    Bone remodeling is a lifetime process. Peak bone mass is achieved in the twenties, and that value is very important for skeleton health in older years of life. Modern life style with its diet poor in nutrients, and very low intensity of physical activity negatively influences health in general, and bone health as well. Bones are adapting to changes in load, so applying mechanical strain to bones results in greater bone mass and hardness. That makes physical activity important in maintaining skeleton health. Numerous studies confirm good influence of regular exercising to bone health, and connection of physical activity in youth to better bone density in older age. To activate bone remodeling mechanisms, it is necessary to apply mechanical strain to bones by exercise. Considering global problem of bone loss and osteoporosis new ways of activating young people to practice sports and active stile of life are necessary to maintain skeleton health and health in general. This paper aims to review physiological mechanisms of bone remodeling that are influenced by physical exercise.

  20. Cellular metabolism and disease: what do metabolic outliers teach us?

    PubMed Central

    DeBerardinis, Ralph J.; Thompson, Craig B.

    2012-01-01

    An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

  1. Bone biopsy in renal osteodystrophy: continued insights into a complex disease.

    PubMed

    Christov, Marta; Pereira, Renata; Wesseling-Perry, Kate

    2013-03-01

    The pathogenesis and optimal therapy of renal bone disease remains poorly understood in chronic kidney disease (CKD) and dialysis patients. Bone biopsy is thus far the only window into cellular and molecular events in bone. This review will focus on recent insights into the pathophysiology of renal bone disease, as highlighted by bone biopsy, and discuss implications for treatment. Abnormalities in bone physiology start very early in children and adults with CKD, when most clinically measurable mineral metabolism parameters are normal. In addition, racial differences, known to exist in serum markers such as parathyroid hormone, also appear prominent in the bone, suggesting that clinical treatment guidelines may not address the needs of all patient populations. The effects of treatments for secondary hyperparathyroidism on bone may be unexpected. With the help of bone biopsy studies, molecular insights into the pathogenesis of renal osteodystrophy are beginning to emerge. Current therapies may have unexpected effects on bone physiology.

  2. Paget’s disease of bone: an osteoimmunological disorder?

    PubMed Central

    Numan, Mohamed S; Amiable, Nathalie; Brown, Jacques P; Michou, Laëtitia

    2015-01-01

    Osteoimmunology represents a large area of research resulting from the cross talk between bone and immune systems. Many cytokines and signaling cascades are involved in the field of osteoimmunology, originating from various cell types. The RANK/receptor activator of nuclear factor Kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling has a pivotal role in osteoimmunology, in addition to proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17. Clinically, osteoimmunological disorders, such as rheumatoid arthritis, osteoporosis, and periodontitis, should be classified according to their pattern of osteoimmunological serum biomarkers. Paget’s disease of bone is a common metabolic bone disorder, resulting from an excessively increased bone resorption coupled with aberrant bone formation. With the exception of the cellular responses to measles virus nucleocapsid protein and the interferon-gamma signature, the exact role of the immune system in Paget’s disease of bone is not well understood. The cytokine profiles, such as the increased levels of IL-6 and the interferon-gamma signature observed in this disease, are also very similar to those observed in other osteoimmunological disorders. As a potential osteoimmunological disorder, the treatment of Paget’s disease of bone may also benefit from progress made in targeted therapies, in particular for receptor activator of nuclear factor Kappa-B ligand and IL-6 signaling inhibition. PMID:26316708

  3. Dietary Pseudopurpurin Improves Bone Geometry Architecture and Metabolism in Red-Bone Guishan Goats

    PubMed Central

    Han, TieSuo; Li, Peng; Wang, JianGuo; Liu, GuoWen; Wang, Zhe; Ge, ChangRong; Gao, ShiZheng

    2012-01-01

    Red-colored bones were found initially in some Guishan goats in the 1980s, and they were designated red-boned goats. However, it is not understood what causes the red color in the bone, or whether the red material changes the bone geometry, architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in the red-colored material of the bone in red-boned goats by high-performance liquid chromatography–electrospray ionization–mass spetrometry and nuclear magnetic resonance analysis. Pseudopurpurin is one of the main constituents of Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical properties and micro-computed tomography showed that the red-boned goats displayed an increase in the trabecular volume fraction, trabecular thickness, and the number of trabeculae in the distal femur. The mean thickness, inner perimeter, outer perimeter, and area of the femoral diaphysis were also increased. In addition, the trabecular separation and structure model index of the distal femur were decreased, but the bone mineral density of the whole femur and the mechanical properties of the femoral diaphysis were enhanced in the red-boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA was higher, and the ratio of the receptor activator of the nuclear factor kappa B ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned goats compared with common goats. To confirm further the effect of pseudopurpurin on bone geometry, architecture, and metabolism, Wistar rats were fed diets to which pseudopurpurin was added for 5 months. Similar changes were observed in the femurs of the treated rats. The above results demonstrate that pseudopurpurin has a close affinity with the mineral salts of bone, and consequently a high level of mineral salts in the bone cause an improvement in bone strength and an enhancement in the structure and metabolic functions of the bone. PMID:22624037

  4. Alzheimer's as a metabolic disease.

    PubMed

    Demetrius, Lloyd A; Driver, Jane

    2013-12-01

    Empirical evidence indicates that impaired mitochondrial energy metabolism is the defining characteristic of almost all cases of Alzheimer's disease (AD). Evidence is reviewed supporting the general hypothesis that the up-regulation of OxPhos activity, a metabolic response to mitochondrial dysregulation, drives the cascade of events leading to AD. This mode of metabolic alteration, called the Inverse Warburg effect, is postulated as an essential compensatory mechanism of energy production to maintain the viability of impaired neuronal cells. This article appeals to the inverse comorbidity of cancer and AD to show that the amyloid hypothesis, a genetic and neuron-centric model of the origin of sporadic forms of AD, is not consistent with epidemiological data concerning the age-incidence rates of AD. A view of Alzheimer's as a metabolic disease-a condition consistent with mitochondrial dysregulation and the Inverse Warburg effect, will entail a radically new approach to diagnostic and therapeutic strategies.

  5. Cancer as a metabolic disease

    PubMed Central

    2010-01-01

    Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention. PMID:20181022

  6. Bone health and vitamin D status in alcoholic liver disease.

    PubMed

    Kizilgul, M; Ozcelik, O; Delibasi, T

    2016-07-01

    Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.

  7. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    PubMed

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  8. Bone Vascularization in Normal and Disease Conditions

    PubMed Central

    Carulli, Christian; Innocenti, Massimo; Brandi, Maria Luisa

    2013-01-01

    Bone vasculature is essential for many processes, such as skeletal development and growth, bone modeling and remodeling, and healing processes. Endothelium is an integral part of bone tissue, expressing a physiological paracrine function via growth factors and chemokines release, and interacting with several cellular lines. Alterations of the complex biochemical interactions between vasculature and bone cells may lead to various clinical manifestations. Two different types of pathologies result: a defect or an excess of bone vasculature or endothelium metabolism. Starting from the molecular basis of the interactions between endothelial and bone cells, the Authors present an overview of the recent acquisitions in the physiopathology of the most important clinical patterns, and the modern therapeutic strategies for their treatments. PMID:23986744

  9. Black bone disease in a healing fracture.

    PubMed

    Thiam, Desmond; Teo, Tse Yean; Malhotra, Rishi; Tan, Kong Bing; Chee, Yu Han

    2016-01-28

    Black bone disease refers to the hyperpigmentation of bone secondary to prolonged usage of minocycline. We present a report of a 34-year-old man who underwent femoral shaft fracture fixation complicated by deep infection requiring debridement. The implants were removed 10 months later after long-term treatment with minocycline and fracture union. A refracture of the femoral shaft occurred 2 days after implant removal and repeat fixation was required. Intraoperatively, abundant heavily pigmented and dark brown bone callus was noted over the old fracture site. There was no evidence of other bony pathology and the appearance was consistent with minocycline-associated pigmentation. As far as we are aware, this is the first case of black bone disease affecting callus within the interval period of bone healing. We also discuss the relevant literature on black bone disease to bring light on this rare entity that is an unwelcomed surprise to operating orthopaedic surgeons.

  10. [Bone and Men's Health. Androgen replacement therapy and bone metabolism].

    PubMed

    Ogawa, Sumito

    2010-02-01

    During aging process in men, decline of androgen level is involved in symptoms of hypogonadism, and recent findings suggest that sex hormones are crucial for skeletal development and maintenance of bone mineral properties. In practice, androgen replacement therapy has not been established for bone-related symptoms in late onset hypogonadisim or male osteoporosis. Whereas recent evidences suggest that bone mineral properties are improved by androgen replacement therapy in aging male, further studies including large clinical trials are necessary to assess long-term benefits and risks by the therapy.

  11. Gene Therapy for Metabolic Diseases

    PubMed Central

    Chandler, Randy J.; Venditti, Charles P.

    2016-01-01

    SUMMARY Gene therapy has recently shown great promise as an effective treatment for a number of metabolic diseases caused by genetic defects in both animal models and human clinical trials. Most of the current success has been achieved using a viral mediated gene addition approach, but gene-editing technology has progressed rapidly and gene modification is being actively pursued in clinical trials. This review focuses on viral mediated gene addition approaches, because most of the current clinical trials utilize this approach to treat metabolic diseases. PMID:27853673

  12. Effects of simulated weightlessness on bone mineral metabolism

    NASA Technical Reports Server (NTRS)

    Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

    1984-01-01

    It is pointed out that prolonged space flight, bedrest, and immobilization are three factors which can produce a negative calcium balance, osteopenia, and an inhibition of bone formation. It is not known whether the effects of gravity on bone mineral metabolism are mediated by systemic endocrine factors which affect all bones simultaneously, or by local factors which affect each bone individually. The present investigation has the objective to test the relative importance of local vs. systemic factors in regulating the bone mineral response to conditions simulating weightlessness. Experiments were conducted with male Sprague-Dawley rats. The test conditions made it possible to compare the data from weighted and unweighted bones in the same animal. The obtained findings indicate that a decrease in bone mass relative to control value occurs rapidly under conditions which simulate certain aspects of weightlessness. However, this decrease reaches a plateau after 10 days.

  13. Bone Metabolism in Obesity and Weight Loss

    PubMed Central

    Shapses, Sue A.; Sukumar, Deeptha

    2014-01-01

    Excess body weight due to obesity has traditionally been considered to have a positive effect on bone; however, more recent findings suggest that bone quality is compromised. Both obesity and caloric restriction increase fracture risk and are regulated by endocrine factors and cytokines that have direct and indirect effects on bone and calcium absorption. Weight reduction will decrease bone mass and mineral density, but this varies by the individual’s age, gender, and adiposity. Dietary modifications, exercise, and medications have been shown to attenuate the bone loss associated with weight reduction. Future obesity and weight loss trials would benefit from assessment of key hormones, adipokine and gut peptides that regulate calcium absorption, and bone mineral density and quality by using sensitive techniques in high-risk populations. PMID:22809104

  14. Dietary nitrogen and calcium modulate bone metabolism in young goats.

    PubMed

    Elfers, Kristin; Liesegang, Annette; Wilkens, Mirja R; Breves, Gerhard; Muscher-Banse, Alexandra S

    2016-11-01

    Ruminants, possessing the rumino-hepatic circulation, are thought to cope easily with reduced dietary nitrogen (N) supply which is of economic and environmental interest to diminish N output. Nevertheless, feeding an N reduced diet to young goats resulted in a decrease in calcitriol and calcium (Ca) plasma concentrations. Although a dietary Ca reduction alone stimulated calcitriol synthesis and plasma Ca concentrations were restored, in combination with a reduced N supply this stimulating effect was abolished. Based on the important role bone tissue plays in maintaining Ca homeostasis, aim of the present study was to determine effects of an N reduced diet with or without a concomitant Ca reduction on bone metabolism in young goats. A dietary N reduction alone resulted in a significant rise in plasma concentrations of bone resorption marker C-terminal telopeptide of type I collagen (CTX) and bone formation marker osteocalcin (OC), while reduced intake of Ca as well as the combination of both dietary interventions increased bone markers only slightly. Bone mineral content and bone mineral density of metatarsi were decreased by reduced N intake, while Ca and phosphorus (P) content of dried bones remained unaffected. In contrast, a dietary Ca reduction alone led to decreased Ca and P content of dried bones. From these data it can be concluded that a dietary N reduction alone or in combination with a reduced dietary Ca supply modulated bone metabolism in young goats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Characterization of bone turnover and energy metabolism in a rat model of primary and secondary osteoporosis.

    PubMed

    Bauer, Natali B; Khassawna, Thaqif El; Goldmann, Fee; Stirn, Martina; Ledieu, David; Schlewitz, Gudrun; Govindarajan, Parameswari; Zahner, Daniel; Weisweiler, David; Schliefke, Nathalie; Böcker, Wolfgang; Schnettler, Reinhard; Heiss, Christian; Moritz, Andreas

    2015-04-01

    An experimental rat model served for evaluation of bone- and energy metabolism in early and late stages of osteoporosis. For the early stage, we hypothesized that bilateral ovariectomy (OVX)+multi-deficiency diet (OVXD; depletion of vitamin D, calcium, vitamin K, phosphorus) would induce increased bone turnover while the late stage would be characterized by enhanced bone catabolism. Obesity, insulin resistance and hyperleptinemia would be seen during the whole course of disease. Healthy female Sprague Dawley rats (n=41) aged 10 weeks were randomly assigned to sham and treatment groups and sacrificed at 3, 12, and 14 months after the study began. In the early phase, OVXD was associated with an increase in body weight, but not, however, in later stages. There was a decrease in bone mineral density and relative bone volume (BV/TV) as assessed by Dual Energy X-ray Absorptiometry and micro computed tomography that was most severe in the later stages of disease, indicating bone catabolism. Osteocalcin limiting bone formation was increased initially, whereas later stages (14 months) were characterized by elevated osteopontin, suggesting bone remodeling. Severe hyperparathyroidism was present during all stages of disease. Only the early phases of disease were characterized by hyperinsulinemia and increased adrenocorticotrophic stimulating hormone, whereas in the late stage hypoleptinemia rather than hyperleptinemia was seen. Markers of bone and energy metabolism reflected both an increased bone turn over and ongoing bone remodeling associated with initial hyperinsulinemia. Osteopontin and osteocalcin can be used to differentiate early and late stages of osteoporosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. [Clinical condition and therapy of bone diseases].

    PubMed

    Miura, Kohji; Oznono, Keiichi

    2013-12-01

    Skeletal dysplasia is the term which represents disorders including growth and differentiation of bone, cartilage and ligament. A lot of diseases are included, and new disorders have been added. However, the therapy of most bone diseases is less well-established. Achondroplasia, hypochondroplasia, and osteogenesis imperfecta are most frequent bone diseases. There is no curative treatment for these diseases, however, supportive therapies are available ; for example, growth-hormone therapy for achondroplasia and hypochondroplasia, and bisphosphonate therapy for osteogenesis imperfecta. In addition, enzyme replacement therapy for hypophosphatasia is now on clinical trial.

  17. [Biochemical markers of bone metabolism and their importance].

    PubMed

    Obermayer-Pietsch, B; Schwetz, V

    2016-06-01

    Laboratory analyses of biochemical markers for bone and mineral metabolism can play a key role in the assessment of patients with osteoporosis. They may help to assess bone turnover in the diagnostic work-up and aid decision-making as well as selection of pharmaceutical therapy options. Recent publications on therapy response have shown that biochemical markers of bone turnover are valuable tools for the evaluation of therapy success in individual osteoporosis patients and the assessment of bone mineral density gain during therapy.

  18. Effect of Microgravity on Bone Tissue and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session TA4 includes short reports concerning: (1) Human Bone Tissue Changes after Long-Term Space Flight: Phenomenology and Possible Mechanics; (2) Prediction of Femoral Neck Bone Mineral Density Change in Space; (3) Dietary Calcium in Space; (4) Calcium Metabolism During Extended-Duration Space Flight; (5) External Impact Loads on the Lower Extremity During Jumping in Simulated Microgravity and the Relationship to Internal Bone Strain; and (6) Bone Loss During Long Term Space Flight is Prevented by the Application of a Short Term Impulsive Mechanical Stimulus.

  19. Effects of obesity on bone metabolism

    USDA-ARS?s Scientific Manuscript database

    Despite being a risk factor for many chronic health disorders, obesity is thought to promote bone formation and protect against osteoporosis in humans. Although body mass has a positive effect on bone health, whether mass derived from an obesity condition or excessive fat accumulation is beneficial ...

  20. Adipokines as drug targets in joint and bone disease.

    PubMed

    Scotece, Morena; Conde, Javier; Vuolteenaho, Katriina; Koskinen, Anna; López, Veronica; Gómez-Reino, Juan; Lago, Francisca; Moilanen, Eeva; Gualillo, Oreste

    2014-03-01

    White adipose tissue is now recognized to be a multifactorial organ secreting several adipose-derived factors that have been collectively termed 'adipokines'. Adipokines are pleiotropic molecules that contribute to the so-called 'low-grade inflammatory state' of obese subjects creating a cluster of metabolic aberrations including autoimmune and inflammatory diseases that affect joints and bone. The aim of this review is to present knowledge about the role of adipokines in bone and cartilage function, as well as in inflammatory and degenerative joint disease. We discuss clinical implications and then survey attempts to exploit this role for therapeutic gain, which holds potential as a novel approach for drug development in bone and joint disease.

  1. Melatonin: Bone Metabolism in Oral Cavity

    PubMed Central

    López-Martínez, Fanny; Olivares Ponce, Patricia N.; Guerra Rodríguez, Miriam; Martínez Pedraza, Ricardo

    2012-01-01

    Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000) may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981). Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decrease bone mass resorption by suppressing through down regulation of the RANK-L, as suggested by Penarrocha Diago et al. (2005) and Steflik et al. (1994). These data point an osteogenic effect towards that may be of melatonin of clinical importance, as it could be used as a therapeutic agent in situations in which would be advantageous bone formation, such as in the treatment of fractures or osteoporosis or their use as, a bioactive surface on implant as suggested by Lissoni et al. (1991). PMID:22927853

  2. Melatonin: bone metabolism in oral cavity.

    PubMed

    López-Martínez, Fanny; Olivares Ponce, Patricia N; Guerra Rodríguez, Miriam; Martínez Pedraza, Ricardo

    2012-01-01

    Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000) may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981). Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decrease bone mass resorption by suppressing through down regulation of the RANK-L, as suggested by Penarrocha Diago et al. (2005) and Steflik et al. (1994). These data point an osteogenic effect towards that may be of melatonin of clinical importance, as it could be used as a therapeutic agent in situations in which would be advantageous bone formation, such as in the treatment of fractures or osteoporosis or their use as, a bioactive surface on implant as suggested by Lissoni et al. (1991).

  3. Radionuclide studies of bone metabolism: do bone uptake and bone plasma clearance provide equivalent measurements of bone turnover?

    PubMed

    Blake, Glen M; Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac

    2011-09-01

    Quantitative radionuclide imaging using (18)F-fluoride positron emission tomography (18F-PET) or (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans provides a novel tool for studying regional and whole skeleton bone turnover that complements the information provided by biochemical markers. Radionuclide bone scans can be quantified by measuring either tracer uptake or, if blood sampling is performed, bone plasma clearance. This study examines whether these two methods provide equivalent information about bone turnover. We examined data from two clinical trials of the bone anabolic agent teriparatide. In Study 1 twenty osteoporotic women had 18F-PET scans of the lumbar spine at baseline and after 6 months treatment with teriparatide. Bone uptake in the lumbar spine was expressed as standardised uptake values (SUV) and blood samples taken to evaluate plasma clearance. In Study 2 ten women had (99m)Tc-MDP scans at baseline, 3 and 18 months after starting teriparatide. Blood samples were taken and whole skeleton plasma clearance and bone uptake calculated. In Study 1 spine plasma clearance increased by 23.8% after 6-months treatment (P=0.0003), whilst SUV increased by only 3.0% (P=0.84). In Study 2 whole skeleton plasma clearance increased by 37.1% after 18-months treatment (P=0.0002), whilst the 4-hour whole skeleton uptake increased by only 25.5% (P=0.0001). During treatment the 18F- plasma concentration decrease by 20% and (99m)Tc-MDP concentration by 13%, and these latter changes were sufficient to explain the differences between the uptake and plasma clearance results. Measurements of response to treatment using bone uptake and plasma clearance gave different results because the effects of teriparatide on bone resulted in a sufficiently increased demand for radionuclide tracer from the skeleton that the concentration in the circulation decreased. Similar effects may occur with other therapies that have a large enough effect on bone metabolism. In these

  4. [The Idiopathic Parkinson's disease: A metabolic disease?].

    PubMed

    Rieu, I; Boirie, Y; Morio, B; Derost, P; Ulla, M; Marques, A; Debilly, B; Bannier, S; Durif, F

    2010-10-01

    Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient.

  5. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    PubMed

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  6. Metabolic Syndrome and Urologic Diseases

    PubMed Central

    Gorbachinsky, Ilya; Akpinar, Haluk; Assimos, Dean G

    2010-01-01

    Metabolic syndrome (MetS) is a complex entity consisting of multiple interrelated factors including insulin resistance, central adiposity, dyslipidemia, endothelial dysfunction and atherosclerotic disease, low-grade inflammation, and in males, low testosterone levels. MetS has been linked to a number of urologic diseases including nephrolithiasis, benign prostatic hyperplasia and lower urinary tract symptoms, erectile dysfunction, male infertility, female incontinence, and prostate cancer. This article reviews the relationships between MetS and these entities. Urologists need to be cognizant of the impact that MetS has on urologic diseases as well as on overall patient health. PMID:21234260

  7. How Is Paget's Disease of Bone Diagnosed?

    MedlinePlus

    ... of a chemical substance called serum alkaline phosphatase (SAP), it is a sign that the disease may be present. SAP is a type of enzyme made by bone cells that is overproduced by pagetic bone. The SAP level for someone age 60 or older typically ...

  8. Donepezil regulates energy metabolism and favors bone mass accrual.

    PubMed

    Eimar, Hazem; Alebrahim, Sharifa; Manickam, Garthiga; Al-Subaie, Ahmed; Abu-Nada, Lina; Murshed, Monzur; Tamimi, Faleh

    2016-03-01

    The autonomous nervous system regulates bone mass through the sympathetic and parasympathetic arms. The sympathetic nervous system (SNS) favors bone loss whereas the parasympathetic nervous system (PNS) promotes bone mass accrual. Donepezil, a central-acting cholinergic agonist, has been shown to down-regulate SNS and up-regulate PNS signaling tones. Accordingly, we hypothesize that the use of donepezil could have beneficial effects in regulating bone mass. To test our hypothesis, two groups of healthy female mice were treated either with donepezil or saline. Differences in body metabolism and bone mass of the treated groups were compared. Body and visceral fat weights as well as serum leptin level were increased in donepezil-treated mice compared to control, suggesting that donepezil effects on SNS influenced metabolic activity. Donepezil-treated mice had better bone quality than controls due to a decrease in osteoclasts number. These results indicate that donepezil is able to affect whole body energy metabolism and favors bone mass in young female WT mice.

  9. Gut microbiome and metabolic diseases.

    PubMed

    Fukuda, Shinji; Ohno, Hiroshi

    2014-01-01

    The prevalence of obesity and obesity-related disorders is increasing worldwide. In the last decade, the gut microbiota has emerged as an important factor in the development of obesity and metabolic syndrome, through its interactions with dietary, environmental, and host genetic factors. Various studies have shown that alteration of the gut microbiota, shifting it toward increased energy harvest, is associated with an obese phenotype. However, the molecular mechanisms by which the gut microbiota affects host metabolism are still obscure. In this review, we discuss the complexity of the gut microbiota and its relationship to obesity and obesity-related diseases. Furthermore, we discuss the anti-obesity potential of probiotics and prebiotics.

  10. Kinetic aspects of bone mineral metabolism

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1973-01-01

    Two techniques were studied for measuring changes in bone mass in rats. One technique measures the Ar-37 produced from calcium during neutron irradiation and the other measures the changes in the Na-22 content which has been incorporated within the rat bone. Both methods are performed in VIVO and cause no significant physiological damage. The Ar-37 leaves the body of a rat within an hour after being produced, and it can be quantitatively collected and measured with a precision of - or + 2% on the same rat. With appropriate irradiation conditions it appears that the absolute quantity of calcuim in any rat can be determined within - or + 3% regardless of animal size. The Na-22 when uniformly distributed in bone, can be used to monitor bone mineral turnover and this has been demonstrated in conditions of calcium deficiency during growth and also pregnancy coupled with calcium deficiency.

  11. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    PubMed

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. High-density lipoprotein (HDL) metabolism and bone mass.

    PubMed

    Papachristou, Nicholaos I; Blair, Harry C; Kypreos, Kyriakos E; Papachristou, Dionysios J

    2017-05-01

    It is well appreciated that high-density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models, have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in metabolic pathways of HDL favors adipoblastic differentiation and restrains osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regard to the HDL-bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way toward the development of novel and more effective therapies against these conditions. © 2017 Society for Endocrinology.

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

    PubMed

    Lombardi, Giovanni; Sanchis-Gomar, Fabian; Perego, Silvia; Sansoni, Veronica; Banfi, Giuseppe

    2016-11-01

    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.

  14. Computer-assisted quantitative evaluation of bisphosphonate treatment for Paget's disease of bone using the bone scan index

    PubMed Central

    Nagano, Satoshi; Nakamura, Shunsuke; Shimada, Hirofumi; Yokouchi, Masahiro; Setoguchi, Takao; Ishidou, Yasuhiro; Sasaki, Hiromi; Komiya, Setsuro

    2016-01-01

    The purpose of the present study was to analyze the effect of treatment of Paget's disease of bone (PDB) with bone scintigraphy using a computer-assisted diagnosis system (BONENAVI) that quantitatively evaluates bone metabolism. Seven patients with PDB (three male, four female; average age, 60 years; age range, 33–80 years) underwent bone scintigraphy and measurement of serum alkaline phosphatase (ALP), bone-specific ALP (BAP), serum cross-linked N-telopeptide (NTx) of type I collagen, urinary NTx, and deoxypyridinoline (DPD) before and after bisphosphonate treatment. Bone scan index (BSI), artificial neural network (ANN) value, and hotspot number (HSn) were calculated using BONENAVI software. Mean follow-up period was 22 months (range, 11–35 months). Among three BONENAVI parameters (ANN, BSI, and HSn), only BSI was significantly lower after bisphosphonate treatment as compared with before. All bone metabolic markers excluding DPD were significantly lower following bisphosphonate treatment than before. Bone formation markers (ALP and BAP) were significantly lower than bone resorption markers (U-NTx and S-NTx). The correlation of BONENAVI parameters with four bone metabolic markers was analyzed before and after bisphosphonate treatment. Before treatment, the majority of the four markers did not correlate with the BONENAVI parameters. In contrast, post-treatment ALP, BAP, and U-NTx were significantly correlated with BSI and HSn. To the best of our knowledge, this is the first study to evaluate the treatment of PDB by bone scintigraphy using a computer-assisted diagnosis system that quantitatively evaluates bone metabolism. The findings demonstrated that, using BONENAVI software, bone scintigraphy is able to quantitatively and spatially evaluate the bisphosphonate treatment effect, particularly in patients with polyostotic PDB. PMID:28105116

  15. Effects of magnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants.

    PubMed

    Belluci, Marina Montosa; Giro, Gabriela; del Barrio, Ricardo Andrés Landazuri; Pereira, Rosa Maria Rodrigues; Marcantonio, Elcio; Orrico, Silvana Regina Perez

    2011-07-01

    This study evaluated the effect of magnesium dietary deficiency on bone metabolism and bone tissue around implants with established osseointegration. For this, 30 rats received an implant in the right tibial metaphysis. After 60 days for healing of the implants, the animals were divided into groups according to the diet received. Control group (CTL) received a standard diet with adequate magnesium content, while test group (Mg) received the same diet except for a 90% reduction of magnesium. The animals were sacrificed after 90 days for evaluation of calcium, magnesium, osteocalcin and parathyroid hormone (PTH) serum levels and the deoxypyridinoline (DPD) level in the urine. The effect of magnesium deficiency on skeletal bone tissue was evaluated by densitometry of the lumbar vertebrae, while the effect of bone tissue around titanium implants was evaluated by radiographic measurement of cortical bone thickness and bone density. The effect on biomechanical characteristics was verified by implant removal torque testing. Magnesium dietary deficiency resulted in a decrease of the magnesium serum level and an increase of PTH and DPD levels (P ≤ 0.05). The Mg group also presented a loss of systemic bone mass, decreased cortical bone thickness and lower values of removal torque of the implants (P ≤ 0.01). The present study concluded that magnesium-deficient diet had a negative influence on bone metabolism as well as on the bone tissue around the implants. © 2010 John Wiley & Sons A/S.

  16. Effect of impact exercise on bone metabolism.

    PubMed

    Vainionpää, A; Korpelainen, R; Väänänen, H K; Haapalahti, J; Jämsä, T; Leppäluoto, J

    2009-10-01

    Regular impact exercise in premenopausal women caused positive osteogenic effects associated to low basal serum parathormone (PTH) but had no effects on bone turnover markers PINP or TRACP5b. The low serum basal PTH levels during impact exercise may be a sign of increased incorporation of calcium to bone. This study aimed to determine the long-term effects of high-impact exercise on bone turnover and calciotropic hormones. We performed a 12-month population-based, randomized, controlled exercise trial in 120 women (age 35-40 years) randomly assigned to an exercise group (EG; n = 60) or a control group (CG; n = 60). The exercise regimen consisted of supervised high-impact exercises three times per week. Daily impact loading was assessed by using an accelerometer. Bone turnover markers and calciotropic hormones were analyzed at 0, 6, and 12 months. Twelve months of impact exercise did not reveal any treatment effects in bone turnover markers PINP or TRAPC5b, whereas serum basal PTH decreased significantly more in the EG than in the CG (-11.2 vs. -2.2 pg/mL; p = 0.03). The change in PTH was dose dependent and most clearly seen in subjects with 96 to 130 daily impacts at 2.5 to 5.3 g (e.g., running or jumping). Regular impact exercise does not cause persistent alterations in bone turnover emphasizing necessity of continuous training to achieve bone benefits. Impact exercise training lowers the serum basal PTH levels and possibly enables greater difference between the basal PTH and transient exercise-induced PTH peaks leading to osteogenic effects.

  17. Epidemiology and pathology of Paget's disease of bone - a review.

    PubMed

    Nebot Valenzuela, Elena; Pietschmann, Peter

    2017-02-01

    Paget's disease of bone (PDB) is a noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. As a result, there is deformity and enlargement of the bone with a defective and disorganized pattern. Here, we review the epidemiology, etiology, pathology, macrostructure, histology, and quantitative histomorphometry findings of PDB. Hyperosteoclastosis and poor definition of the boundary between cortical and medullary bone are the main histological findings in PDB. Additionally, Pagetic bone is also characterized by hypertrophy and alteration of trabecular parameters.

  18. Sirtuin and metabolic kidney disease.

    PubMed

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-10-01

    Sirtuin is a nicotinamide adenine dinucleotide-dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti-fibrosis effects, anti-oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule-specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy.

  19. Bone metabolism of male rats chronically exposed to cadmium

    SciTech Connect

    Brzoska, Malgorzata M. . E-mail: mmbr@poczta.onet.pl; Moniuszko-Jakoniuk, Janina

    2005-09-15

    Recently, based on a female rat model of human exposure, we have reported that low-level chronic exposure to cadmium (Cd) has an injurious effect on the skeleton. The purpose of the current study was to investigate whether the exposure may also affect bone metabolism in a male rat model and to estimate the gender-related differences in the bone effect of Cd. Young male Wistar rats received drinking water containing 0, 1, 5, or 50 mg Cd/l for 12 months. The bone effect of Cd was evaluated using bone densitometry and biochemical markers of bone turnover. Renal handling of calcium (Ca) and phosphate, and serum concentrations of vitamin D metabolites, calcitonin, and parathormone were estimated as well. At treatment with 1 mg Cd/l, corresponding to the low environmental exposure in non-Cd-polluted areas, the bone mineral content (BMC) and density (BMD) at the femur and lumbar spine (L1-L5) and the total skeleton BMD did not differ compared to control. However, from the 6th month of the exposure, the Z score BMD indicated osteopenia in some animals and after 12 months the bone resorption very clearly tended to an increase. The rats' exposure corresponding to human moderate (5 mg Cd/l) and especially relatively high (50 mg Cd/l) exposure dose- and duration-dependently disturbed the processes of bone turnover and bone mass accumulation leading to formation of less dense than normal bone tissue. The effects were accompanied by changes in the serum concentration of calciotropic hormones and disorders in Ca and phosphate metabolism. It can be concluded that low environmental exposure to Cd may be only a subtle risk factor for skeletal demineralization in men. The results together with our previous findings based on an analogous model using female rats give clear evidence that males are less vulnerable to the bone effects of Cd compared to females.

  20. PPARs: diverse regulators in energy metabolism and metabolic diseases.

    PubMed

    Wang, Yong-Xu

    2010-02-01

    The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.

  1. Cholesterol metabolism in Huntington disease.

    PubMed

    Karasinska, Joanna M; Hayden, Michael R

    2011-09-06

    The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

  2. Thyroid diseases and bone health.

    PubMed

    Williams, G R; Bassett, J H D

    2017-08-29

    Thyroid hormones are essential for skeletal development and are important regulators of bone maintenance in adults. Childhood hypothyroidism causes delayed skeletal development, retarded linear growth and impaired bone mineral accrual. Epiphyseal dysgenesis is evidenced by classic features of stippled epiphyses on X-ray. In severe cases, post-natal growth arrest results in a complex skeletal dysplasia. Thyroid hormone replacement stimulates catch-up growth and bone maturation, but recovery may be incomplete dependent on the duration and severity of hypothyroidism prior to treatment. A severe phenotype characteristic of hypothyroidism occurs in children with resistance to thyroid hormone due to mutations affecting THRA encoding thyroid hormone receptor α (TRα). Discovery of this rare condition recapitulated animal studies demonstrating that TRα mediates thyroid hormone action in the skeleton. In adults, thyrotoxicosis is well known to cause severe osteoporosis and fracture, but cases are rare because of prompt diagnosis and treatment. Recent data, however, indicate that subclinical hyperthyroidism is associated with low bone mineral density (BMD) and an increased risk of fracture. Population studies have also shown that variation in thyroid status within the reference range in post-menopausal women is associated with altered BMD and fracture risk. Thus, thyroid status at the upper end of the euthyroid reference range is associated with low BMD and increased risk of osteoporotic fragility fracture. Overall, extensive data demonstrate that euthyroid status is required for normal post-natal growth and bone mineral accrual, and is fundamental for maintenance of adult bone structure and strength.

  3. Chronic Kidney Disease: Mineral and Bone Disorder in Children

    PubMed Central

    Wesseling-Perry, Katherine; Salusky, Isidro B.

    2014-01-01

    Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Early increases in bone and plasma fibroblast growth factor 23 (FGF23) are associated with early defects in skeletal mineralization. Later in the course of CKD, secondary hyperparathyroidism—due to a combination of declining calcitriol values and phosphate retention—results in high turnover renal osteodystrophy while elevated levels of both phosphate and FGF23 contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves high turnover bone disease but fails to correct defects in skeletal mineralization. Since overtreatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must therefore be carefully titrated to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents and new treatment paradigms may effectively suppress serum PTH levels while limiting intestinal calcium absorption and skeletal FGF23 stimulation and may provide future therapeutic alternatives for children with CKD. PMID:23465503

  4. [Bone quality in lifestyle-related diseases].

    PubMed

    Saito, Mitsuru; Marumo, Keishi

    2011-05-01

    Lifestyle-related diseases deteriorate bone quality in terms of material properties. Collagen cross-link formation is thought to be a determinant of material strength. Hyperglycemia, oxidative stress, carbonyl stress, and hyperhomocysteinemia induce the reduction in beneficial enzymatic cross-links and the accumulation of disadvantageous non-enzymatic cross-link, Advanced glycation end products (AGEs, Pentosidine) in bone. In this review, we describe that lifestyle-related diseases are crucial determinants of detrimental crosslinking of bone collagen that have been reported in the literature.

  5. Metabolic Imaging in Parkinson Disease.

    PubMed

    Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

    2017-01-01

    This review focuses on recent human (18)F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how (18)F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of (18)F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  6. Glutathione metabolism and Parkinson's disease.

    PubMed

    Smeyne, Michelle; Smeyne, Richard Jay

    2013-09-01

    It has been established that oxidative stress, defined as the condition in which the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson disease. Glutathione is a ubiquitous thiol tripeptide that acts alone or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals, and peroxynitrites. In this review, we examine the synthesis, metabolism, and functional interactions of glutathione and discuss how these relate to the protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson disease.

  7. [Mechanobiology and bone metabolism: Clinical relevance for fracture treatment].

    PubMed

    Haffner-Luntzer, M; Liedert, A; Ignatius, A

    2015-12-01

    Mechanical stimuli are known to significantly influence bone metabolism and fracture healing. Various studies have demonstrated the involvement of complex molecular mechanotransduction pathways, such as the Wnt/beta-catenin, bone morphogenetic protein (BMP) and estrogen receptor signaling pathways in mechanotransduction. Mechanotransduction is influenced by aging and the comorbidities of the patient. Pharmacological modulation of signal transduction influences bone formation and the mechanosensitivity of skeletal tissue. The combination of pharmacological and biomechanical therapies may be useful for the treatment of fractures with impaired healing.

  8. The heterogeneity of bone disease in cirrhosis: a multivariate analysis.

    PubMed

    Crawford, Bronwyn A L; Kam, C; Donaghy, A J; McCaughan, G W

    2003-12-01

    This study aimed to assess the clinical, biochemical and hormonal factors contributing to low bone density in a large ambulatory group of patients with cirrhosis of diverse aetiology. Bone density of the lumbar spine, neck of femur, total hip, total body, as well as total body fat, was measured by dual X-ray (DEXA) absorptiometry in 81 men and 32 women (average age 50.3 years). Morning blood and urine samples were taken for hormonal and biochemical analysis. Viral hepatitis was the most common cause of cirrhosis (54%) and the severity of cirrhosis ranged from Child-Pugh A5-C14. Osteoporosis was most common in the lumbar spine but was present at any site in 31% of women and 22% of men, with osteopenia present in another 40% of both genders. Urinary deoxypyridinoline, a marker of bone resorption, was elevated in 56% of patients and was associated with increasing severity of cirrhosis and a higher prevalence of osteoporosis, particularly of the lumbar spine. Hip-bone density was primarily affected by low 25-hydroxyvitamin D levels and was associated with secondary hyperparathyroidism in one third of these patients. Additional important predictors for low bone density at all sites were age in women and testosterone in men. These findings indicate that, although the pathophysiology of osteoporosis in chronic liver disease is heterogeneous, high bone turnover may be the underlying pathophysiological mechanism in a significant subgroup of cirrhotic patients and may reflect metabolic effects of hypogonadism or secondary hyperparathyroidism on bone.

  9. Periodontal disease in Paget’s disease of bone

    PubMed Central

    Nuti, Niccolò; Ferrari, Marco

    2015-01-01

    Summary A 59-year-old man suffering from Paget’s disease of bone and periodontal disease was examined in anticipation of bisphosphonate treatment. The previous therapy with clodronate resulted ineffective and markers of bone turnover were markedly elevated. Periodontal disease was correctly approached and treated with an excellent outcome. 5 mg zoledronate iv infusion induced a remarkable reduction of bone markers which persisted on time within the normal range. After zoledronate treatment no signs of osteonecrosis of the jaw (ONJ) were observed. A correct management of periodontal disease is mandatory in pagetic patients on bisphosphonate treatment. PMID:26604949

  10. Effects of hyperglycemia on bone metabolism and bone matrix in goldfish scales.

    PubMed

    Kitamura, Kei-Ichiro; Andoh, Tadashi; Okesaku, Wakana; Tazaki, Yuya; Ogai, Kazuhiro; Sugitani, Kayo; Kobayashi, Isao; Suzuki, Nobuo; Chen, Wenxi; Ikegame, Mika; Hattori, Atsuhiko

    2017-01-01

    Increased risk of fracture associated with type 2 diabetes has been a topic of recent concern. Fracture risk is related to a decrease in bone strength, which can be affected by bone metabolism and the quality of the bone. To investigate the cause of the increased fracture rate in patients with diabetes through analyses of bone metabolism and bone matrix protein properties, we used goldfish scales as a bone model for hyperglycemia. Using the scales of seven alloxan-treated and seven vehicle-treated control goldfish, we assessed bone metabolism by analyzing the activity of marker enzymes and mRNA expression of marker genes, and we measured the change in molecular weight of scale matrix proteins with SDS-PAGE. After only a 2-week exposure to hyperglycemia, the molecular weight of α- and β-fractions of bone matrix collagen proteins changed incrementally in the regenerating scales of hyperglycemic goldfish compared with those of euglycemic goldfish. In addition, the relative ratio of the γ-fraction significantly increased, and a δ-fraction appeared after adding glyceraldehyde-a candidate for the formation of advanced glycation end products in diabetes-to isolated type 1 collagen in vitro. The enzymatic activity and mRNA expression of osteoblast and osteoclast markers were not significantly different between hyperglycemic and euglycemic goldfish scales. These results indicate that hyperglycemia is likely to affect bone quality through glycation of matrix collagen from an early stage of hyperglycemia. Therefore, non-enzymatic glycation of collagen fibers in bone matrix may lead to the deterioration of bone quality from the onset of diabetes.

  11. Effect of swimming on bone metabolism in adolescents.

    PubMed

    Derman, Orhan; Cinemre, Alphan; Kanbur, Nuray; Doğan, Muhsin; Kiliç, Mustafa; Karaduman, Erdem

    2008-01-01

    Physical activity has been shown to have a positive effect on bone metabolism among adolescents. The objective of this study was to determine the effect of swimming on bone metabolism during adolescence. Swimming, as a non-weight-bearing sport, has been considered to be insignificant in the maintenance of bone mass. We studied whether swimming is associated with a higher peak bone mass. Forty swimmers (males aged 10-17 years and females aged 9-16 years) were studied. The control group consisted of the same number of adolescents aged between 10-16 years who did not swim; distribution of male and female gender was similar in the non-swimming control group compared to the swimming group. Adolescents were matched for age, gender and pubertal stages based on Tanner staging. All subjects underwent combined measurement of bone mineral metabolism by dual-energy X-ray absorptiometry of total body calcium content, and specific biochemical markers of turnover including osteocalcin, calcium, phosphorus and alkaline phosphatase. Bone age (determined by Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist), weight, height, ideal body weight, ideal body weight ratio, body mass index, Tanner classification (rated by examiner), diet, history of tobacco and alcohol exposure, exercise, socioeconomic status and history of chronic illness and medications were recorded to evaluate potential mediators that would affect bone metabolism. Tanner staging was used to assess puberty, and diet was evaluated based on reported consumption of milk, yogurt and cheese and cola/caffeine beverage consumption daily. There was significant difference in bone mineral content between adolescent male swimmers and the control group males. Consumption of cola beverages were significantly higher among the control group compared with the swimmer group. Ideal body weight ratio was significantly high among the female control group compared with female swimmers. Milk consumption was

  12. The bone scan in inflammatory osseous disease.

    PubMed

    Handmaker, H; Leonards, R

    1976-01-01

    The 99mTc-phosphate bone scan has become a sensitive, reliable, and safe method for evaluating the patient with suspected inflammatory disease of bone. The scan may become positive as early as the first 24 hr after the symptoms and 10-14 days before roentgenographic changes occur. It can be used to differentiate successfully a variety of diseases from osteomyelitis, and in conjunction with 67Ga-citrate scan has become a mainstay in the work-up of the patient with infectious disease. Applications of the bone scan to infectious diseases in pediatric practice are especially helpful, since these diseases are common problems in this age group. Increased experience with the 99mTc-phosphate bone scan has already defined several areas of "limitations" in evaluating inflammatory disease. "Cold" defects, negative scans in early stages of osteomyelitis, and "extended uptake" may all pose problems in interpretation, but careful correlation of the bone scan results with clinical history and physical findings, blood cultures, and roentgenography will significantly reduce these problems.

  13. Evaluation of milk basic protein supplementation on bone density and bone metabolism in Chinese young women.

    PubMed

    Zou, Zhi-Yong; Lin, Xiao-Ming; Xu, Xian-Rong; Xu, Rui; Ma, Le; Li, Ying; Wang, Ming-Fang

    2009-08-01

    Milk is a good source of bioavailable calcium compared with other foods. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The objective of this study was to examine the effects of MBP on bone mineral density (BMD) and bone metabolism of healthy young women. Eighty-four healthy young women were randomly assigned to three groups: control group, whole milk group or MBP group treated with milk containing 40 mg MBP for 8 months. The bone mineral density of total body, the lumbar vertebrae L2-L4 and the left forearm of each subject were measured by dual-energy X-ray absorptiometry (DEXA) at 0 and 8 months of treatment. Serum indexes of bone metabolism were measured at 0, 3, 6 and 8 months. Eighty-one subjects who completed the study in accordance with the protocol were included in the analysis. Total BMD in all groups significantly increased compared with baseline values. However, no significant difference on the mean rate of gain of total BMD was observed among the MBP group (2.19%), the whole milk group (2.63%) and the control group (1.61%). Serum cross-linked N-teleopeptides of type-I collagen (NTx) in MBP group at 8 months and in whole milk group at 6 months were significantly decreased from baseline. There were no significant differences between whole milk group and MBP group; however, after combining the milk groups, NTx had significantly decreased from baseline. No significant increase was observed in serum bone-specific alkaline phosphatase (BAP) in both whole milk group and MBP group. No significant effect of MBP on bone mineral density and bone metabolism was observed, but milk supplementation was effective in suppressing bone resorption.

  14. Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women.

    PubMed

    Uenishi, K; Ishida, H; Toba, Y; Aoe, S; Itabashi, A; Takada, Y

    2007-03-01

    Effect of milk basic protein on bone metabolism in healthy young women. Milk has more beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The object of this study was to examine the effect of MBP on the bone mineral density and bone metabolism of healthy young women. Thirty-five healthy young women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for 6 months. The bone mineral density (BMD) of the lumbar vertebrae L2-L4 of each subject was measured by dual-energy X-ray absorptiometry (DXA) at 0 and 6 months of treatment. Serum and urine indexes of bone metabolism were measured at 0, 3 and 6 months. All subjects completed the study in accordance with the protocol. The mean rate of gain of lumbar BMD in the MBP group (1.57%) was significantly higher than in the placebo group (0.13%, P=0.042). When compared with the placebo group, urinary cross-linked N-telopeptides of type-I collagen (NTx) were significantly decreased, and serum osteocalcin was significantly increased in the MBP group at 6 months. These results suggested that MBP supplementation was effective in increasing BMD in young women and that this increase in BMD may be primarily mediated through the promotion of bone formation and inhibition of bone resorption by MBP supplementation.

  15. Effect of the types of dietary fats and non-dietary oils on bone metabolism.

    PubMed

    El-Sayed, Eman; Ibrahim, Khadiga

    2017-03-04

    Nutrients beyond calcium and vitamin D have a role on bone health, and in treatment and prevention of osteoporosis. Quality and quantity of dietary fat may have consequences on skeletal health. Diets with highly saturated fat content produce deleterious effects on bone mineralization in growing animals. Conversely, dietary n-3-long chain polyunsaturated fatty acids play an important role in bone metabolism and may help in prevention and treatment of bone disease. Some reports suggest a correlation between the dietary ratio of n-6 and n-3 polyunsaturated fatty acids and bone formation. Specific dietary fatty acids were found to modulate prostanoid synthesis in bone tissue and improve bone formation in both animal and clinical trials. The skeletal benefits of dietary isoprenoids are extremely documented. Higher isoprenoids intake may relate to higher bone mineral density. Dietary supplements containing fish oil, individual polyunsaturated fatty acids, and isoprenoids could be used as adjuvant with bone medications in osteoportic conditions but their doses must be considered to avoid detrimental effect of over dosages.

  16. Serum markers of bone metabolism show bone loss in hibernating bears

    USGS Publications Warehouse

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.

  17. Dietary protein, calcium metabolism and bone health in humans

    USDA-ARS?s Scientific Manuscript database

    Protein is the major structural constituent of bone (50% by volume). But it is also a major source of metabolic acid, especially protein from animal sources because it contains sulfur amino acids that generate sulfuric acid. Increased potential renal acid load has been closely associated with increa...

  18. Bone metabolism: a note on the significance of mouse models.

    PubMed

    Raska, O; Bernásková, K; Raska, I

    2009-01-01

    This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possible limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing unforeseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other.

  19. Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells

    PubMed Central

    Chang, Chawnshang; Yeh, Shuyuan; Lee, Soo Ok; Chang, Ta-min

    2013-01-01

    The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgen/AR-related diseases. PMID:24653668

  20. [Alterations of bone metabolism in children and adolescents with diabetes mellitus type 1].

    PubMed

    Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

    2011-01-01

    Diabetes mellitus type 1 is one of the most common chronic diseases in children and adolescents. The incidence of diabetes mellitus type 1 is increasing rapidly worldwide. Recently, the largest rate of increase is observed in children aged 0-4 years. Chronic hyperglycemia leads to microvascular and macrovascular complications including retinopathy, nephropathy, neuropathy and cardiomyopathy. Pathological changes occur in the bone structure. The lack of diagnosis and treatment of alterations of the bone tIssue metabolism may lead to osteoporosis, which is characterized by much reduced bone mineral density and changes in the microarchitecture of the bone tIssue, which in consequence results in increased susceptibility to fractures. Diabetes mellitus type 1 most often starts before achieving peak bone mass, which constitutes a point of reference for predicting risk of fractures in a later period of life. Mechanisms responsible for loss of the bone tIssue in diabetes of type 1 still remain unexplained. Many research findings indicate the anabolic role of insulin and insulin-like growth factors, mainly IGF-1. The aim of this manuscript is to review recent papers about alterations of bone metabolism in children and adolescents with diabetes mellitus type 1.

  1. Changes in Bone Metabolism in Young Castrated Male Rats

    PubMed Central

    Ryu, Seong-Jun; Ryu, Dal-Sung; Kim, Jong-Yeol; Park, Jeong-Yoon; Kim, Kyung-Hyun; Chin, Dong-Kyu; Kim, Keun-Su; Cho, Yong-Eun

    2016-01-01

    Purpose To determine the window of time during which osteoporosis affects the management of spinal surgery and the mechanism of bone metabolism changes in males with osteoporosis by examining changes in bone metabolism in young castrated male rats. Materials and Methods A total of 30 Sprague-Dawley rats were randomly allocated into two study groups. Group 1 (control) received a sham surgery and Group 2 received bilateral orchiectomy to change bone mineral density (BMD). Serum osteocalcin, alkaline phosphatase (ALP), and collagen type 1 cross-linked C-telopeptide (CTX) were analyzed at postoperative date (POD) 8, 10, and 12 weeks. BMDs were measured using micro computed tomography scans. Results Femoral and lumbar BMDs were decreased in the orchiectomy groups. BMDs in the sham and orchiectomy groups showed statistically differences at POD 8, 10, and 12 weeks for the femur (p=0.032, 0.008, 0.008) and lumbar spine (p=0.151, 0.008, 0.008, respectively). Serum osteocalcin, ALP, and CTX decreased gradually; however, N-terminal type 1 procollagen (P1NP) showed a slight increase yet no significant change. Conclusion In young castrated male rats, a significant decrease in BMD was observed after orchiectomy due to the mixture of two detrimental factors. Young castrated male rats did not reach peak BMD. Increased bone turnover causes bone resorption to exceed bone formation. This study may contribute to the creation of a valuable model for studies of male osteoporosis and the spinal surgery field. PMID:27593866

  2. Bone disease in pediatric rheumatologic disorders.

    PubMed

    Burnham, Jon M; Leonard, Mary B

    2004-02-01

    Children with rheumatic disorders have multiple risk factors for impaired bone health, including delayed growth and development, malnutrition, decreased weight-bearing activity, inflammation, and glucocorticoid therapy. The impact of rheumatic disease during childhood may be immediate, resulting in fragility fractures, or delayed, because of suboptimal peak bone mass accrual. Recent years have seen increased interest in the effects of pediatric rheumatic disorders on bone mineralization, such as juvenile rheumatoid arthritis, systemic lupus erythematosus, and juvenile dermatomyositis. This review outlines the expected gains in bone size and mass during childhood and adolescence, and summarizes the advantages and disadvantages of available technologies for the assessment of skeletal growth and fragility in children. The varied threats to bone health in pediatric rheumatic disorders are reviewed, with emphasis on recent insights into the molecular mechanisms of inflammation-induced bone resorption. The literature assessing bone deficits and risk factors for impaired bone health in pediatric rheumatic disorders is reviewed, with consideration of the strengths and limitations of prior studies. Finally, future research directions are proposed.

  3. Inherited human diseases of heterotopic bone formation

    PubMed Central

    Shore, Eileen M.; Kaplan, Frederick S.

    2013-01-01

    Human disorders of hereditary and nonhereditary heterotopic ossification are conditions in which osteogenesis occurs outside of the skeleton, within soft tissues of the body. The resulting extraskeletal bone is normal. The aberration lies within the mechanisms that regulate cell-fate determination, directing the inappropriate formation of cartilage or bone, or both, in tissues such as skeletal muscle and adipose tissue. Specific gene mutations have been identified in two rare inherited disorders that are clinically characterized by extensive and progressive extraskeletal bone formation—fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In fibrodysplasia ossificans progressiva, activating mutations in activin receptor type-1, a bone morphogenetic protein type I receptor, induce heterotopic endochondral ossification, which results in the development of a functional bone organ system that includes skeletal-like bone and bone marrow. In progressive osseous heteroplasia, the heterotopic ossification leads to the formation of mainly intramembranous bone tissue in response to inactivating mutations in the GNAS gene. Patients with these diseases variably show malformation of normal skeletal elements, identifying the causative genes and their associated signaling pathways as key mediators of skeletal development in addition to regulating cell-fate decisions by adult stem cells. PMID:20703219

  4. Basis of bone metabolism around dental implants during osseointegration and peri-implant bone loss.

    PubMed

    Insua, Angel; Monje, Alberto; Wang, Hom-Lay; Miron, Richard J

    2017-07-01

    Despite the growing number of publications in the field of implant dentistry, there are limited studies to date investigating the biology and metabolism of bone healing around dental implants and their implications in peri-implant marginal bone loss. The aim of this review article is to provide a thorough understanding of the biological events taking place during osseointegration and the subsequent early and late phases of bone remodeling around dental implants. An update on the coupling mechanism occurring during bone resorption-bone remodeling is provided, focused on the relevance of the osteocytes, bone lining cells and immune cells during bone maintenance. An electronic and manual literature search was conducted by three independent reviewers in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases for articles up to September 2016 with no language restriction. Local bone metabolism is subject to signals from systemic calcium-phosphate homeostasis and bone remodeling. Three areas of interest were reviewed due to recent reported compromises in bone healing including the putative effects of (1) cholesterol, (2) hyperlipidemia, and (3) low vitamin D intake. Moreover, the prominent influence of osteocytes and immune cells is discussed as being key regulators during dental implant osseointegration and maintenance. These cells are of crucial importance in the presence of biofilm accumulation and their associated byproducts that leads to hard and soft tissue breakdown; the so called peri-implantitis. Factors that could negatively impact osteoclastogenesis or osteal macrophage activation should be monitored in future research including implant placement/torque protocols, bone characteristics, as well as meticulous maintenance programs to favor osseointegration and future long-term stability and success of dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res

  5. [Role of incretins in the regulation of bone metabolism].

    PubMed

    Yamada, Chizumi

    2011-05-01

    Diabetes is associated with increased risk of osteoporosis. Gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide(GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones released upon meal ingestion, and GIP and/or GLP-1 signaling is decreased in diabetic state. We have demonstrated that both GIP receptor knockout mice and GLP-1 receptor knockout mice have osteoporosis. GIP has anabolic effects on bone mainly by stimulating osteoblastic bone formation through intermittent elevation of intracellular cAMP levels. On the other hand, GLP-1 is suggested to regulate bone resorption indirectly through the thyroid C cell. Our studies show that incretins play important roles in bone metabolism by distinct mechanisms.

  6. Primary extra nodal Hodgkin disease: Bone presentation.

    PubMed

    Nikolica, Goran; Badnjar, Zorka; Cadjenovic, Tanja; Raceta-Masic, Dijana

    2014-01-01

    Extra nodal and extra lymphatic propagation of Hodgkin's disease is a characteristic of the fourth stage of disease when the organs are affected. Primary appearances of the disease outside the lymph node is a rare event. Therefore, it makes diagnostic problem. Skeletal system is possible localization of primary extra nodal Hodgkin's disease. Women, 42-years-old, was admitted to hospital because of swelling and pain in the right shoulder. After imaging and histological examination diagnosed Hodgkin's nodular sclerosing histological subtype disease has been established. The patient starts to receive chemotherapy. Primary extra nodal Hodgkin's disease of bone is manifested with painful swelling in geared area. Imaging method shows destruction of the affected bone, with swelling of the soft tissues. Propagation in soft tissue is not accompanied by their destruction, but rather manifested swelling of the surrounding soft tissue.

  7. Alterations of bone and mineral metabolism in diabetes mellitus. Part I. An overview.

    PubMed

    Hough, F S

    1987-07-18

    A critical review of the literature leads to the conclusion that alterations of bone and mineral metabolism occur both in diabetic patients and in animals with experimentally induced insulin deficiency syndromes. The coexistence of juvenile insulin-dependent diabetes mellitus (type 1) and radiological evidence of decreased bone mass (osteopenia) appears to be firmly established. Available data support the view that these patients have an increased propensity to skeletal fracture. Adult-onset, non-insulin-dependent diabetic populations, more heterogeneous as regards the type of diabetes, the therapy and the presence of complications or coexistent disease, are characterised by subpopulations with either a decreased, a normal or an increased bone mass. The pathogenesis of diabetic osteopenia is multifactorial. Data obtained from studies employing appropriate animal models of chronic insulin deficiency indicate that various metabolic and hormonal abnormalities may be involved.

  8. Paget's Disease of Bone and Osteoarthritis: Different Yet Related

    MedlinePlus

    ... For more information about Paget’s disease , contact: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: ... drug products. NIH Pub. No. 15-7919 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ...

  9. Paget's Disease of Bone: Approach to Its Historical Origins.

    PubMed

    Menéndez-Bueyes, Luis R; Soler Fernández, María Del Carmen

    Paget's disease of bone is the second most common bone disease after osteoporosis. It is characterized by focal regions of highly exaggerated bone remodeling, with abnormalities in all phases of the remodeling process. This study aims to investigate the hypothesis of a possible British origin of Paget's disease of bone by studying the worldwide geographic distribution of cases identified in ancient skeletons excavated from archaeological sites. The methodology consists in reviewing cases of Paget's disease of bone described in the literature.

  10. Infectious, inflammatory, and metabolic diseases affecting the athlete's spine.

    PubMed

    Metz, Lionel N; Wustrack, Rosanna; Lovell, Alberto F; Sawyer, Aenor J

    2012-07-01

    Sports and weight-bearing activities can have a positive effect on bone health in the growing, mature, or aging athlete. However, certain athletic activities and training regimens may place the athlete at increased risk for stress fractures in the spine. In addition, some athletes have an underlying susceptibility to fracture due to either systemic or focal abnormalities. It is important to identify and treat these athletes in order to prevent stress fractures and reduce the risk of osteoporosis in late adulthood. Therefore, the pre-participation physical examination offers a unique opportunity to screen athletes for metabolic bone disease through the history and physical examination. Positive findings warrant a thorough workup including a metabolic bone laboratory panel, and possibly a DEXA scan, which includes a lateral spine view.

  11. Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model.

    PubMed

    Rendina, Elizabeth; Hembree, Kelsey D; Davis, McKale R; Marlow, Denver; Clarke, Stephen L; Halloran, Bernard P; Lucas, Edralin A; Smith, Brenda J

    2013-01-01

    Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.

  12. Nanotechnology controlled drug delivery for treating bone diseases.

    PubMed

    Yang, Lei; Webster, Thomas J

    2009-08-01

    Rapid developments at the intersection of nanotechnology and controlled drug delivery have triggered exceptional growth in treating various bone diseases. As a result, over the past decade, nanotechnology has contributed tremendously to controlling drug delivery for treating various bone diseases, and in many cases, has led to increased bone regeneration. In this review paper, the recent experimental progress towards using nanotechnology to treat bone-specific diseases is reviewed. Novel applications of different types of nanomaterials (from nanoparticles to 3D nanostructured scaffolds) for treating bone diseases are summarized. In addition, fundamental principles for utilizing nanomaterials to create better drug delivery systems, especially for treating bone diseases and regenerating bone, are emphasized.

  13. Intestinal microflora and metabolic diseases.

    PubMed

    Serino, M; Luche, E; Chabo, C; Amar, J; Burcelin, R

    2009-09-01

    Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity-such as found in the intestinal microflora-and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease-to cite but a few-the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.

  14. Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases.

    PubMed

    Zhang, Qian; Chen, Bin; Yan, Fuhua; Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

  15. Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

    PubMed Central

    Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy. PMID:24696846

  16. Perspective on the impact of weightlessness on calcium and bone metabolism

    NASA Technical Reports Server (NTRS)

    Holick, M. F.

    1998-01-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  17. Perspective on the impact of weightlessness on calcium and bone metabolism

    NASA Technical Reports Server (NTRS)

    Holick, M. F.

    1998-01-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  18. Perspective on the impact of weightlessness on calcium and bone metabolism.

    PubMed

    Holick, M F

    1998-05-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  19. Paget's disease of bone (osteitis deformans).

    PubMed

    Ankrom, M A; Shapiro, J R

    1998-08-01

    Paget's disease of bone is important in geriatric populations because it is the second most common bone disorder after osteoporosis. In older people, it may be responsible for chronic back pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression. Paget's disease can reduce both function and mobility in the older people. In addition to newer tests for assessing the activity of Paget's disease, effective therapy is available in the form of salmon calcitonin for nasal administration and new third generation bisphosphonates. Frequently, treatment can reverse the course of the disease. For these reasons, it is feasible for the physician to adopt an aggressive approach to diagnosis and treatment. The objective should be to relieve pain, improve mobility, and forestall debilitating complications. This review will focus on the manifestations and clinical management of Paget's disease. Two cases are presented that illustrate common management problems in older patients.

  20. Different sympathetic pathways control the metabolism of distinct bone envelopes.

    PubMed

    Bataille, Caroline; Mauprivez, Cédric; Haÿ, Eric; Baroukh, Brigitte; Brun, Adrian; Chaussain, Catherine; Marie, Pierre J; Saffar, Jean-Louis; Cherruau, Marc

    2012-05-01

    Bone remodeling, the mechanism that modulates bone mass adaptation, is controlled by the sympathetic nervous system through the catecholaminergic pathway. However, resorption in the mandible periosteum envelope is associated with cholinergic Vasoactive Intestinal Peptide (VIP)-positive nerve fibers sensitive to sympathetic neurotoxics, suggesting that different sympathetic pathways may control distinct bone envelopes. In this study, we assessed the role of distinct sympathetic pathways on rat femur and mandible envelopes. To this goal, adult male Wistar rats were chemically sympathectomized or treated with agonists/antagonists of the catecholaminergic and cholinergic pathways; femora and mandibles were sampled. Histomorphometric analysis showed that sympathectomy decreased the number of preosteoclasts and RANKL-expressing osteoblasts in mandible periosteum but had no effect on femur trabecular bone. In contrast, pharmacological stimulation or repression of the catecholaminergic cell receptors impacted the femur trabecular bone and mandible endosteal retromolar zone. VIP treatment of sympathectomized rats rescued the disturbances of the mandible periosteum and alveolar wall whereas the cholinergic pathway had no effect on the catecholaminergic-dependent envelopes. We also found that VIP receptor-1 was weakly expressed in periosteal osteoblasts in the mandible and was increased by VIP treatment, whereas osteoblasts of the retromolar envelope that was innervated only by tyrosine hydroxylase-immunoreactive fibers, constitutively expressed beta-2 adrenergic receptors. These data highlight the complexity of the sympathetic control of bone metabolism. Both the embryological origin of the bone (endochondral for the femur, membranous for the mandibular periosteum and the socket wall) and environmental factors specific to the innervated envelope may influence the phenotype of the sympathetic innervation. We suggest that an origin-dependent imprint of bone cells through

  1. Bone Disease in Newly Diagnosed Lupus Nephritis Patients

    PubMed Central

    Resende, Aline Lázara; dos Reis, Luciene Machado; Dias, Cristiane Bitencourt; Custódio, Melani Ribeiro; Jorgetti, Vanda; Woronik, Viktoria

    2014-01-01

    Introduction Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology. Methods We studied 15 pre-menopausal patients with ≤2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D3 [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis. Results LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m2. They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.±9.1 vs. 22.9±5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient’s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls. Discussion Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters

  2. Evaluation of bone metabolism and bone mass in patients with type-2 diabetes mellitus.

    PubMed Central

    Oz, S. Gul; Guven, Gulay Sain; Kilicarslan, Alpaslan; Calik, Nursel; Beyazit, Yavuz; Sozen, Tumay

    2006-01-01

    The objectives of this study were to determine whether type-2 diabetes was associated with a higher bone mineral density (BMD) in men and women and to evaluate the differences in mineral metabolism between diabetic and normal subjects by using biochemical bone turnover markers. In this study, 52 patients (37 females/15 males) aged 41-64 with type-2 diabetes mellitus and 48 nondiabetic control subjects (34 females/14 males) were evaluated. In men, BMD was significantly higher in diabetics at the forearm (p <0.05), whereas in women tended to be higher at the hip (p=0.002). Serum osteocalcin (p<0.0001), bone alkaline phosphatase (BAP) (p<0.05) and carboxyterminal telopeptide (CTx) (p<0.05) were higher in the control group than in diabetics. In men, serum osteocalcin (p<0.05) and CTx (p<0.005) and, in women, serum osteocalcin (p<0.0001) and BAP (p<0.05) were lower in diabetic subjects. In conclusion, our findings suggest that although bone formation is decreased in type-2 diabetes, diabetic patients are not susceptible to bone resorption. This low bone turnover can slow the rate of bone loss and cause a higher bone density than expected for their age. PMID:17052049

  3. [Bone loss and bone metabolism in astronauts during long-duration space flight].

    PubMed

    Ohshima, Hiroshi

    2006-01-01

    Significant bone loss is one of the most serious medical concerns during long-duration space flight. This article provides the results of bone loss and bone metabolism obtained from American and Russian long-duration human space flight. Bone loss in astronauts before and after long-duration space flight was evaluated by dual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). DXA revealed bone loss at rates of 0.9%/month in the lumbar spine and 1.5%/month in the femoral neck. QCT revealed cortical, trabecular and integral BMD in the femoral neck at rates of 0.5%/month, 2.5%/month, and 1.5%/month, respectively. Biochemical markers of bone resorption increased during space flight and several months after landing. Bone formation marker was unchanged during space flight, but since 3 weeks after landing it was significantly higher than before flight. A calcium kinetics study confirmed that bone resorption increased, and intestinal calcium absorption decreased during space flight.

  4. [Cytokines in bone diseases. Anti-cytokine therapies for bone and joint diseases].

    PubMed

    Tanaka, Yoshiya

    2010-10-01

    The efficacy of biologics targeting inflammatory cytokines such as TNF and IL-6 for bone and joint diseases has been emerging. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damage. By the use of TNF-inhibitors, clinical remission, structural remission and functional remission have become possible during the treatment of RA. Especially, the progress of joint and bone destruction is completely suppressed by TNF-inhibitors in the vast majority of RA patients. On the other hand, anti-RANKL antibody inhibits joint destruction as well as systemic osteoporosis, though no effects on synovitis of RA. Thus, differential efficacy of different therapies in bone destruction and osteoporosis would warrant further study to clarify the mechanisms of bone and joints diseases.

  5. New developments in biological markers of bone metabolism in osteoporosis.

    PubMed

    Garnero, Patrick

    2014-09-01

    Over the last 15 years several biological markers of bone turnover have been developed with increased specificity and sensitivity. In osteoporosis clinical studies, the IOF and IFCC organizations have recently recommended the measurements of serum type I collagen N-propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) as markers of bone formation and bone resorption, respectively. However these markers have some limitations including a lack of specificity for bone tissue, their inability to reflect osteocyte activity or periosteal apposition. In addition they do not allow the investigation of bone tissue quality an important determinant of skeletal fragility. To address these limitations, new developments in markers of bone metabolism have been recently achieved. These include assays for periostin, a matricellular protein preferentially localized in the periosteal tissue, sphingosine 1-phosphate, a lipid mediator which acts mainly on osteoclastogenesis and the osteocyte factors such as sclerostin and FGF-23. Recent studies have shown an association between the circulating levels of these biological markers and fracture risk in postmenopausal women or elderly men, although data require confirmation in additional prospective studies. Finally, recent studies suggest that the measurements of circulating microRNAs may represent a novel class of early biological markers in osteoporosis. It is foreseen that with the use of genomics and proteomics, new markers will be developed to ultimately improve the management of patients with osteoporosis.

  6. Ageing, metabolism and cardiovascular disease.

    PubMed

    Costantino, Sarah; Paneni, Francesco; Cosentino, Francesco

    2016-04-15

    Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  7. Ageing, metabolism and cardiovascular disease

    PubMed Central

    Costantino, Sarah; Paneni, Francesco

    2015-01-01

    Abstract Age is one of the major risk factors associated with cardiovascular disease (CVD). About one‐fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66Shc, JunD and NF‐kB. This overview will provide the background for attractive molecular targets to prevent age‐driven pathology in the vasculature and the heart. PMID:26391109

  8. Acute effect of a supplemented milk drink on bone metabolism in healthy postmenopausal women is influenced by the metabolic syndrome.

    PubMed

    Thomas, Sunethra D C; Morris, Howard A; Nordin, B E C

    2015-09-25

    Dietary factors acutely influence the rate of bone resorption, as demonstrated by changes in serum bone resorption markers. Dietary calcium exerts its effect by reducing parathyroid hormone levels while other components induce gut incretin hormones both of which reduce bone resorption markers. The impact of dietary calcium on bone turnover when energy metabolism is modulated such as in metabolic syndrome has not been explored. This study was designed investigate whether metabolic syndrome or a greater amount of visceral fat influences the impact of dietary calcium on bone turnover. The influence of the metabolic syndrome on effects of dietary calcium on bone turnover in community dwelling postmenopausal women was studied. Twenty five volunteers consumed 200 mL of low fat milk with additional 560 mg calcium (one serve of Milo®) in the evening on one occasion. Fasting morning serum biochemistry before and after the milk drink with lumber spine bone density, bone mineral content, fat and lean mass using dual energy X-ray absorptiometry (DXA) and waist circumference were measured. The women were divided into 2 groups using the waist measurement of 88 cm, as a criterion of metabolic syndrome. Student's t tests were used to determine significant differences between the 2 groups. The lumbar spine mineral content was higher in women with metabolic syndrome. After consuming the milk drink, serum bone resorption marker C terminal telopeptide (CTX) was suppressed to a significant extent in women with metabolic syndrome compared to those without. The results suggests that dietary calcium may exert a greater suppression of bone resorption in post-menopausal women with metabolic syndrome than healthy women. Despite substantial evidence for close links between energy metabolism and bone metabolism this is the first report suggesting visceral fat or metabolic syndrome may influence the effects of dietary calcium on bone metabolism.

  9. [Syringomyelia and associated bone and joint diseases].

    PubMed

    Alnot, J-Y; Rossarie, R; Welby, F

    2007-05-01

    Syringomyelia can occur in patients presenting bone and joint diseases of various origins. When joint destruction of the shoulder or elbow produces little pain, a neurological cause might be involved. In this case, the disease history can be of utmost importance because an initial diagnosis of rheumatoid polyarthritis, polyosteoarthritis, or destructive joint disease can be misleading before the syringomyelic origin of the bone and joint disease becomes patent. We report two cases illustrating this association and the diagnostic pitfalls which can delay recognition of the syringomyelia. Better awareness of the prevalence of this condition should be helpful in establishing the diagnosis and in selecting patients who can benefit from neurosurgical treatment. The two cases presented here suggest that syringomyelia could be underdiagnosed in certain patients with an initially atypical presentation. A review of the current knowledge of syringomyelia suggests that arthroplasty is generally not advisable for destroyed dislocated syringomyelic joints.

  10. Nuclear Receptors in Bone Physiology and Diseases

    PubMed Central

    Youn, Min-Young; Inoue, Kazuki; Takada, Ichiro; Kouzmenko, Alexander; Kato, Shigeaki

    2013-01-01

    During the last decade, our view on the skeleton as a mere solid physical support structure has been transformed, as bone emerged as a dynamic, constantly remodeling tissue with systemic regulatory functions including those of an endocrine organ. Reflecting this remarkable functional complexity, distinct classes of humoral and intracellular regulatory factors have been shown to control vital processes in the bone. Among these regulators, nuclear receptors (NRs) play fundamental roles in bone development, growth, and maintenance. NRs are DNA-binding transcription factors that act as intracellular transducers of the respective ligand signaling pathways through modulation of expression of specific sets of cognate target genes. Aberrant NR signaling caused by receptor or ligand deficiency may profoundly affect bone health and compromise skeletal functions. Ligand dependency of NR action underlies a major strategy of therapeutic intervention to correct aberrant NR signaling, and significant efforts have been made to design novel synthetic NR ligands with enhanced beneficial properties and reduced potential negative side effects. As an example, estrogen deficiency causes bone loss and leads to development of osteoporosis, the most prevalent skeletal disorder in postmenopausal women. Since administration of natural estrogens for the treatment of osteoporosis often associates with undesirable side effects, several synthetic estrogen receptor ligands have been developed with higher therapeutic efficacy and specificity. This review presents current progress in our understanding of the roles of various nuclear receptor-mediated signaling pathways in bone physiology and disease, and in development of advanced NR ligands for treatment of common skeletal disorders. PMID:23589826

  11. Emerging strategies and therapies for treatment of Paget’s disease of bone

    PubMed Central

    Michou, Laëtitia; Brown, Jacques P

    2011-01-01

    Paget’s disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normalize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are reviewed: ie, pulse treatment with zoledronic acid; denosumab, a fully human monoclonal antibody directed against RANK ligand; tocilizumab, an interleukin-6 receptor inhibitor; odanacatib

  12. Assessment of bone turnover markers to predict mineral and bone disorder in men with pre-dialysis non-diabetic chronic kidney disease.

    PubMed

    Davina, Joseph Jessy; Priyadarssini, M; Rajappa, Medha; Parameswaran, Sreejith; Sahoo, Jayaprakash; Mohan Raj, P S; Revathy, G; Palanivel, C; Marella, Marie Gilbert

    2017-06-01

    Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry. CKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power. The combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Effects of vitamin K on calcium and bone metabolism.

    PubMed

    Zittermann, A

    2001-11-01

    The K vitamins, a group of napthoquinones, are required for the carboxylation of a limited number of proteins including the bone matrix protein osteocalcin. Vitamin K1 (phylloquinone) and vitamin K2 (menaquinones), differ regarding food source (green vegetables and fermented products, respectively), bioavailability and intermediate metabolism. Epidemiological studies provide evidence for an association between a low vitamin K intake and an enhanced osteoporotic fracture risk. Doses of vitamin K1 up to 15 times the current recommended dietary allowance have successfully been used to reduce the percentage of undercarboxylated osteocalcin in the circulation. Studies demonstrating clear beneficial effects on bone health, however, are still lacking. In contrast, therapy with very high pharmacological doses of the vitamin K2 menatetrenone has impressively been used to prevent further bone mineral loss and fracture risk in osteoporotic patients.

  14. Bones of contention: bone mineral density recovery in celiac disease--a systematic review.

    PubMed

    Grace-Farfaglia, Patricia

    2015-05-07

    Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.

  15. Pediatric nephrolithiasis and the link to bone metabolism.

    PubMed

    Schwaderer, Andrew Lawrence; Kusumi, Kirsten; Ayoob, Rose Mary

    2014-04-01

    To review the recent publications describing the link between pediatric nephrolithiasis and bone metabolism. Nephrolithiasis incidence is increasing in children and is associated with low bone mineral density (BMD). Affected children are conceptually at risk for fractures and osteoporosis. In addition to abnormal calcium metabolism, inflammation, genetic makeup and dietary habits are being recognized as important factors in the pathophysiology of nephrolithiasis and low bone density. Findings from retrospective reviews suggest that low BMD in children may be improved with citrate or thiazide treatment. The healthcare burden from low BMD with subsequent osteoporosis and fracture risk is immense with potential far-reaching effects in patient quality of life and healthcare expense. Bone mass is acquired in the pediatric age range, thus it is important to identify and treat at-risk children. Retrospective reviews in pediatric patients indicate that citrate or thiazide diuretic treatment may improve BMD. We now understand that a relationship exists between nephrolithiasis and low BMD. To improve healthcare for our current patients as well as protect their future health it is important to identify low BMD and initiate strategies to improve BMD in 'at-risk' children.

  16. Opportunities for genetic improvement of metabolic diseases

    USDA-ARS?s Scientific Manuscript database

    Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors and status of gene...

  17. Sleep deprivation induces abnormal bone metabolism in temporomandibular joint

    PubMed Central

    Geng, Wei; Wu, Gaoyi; Huang, Fei; Zhu, Yong; Nie, Jia; He, Yuhong; Chen, Lei

    2015-01-01

    Background: The purpose of this study was to explore the effect of experimental sleep deprivation (SD) on the temporomandibular joint (TMJ) of rats and the possible mechanism related to abnormal bone metabolism. Material and methods: SD was induced by a modified multiple platform method and assessed by serum adrenocorticotropic hormone (ACTH) level. TMJs were detached and stained with hematoxylin and eosin (H&E). Expression of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) was evaluated by quantitative reverse transcription polymerase chain reaction, H&E staining, immunohistochemical staining and enzyme linked immunosorbent assay. Results: Compared with controls, SD significantly increased serum ACTH, indicating that the SD model was successful. In the SD group, H&E staining revealed greater vessel hyperplasia in the synovial membrane and thicker hypertrophic layers in condylar cartilages. Compared with controls, RNA and protein expression of the inflammatory factors IL-1β and TNF-α and the bone metabolism-related factor RANKL increased in condylar cartilage in the SD group, whereas OPG and the OPG/RANKL ratio decreased. Immunohistochemical staining revealed that OPG/RANKL immunopositive cells were mainly located in hypertrophic layers. Conclusions: These results suggest that sleep deprivation might play an important role in the occurrence and development of temporomandibular disorders, which may occur through abnormal secretion of inflammatory and bone metabolism-related factors. PMID:25785010

  18. A case of brittle bone disease.

    PubMed

    Khan, M K; Hossain, M B

    2004-07-01

    Brittle bone disease--synonym, osteogenesis imperfecta is a rare genetic disorder of collagen synthesis associated with broad spectrum of musculoskeletal problem, where bones break easily. Recently we got a case of OI, whose name is Babu, 3 days old, full term bay with uneventful home delivery. The baby had multiple fractures in all the extremities with deformities with blue sclera with bilateral inguinal hernia. Other systems were found normal. On 10th day of life he was operated for inguinal hernia with satisfactory postoperative recovery and subsequently he was referred to the orthopedic department for further management.

  19. High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model.

    PubMed

    Larmonier, C B; McFadden, R-M T; Hill, F M; Schreiner, R; Ramalingam, R; Besselsen, D G; Ghishan, F K; Kiela, P R

    2013-07-01

    Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

  20. High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

    PubMed Central

    Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

    2013-01-01

    Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

  1. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  2. The association of chronic kidney disease-mineral bone disorder and cardiovascular risk.

    PubMed

    Eddington, Helen; Kalra, Philip A

    2010-05-01

    Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

  3. Hormonal regulation of medullary bone metabolism in the laying hen

    SciTech Connect

    Harrison, J.R.

    1987-01-01

    A new organ culture system for the study of bone formation has been developed using medullary bone, a non-structural, metabolically active form of bone which is found in the marrow cavities of egg-laying birds. In the presence of fetal calf serum, bone explants were viable in culture by morphological criteria, and retained large numbers of osteoblasts and osteoclasts. Incorporation of /sup 3/H-proline into collagenase-digestible protein (CDP) and non-collagen protein (NCP) was determined using purified bacterial collagenase. Collagen accounted for over 10% of the total protein labeled. The calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), caused a dose-dependent inhibition of /sup 3/H-proline incorporation into CDP. The effective dose range of 1,25(OH)2D3 was 0.1 nM to 100 nM, while that of PTH was 1.0 nM to 100 nM. The effect of both hormones was specific for collagen, since /sup 3/H-proline incorporation into NCP was unaffected. Hydroxyproline analysis of bone explants and culture medium revealed that both hormones decreased the total hydroxyroline content of the cultures, suggesting that the inhibition of /sup 3/H-proline incorporation into DCP is due to inhibition of collagen synthesis.

  4. Hormonal alterations in PCOS and its influence on bone metabolism.

    PubMed

    Krishnan, Abhaya; Muthusami, Sridhar

    2017-02-01

    According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women. © 2017 Society for Endocrinology.

  5. Amino acid supplementation alters bone metabolism during simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  6. Amino acid supplementation alters bone metabolism during simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  7. Endocrine and metabolic manifestations in inflammatory bowel disease.

    PubMed

    Tigas, Stelios; Tsatsoulis, Agathocles

    2012-01-01

    Extraintestinal manifestations from nearly every organ system are common in inflammatory bowel disease (IBD). This review article describes the epidemiology, pathogenesis, diagnosis and management of the main endocrine and metabolic manifestations in IBD, including metabolic bone disease, growth retardation, hypogonadism, pubertal delay, lipid abnormalities and insulin resistance. These clinical problems are commonly interrelated and they share a common basis, influenced by disease-related inflammation and nutritional status. In addition to nutritional support, every effort should be made to achieve and maintain disease remission, thus correcting the underlying chronic inflammation. The criteria for screening and diagnosing osteoporosis are described and treatment options are discussed (lifestyle advice, vitamin D and calcium supplementation, use of bisphosphonates or other specific antiosteoporotic agents, correction of hypogonadism). Chronic glucocorticoid therapy may affect growth as well as predispose to osteoporosis. The diagnosis and management of growth failure, pubertal delay and hypogonadism in IBD are discussed.

  8. Isoflavone metabolism and bone-sparing effects of daidzein-metabolites

    PubMed Central

    Uehara, Mariko

    2013-01-01

    Several dietary phytochemicals exhibit anti-oxidative, anti-inflammatory and anti-osteoporotic activities relevant to prevention of chronic diseases, including lifestyle-related diseases. Soybean isoflavones are similar in structure to estrogen and have received considerable attention as potential alternatives to hormone replacement therapy. Daidzein, a major isoflavone found in soybean, is metabolized to equol by intestinal microflora; this metabolite exhibits stronger estrogenic activity than daidzein. Recent studies suggest that the clinical effectiveness of isoflavones might be due to their ability to produce equol in the gut. This review focused on the metabolic pathway of equol and possible bioactivities of equol and O-desmethylangolensin, another metabolite of daidzein, with regard to bone metabolism and the status of intestinal microflora. Furthermore, we considered risk-benefit analyses of isoflavones and their metabolites. PMID:23704808

  9. Can acetazolamide be used to treat diseases involving increased bone mineral density?

    PubMed Central

    González-Rodríguez, Juan David; Luis-Yanes, María Isabel; Inglés-Torres, Esther; Arango-Sancho, Pedro; Cabrera-Sevilla, José Eugenio; Duque-Fernández, María Rosario; Gil-Sánchez, Salvador; García-Nieto, Víctor Manuel

    2016-01-01

    Summary Sclerosing bone dysplasias are a series of clinically and genetically heterogeneous diseases characterized by functional failure of the osteoclasts in bone resorption, leading to an excessive amount of bone mineral density (BMD) which could have serious clinical consequences. We treated three children affected with seriously high levels of BMD with acetazolamide, with the intention of inducing metabolic acidosis, thus increasing bone resorption and reducing BMD. All our patients tolerated and followed the treatment well and the clinical response was satisfactory in all cases. PMID:27904825

  10. Celiac disease and bone fractures: a systematic review and meta-analysis.

    PubMed

    Heikkilä, Katriina; Pearce, Jo; Mäki, Markku; Kaukinen, Katri

    2015-01-01

    Celiac disease, an autoimmune disease induced by dietary gluten, is associated with metabolic bone disorders, such as low bone mineral density. However, it is unclear whether this translates into an association between celiac disease and such hard clinical outcomes as bone fractures. To systematically review and pool the evidence for the relationship of celiac disease with prevalence and incidence of bone fractures. We systematically searched Pubmed, Scopus, Web of Science, and Cochrane Library in January 2014 for studies of celiac disease and bone fractures. Observational studies of any design, in which bone fracture outcomes were compared in individuals with and without celiac disease were included. Two investigators independently extracted results from eligible studies. In the meta-analyses of case-control and cross-sectional studies, bone fractures were almost twice as common in individuals with a clinically diagnosed celiac disease as in those without the disease. In the meta-analyses of prospective studies, celiac disease at baseline was associated with a 30% increase (95% confidence interval [CI]: 1.14, 1.50) in the risk of any fracture and a 69% increase in the risk of hip fracture (95% CI: 1.10, 2.59). The two studies of unrecognized celiac disease (elevated circulating concentrations of celiac disease-specific autoantibodies but no celiac disease diagnosis) had contradicting findings. Our findings suggest that clinically diagnosed celiac disease and bone fractures co-occur and that celiac disease was associated with an increased risk of hip fractures as well as fractures in general. Further research would be needed to determine whether unrecognized celiac disease is associated with the risk of bone fractures.

  11. The Role of IL-1β in the Bone Loss during Rheumatic Diseases

    PubMed Central

    Ruscitti, Piero; Cipriani, Paola; Carubbi, Francesco; Liakouli, Vasiliki; Di Benedetto, Paola; Berardicurti, Onorina; Alesse, Edoardo; Giacomelli, Roberto

    2015-01-01

    Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin- (IL-) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL-1β in the pathogenesis of bone loss. Furthermore, we analysed the role of IL-1β in bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti-IL-1β therapy in this field. PMID:25954061

  12. Fracture, aging and disease in bone

    SciTech Connect

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

  13. An Insight in to Paget's Disease of Bone

    PubMed Central

    Sabharwal, Robin; Gupta, Shivangi; Sepolia, Shipra; Panigrahi, Rajat; Mohanty, Saumyakanta; Subudhi, Santosh Kumar; Kumar, Manish

    2014-01-01

    Paget's disease of bone (PDB) is a common disorder which may affect one or many bones. Although many patients are asymptomatic, a variety of symptoms and complications may occur. PDB is a focal disorder of bone turnover characterized by excessive bone resorption coupled with bone formation. PDB begins with a period of increased osteoclastic activity and bone resorption, followed by increased osteoblast production of woven bone that is poorly mineralized. In the final phase of the disease process, dense cortical and trabecular bone deposition predominates, but the bone is sclerotic and poorly organized and lacks the structural integrity and strength of normal bone. This article briefly reviews the etiopathogenesis, clinical radiographic and histological features of Paget's disease. PMID:24665195

  14. The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism.

    PubMed

    Aqeilan, Rami I; Hassan, Mohammad Q; de Bruin, Alain; Hagan, John P; Volinia, Stefano; Palumbo, Titziana; Hussain, Sadiq; Lee, Suk-Hee; Gaur, Tripti; Stein, Gary S; Lian, Jane B; Croce, Carlo M

    2008-08-01

    The WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor. We have previously shown that targeted ablation of the Wwox gene in mouse increases the incidence of spontaneous and chemically induced tumors. To investigate WWOX function in vivo, we examined Wwox-deficient (Wwox(-/-)) mice for phenotypical abnormalities. Wwox(-/-) mice are significantly reduced in size, die at the age of 2-3 weeks, and suffer a metabolic disorder that affects the skeleton. Wwox(-/-) mice exhibit a delay in bone formation from a cell autonomous defect in differentiation beginning at the mineralization stage shown in calvarial osteoblasts ex vivo and supported by significantly decreased bone formation parameters in Wwox(-/-) mice by microcomputed tomography analyses. Wwox(-/-) mice develop metabolic bone disease, as a consequence of reduced serum calcium, hypoproteinuria, and hypoglycemia leading to increased osteoclast activity and bone resorption. Interestingly, we find WWOX physically associates with RUNX2, the principal transcriptional regulator of osteoblast differentiation, and on osteocalcin chromatin. We show WWOX functionally suppresses RUNX2 transactivation ability in osteoblasts. In breast cancer MDA-MB-242 cells that lack endogenous WWOX protein, restoration of WWOX expression inhibited Runx2 and RUNX2 target genes related to metastasis. Affymetrix mRNA profiling revealed common gene targets in multiple tissues. In Wwox(-/-) mice, genes related to nucleosome assembly and cell growth genes were down-regulated, and negative regulators of skeletal metabolism exhibited increased expression. Our results demonstrate an essential requirement for the WWOX tumor suppressor in postnatal survival, growth, and metabolism and suggest a central role for WWOX in regulation of bone tissue formation.

  15. Measuring Bone Metabolism with Fluoride PET: Methodological Considerations.

    PubMed

    Apostolova, Ivayla; Brenner, Winfried

    2010-07-01

    In recent years the more widespread availability of PET systems and the development of hybrid PET/computed tomography (CT) imaging, allowing improved morphologic characterization of sites with increased tracer uptake, have improved the accuracy of diagnosis and strengthened the role of 18F-fluoride PET for quantitative assessment of bone pathology. This article reviews the role of 18F-fluoride PET in the skeleton, with a focus on (1) the underlying physiologic and pathophysiological processes of different conditions of bone metabolism and (2) methodological aspects of quantitative measurement of 18F-fluoride kinetics. Recent comparative studies have demonstrated that 18F-fluoride PET and, to an even greater extent, PET/CT are more accurate than 99mTc-bisphosphonate single-photon emission CT for the identification of malignant and benign lesions of the skeleton. Quantitative 18F-flouride PET has been shown valuable for direct non-invasive assessment of bone metabolism and monitoring response to therapy. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Ethnic differences in calcium, phosphate and bone metabolism.

    PubMed

    Redmond, J; Jarjou, L M A; Zhou, B; Prentice, A; Schoenmakers, I

    2014-05-01

    The prevalence of osteoporosis and the incidence of age-related fragility fracture vary by ethnicity. There is greater than 10-fold variation in fracture probabilities between countries across the world. Mineral and bone metabolism are intimately interlinked, and both are known to exhibit patterns of daily variation, known as the diurnal rhythm (DR). Ethnic differences are described for Ca and P metabolism. The importance of these differences is described in detail between select ethnic groups, within the USA between African-Americans and White-Americans, between the Gambia and the UK and between China and the UK. Dietary Ca intake is higher in White-Americans compared with African-Americans, and is higher in White-British compared with Gambian and Chinese adults. Differences are observed also for plasma 25-hydroxy vitamin D, related to lifestyle differences, skin pigmentation and skin exposure to UVB-containing sunshine. Higher plasma 1,25-dihydroxy vitamin D and parathyroid hormone are observed in African-American compared with White-American adults. Plasma parathyroid hormone is also higher in Gambian adults and, in winter, in Chinese compared with White-British adults. There may be ethnic differences in the bone resorptive effects of parathyroid hormone, with a relative skeletal resistance to parathyroid hormone observed in some, but not all ethnic groups. Renal mineral excretion is also influenced by ethnicity; urinary Ca (uCa) and urinary P (uP) excretions are lower in African-Americans compared with White-Americans, and in Gambians compared with their White-British counterparts. Little is known about ethnic differences in the DR of Ca and P metabolism, but differences may be expected due to known differences in lifestyle factors, such as dietary intake and sleep/wake pattern. The ethnic-specific DR of Ca and P metabolism may influence the net balance of Ca and P conservation and bone remodelling. These ethnic differences in Ca, P and the bone metabolism may

  17. [The effect of osteopenia prevention in very small premature infants on hormonal parameters of calcium metabolism and bone mineralization].

    PubMed

    Reinken, L; Obladen, M; Dockx-Reinken, F; Lindemann, C

    1989-01-01

    In 23 very low birth weight infants the influence of mineral supplementation with 0.4 mmol calciumgluconate and 0.2 mmol glucose-1-phosphate/dl human milk on concentrations of 25-OH-D3, parathyroid hormone, calcitonine, calcium, phosphorus and activity of alkaline phosphatase was studied on days 3, 8, 28 and 56. On days 28 and 56 respectively, degree of bone mineralisation was classified. 8 preterm infants received supplementation before day 28, 7 infants after day 28, 8 infants had no supplementation. All preterm infants received beginning with day 7 vitamin D3 1000 IU/day. In all preterms mean concentrations of 25-OH-D3 were normal and increasing with age. Concentrations of parathyroid hormone and calcitonine were first of all increased and decreased with age, especially in supplemented infants. Light metabolic bone disease without fractures occurred in 4 infants of supplemented groups. Non-supplemented group contains 5 infants with severe metabolic bone disease without fractures. Results indicate intact metabolism and secretion of 25-OH-D3, parathyroid hormone and calcitonine. Decrease of calcitonine concentration in mineral supplemented preterms is a reference to a better mineral supply. Mineral supplementation is followed by an increase in bone mineralisation with prevention of severe metabolic bone disease.

  18. GORHAM-STOUT SYNDROME: PHANTOM BONE DISEASE

    PubMed Central

    El-Kouba, Gabriel; de Araújo Santos, Romilton; Pilluski, Paulo César; Severo, Antonio; Lech, Osvandré

    2015-01-01

    Gorham-Stout syndrome is a disease that presents idiopathic osteolysis of a bone or closely contiguous area. The etiology is unknown. It is a rare condition that is difficult to diagnose, and its treatment is controversial. It affects individuals irrespective of age or sex. In this study, we conducted a bibliographic review of the disease, specifically focusing on the differential diagnosis, and we demonstrated the follow-up on a patient with this syndrome from the time of its diagnosis, through treatment, to its current state of evolution. PMID:27026974

  19. Analysis of bone protein and mineral composition in bone disease using synchrotron infrared microspectroscopy

    NASA Astrophysics Data System (ADS)

    Miller, Lisa M.; Hamerman, David; Chance, Mark R.; Carlson, Cathy S.

    1999-10-01

    Infrared (IR) microspectroscopy is an analytical technique that is highly sensitive to the chemical components in bone. The brightness of a synchrotron source permits the examination of individual regions of bone in situ at a spatial resolution superior to that of a conventional infrared source. At Beamlines U10B and U2B at the National Synchrotron Light Source, we are examining the role of bone chemical composition in bone disease. In osteoarthritis (OA), it has been demonstrated that the bone underlying the joint cartilage (subchondral bone) becomes thickened prior to cartilage breakdown. Using synchrotron infrared microspectroscopy, we have examined the chemical composition of the subchondral bone in histologically normal and OA monkeys. Results demonstrate that the subchondral bone of OA monkeys is significantly more mineralized than the normal bone, primarily due to an increase in carbonate concentration in the OA bone. High resolution analysis indicates that differences in carbonate content are uniform throughout the subchondral bone region, suggesting that high subchondral bone carbonate may be a marker for OA. Conversely, increases in phosphate content are more pronounced in the region near the marrow space, suggesting that, as the subchondral bone thickens, the bone also becomes more mineralized. Osteoporosis is a disease characterized by a reduction in bone mass and a skeleton that is more susceptible to fracture. To date, it is unclear whether bone remodeled after the onset of osteoporosis differs in chemical composition from older bone. Using fluorescence-assisted infrared microspectroscopy, we are comparing the composition of monkey bone remodeled at various time points after the onset of osteoporosis (induced by ovariectomy). We find that the chemical composition of bone remodeled one year after ovariectomy and one year prior to necropsy is similar to normal bone. On the other hand, bone remodeled two years after ovariectomy is less mature, indicated

  20. [Analysis of Musculoskeletal Systems and Their Diseases. Integrated treatments for osteoporosis toward harmony of bone and muscle].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2015-08-01

    Osteoporosis and sarcopenia directly affect healthy life expectancy in elderly people ; therefore, both diseases become social problem around the world. Sarcopenia increases the risk of osteoporotic fracture. Thus, not only agents affecting bone tissue directly but also treatments for sarcopenia are important for management of osteoporosis. Recently, it has been shown that there is an interaction between bone and muscle. Several hormones affect muscle and bone simultaneously. Moreover, myokines secreted from muscle are reported to regulate bone metabolism. On the other hand, several systemic and local factors derived from bone also affect muscle tissue. Therefore, further studies are necessary to develop the integrated treatments for osteoporosis toward harmony of bone and muscle.

  1. Diagnosis and management of Paget's disease of bone.

    PubMed

    Griz, Luiz; Fontan, Daniele; Mesquita, Patricia; Lazaretti-Castro, Marise; Borba, Victoria Zeghbi Cochenski; Borges, João Lindolfo Cunha; Fontenele, Thyciara; Maia, Juliana; Bandeira, Francisco

    2014-08-01

    To conduct a literature review on the diagnosis and management of Paget's disease of bone. This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. We present a scientific statement on Paget's disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.

  2. Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

    PubMed

    Loddenkemper, Konstanze; Bohl, Nicole; Perka, Carsten; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2006-02-01

    Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)

  3. [New therapies for children affected by bone diseases].

    PubMed

    Ballhausen, Diana; Dépraz, Nuria Garcia; Kern, Ilse; Unger, Sheila; Bonafé, Luisa

    2012-02-22

    Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

  4. Competitive season of triathlon does not alter bone metabolism and bone mineral status in male triathletes.

    PubMed

    Maïmoun, L; Galy, O; Manetta, J; Coste, O; Peruchon, E; Micallef, J P; Mariano-Goulart, D; Couret, I; Sultan, C; Rossi, M

    2004-04-01

    This longitudinal study evaluated the effects of a triathlon season on bone metabolism and hormonal status. Seven male competitive triathletes (mean age 19.3 years, range 18 - 20) with 5.0 +/- 0.3 years of competition experience were tested twice during the season: at the beginning of training and 32 weeks later. Total and regional bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry, while bone turnover was evaluated by specific biochemical markers: bone-specific alkaline phosphatase (B-ALP), osteocalcin, and urinary type I collagen C-telopeptide. In addition, sexual, calciotropic and somatotropic hormones were also analyzed. After 32 weeks, a BMD increase was found at the lumbar spine (1.9 %; p = 0.031) and skull (3.1 %; p = 0.048), while no variation was observed for total body or at the proximal femur. The B-ALP level decreased (-23.2 %; p = 0.031), but no variation was found for the other bone markers. 1.25 (OH) (2)D3, IGF-1 and the bioavailability IGF-1 index (IGF-1/IGFBP-3) increased by 18.3 % (p = 0.047), 29 % (p = 0.048), 33 % (p = 0.011), respectively, while PTH, testosterone, IGFBP-3 and cortisol concentrations were unchanged. In conclusion, the triathlon season had a moderately favourable effect on BMD, although a slowing down of bone formation activity was observed. No variation in hormonal levels was observed that could have limited the effects of exercise on bone tissue.

  5. Circadian rhythms in liver metabolism and disease

    PubMed Central

    Ferrell, Jessica M.; Chiang, John Y.L.

    2015-01-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  6. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease.

  7. Bone mineral density and metabolism in familial dysautonomia.

    PubMed

    Maayan, C; Bar-On, E; Foldes, A J; Gesundheit, B; Pollak, R Dresner

    2002-05-01

    Familial dysautonomia (FD) patients suffer from multiple fractures and have reduced bone pain, which defers the diagnosis. The pathogenesis of bone fragility in FD is unknown. This study aimed to characterize bone mineral metabolism and density in FD. Seventy-nine FD patients aged 8 months to 48 years (mean age 13.9 +/- 10.4 years, median 12.3) were studied. Clinical data included weight, height, bone age, weekly physical activity and history of fractures. Bone mineral density (BMD) of the lumbar spine (n = 43), femoral neck (n = 26), total hip (n = 22) and whole body (n = 15) were determined by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D3, osteocalcin, bone alkaline phosphatase (B-ALP), parathyroid hormone and urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined in 68 patients and age- and sex-matched controls. Forty-two of 79 patients (53%) sustained 75 fractures. Twenty-four of 43 patients had a spine Z-score < -2.0, and 13 of 26 had a femoral neck Z-score < -2.0. Mean femoral neck BMD Z-score was lower in patients with fractures compared with those without (-2.5 +/- 0.9 vs -1.5 +/- 1.0, p = 0.01). Mean body mass index (BMI) was 16 kg/m2 in prepubertal patients and 18.4 kg/m2 in postpubertal patients. Bone age was significantly lower than chronological age (75.5 vs 99.3 months in prepubertal patients, p < 0.001; 151 vs 174 in postpubertal patients, p < 0.05). NTx and osteocalcin levels were higher in FD patients compared with controls (400 +/- 338 vs 303 +/- 308, BCE/mM creatinine p < 0.02; 90 +/- 59.5 vs 61.8 +/- 36.9 ng/ml, p < 0.001, respectively). B-ALP was lower in FD patients compared with controls (44.66 +/- 21.8 vs 55.36 +/- 36.6 ng/ml, p < 0.04). Mean spine Z-score was significantly lower in physically inactive compared with active patients (-3.00 +/- 1.70 vs -1.77 +/- 1.3, respectively, p = 0.05). We conclude that fractures in FD patients are associated with reduced BMD. FD patients have increased NTx and osteocalcin

  8. The role of bone in CKD-mediated mineral and vascular disease.

    PubMed

    Khouzam, Nadine M; Wesseling-Perry, Katherine; Salusky, Isidro B

    2015-09-01

    Cardiovascular disease is the leading cause of death in pediatric patients with chronic kidney disease (CKD), and vascular calcifications start early in the course of CKD. Based on the growing body of evidence that alterations of bone and mineral metabolism and the therapies designed to treat the skeletal consequences of CKD are linked to cardiovascular calcifications, the Kidney Disease, Improving Global Outcomes (KDIGO) working group redefined renal osteodystrophy as a systemic disorder of mineral and bone metabolism due to CKD, and this newly defined disorder is now known as "chronic kidney disease-mineral bone disorder (CKD-MBD)". Elevated fibroblast growth factor 23 (FGF23), a bone-derived protein, is the first biochemical abnormality to be associated with CKD-MBD, and high FGF23 levels correlate with increased cardiovascular morbidity and mortality, suggesting that bone is central to both initiating and perpetuating the abnormal mineral metabolism and vascular disease in CKD. The current standard therapies for CKD-MBD affect FGF23 levels differently; non-calcium-based binders with or without concurrent use of dietary phosphate restriction reduce FGF23 levels, while calcium-based binders seem to either increase or have no effect on FGF23 levels. Active vitamin D sterols increase FGF23 levels, whereas therapy with calcimimetics decreases FGF23 levels. Thus, the appropriate therapy that will minimize the rise in FGF23 and prevent cardiovascular morbidity remains to be defined.

  9. Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview.

    PubMed

    Litten-Brown, J C; Corson, A M; Clarke, L

    2010-06-01

    The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to

  10. Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

    PubMed

    Laurent, M R; Cook, M J; Gielen, E; Ward, K A; Antonio, L; Adams, J E; Decallonne, B; Bartfai, G; Casanueva, F F; Forti, G; Giwercman, A; Huhtaniemi, I T; Kula, K; Lean, M E J; Lee, D M; Pendleton, N; Punab, M; Claessens, F; Wu, F C W; Vanderschueren, D; Pye, S R; O'Neill, T W

    2016-11-01

    We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits.

  11. Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.

    PubMed

    Marie, Pierre J

    2015-04-01

    Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

  12. A rare variant of Caffey's disease - X-rays, bone scan and FDG PET findings.

    PubMed

    Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2011-04-01

    An 18-month-old boy with history of fever of 4 months duration and with swelling of the limbs was referred for a bone scan. There were multiple swellings over his upper and lower limbs, with bowing of the lower limbs. His radiological skeletal survey revealed marked periosteal new bone formation surrounding the diaphysis of long bones. A bone scan done with 99m Tc-MDP showed diffusely increased tracer uptake in all the long bones. A fluorodeoxyglucose positron emission tomography (FDG PET) scan done to assess the metabolic activity showed patchy FDG uptake in the long bones, ankle joint and anterior ends of few ribs. His clinical and imaging findings led to the diagnosis of Caffey's disease.

  13. Influence of Metabolism on Epigenetics and Disease

    PubMed Central

    Kaelin, William G.; McKnight, Steven L.

    2013-01-01

    Chemical modifications of histones and DNA, such as histone methylation, histone acetylation, and DNA methylation, play critical roles in epigenetic gene regulation. Many of the enzymes that add or remove such chemical modifications are known, or might be suspected, to be sensitive to changes in intracellular metabolism. This knowledge provides a conceptual foundation for understanding how mutations in the metabolic enzymes SDH, FH, and IDH can result in cancer and, more broadly, for how alterations in metabolism and nutrition might contribute to disease. Here, we review literature pertinent to hypothetical connections between metabolic and epigenetic states in eukaryotic cells. PMID:23540690

  14. Calcium phosphate metabolism and bone mineral density with nocturnal hemodialysis.

    PubMed

    Toussaint, Nigel; Boddington, Janeane; Simmonds, Rosemary; Waldron, Claire; Somerville, Christine; Agar, John

    2006-07-01

    An elevated calcium x phosphate product (Ca x P) is an independent risk factor for vascular calcification and cardiovascular death in dialysis patients. More physiological dialysis in patients undergoing nocturnal hemodialysis (NHD) has been shown to produce biochemical advantages compared with conventional hemodialysis (CHD) including superior phosphate (P) control. Benefits of dialysate with greater calcium (Ca) concentration are also reported in NHD to prevent Ca depletion and subsequent hyperparathyroidism, but there are concerns that a higher dialysate Ca concentration may contribute to raised serum Ca levels and greater Ca x P and vascular disease. The NHD program at our unit has been established for 4 years, and we retrospectively analyzed Ca and P metabolism in patients undergoing NHD (8-9 h/night, 6 nights/week). Our cohort consists of 11 patients, mean age 49.3 years, who had been on NHD for a minimum of 12 months, mean 34.3 months. Commencement was with low-flux (LF) NHD and 1.5 mmol/L Ca dialysate concentration, with conversion to high-flux (HF) dialyzers after a period (mean duration 18.7 months). We compared predialysis serum albumin, intact parathyroid hormone, P, total corrected Ca, and Ca x P at baseline on CHD, after conversion to LF NHD and during HF NHD. We also prospectively measured bone mineral density (BMD) on all patients entering the NHD program. Bone densitometry (DEXA) scans were performed at baseline (on CHD) and yearly after commencement of NHD. With the introduction of HF dialyzers, the Ca dialysate concentration was concurrently raised to 1.75 mmol/L after demonstration on DEXA scans of worsening osteopenia. Analysis of BMD, for all parameters, revealed a decrease over the first 12 to 24 months (N = 11). When the dialysate Ca bath was increased, the median T and Z scores subsequently increased (data at 3 years, N = 6). The mean predialysis P levels were significantly lower on LF NHD vs. CHD (1.51 vs. 1.77 mmol/L, p = 0.014), while on

  15. [Experimental study on effect of Salvia miltiorrhiza on alveolar bone metabolism and variation in bone mass in diabetic rats].

    PubMed

    Miao, Bo; Wang, Jianbo; Zhu, Yang; Yue, Changjun; Chen, Ming

    2012-06-01

    To study the effect of Salvia miltiorrhiza on alveolar bone metabolism and variation in bone mass in diabetic rats, in order to detect whether it has an inhibitory effect on alveolar bone osteoporosis caused by diabetics. Intraperitoneal injection of alloxan induced diabetes in rats. After one week of observation and maintenance of stable blood sugar level, they were treated with S. miltiorrhiza. The rats were sacrificed at the eighth week after fasting for 12 h and blood samples were collected for analysis of blood glucose and rate of bone metabolism. Meanwhile, their alveolar bones were collected for determining bone mineral density (BMD) and histological sections were made for histomorphology observation. Diabetic rats showed varying degrees of abnormality in bone metabolism indicators and significant reduction in bone mineral density. After treatment with S. miltiorrhiza, their symptoms reduced to some extend and all indicators were improved especially bone density. S. miltiorrhiza has a certain inhibitory effect on alveolar bone osteoporosis in diabetic rats in early stage.

  16. Abnormal erythrocyte metabolism in hepatic disease.

    PubMed

    Smith, J R; Kay, N E; Gottlieb, A J; Oski, F A

    1975-12-01

    Erythrocyte (RBC) metabolic studies were done on 114 patients with severe hepatic disease. Heinz body formation after incubation of RBCs with acetyl phenylhydrazine was found to be significantly higher in patients than in controls. RBC-reduced glutathione levels were lower than those of controls both before and after incubation with acetyl phenylhydrazine, and patients with the highest Heinz body counts had the lowest reduced glutathione levels. RBC methylene blue-stimulated hexose monophosphate (HMP) shunt metabolism and glucose recycling through the shunt were significantly lower in patients with active hepatic disease than in controls. There was no difference in resting HMP shunt activity or in resting recycling of glucose. Despite impairment of shunt metabolism, total glucose consumption was greater in patients than in controls. The patients with the lowest stimulated HMP shunt metabolism and glucose recycling had the highest Heinz body counts, lowest reduced glutathione, and highest total glucose consumption. A continuum of abnormal shunt metabolism was seen, from a mild reduction of stimulated HMP shunt activity to a severe combined decrease in both the HMP shunt and glucose recycling. When measured, glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and transketolase were normal or increased. Sequential studies were done on 11 patients who had abnormal metabolic studies. Coincident with improvement of HMP shunt metabolism, the Heinz body counts became lower, reduced glutathione higher, hematocrit higher, and liver function improved. Impaired HMP shunt metabolism appears to be a common, acquired RBC abnormality in patients with severe, active liver disease.

  17. The effects of bortezomib on bone disease in patients with multiple myeloma.

    PubMed

    Mohty, Mohamad; Malard, Florent; Mohty, Bilal; Savani, Bipin; Moreau, Philippe; Terpos, Evangelos

    2014-03-01

    Bortezomib has demonstrated substantial activity in the treatment of patients with multiple myeloma and is widely incorporated into treatment strategies across the different settings. It is interesting to note that data are accumulating to suggest that the activity of bortezomib extends beyond the tumor cell and microenvironment to encompass effects on bone metabolism. Indeed, data from both the preclinical and clinical settings have suggested that bortezomib directly stimulates osteoblast growth and differentiation, while also inhibiting osteoclast development and activity. Notably, in the clinical setting, the bone anabolic effects of bortezomib could be demonstrated by the healing of lytic lesions as noted in some patients. These results are of importance because bone disease is a hallmark of myeloma and therefore any agent that combines antimyeloma activity with positive effects on bone is of substantial interest. However, further studies are needed to establish how the agent should be used for the treatment of patients with bone disease. © 2013 American Cancer Society.

  18. Regulation of pyruvate metabolism and human disease.

    PubMed

    Gray, Lawrence R; Tompkins, Sean C; Taylor, Eric B

    2014-07-01

    Pyruvate is a keystone molecule critical for numerous aspects of eukaryotic and human metabolism. Pyruvate is the end-product of glycolysis, is derived from additional sources in the cellular cytoplasm, and is ultimately destined for transport into mitochondria as a master fuel input undergirding citric acid cycle carbon flux. In mitochondria, pyruvate drives ATP production by oxidative phosphorylation and multiple biosynthetic pathways intersecting the citric acid cycle. Mitochondrial pyruvate metabolism is regulated by many enzymes, including the recently discovered mitochondria pyruvate carrier, pyruvate dehydrogenase, and pyruvate carboxylase, to modulate overall pyruvate carbon flux. Mutations in any of the genes encoding for proteins regulating pyruvate metabolism may lead to disease. Numerous cases have been described. Aberrant pyruvate metabolism plays an especially prominent role in cancer, heart failure, and neurodegeneration. Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.

  19. Current concepts regarding calcium metabolism and bone health in sarcoidosis.

    PubMed

    Baughman, Robert P; Papanikolaou, Ilias

    2017-09-01

    Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

  20. Metabolic Disturbances in Diseases with Neurological Involvement

    PubMed Central

    Duarte, João M. N.; Schuck, Patrícia F.; Wenk, Gary L.; Ferreira, Gustavo C.

    2014-01-01

    Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID:25110608

  1. Mediators of inflammation and bone remodeling in rheumatic disease

    PubMed Central

    Shaw, Anita T.; Gravallese, Ellen M.

    2015-01-01

    Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure the proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis (RA) and spondyloarthritis (SpA), a disease category that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases. PMID:26481971

  2. Bone metabolic activity measured with positron emission tomography and [[sup 18]F] fluoride ion in renal osteodystrophy: Correlation with bone histomorphometry

    SciTech Connect

    Messa, C.; Goodman, W.G.; Hoh, C.K.; Choi, Y.; Nissenson, A.R.; Salusky, I.B.; Phelps, M.E.; Hawkins, R.A. )

    1993-10-01

    The authors evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [[sup 18]F] fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [[sup 18]F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [[sup 18]F] fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystropy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.

  3. Bone mineral density, quantitative ultrasound parameters and bone metabolism in postmenopausal women with depression.

    PubMed

    Atteritano, Marco; Lasco, Antonino; Mazzaferro, Susanna; Macrì, Ida; Catalano, Antonino; Santangelo, Antonino; Bagnato, Gianluca; Bagnato, Gianfilippo; Frisina, Nicola

    2013-09-01

    Low bone mineral density, which increases the risk of stress fragility fractures, is a frequent, often persistent finding in patients with major depressive disorder (MDD). The clinical association between major depressive disorder and osteopenia is still unclear, although several factors are associated with a loss of bone mass. The aim of our study, therefore, was to evaluate bone mineral density and bone metabolism in patients with MDD. Bone mineral density was evaluated in fifty postmenopausal women with MDD, and in 50 matched postmenopausal control women by dual-energy X-ray absorptiometry of the lumbar spine and femur, and by ultrasonography of the calcaneus and phalanges. Serum levels of 25-hydroxivitamin D, parathyroid hormone, Osteoprotegerin/Receptor Activator for Nuclear Factor κB Ligand ratio, bone turnover markers, serum and urinary cortisol were examined. Bone mineral density of the lumbar spine (BMD: 0.72 ± 0.06 vs. 0.82 ± 0.09 g/cm(2), p < 0.001), femoral neck (BMD: 0.58 ± 0.04 vs. 0.71 ± 0.07 g/cm(2), p < 0.001) and total femur (BMD 0.66 ± 0.09 vs. 0.54 ± 0.06 g/cm(2), p < 0.001); and ultrasound parameters at calcaneus (SI: 81.30 ± 6.10 vs. 93.80 ± 7.10, p < 0.001) and phalanges (AD-SOS: 1915.00 ± 37.70 vs. 2020.88 ± 39.46, p < 0.001; BTT : 1.30 ± 0.8 vs. 1.45 ± 0.9, p < 0.001) are significantly lower in patients with MDD compared with controls. Moreover bone turnover markers, parathyroid hormone levels and Receptor Activator for Nuclear Factor κB Ligand are significantly higher in MDD patients compared with controls, while serum levels of 25-hydroxivitamin D and osteoprotegerin are significantly lower. There are no differences in urinary excretion and serum cortisol between groups. Postmenopausal women with depressive disorder have an elevated risk for osteoporosis. Our data suggest that a high level of parathyroid hormone may play a role in the pathogenetic process underlying osteopenia in these patients.

  4. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

    PubMed

    Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

    2016-09-01

    Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. The effect of milk supplements on calcium metabolism, bone metabolism and calcium balance.

    PubMed

    Recker, R R; Heaney, R P

    1985-02-01

    Twenty-two healthy postmenopausal women were divided into two groups, one group of 13 received milk supplementation of 24 oz per day and the other group of 9 controls received no intervention during two years of observation. Extensive inpatient metabolic balance and radiocalcium kinetic studies were performed at the beginning and at the end of one year of observation. In the milk supplement group, fractional calcium absorption (x +/- SD) decreased from .243 +/- .058 to .176 +/- .058, absorbed calcium increased from .159 +/- .052 gm/d to .248 +/- .063 gm/d, urine calcium increased from .117 +/- .034 gm/d to .146 +/- .027 gm/d, bone accretion decreased from .385 +/- .079 gm/d to .326 +/- .063 gm/d, bone resorption decreased from .446 +/- .098 gm/d to .342 +/- .106 gm/d and endogenous fecal calcium increased from .105 +/- .023 gm/d to .120 +/- .021 gm/d. All these changes were significant within the group and the mean changes were significantly different from the mean changes observed in the control group. Calcium balance in the milk supplemented group improved from -.061 +/- .056 gm/d to -.017 gm/d +/- .073 gm/d. Predicted changes in calcium and bone metabolism held true except that the suppression of bone remodeling was less than previously found using calcium carbonate supplements. We conclude that milk and milk products can be recommended as sources of calcium, that data on the effects of increasing calcium intake from other sources can be applied to milk and that milk may offer an advantage because it does not suppress bone remodeling as severely as calcium carbonate.

  6. Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

    PubMed

    Yamaguchi, Masayoshi

    2006-11-01

    Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

  7. Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems

    PubMed Central

    Johnsson, Martin; Jonsson, Kenneth B.; Andersson, Leif; Jensen, Per; Wright, Dominic

    2015-01-01

    Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL) and expression QTL (eQTL) mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken) and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone. PMID:26023928

  8. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

    PubMed

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

  9. The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss

    PubMed Central

    Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc

    2016-01-01

    ABSTRACT Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption. PMID:27956598

  10. 18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis.

    PubMed

    Irmler, Ingo M; Gebhardt, Peter; Hoffmann, Bianca; Opfermann, Thomas; Figge, Marc-Thilo; Saluz, Hans P; Kamradt, Thomas

    2014-07-22

    Evaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A noninvasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research for staging of autoimmune disease severity or efficacy of therapeutical intervention. Sodium 18 F-fluoride (18 F-NaF) is a bone-seeking tracer well-suited for molecular imaging. Therefore, we systematically examined the use of 18 F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis for quantification of pathological bone metabolism. F-fluoride was injected into mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints in the fore- and hindpaws was analyzed by PET measurements. For validation of bone metabolism quantified by 18 F-fluoride PET, bone surface parameters of high-resolution μCT measurements were used. Before clinical arthritis onset, no distinct accumulation of 18 F-fluoride was detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course of experimental autoimmune disease, 18 F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, 18 F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT enabled identification of exact localization of 18 F-fluoride signaling in bone and soft tissue. The results of this study suggest that small-animal PET/CT using 18 F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the possibility to perform repeated noninvasive

  11. Update on Bone Health in Pediatric Chronic Disease.

    PubMed

    Williams, Kristen M

    2016-06-01

    Children and adolescents with chronic disease are predisposed to impaired bone health. Pediatric illness, including type 1 diabetes mellitus, celiac disease, and cystic fibrosis, have significant risk of low bone mineralization and fracture due to underlying inflammation, malabsorption, lack of physical activity, and delayed puberty. Dual-energy x-ray absorptiometry is the primary imaging method to assess bone health in this population. The purpose of this review is to update readers about the assessment and management of bone health in children with common pediatric chronic illnesses and review recent advances in the prevention and treatment of impaired bone health.

  12. Effect of copper on liver and bone metabolism in malnutrition.

    PubMed

    Güler, A H; Sapan, N; Ediz, B; Genç, Z; Ozkan, K

    1994-01-01

    This study was planned to investigate the effects of copper (Cu) deficiency on liver and bone metabolism in malnourished children. Serum total calcium (Ca), inorganic phosphorus (P), Ca/P, Cu/Ca, Cu/P ratios and alkaline phosphatase (ALP) activity values were analyzed. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT) enzyme activities and the ALT/AST (De Ritis) ratio as well as their correlations with Cu were tested to determine liver function. The results of the study showed that Cu deficiency directly affects the organic matrix formation, and by the suppression of ALP activity, indirectly causes decalcification. In the liver, however, no direct effect of Cu deficiency was seen. Deterioration in liver function and Cu deficiency increased parallel with the severity of malnutrition. Thus we concluded that a correlation exists between Cu and the parameters that indicate liver function.

  13. Nutrient sensing and inflammation in metabolic diseases.

    PubMed

    Hotamisligil, Gökhan S; Erbay, Ebru

    2008-12-01

    The proper functioning of the pathways that are involved in the sensing and management of nutrients is central to metabolic homeostasis and is therefore among the most fundamental requirements for survival. Metabolic systems are integrated with pathogen-sensing and immune responses, and these pathways are evolutionarily conserved. This close functional and molecular integration of the immune and metabolic systems is emerging as a crucial homeostatic mechanism, the dysfunction of which underlies many chronic metabolic diseases, including type 2 diabetes and atherosclerosis. In this Review we provide an overview of several important networks that sense and manage nutrients and discuss how they integrate with immune and inflammatory pathways to influence the physiological and pathological metabolic states in the body.

  14. Disruption of Calcium Homeostasis During Exercise as a Mediator of Bone Metabolism

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-12-1-0364 TITLE: Disruption of Calcium Homeostasis during Exercise as a Mediator of Bone Metabolism PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0364 Disruption of Calcium Homeostasis during Exercise as a Mediator of Bone Metabolism 5b. GRANT NUMBER...Meeting of the American College of Sports Medicine (Appendix A). 15. SUBJECT TERMS calcium homeostasis , exercise, bone resorption, parathyroid hormone

  15. Hepatic diseases related to triglyceride metabolism.

    PubMed

    Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

    2013-10-01

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

  16. Imbalanced cholesterol metabolism in Alzheimer's disease.

    PubMed

    Xue-shan, Zhao; Juan, Peng; Qi, Wu; Zhong, Ren; Li-hong, Pan; Zhi-han, Tang; Zhi-sheng, Jiang; Gui-xue, Wang; Lu-shan, Liu

    2016-05-01

    Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by β-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

  17. Periodontitis and bone metabolism in patients with advanced heart failure and after heart transplantation

    PubMed Central

    Mizani, Iman; Salaverry, Kristina Rodriguez; Chang, Jaime; Wu, Christina; Jones, Meaghan; Kennel, Peter J.; Brunjes, Danielle L.; Choo, Tse‐Hwei; Kato, Tomoko S.; Mancini, Donna; Grbic, John; Schulze, P. Christian

    2017-01-01

    Abstract Aims Heart failure (HF) is a multi­organ, pro‐inflammatory syndrome that impairs bone metabolism. Pro‐inflammatory cytokines and bone catabolism enhance periodontal disease, a local inflammatory, bacteria‐induced disease that causes bone loss and periodontal soft tissue destruction. Methods and results Medical and dental examinations were performed on patients with HF (n = 39), following heart transplantation (post‐HTx, n = 38) and controls (n = 32). Blood, saliva, and gingival crevicular fluid were analysed for bone metabolism and inflammation markers. HF average New York Heart Association classification was III. Average time since HTx was 1414 days. Pro‐inflammatory tumour necrosis factor‐alpha was higher in HF and HTx as compared with controls (P < 0.05). Both HF and HTx participants had higher levels of bone resorption marker C‐terminal telopeptide and parathyroid hormone with subjects in the HF group having the highest serum levels of all groups (P ≤ 0.05). In contrast, 25‐hydroxyvitamin D was lowest in HF. HF patients had greater clinical attachment loss, cumulative pockets depth (greater than 3 mm) and probing depth (P < 0.05) as compared with controls. Cumulative pockets depth correlated significantly with measures of the inflammatory burden, β‐glucuronidase in saliva (r = 0.4863, P < 0.01), interleukin‐1b in saliva (r = 0.5149, P < 0.01), and gingival crevicular fluid (r = 0.6056, P < 0.001) in HF. However, adjustment of periodontal results for measures of oral hygiene (plaque, bleeding on probing), systemic 25‐hydroxyvitamin D, and race attenuated significant differences between groups. Conclusions Patients with HF exhibit more severe periodontal disease associated with increased bone turnover markers when compared with control patients. However, local and systemic factors may account for this association and should be evaluated in future studies. PMID:28451454

  18. Paternal epigenetic programming: evolving metabolic disease risk.

    PubMed

    Hur, Suzy S J; Cropley, Jennifer E; Suter, Catherine M

    2017-04-01

    Parental health or exposures can affect the lifetime health outcomes of offspring, independently of inherited genotypes. Such 'epigenetic' effects occur over a broad range of environmental stressors, including defects in parental metabolism. Although maternal metabolic effects are well documented, it has only recently been established that that there is also an independent paternal contribution to long-term metabolic health. Both paternal undernutrition and overnutrition can induce metabolic phenotypes in immediate offspring, and in some cases, the induced phenotype can affect multiple generations, implying inheritance of an acquired trait. The male lineage transmission of metabolic disease risk in these cases implicates a heritable factor carried by sperm. Sperm-based transmission provides a tractable system to interrogate heritable epigenetic factors influencing metabolism, and as detailed here, animal models of paternal programming have already provided some significant insights. Here, we review the evidence for paternal programming of metabolism in humans and animal models, and the available evidence on potential underlying mechanisms. Programming by paternal metabolism can be observed in multiple species across animal phyla, suggesting that this phenomenon may have a unique evolutionary significance.

  19. Lessons from rare diseases of cartilage and bone.

    PubMed

    Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

    2015-06-01

    Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction.

  20. Peripheral cholesterol, metabolic disorders and Alzheimer's disease.

    PubMed

    Ledesma, Maria Dolores; Dotti, Carlos Gerardo

    2012-01-01

    Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that, altogether, constitute a major cause of death in our societies.

  1. Impact of lanthanum carbonate on cortical bone in dialysis patients with adynamic bone disease.

    PubMed

    Yajima, Aiji; Inaba, Masaaki; Tominaga, Yoshihiro; Tanaka, Motoko; Otsubo, Shigeru; Nitta, Kosaku; Ito, Akemi; Satoh, Shigeru

    2013-04-01

    Among the most serious problems in patients with chronic kidney disease (CKD) is fragility of cortical bone caused by cortical thinning and increased cortical porosity; the cortical fragility is sometimes irreversible, with fractures generally initiating from cortical bone. Therefore, development of treatments for problems of cortical bone is urgently desired. Cortical bone has the three surfaces, including the periosteal surface, intracortical spaces and endocortical surface. Bone turnover at the endocortical surface and intracortical resorption spaces are increased as compared with that at cancellous surface. Bone growth sometimes depends on apposition at the periosteal surface. We treated hyperphosphatemia in two hemodialysis patients with adynamic bone disease with 750-1500 mg/day of lanthanum carbonate, which is a non-calcium containing phosphate binder; the treatment resulted in a decrease of the serum phosphorus levels (P levels), without significant change of the serum intact parathyroid hormone levels. We now report that treatment of these patients with lanthanum carbonate increased mineralization of the periosteal surface, increased bone mass within the intracortical resorption spaces and increased mineralization of the minimodeling surface at the endocortical surface. In addition, woven bone volume in cortical bone was decreased and mineralization of bone units, namely, osteons, was increased. Although these findings were not observed across all surfaces of the cortical bone in the patients, it is expected that lanthanum carbonate would increase the cortical stability in CKD patients, with consequent reduction in the fracture rate in these patients.

  2. Mineral metabolism and cardiovascular disease in CKD.

    PubMed

    Fujii, Hideki; Joki, Nobuhiko

    2017-03-01

    The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease. Most notable is fibroblast growth factor-23 (FGF23), which is thought to be independently associated with cardiac remodeling. Slow progression of cardiac disorders, such as vascular calcification and cardiac remodeling, characterizes cardiac disease due to CKD-MBD. In contrast, fatal arrhythmia may be induced when QT prolongation occurs with CKD-MBD treatment, such as with lower Ca dialysate or the use of calcimimetics. Sudden onset of fatal cardiac events, such as heart failure and sudden cardiac death, due to fatal arrhythmia would be another distinctive phenomenon of CKD-MBD. This may be defined as CKD-MBD-specific cardiac complex syndrome.

  3. Neurodegenerative disorders and metabolic disease.

    PubMed

    Pierre, Germaine

    2013-08-01

    Most genetic causes of neurodegenerative disorders in childhood are due to neurometabolic disease. There are over 200 disorders, including aminoacidopathies, creatine disorders, mitochondrial cytopathies, peroxisomal disorders and lysosomal storage disorders. However, diagnosis can pose a challenge to the clinician when patients present with non-specific problems like epilepsy, developmental delay, autism, dystonia and ataxia. The variety of specialist tests involved can also be daunting. This review aims to give a practical approach to the investigation and diagnosis of neurometabolic disease from the neonatal period to late childhood while prioritising disorders where there are therapeutic options. In particular, patients who have a complex clinical picture of several neurological and non-neurological features should be investigated.

  4. Disease-specific clinical problems associated with the subchondral bone.

    PubMed

    Pape, Dietrich; Filardo, Giuseppe; Kon, Elisaveta; van Dijk, C Niek; Madry, Henning

    2010-04-01

    The subchondral bone is involved in a variety of diseases affecting both the articular cartilage and bone. Osteochondral defects in distinct locations and of variable sizes are the final results of different etiologies. These include traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Traumatic osteochondral defects are caused by osteochondral fractures, separating an osteochondral fragment that includes articular cartilage and both subchondral and trabecular bone from the joint surface. In osteochondritis dissecans, the disease originates in the subchondral bone and secondarily affects the articular cartilage. Location, stage, size, and depth of osteochondral lesions play a role in the treatment of traumatic osteochondral defects and osteochondritis dissecans. Surgical options include fragment refixation, transplantation of osteochondral autografts, or bone restoration by impacted cancellous bone grafts combined with autologous chondrocyte transplantation. An insufficiency fracture of the subchondral bone may be the initiating factor of what was formerly believed to be a spontaneous osteonecrosis of the knee (SPONK). Recent histopathological studies suggest that each stage of SPONK reflects different types of bone repair reactions following a fracture of the subchondral bone plate. Osteoarthritis is a disease that does affect not only the articular cartilage, but also the subchondral bone. Reconstructive surgical techniques aim at preserving joint function, inducing fibrocartilaginous repair, and at correcting malalignment. This review summarizes the current status of the clinical treatment of traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis as they affect the subchondral bone region and its adjacent structures.

  5. Lipoprotein metabolism differs between Marek's disease susceptible and resistant chickens.

    PubMed

    Yuan, P; Yu, Y; Luo, J; Tian, F; Zhang, H; Chang, S; Ramachandran, R; Zhang, L; Song, J

    2012-10-01

    Marek's disease (MD) is a lymphoproliferative disease of chickens caused by MD virus and has an important impact on the poultry industry worldwide. There have been reports showing different physiological characteristics between MD susceptible and resistant chickens. However, little is known about whether there are differences in lipid metabolism between MD susceptible and resistant lines of chickens. In this study, we examined the BW and the weight of tissues (abdominal fat, breast muscle with bone, leg muscle with bone, liver, and heart), the lipoprotein-cholesterol concentrations and distributions, and the plasma and tissue levels of adiponectin and its receptors in the highly resistant and susceptible lines during chicken growth. Our data showed that the increase in total cholesterol during growth was mainly due to the elevation of cholesterol in the low-density/very low-density lipoprotein fraction in MD susceptible chickens, whereas the increase of total cholesterol was mainly attributable to the increase in high-density lipoprotein-cholesterol in MD resistant chickens. Meanwhile, the MD resistant line appeared to have increased plasma adiponectin levels compared with MD susceptible chickens during growth. Taken together, our data suggested that lipoprotein-cholesterol and adiponectin metabolism are different between MD susceptible and resistant chickens.

  6. Current perspectives on bisphosphonate treatment in Paget’s disease of bone

    PubMed Central

    Wat, Winnie Zee Man

    2014-01-01

    Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its

  7. Brain Iron Metabolism Dysfunction in Parkinson's Disease.

    PubMed

    Jiang, Hong; Wang, Jun; Rogers, Jack; Xie, Junxia

    2017-05-01

    Dysfunction of iron metabolism, which includes its uptake, storage, and release, plays a key role in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease, and Huntington's disease. Understanding how iron accumulates in the substantia nigra (SN) and why it specifically targets dopaminergic (DAergic) neurons is particularly warranted for PD, as this knowledge may provide new therapeutic avenues for a more targeted neurotherapeutic strategy for this disease. In this review, we begin with a brief introduction describing brain iron metabolism and its regulation. We then provide a detailed description of how iron accumulates specifically in the SN and why DAergic neurons are especially vulnerable to iron in PD. Furthermore, we focus on the possible mechanisms involved in iron-induced cell death of DAergic neurons in the SN. Finally, we present evidence in support that iron chelation represents a plausable therapeutic strategy for PD.

  8. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  9. Nephrolithiasis-associated bone disease: pathogenesis and treatment options

    PubMed Central

    Sakhaee, Khashayar; Maalouf, Naim M.; Kumar, Rajiv; Pasch, Andreas; Moe, Orson W.

    2011-01-01

    Nephrolithiasis remains a formidable health problem in the United States and worldwide. A very important but underaddressed area in nephrolithiasis is the accompanying bone disease. Epidemiologic studies have shown that osteoporotic fractures occur more frequently in patients with nephrolithiasis than in the general population. Decreased bone mineral density and defects in bone remodeling are commonly encountered in patients with calcium nephrolithiasis. The pathophysiologic connection of bone defects to kidney stones is unknown. Hypercalciuria and hypocitraturia are two important risk factors for stone disease, and treatments with thiazide diuretics and alkali, respectively, have been shown to be useful in preventing stone recurrence in small prospective trials. However, no studies have examined the efficacy of these agents or other therapies in preventing continued bone loss in calcium stone formers. This manuscript reviews the epidemiology, pathophysiology, and potential treatments of bone disease in patients with nephrolithiasis. PMID:21124301

  10. A Metabolic Study of Huntington's Disease.

    PubMed

    Nambron, Rajasree; Silajdžić, Edina; Kalliolia, Eirini; Ottolenghi, Chris; Hindmarsh, Peter; Hill, Nathan R; Costelloe, Seán J; Martin, Nicholas G; Positano, Vincenzo; Watt, Hilary C; Frost, Chris; Björkqvist, Maria; Warner, Thomas T

    2016-01-01

    Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls. Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority

  11. Inflammatory mechanisms linking obesity and metabolic disease.

    PubMed

    Saltiel, Alan R; Olefsky, Jerrold M

    2017-01-03

    There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.

  12. [Secondary osteoporosis UPDATE. Bone metabolic change and osteoporosis during pregnancy and lactation].

    PubMed

    Kurabayashi, Takumi; Tamura, Ryo; Hata, Yuki; Nishijima, Shota; Tsuneki, Ikunosuke; Tamura, Masaki; Yanase, Toru

    2010-05-01

    Calcium transfer from the mother to the infant during pregnancy and lactation plays an extremely important role in the bone health of the mother and neonate. Calcium aids in bone health through all ages but is especially crucial during pregnancy and lactation. Changes in the structure and metabolism of bone during pregnancy and the early stage of postpartum are evaluated by investigating bone mineral density (BMD), bone histomorphometry and bone markers of human or animal models. The bone resorption increased at the end of pregnancy and lactation, and the bone formation increases and the bone structure is almost recovered after cessation of lactating in postpartum. Puerperal BMD remained static over the subsequent 5-10 years. If the women have a low BMD at this stage of their reproductive life, it tends not to improve over this time. Perhaps identification of this at-risk group may lead to effective interventions to reduce fracture risk in later life.

  13. Protecting Bone Health in Pediatric Rheumatic Diseases: Pharmacological Considerations.

    PubMed

    Zhang, Yujuan; Milojevic, Diana

    2017-06-01

    Bone health in children with rheumatic conditions may be compromised due to several factors related to the inflammatory disease state, delayed puberty, altered life style, including decreased physical activities, sun avoidance, suboptimal calcium and vitamin D intake, and medical treatments, mainly glucocorticoids and possibly some disease-modifying anti-rheumatic drugs. Low bone density or even fragility fractures could be asymptomatic; therefore, children with diseases of high inflammatory load, such as systemic onset juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, and those requiring chronic glucocorticoids may benefit from routine screening of bone health. Most commonly used assessment tools are laboratory testing including serum 25-OH-vitamin D measurement and bone mineral density measurement by a variety of methods, dual-energy X-ray absorptiometry as the most widely used. Early disease control, use of steroid-sparing medications such as disease-modifying anti-rheumatic drugs and biologics, supplemental vitamin D and calcium, and promotion of weight-bearing physical activities can help optimize bone health. Additional treatment options for osteoporosis such as bisphosphonates are still controversial in children with chronic rheumatic diseases, especially those with decreased bone density without fragility fractures. This article reviews common risk factors leading to compromised bone health in children with chronic rheumatic diseases and discusses the general approach to prevention and treatment of bone fragility.

  14. Outcomes of bone density measurements in coeliac disease.

    PubMed

    Bolland, Mark J; Grey, Andrew; Rowbotham, David S

    2016-01-29

    Some guidelines recommend that patients with newly diagnosed coeliac disease undergo bone density scanning. We assessed the bone density results in a cohort of patients with coeliac disease. We searched bone density reports over two 5-year periods in all patients from Auckland District Health Board (2008-12) and in patients under 65 years from Counties Manukau District Health Board (2009-13) for the term 'coeliac.' Reports for 137 adults listed coeliac disease as an indication for bone densitometry. The average age was 47 years, body mass index (BMI) 25 kg/m(2), and 77% were female. The median time between coeliac disease diagnosis and bone densitometry was 261 days. The average bone density Z-score was slightly lower than expected (Z-score -0.3 to 0.4) at the lumbar spine, total hip and femoral neck, but 88-93% of Z-scores at each site lay within the normal range. Low bone density was strongly related to BMI: the proportions with Z-score <-2 for BMI <20, 20-25, 25-30, and >30 kg/m(2) were 28%, 15%, 6% and 0% respectively. Average bone density was normal, suggesting that bone density measurement is not indicated routinely in coeliac disease, but could be considered on a case-by-case basis for individuals with strong risk factors for fracture.

  15. The complexity of bone architecture: A tool to differentiate bone diseases

    NASA Astrophysics Data System (ADS)

    Saparin, Peter I.; Gowin, Wolfgang; Kurths, Jürgen; Felsenberg, Dieter

    2000-02-01

    We introduce a generalization of symbolic dynamics to analyze two-dimensional objects and propose measures of complexity to quantify the structure of symbol encoded images. This technique is applied to evaluate the architecture of human cancellous bone by analyzing computed tomography images of vertebrae acquired from specimens and in vivo. The pixels of the preprocessed images are encoded using a mixture of static and dynamic encoding. The architecture of encoded cancellous bone is evaluated as a whole using measures of complexity. A set of new parameters are introduced to quantify the different aspects of structure: complexity and degree of disorder of the architecture as a whole, or spatial arrangements of hard or soft elements of the bone separately. It is found that the complexity of the bone structure relates to its density exponentially. Normal bone has a complex ordered structure, while the architecture during the initial stage of bone loss is characterized by lower complexity and a maximal level of disorder. Increased bone loss leads again to ordered structure, however, its complexity is minimal. This phenomenon was observed in a series of osteoporotic specimens as well as in vivo in patients treated with fluor, and hormone replacement therapy. We found that different bone diseases demonstrate distinctive features captured by the measurements of complexity of the bone's structural composition. It is shown that the application of the proposed technique leads to new insights for understanding of the bone's response on medical treatment and provide important additional information for the diagnostics of bone diseases.

  16. Bone marrow manifestations in multicentric Castleman disease.

    PubMed

    Ibrahim, Hazem A H; Balachandran, Kirsty; Bower, Mark; Naresh, Kikkeri N

    2016-03-01

    This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8-MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8-latency-associated nuclear antigen (LANA1), Epstein-Barr virus-encoded small RNA and light chains. Presence of significant numbers of HHV8-LANA1(+) lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8-LANA1 immunohistochemistry. © 2016 John Wiley & Sons Ltd.

  17. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions

    PubMed Central

    Rubin, Mishaela R; Patsch, Janina M

    2016-01-01

    Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk. PMID:27019762

  18. Bone scintigraphy in children with cat scratch disease.

    PubMed

    Donoso, Gilda; Paulsen, Cesar; Riquelme, Paulina; Lobo, Gabriel; Gutierrez, Daniela; Perez, Andrés; Jiménez, César

    2013-12-01

    The objective of this study was to evaluate the degree and incidence of bone involvement in patients with cat scratch disease. Patients admitted between 2004 and 2011 at the pediatric department for cat scratch disease and a positive serology for Bartonella henselae were identified. Only those having undergone a bone scintigraphy (BS) were included in this retrospective study. Sixteen girls and 8 boys with a mean age of 7 years were studied. Bone scintigraphy was positive in 6 (25%), but only 2 had bone pain. Axial involvement was present in all 6 patients, and appendicular lesions in 3 of them. Three patients had a BS control, with improvement or normalization after treatment with antibiotics. Bone involvement occurs infrequently in patients with cat scratch disease and is not always associated with specific signs. Cat scratch disease must be suspected in patients with fever of unknown origin presenting multifocal lesions on BS.

  19. Low bone mineral density in adult patients with coeliac disease.

    PubMed

    Szymczak, Jadwiga; Bohdanowicz-Pawlak, Anna; Waszczuk, Ewa; Jakubowska, Joanna

    2012-01-01

    Calcium and vitamin D malabsorption in coeliac disease (CD) predispose to skeletal demineralisation. The aim of this study was to evaluate the prevalence of bone mineral density (BMD) and calcium deficiencies in adult patients with CD and assess whether a gluten-free diet is sufficiently effective for BMD restoration. BMD and biochemical parameters of bone and mineral metabolism were measured in 35 adult CD patients receiving (19) or not receiving (16) a gluten-free diet (GFD) and in 36 controls. Then the CD patients were treated with a GFD and calcium (1.0 g/day) plus alfacalcidol (0.25-1 μg/day) for one year. Reduced BMD was diagnosed in 57-77% of the patients. Mean calcaemia, calciuria, and 25(OH) vitamin D were lower, but serum PTH and bone-turnover markers (ALP, osteocalcin, ICTP) were significantly higher in the CD patients than in the controls. In the patients on the diet (GFD(+)), BMD was higher than in the GFD(-) patients, but lower than in the controls. The biochemical parameters were normal in the GFD(+) patients except for diminished calciuria. Mean BMD after one year of treatment significantly increased (p < 0.05), mostly in the lumbar spine (mean: 7.3%), but decreased in five patients who did not strictly adhere to the GFD. Deficiencies in calcium, vitamin D, and BMD are very common in adult CD patients. Gluten avoidance increased BMD, although the values remained markedly lower in several patients. Because of chronic calcium deficiency despite GFD, calcium and vitamin D supplementation in most adult CD patients is proposed.

  20. Effects of herbal Epimedium on the improvement of bone metabolic disorder through the induction of osteogenic differentiation from bone marrow-derived mesenchymal stem cells

    PubMed Central

    Kim, Do Rim; Lee, Ji Eun; Shim, Kyung Jun; Cho, Jin Hyoung; Lee, Ho Chul; Park, Seong Kyu; Chang, Mun Seog

    2016-01-01

    Herbal Epimedium (HE) has been commonly used as a tonic, antirheumatic agent and in the treatment of bone-associated diseases including osteoporosis. Treatment for osteoporosis is important to increase bone mass density and maintain to balance of bone remodeling. The present study was performed to investigate the effects of HE on mouse bone marrow mesenchymal stem cell (mBMMSC) proliferation and osteogenic differentiation, using MTT assays, proliferating cell nuclear antigen (PCNA) detection and apoptosis and differentiation assays. HE was demonstrated to inhibit the proliferation of mBMMSCs up to 45.43±3.33% and to decrease the level of PCNA expression compared with untreated cells. HE also induced late apoptosis at 24 and 48 h after treatment up to 71.93 and 67.03%, respectively, while only 14.93% of untreated cells exhibited apoptosis. By contrast, HE induced differentiation of mBMMSCs into an osteogenic lineage at the beginning of three weeks after commencement of treatment. This suggested that HE is a candidate as an inducer of osteogenesis from bone marrow mesenchymal stem cells, and additionally has potential for use in the treatment of bone metabolic disorders such as osteoporosis. PMID:27959402

  1. Bone Metabolism in Cerebral Palsy and the Effect of Light-Emitting Diode (LED) Irradiation

    PubMed Central

    Yamamoto, Kengo; Ohshiro, Toshio; Ohshiro, Takafumi

    2012-01-01

    In recent years, through the availability of examination by bone metabolism markers, diagnosis and treatment for osteoporosis in elderly people has been greatly advanced. However, bone metabolism in cases of cerebral palsy has not been fully examined. Though children with cerebral palsy tend to be susceptible to insufficiency fractures, a method of treatment for insufficiency fractures has not been established. In the longitudinal progress of bone metabolism, although there was a difference depending on the severity, reduced bone resorption tended to be mild but osteo-genesis tended to decrease in the severe cases. Osteogenesis and bone resorption markers decreased at around ages 8 and 15. The bone resorption marker maintained mild advancement after age 15. With LED irradiation, all of IGF-1, ucOC, osteogenic marker; BAP, and urinary bone resorption marker; NTx/Cr showed a tendency to normalize. In particular, IGF-1, BAP, and NTx/Cr increased significantly one month after irradiation, compared to the non-irradiation group. Bone density assessed by the DIP method showed no apparent change in the short term either. Irradiation by a commercial LED light bulb indicated a possible positive effect on bone metabolism for children with severe cerebral palsy. PMID:24610978

  2. Bone Marrow Therapies for Chronic Heart Disease.

    PubMed

    Behbahan, Iman Saramipoor; Keating, Armand; Gale, Robert Peter

    2015-11-01

    Chronic heart failure is a leading cause of death. The demand for new therapies and the potential regenerative capacity of bone marrow-derived cells has led to numerous clinical trials. We critically discuss current knowledge of the biology and clinical application of bone marrow cells. It appears unlikely that bone marrow cells can develop into functional cardiomyocyte after infusion but may have favorable paracrine effects. Most, but not all, clinical trials report a modest short- but not long-term benefit of infusing bone marrow-derived cells. Effect size appears to correlate with stringency of study-design: the most stringent trials report the smallest effect-sizes. We conclude there may be short- but not substantial long-term benefit of infusing bone marrow-derived cells into persons with chronic heart failure and any benefit observed is unlikely to result from trans-differentiation of bone marrow-derived cells into functioning cardiomyocytes. © 2015 AlphaMed Press.

  3. Modeling Metabolism and Disease in Bioarcheology.

    PubMed

    Qualls, Clifford; Appenzeller, Otto

    2015-01-01

    We examine two important measures that can be made in bioarcheology on the remains of human and vertebrate animals. These remains consist of bone, teeth, or hair; each shows growth increments and each can be assayed for isotope ratios and other chemicals in equal intervals along the direction of growth. In each case, the central data is a time series of measurements. The first important measures are spectral estimates in spectral analyses and linear system analyses; we emphasize calculation of periodicities and growth rates as well as the comparison of power in bands. A low frequency band relates to the autonomic nervous system (ANS) control of metabolism and thus provides information about the life history of the individual of archeological interest. Turning to nonlinear system analysis, we discuss the calculation of SM Pinus' approximate entropy (ApEn) for short or moderate length time series. Like the concept that regular heart R-R interval data may indicate lack of health, low values of ApEn may indicate disrupted metabolism in individuals of archeological interest and even that a tipping point in deteriorating metabolism may have been reached just before death. This adds to the list of causes of death that can be determined from minimal data.

  4. Modeling Metabolism and Disease in Bioarcheology

    PubMed Central

    Qualls, Clifford; Appenzeller, Otto

    2015-01-01

    We examine two important measures that can be made in bioarcheology on the remains of human and vertebrate animals. These remains consist of bone, teeth, or hair; each shows growth increments and each can be assayed for isotope ratios and other chemicals in equal intervals along the direction of growth. In each case, the central data is a time series of measurements. The first important measures are spectral estimates in spectral analyses and linear system analyses; we emphasize calculation of periodicities and growth rates as well as the comparison of power in bands. A low frequency band relates to the autonomic nervous system (ANS) control of metabolism and thus provides information about the life history of the individual of archeological interest. Turning to nonlinear system analysis, we discuss the calculation of SM Pinus' approximate entropy (ApEn) for short or moderate length time series. Like the concept that regular heart R-R interval data may indicate lack of health, low values of ApEn may indicate disrupted metabolism in individuals of archeological interest and even that a tipping point in deteriorating metabolism may have been reached just before death. This adds to the list of causes of death that can be determined from minimal data. PMID:26347356

  5. The effect of sphingosine-1-phosphate on bone metabolism in humans depends on its plasma/bone marrow gradient.

    PubMed

    Kim, B-J; Shin, K-O; Kim, H; Ahn, S H; Lee, S H; Seo, C-H; Byun, S-E; Chang, J S; Koh, J-M; Lee, Y-M

    2016-03-01

    Although recent studies provide clinical evidence that sphingosine-1-phosphate (S1P) may primarily affect bone resorption in humans, rather than bone formation or the osteoclast-osteoblast coupling phenomenon, those studies could not determine which bone resorption mechanism is more important, i.e., chemorepulsion of osteoclast precursors via the blood to bone marrow S1P gradient or receptor activator of NF-κB ligand (RANKL) elevation in osteoblasts via local S1P. To investigate how S1P mainly contributes to increased bone resorption in humans, we performed this case-control study at a clinical unit in Korea. Blood and bone marrow samples were contemporaneously collected from 70 patients who underwent hip surgery due to either osteoporotic hip fracture (HF) (n = 10) or other causes such as osteoarthritis (n = 60). After adjusting for sex, age, BMI, smoking, alcohol, previous fracture, diabetes, and stroke, subjects with osteoporotic HF demonstrated a 3.2-fold higher plasma/bone marrow S1P ratio than those without HF, whereas plasma and bone marrow S1P levels were not significantly different between these groups. Consistently, the risk of osteoporotic HF increased 1.38-fold per increment in the plasma/bone marrow S1P ratio in a multivariate adjustment model. However, the odds ratios for prevalent HF according to the increment in the plasma and bone marrow S1P level were not statistically significant. Our current results using simultaneously collected blood and bone marrow samples suggest that the detrimental effects of S1P on bone metabolism in humans may depend on the S1P gradient between the peripheral blood and bone marrow cavity.

  6. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease.

    PubMed

    Panwar, Bhupesh; Gutiérrez, Orlando M

    2016-07-01

    Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD. In addition, emerging evidence has suggested that iron homeostasis interacts with bone and mineral metabolism on multiple levels, opening up new avenues of investigation into the genesis of disordered iron metabolism in CKD. Building on recent advances in our understanding of normal iron physiology and abnormalities in iron homeostasis in CKD, this review characterizes how anemia related to disordered iron metabolism develops in the setting of CKD. In addition, this review explores our emerging recognition of the connections between iron homeostasis and mineral metabolism and their implications for the management of altered iron status and anemia of CKD. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  8. [Lifestyle-related diseases and an inter-organ metabolic network].

    PubMed

    Miyachi, Yasutaka; Tsuchiya, Kyoichiro; Ogawa, Yoshihiro

    2016-03-01

    Lifestyle-related diseases such as type 2 diabetes, hypertension and dyslipidemia are a prominent cause of mortality in Japan, and there is a strong requirement for elucidation of detailed molecular mechanisms and effective therapeutic strategies. Obesity-induced adipose tissue inflammation leads to dysregulation of adipokine production, which can cause lifestyle-related diseases. The interaction of organ systems via endocrine or neural networks is recognized as an important factor in the pathogenesis and promotion of lifestyle-related diseases. Therefore, further investigation for the interaction between adipose tissues and bones can provide new treatment strategies of metabolic bone disorders.

  9. Invasive versus non-invasive diagnosis of renal bone disease.

    PubMed

    Fournier, A; Oprisiu, R; Said, S; Sechet, A; Ghazali, A; Marié, A; el Esper, I; Brazier, M; Achard, J M; Morinière, P

    1997-07-01

    At present, bone histomorphometry remains the gold standard for the diagnosis of the various types of renal bone disease. In the search for a non-invasive method of diagnosis, biochemical serum markers of bone remodelling, in addition to serum intact parathyroid hormone and aluminium determinations, have been proposed as the most reliable tools and are at present widely used in clinical practice. Their respective diagnostic values, as separate items and in combined analysis, are thoroughly discussed in the present review.

  10. Laser osteoperforation for treatment of inflammatory and destructive bone diseases

    NASA Astrophysics Data System (ADS)

    Privalov, V. A.; Krochek, I. V.; Abushkin, I. A.; Shumilin, I. I.; Lappa, A. V.

    2009-07-01

    The method of laser osteoperforation was developed in experiment and then applied for treatment of 508 patients with osteomyelitis, 51 patients with nonunion and pseudo-joint and 34 patients with different forms of osteochondropathy. The clinical trial proved the efficiency of laser osteoperforation for treatment of both inflammatory and destructive bone diseases. This method is minimally invasive, promotes rapid reduction of bone and soft tissue inflammation, and apparently stimulates bone reparation.

  11. Dried Plum’s Unique Capacity to Reverse Bone Loss and Alter Bone Metabolism in Postmenopausal Osteoporosis Model

    PubMed Central

    Rendina, Elizabeth; Hembree, Kelsey D.; Davis, McKale R.; Marlow, Denver; Clarke, Stephen L.; Halloran, Bernard P.; Lucas, Edralin A.; Smith, Brenda J.

    2013-01-01

    Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum’s unique effects on bone. PMID:23555991

  12. Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

    PubMed Central

    Iwasaki, Yoshiko; Kazama, Junichiro James

    2017-01-01

    Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone. PMID:28421193

  13. Mitochondria: mitochondrial RNA metabolism and human disease.

    PubMed

    Nicholls, Thomas J; Rorbach, Joanna; Minczuk, Michal

    2013-04-01

    Post-transcriptional control of RNA stability, processing, modification, and degradation is key to the regulation of gene expression in all living cells. In mitochondria, these post-transcriptional processes are also vital for proper expression of the thirteen proteins encoded by the mitochondrial genome, as well as mitochondrial tRNAs and rRNAs. Our knowledge on mitochondrial RNA (mt-RNA) metabolic pathways, however, is far from complete. All the proteins involved in mt-RNA metabolism are encoded by the nucleus, and must be imported into the organelle. Mutations in these nuclear genes can lead to perturbations in mitochondrial RNA processing, modification, stability and decay and thus are a cause of human mitochondrial disease. This review summarises the current knowledge on mt-RNA metabolism and its links with human mitochondrial pathologies.

  14. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease.

    PubMed

    Delitala, Alessandro P; Fanciulli, Giuseppe; Maioli, Margherita; Delitala, Giuseppe

    2017-03-01

    Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism.

  15. Heparanase inhibits osteoblastogenesis and shifts bone marrow progenitor cell fate in myeloma bone disease

    PubMed Central

    Ruan, Jian; Trotter, Timothy N.; Nan, Li; Luo, Rongcheng; Javed, Amjad; Sanderson, Ralph D.; Suva, Larry J.; Yang, Yang

    2013-01-01

    A major cause of morbidity in patients with multiple myeloma is the development and progression of bone disease. Myeloma bone disease is characterized by rampant osteolysis in the presence of absent or diminished bone formation. Heparanase, an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate chains, is upregulated in a variety of human cancers including multiple myeloma. We and others have shown that heparanase enhances osteoclastogenesis and bone loss. However, increased osteolysis is only one element of the spectrum of myeloma bone disease. In the present study, we hypothesized that heparanase would also affect mesenchymal cells in the bone microenvironment and investigated the effect of heparanase on the differentiation of osteoblast/stromal lineage cells. Using a combination of molecular, biochemical, cellular and in vivo approaches, we demonstrated that heparanase significantly inhibited osteoblast differentiation and mineralization, and reduced bone formation in vivo. In addition, heparanase also shifts the differentiation potential of osteoblast progenitors from osteoblastogenesis to adipogenesis. Mechanistically, this shift in cell fate is due, at least in part, to heparanase-enhanced production and secretion of the Wnt signaling pathway inhibitor DKK1 by both osteoblast progenitors and myeloma cells. Collectively, these data provide important new insights into the role of heparanase in all aspects of myeloma bone disease and strongly support the use of heparanase inhibitors in the treatment of multiple myeloma. PMID:23895995

  16. Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis.

    PubMed

    Zhang, Ying; Zheng, Yu-xin; Zhu, Jun-ming; Zhang, Jian-min; Zheng, Zhe

    2015-07-01

    The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference (SMD)=-0.30, 95% confidence interval (CI) [-0.61, -0.05]), trochanter (mean difference (MD)=-0.07, 95% CI [-0.10, -0.05]), femoral neck (MD=-0.05, 95% CI [-0.09, -0.02]), and total body bone mineral density (MD=-0.33, 95% CI [-0.51, -0.15]); (2) a reduction in 25-hydroxyvitamin D (MD=-3.37, 95% CI [-5.94, -0.80]) and an increase in serum alkaline phosphatase (SMD=0.71, 95% CI [0.38, 1.05]); (3) no significant changes in serum parathyroid hormone, calcium, or phosphorus. Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children.

  17. Radionuclide bone imaging and densitometry

    SciTech Connect

    Mettler, F.A.

    1988-01-01

    This book contains 13 selections. Some of the titles are: Radionuclides and the Normal Bone Scan; The Radionuclide Bone Scan in Malignant Disease; Pediatric Applications of Radionuclide Bone Imaging; The Radionuclide Bone Scan in Arthritis and Metabolic and Miscellaneous Disorders; and Soft Tissue Activity on the Radionuclide Bone Scan.

  18. 'Magic bullets' for bone diseases: progress in rational design of bone-seeking medicinal agents.

    PubMed

    Zhang, Sufeng; Gangal, Geeti; Uludağ, Hasan

    2007-03-01

    An ideal therapeutic agent for bone diseases should act solely on bone tissue with no pharmacological activity at other anatomical sites. Current therapeutic agents, however, do not usually display a preferential affinity to bones and non-specifically distribute throughout the body after administration. Attempts to design bone-specific agents have relied on engineering a desired therapeutic agent with bone-seeking molecules so that the latter delivers the therapeutic agents specifically to bones. In this critical review, we summarize the latest attempts to engineer bone-seeking therapeutic agents based on formulating therapeutic agents with bisphosphonates, a class of compounds with high affinity to biological apatite. We first provide a relevant summary of the structure of bone mineral and bisphosphonates, highlighting the mode of interaction between these two entities. The use of bisphosphonates in the diagnosis of bone diseases is then presented, since this application helps us to understand the bone-carrier properties of bisphosphonates under physiological conditions. A summary of recent attempts to formulate bisphosphonates with traditional therapeutic agents to restrict their activities to bone tissues is then provided, with special emphasis on the structure-function relationships of the engineered compounds. Finally, attempts to use bisphosphonates to deliver macromolecular therapeutics (i.e., proteins) are summarized, based on recent data from the authors' lab. The collective research into bone-seeking medicinal agents is progressively laying the foundation for next-generation 'magic bullets' that display desirable activities at the disease sites with no undesirable activity on other organ systems. (164 references.).

  19. Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog

    PubMed Central

    Burnell, James M.

    1971-01-01

    Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO3/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO3/Ca increased 3.1% and bone Na/Ca increased 3.0%. Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being “unaccounted for.” If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO3= are sufficiently large to account for the “unaccounted for” acid change without postulating changes in cellular metabolic acid production. PMID:5540172

  20. Improvement of adynamic bone disease after renal transplantation.

    PubMed

    Abdallah, K A; Jorgetti, V; Pereira, R C; Reis, L M dos; Pereira, L M; Corrêa, P H S; Borelli, A; Ianhez, L E; Moysés, R M A; David-Neto, E

    2006-01-01

    Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

  1. The current status of bone scintigraphy in malignant diseases.

    PubMed

    Dasgeb, Bahar; Mulligan, Michael H; Kim, Chun K

    2007-12-01

    For the past few decades, planar bone scintigraphy has been the most frequently performed imaging study in the evaluation of metastatic bone disease. Although scintigraphic findings alone are often nonspecific for skeletal pathologies, this technique reportedly has an exquisite sensitivity. However, recently accumulated data on the efficacy of positron emission tomography with fluorine-18 fluorodeoxyglucose and fluorine-18 sodium fluoride as well as magnetic resonance imaging for evaluating skeletal metastatic disease now indicate that conventional planar bone scintigraphy is not very sensitive in the detection of metastatic bone lesions in selected malignancies. Nevertheless, bone scintigraphy still remains the primary imaging modality for evaluation of metastatic bone disease owing mainly to its cost effectiveness and wide availability. In addition, recently introduced hybrid imaging systems combining single-photon emission computed tomography and spiral computed tomography, although not widely available yet, increase considerably both the sensitivity and specificity of bone scintigraphy. This article focuses primarily on the current role of bone scintigraphy and its strengths and weaknesses in assessing different types of malignant diseases relative to other imaging modalities in selected malignancies.

  2. Kynurenine pathway metabolism and neuroinflammatory disease

    PubMed Central

    Braidy, Nady; Grant, Ross

    2017-01-01

    Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response. Under physiological conditions, QUIN is metabolized to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), which represents an important metabolic cofactor and electron transporter. NAD+ also serves as a substrate for the DNA ‘nick sensor’ and putative nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP). Free radical initiated DNA damage, PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease. PMID:28250737

  3. Effects of raloxifene on lipid and bone metabolism in postmenopausal women with type 2 diabetes.

    PubMed

    Mori, Hiroko; Okada, Yosuke; Kishikawa, Hirofumi; Inokuchi, Nobuo; Sugimoto, Hidekatsu; Tanaka, Yoshiya

    2013-01-01

    Evidence suggests that bone quality is poorer and fracture risk is higher in patients with diabetes, even those with normal bone mineral density. The aim of this study was to determine the effects of raloxifene on lipid, bone, and glucose metabolism in postmenopausal women with type 2 diabetes. The study subjects (144 postmenopausal women aged less than 80 years with type 2 diabetes) were randomly assigned into three groups: no medication, alfacalcidol 1 μg/day, or raloxifene hydrochloride 60 mg/day. The primary endpoint was the change in LDL-C at 6 months. Raloxifene significantly decreased the levels of bone metabolism markers NTX and BAP at 6 months in patients with diabetes. The primary endpoint, LDL-C at 6 months, was significantly lower in the raloxifene group than in the other two groups. However, percent changes in HDL-C were not significantly different among the three groups. Although glucose metabolism was unaffected, homocysteine, a bone quality marker, was significantly decreased at 6 months in the raloxifene group. The percent improvement in LDL-C did not correlate with percent improvement in any bone metabolism or bone quality markers. Raloxifene, unlike estrogen, improved LDL-C and decreased homocysteine, indicating that raloxifene can potentially improve LDL-C as well as bone quality in postmenopausal women with type 2 diabetes.

  4. Effect of odanacatib on root resorption and alveolar bone metabolism during orthodontic tooth movement.

    PubMed

    Wei, X X; Chu, J P; Zou, Y Z; Ru, N; Cui, S X; Bai, Y X

    2015-12-22

    The aim of this study was to investigate the effect of local administration of odanacatib (ODN) on orthodontic root resorption and the status of alveolar bone metabolism in rat molars. All specimens were scanned using microcomputed tomography and then the raw images were reconstructed. The total volume of the root resorption craters of the 60 g-NS (normal saline) group was higher than in the 60 g-ODN group and the control group. In the 60 g-NS group, the bone volume fraction values of alveolar bone were significantly decreased compared with the other 2 groups. There were no significant differences in the bone volume fraction values of the tibiae among the 3 groups. The results of tartrate-resistant acid phosphatase-positive (TRAP+) numbers showed that there was no difference between the 60 g-NS group and the 60 g-ODN group. The expression of cathepsin K was decreased significantly in the 60 g-ODN group. These results indicate that ODN reduces orthodontics-induced external root resorption and increases alveolar bone metabolism. This may be because ODN inhibits the activity of odontoclasts, but maintains the quantity of odontoclasts and enhances bone formation. ODN promotes local alveolar bone metabolism, but does not affect systemic bone metabolism.

  5. Relationship between metabolic syndrome and its components with bone densitometry in postmenopausal women.

    PubMed

    Abbasi, Mahnaz; Farzam, Seyed Amir; Mamaghani, Zahra; Yazdi, Zohreh

    2016-12-15

    Prevention of osteoporosis and bone fracture and the relationship between metabolic syndrome and bone density are controversial issues. The aim of this study was to evaluate the association between metabolic syndrome and its components with bone mineral density in post menopausal women referred for bone mineral density (BMD) test. A total of 143 postmenopausal women with at least one year of menopause experience participated in this cross-sectional study. Demographic and anthropometric characteristics for all participants were collected. Also, biochemical parameters including fasting blood sugar, Cholesterol (HDL and LDL), triglyceride were measured. Association between the components of metabolic syndrome and bone densitometry were analyzed by statistical methods. In this study, 72% of participants did not have metabolic syndrome. Among them, 43.4% and 28.7% had osteoporosis and normal density, respectively. Of remaining participants with metabolic syndrome, 12.6% and 15.4% had osteoporosis and normal density, respectively. Among the metabolic syndrome components, waist circumference, HDL cholesterol, and waist to hip ratio were significantly associated with bone mass (P<0.05). Osteoporotic women had lower waist circumference and waist to hip ratio and higher HDL than women without osteoporosis. On the other hand, women with metabolic syndrome did not have significant differences than women without metabolic syndrome in terms of lumbar and femoral neck density (P>0.05). Results from this study showed that metabolic syndrome and its components did not induce bone mass loss. The discrepancies of the studies in this area call for more large scale studies in population so as to prevent women problems in this area. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  6. Progress in the clinical imaging research of bone diseases on ankle and foot sesamoid bones and accessory ossicles

    PubMed Central

    Li, Xiaozhong; Shi, Lenian; Liu, Taiyun; Wang, Lin

    2012-01-01

    Summary Sesamoid bones and accessory ossicles are research focuses of foot and ankle surgery. Pains of the foot and ankle are related to sesamoid bones and accessory ossicles. The specific anatomical and functional relationship of sesamoid bones and accessory ossicles can cause such bone diseases as the dislocation of sesamoid bones and accessory bones, infection, inflammation and necrosis of sesamoid bones, cartilage softening, tenosynovitis of sesamoid bones and the sesamoid bone syndrome. However, these bone diseases are often misdiagnosed or mistreated. In patients with trauma history, relevant diseases of sesamoid bones and accessory ossicles as above mentioned are highly probable to be misdiagnosed as avulsion fractures. In such cases, radiographic findings may provide a basis for clinical diagnosis. PMID:25343083

  7. Progress in the clinical imaging research of bone diseases on ankle and foot sesamoid bones and accessory ossicles.

    PubMed

    Li, Xiaozhong; Shi, Lenian; Liu, Taiyun; Wang, Lin

    2012-08-01

    Sesamoid bones and accessory ossicles are research focuses of foot and ankle surgery. Pains of the foot and ankle are related to sesamoid bones and accessory ossicles. The specific anatomical and functional relationship of sesamoid bones and accessory ossicles can cause such bone diseases as the dislocation of sesamoid bones and accessory bones, infection, inflammation and necrosis of sesamoid bones, cartilage softening, tenosynovitis of sesamoid bones and the sesamoid bone syndrome. However, these bone diseases are often misdiagnosed or mistreated. In patients with trauma history, relevant diseases of sesamoid bones and accessory ossicles as above mentioned are highly probable to be misdiagnosed as avulsion fractures. In such cases, radiographic findings may provide a basis for clinical diagnosis.

  8. One year B and D vitamins supplementation improves metabolic bone markers.

    PubMed

    Herrmann, Wolfgang; Kirsch, Susanne H; Kruse, Vera; Eckert, Rudolf; Gräber, Stefan; Geisel, Jürgen; Obeid, Rima

    2013-03-01

    Vitamin D and vitamin B deficiency are common in elderly subjects and are important risk factors for osteoporosis and age-related diseases. Supplementation with these vitamins is a promising preventative strategy. The objective of this study was to evaluate the effects of vitamins D3 and B supplementation on bone turnover and metabolism in elderly people. Healthy subjects (n=93; >54 years) were randomly assigned to receive either daily vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg), and calcium carbonate (456 mg) (group A) or only vitamin D3 plus calcium carbonate (group B) in a double blind trial. We measured at baseline and after 6 and 12 months of supplementation vitamins, metabolites, and bone turnover markers. At baseline mean plasma 25-hydroxy vitamin D [25(OH)D] was low (40 or 30 nmol/L) and parathormone was high (63.7 or 77.9 pg/mL). 25(OH)D and parathormone correlated inversely. S-Adenosyl homocysteine and S-adenosyl methionine correlated with bone alkaline phosphatase, sclerostin, and parathormone. One year vitamin D3 or D3 and B supplementation increased plasma 25(OH)D by median 87.6% (group A) and 133.3% (group B). Parathormone was lowered by median 28.3% (A) and 41.2% (B), bone alkaline phosphatase decreased by 2.8% (A) and 16.2% (B), osteocalin by 37.5% (A) and 49.4% (B), and tartrate-resistant-acid-phosphatase 5b by 6.1% (A) and 36.0% (B). Median total homocysteine (tHcy) was high at baseline (group A: 12.6, group B: 12.3 µmol/L) and decreased by B vitamins (group A) to 8.9 µmol/L (29.4%). tHcy lowering had no additional effect on bone turnover. One year vitamin D3 supplementation with or without B vitamins decreased the bone turnover significantly. Vitamin D3 lowered parathormone. The additional application of B vitamins did not further improve bone turnover. The marked tHcy lowering by B vitamins may modulate the osteoporotic risk.

  9. Combined intervention of dietary soybean proteins and swim training: effects on bone metabolism in ovariectomized rats.

    PubMed

    Figard, Hélène; Mougin, Fabienne; Gaume, Vincent; Berthelot, Alain

    2006-01-01

    Soybean proteins, a rich source of isoflavones, taken immediately after an ovariectomy prevent bone loss in rats. Exercise-induced stimuli are essential for bone growth. Few studies exist about the combined effects of swim training and soybean protein supplementation on bone metabolism. So, the purpose of this study was to investigate, in 48 female Sprague-Dawley rats (12 weeks old) the effects of an 8-week swim-training regimen (1 h/day, 5 days/week) and dietary soybean proteins (200 g/kg diet) on bone metabolism. Rats were randomly assigned to four groups: (1) ovariectomized fed with a semisynthetic control diet; (2) ovariectomized fed with a soybean protein-enriched semisynthetic diet; (3) ovariectomized trained to exercise and fed with control diet; (4) ovariectomized trained to exercise and fed with a soybean protein diet. Following the treatment period, body weight gain was identical in the four groups. Soybean protein supplementation increased bone calcium content, and reduced plasma osteocalcin values, without significant modification of calcium balance and net calcium absorption. Swim training enhanced plasma and bone calcium content and calcium balance and net calcium absorption. It did not modify either plasma osteocalcin values or urinary deoxypyridinoline excretion. Both exercise and soybean protein intake increased plasma on bone calcium without modifying net calcium absorption or bone markers. In conclusion, we demonstrated, in ovariectomized rats, that swimming exercise and dietary supplementation with soy proteins do not have synergistic effects on calcium metabolism and bone markers.

  10. Alterations of lipid metabolism in Wilson disease

    PubMed Central

    2011-01-01

    Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date. Patients and Methods This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination). Results A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides. Conclusion Contradictory to previous reports using WD animal models (Atp7b-/- and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment. PMID:21595966

  11. The Intestinal Microbiota in Metabolic Disease

    PubMed Central

    Woting, Anni; Blaut, Michael

    2016-01-01

    Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet–host–microbe interactions. PMID:27058556

  12. Metabolic syndrome and chronic kidney disease.

    PubMed

    Bhowmik, D; Tiwari, S C

    2008-01-01

    Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.

  13. Endocrine manifestations related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

  14. Glutathione Metabolism and Parkinson’s Disease

    PubMed Central

    Smeyne, Michelle

    2013-01-01

    It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson’s disease. PMID:23665395

  15. Homocysteine as a Pathological Biomarker for Bone Disease.

    PubMed

    Behera, Jyotirmaya; Bala, Jyoti; Nuru, Mohammed; Tyagi, Suresh C; Tyagi, Neetu

    2016-11-18

    In the last few decades, perturbation in methyl-group and homocysteine (Hcy) balance have emerged as independent risk factors in a number of pathological conditions including neurodegenerative disease, cardiovascular dysfunction, cancer development, autoimmune disease and kidney disease. Recent studies report Hcy to be a newly recognized risk factor for osteoporosis. Elevated Hcy levels are known to modulate osteoclastgenesis by causing detrimental effects on bone via oxidative stress induced metalloproteinase-mediated extracellular matrix degradation and decrease in bone blood flow. Evidence from previous studies also suggests that the decreased chondrocytes mediated bone mineralization in chick limb-bud mesenchymal cells and during the gestational period of ossification in rat model. However, Hcy imbalance and its role in bone loss, regression in vascular invasion, and osteoporosis, are not clearly understood. More investigations are required to explore the complex interplay between Hcy imbalance and onset of bone disease progression. This article reviews the current body of knowledge on regulation of Hcy mediated oxidative stress and its role in bone remodeling, vascular blood flow and progression of bone disease. This article is protected by copyright. All rights reserved.

  16. Disorders in bone metabolism of female rats chronically exposed to cadmium.

    PubMed

    Brzóska, Małgorzata M; Moniuszko-Jakoniuk, Janina

    2005-01-01

    The effect of cadmium (Cd) on bone metabolism during skeletal development and maturity was investigated on a rat model of human exposure. Young female Wistar rats were exposed to 1, 5, or 50 mg Cd/l in drinking water for 3, 6, 9, and 12 months. Total bone mineral density (T-BMD), bone mineral content (BMC), density (BMD), and bone area at the femur and lumbar spine (L1-L5) were measured densitometrically. Alkaline phosphatase (ALP) and osteocalcin (OC) as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in bone (trabecular and cortical) or serum as bone resorption markers were measured. Renal calcium (Ca) handling and Cd body burden were evaluated as well. At the stage of intensive skeletal development (the first 6 months of the experiment), at all exposure levels, Cd inhibited the processes of bone formation and as a result disturbed the accumulation of bone mass leading to osteopenia (- 1 > Z score/T score BMD > -2.5) and at 5 and 50 mg Cd/l even to more advanced disorders in the BMD. Continuation of the exposure up to skeletal maturity led to high bone turnover with increased resorption enhancing the prevalence of osteopenia or the BMD values having the Z score/T score < -2.5. The results allow for the conclusion that chronic, even low-level exposure to Cd disturbs bone metabolism during skeletal development and maturity by affecting bone turnover most probably through a direct influence on bone formation and resorption, and indirectly via disorders in Ca metabolism. Our findings confirm the hypothesis that environmental exposure to Cd may be a risk factor for low BMD.

  17. Evaluation of bone metabolism in newborn twins using quantitative ultrasound and biochemical parameters.

    PubMed

    Kara, Semra; Güzoğlu, Nilüfer; Göçer, Emine; Arıkan, Fatma Inci; Dilmen, Uğur; Dallar Bilge, Yıldız

    2016-03-01

    Metabolic bone disease (MBD) is one of the important complications of prematurity. Early and adequate nutritional interventions may reduce the incidence and potential complications of MBD. The present study aimed to evaluate bone metabolism in twins via biochemical parameters and quantitative ultrasound (QUS) and to compare the results between twin pairs. Moreover, twin infants were evaluated in terms of potential risk factors likely to have impact on MBD. Forty-three pairs of twins were included in the study. Serum calcium, phosphorus, magnesium, and alkaline phosphatase concentrations were assessed and bone mineral density was measured using QUS (speed of sound, SOS) at postnatal 30 d. Co-twin with the higher birth weight was assigned to Group 1 (n = 36) and the other twin was assigned to Group 2 (n = 36). Birth weight and head circumference were significantly higher in the infants of Group 1 compared with Group 2. No significant difference was found among the groups in terms of gender, history of resuscitation, length of stay in intensive care unit (ICU) or in the incubator, duration of total parenteral nutrition (TPN), type of nutrition, vitamin D use, biochemical parameters, and the SOS value. The factors likely to affect SOS, including type of pregnancy, maternal drug use, gender of infant, birth weight, head circumference at birth, gestational week, length of stay at the ICU, duration of TPN, type of nutrition, resuscitation, vitamin D use, and levels of calcium, phosphorus, magnesium, and alkaline phosphatase were entered into the model. The phosphorus level and the maternal drug use were found to be the factors that significantly reduced SOS, whereas pregnancy after assisted reproductive techniques was found to be a significant enhancing factor.

  18. Novel therapies in benign and malignant bone diseases.

    PubMed

    Rachner, Tilman D; Hadji, Peyman; Hofbauer, Lorenz C

    2012-06-01

    With an ageing population and improving cancer therapies, the two most common benign and malignant bone diseases, osteoporosis and bone metastases, will continue to affect an increasing number of patients. Our expanding knowledge of the molecular processes underlying these conditions has resulted in novel bone targets that are currently being explored in clinical trials. Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years. Potential agents targeting the osteoclast include cathepsin K, currently in phase 3 trials, and src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide a comprehensive overview of the most promising agents currently explored for the treatment of bone diseases.

  19. Effects of liver-derived insulin-like growth factor I on bone metabolism in mice.

    PubMed

    Sjögren, Klara; Sheng, Matilda; Movérare, Sofia; Liu, Jun-Li; Wallenius, Kristina; Törnell, Jan; Isaksson, Olle; Jansson, John-Olov; Mohan, Subburaman; Ohlsson, Claes

    2002-11-01

    Insulin-like growth factor (IGF) I is an important regulator of both skeletal growth and adult bone metabolism. To better understand the relative importance of systemic IGF-I versus locally expressed IGF-I we have developed a transgenic mouse model with inducible specific IGF-I gene inactivation in the liver (LI-IGF-I-/-). These mice are growing normally up to 12 weeks of age but have a disturbed carbohydrate and lipid metabolism. In this study, the long-term effects of liver-specific IGF-I inactivation on skeletal growth and adult bone metabolism were investigated. The adult (week 8-55) axial skeletal growth was decreased by 24% in the LI-IGF-I-/- mice whereas no major reduction of the adult appendicular skeletal growth was seen. The cortical cross-sectional bone area, as measured in the middiaphyseal region of the long bones, was decreased in old LI-IGF-I-/- mice. This reduction in the amount of cortical bone was caused mainly by decreased periosteal circumference and was associated with a weaker bone determined by a decrease in ultimate load. In contrast, the amount of trabecular bone was not decreased in the LI-IGF-I-/- mice. DNA microarray analysis of 30-week-old LI-IGF-I-/- and control mice indicated that only four genes were regulated in bone whereas approximately 40 genes were regulated in the liver, supporting the hypothesis that liver-derived IGF-I is of minor importance for adult bone metabolism. In summary, liver-derived IGF-I exerts a small but significant effect on cortical periosteal bone growth and on adult axial skeletal growth while it is not required for the maintenance of the trabecular bone in adult mice.

  20. Nuclear chromatin-concentrated osteoblasts in renal bone diseases.

    PubMed

    Kazama, Junichiro James; Yamamoto, Suguru; Narita, Ichiei; Kurihara, Satoshi

    2011-06-01

    The morphological appearance of an osteoblast largely alters with its differentiation and maturation, along with the change of cell function. We quantitatively observed the osteoblast morphology and compared it with bone metabolism. Biopsied iliac bone samples obtained from 77 dialysis patients (14 mild change, 37 osteitis fibrosa, 2 osteomalacia, 8 mixed, and 16 adynamic bone) were included in the study. Osteoblast appearances were classified into three groups: (i) type II and III osteoblasts, namely, active osteoblasts characterized by cuboidal or columnar shapes with or without a nuclear clear zone; (ii) type IV osteoblasts, lining osteoblasts characterized by extremely thin cytoplasm; and (iii) type V osteoblasts, apoptotic osteoblasts characterized by nuclear chromatin concentration. The results were quantitatively expressed as the length of bone surface covered by each type of osteoblasts. The type II and III osteoblasts were predominant in osteitis fibrosa, mixed, and mild change. The type IV osteoblasts were overwhelmingly predominant in adynamic bone. The type V osteoblasts appeared most frequently in osteitis fibrosa, followed by mixed and mild change. Both absolute and relative lengths of bone surface covered by the type V osteoblasts were significantly higher in the high-turnover bone group (osteitis fibrosa and mixed) than the low-turnover bone group (adynamic bone and osteomalacia). The type V osteoblasts were slightly correlated with serum intact parathyroid hormone levels. In conclusion, a high bone-turnover condition seems to be associated with the promotion of osteoblastic apoptosis in dialysis patients. This finding may explain the fact that osteopenia develops faster in CKD patients with high turnover of bone.

  1. Iron metabolism: from health to disease.

    PubMed

    Oliveira, Fernando; Rocha, Sara; Fernandes, Rúben

    2014-05-01

    Iron is vital for almost all living organisms by participating in a wide range of metabolic processes. However, iron concentration in body tissues must be tightly regulated since excessive iron may lead to microbial infections or cause tissue damage. Disorders of iron metabolism are among the most common human diseases and cover several conditions with varied clinical manifestations. An extensive literature review on the basic aspects of iron metabolism was performed, and the most recent findings on this field were highlighted as well. New insights on iron metabolism have shed light into its real complexity, and its role in both healthy and pathological states has been recognized. Important discoveries about the iron regulatory machine and imbalances in its regulation have been made, which may lead in a near future to the development of new therapeutic strategies against iron disorders. Besides, the toxicity of free iron and its association with several pathologies has been addressed, although it requires further investigations. This review will provide students in the fields of biochemistry and health sciences a brief and clear overview of iron physiology and toxicity, as well as imbalances in the iron homeostasis and associated pathological conditions. © 2014 Wiley Periodicals, Inc.

  2. A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease.

    PubMed

    Coleman, Robert; Aksnes, Anne-Kirsti; Naume, Bjørn; Garcia, Camilo; Jerusalem, Guy; Piccart, Martine; Vobecky, Nancy; Thuresson, Marcus; Flamen, Patrick

    2014-06-01

    Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124); median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease.

  3. Patients with patellofemoral pain exhibit elevated bone metabolic activity at the patellofemoral joint

    PubMed Central

    Draper, Christine E.; Fredericson, Michael; Gold, Garry E.; Besier, Thor F.; Delp, Scott L.; Beaupre, Gary S.; Quon, Andrew

    2011-01-01

    Summary Patellofemoral pain is characterized by pain behind the kneecap and is often thought to be due to high stress at the patellofemoral joint. While we cannot measure bone stress in vivo, we can visualize bone metabolic activity using 18F NaF PET/CT, which may be related to bone stress. Our goals were to use 18F NaF PET/CT to evaluate whether subjects with patellofemoral pan exhibit elevated bone metabolic activity and to determine whether bone metabolic activity correlates with pain intensity. We examined 20 subjects diagnosed with patellofemoral pain. All subjects received an 18F NaF PET/CT scan of their knees. Uptake of 18F NaF in the patella and trochlea was quantified by computing the standardized uptake value and normalizing by the background tracer uptake in bone. We detected increased tracer uptake in 85% of the painful knees examined. We found that the painful knees exhibited increased tracer uptake compared to the pain-free knees of four subjects with unilateral pain (p=0.0006). We also found a correlation between increasing tracer uptake and increasing pain intensity (r2 = 0.55; p = 0.0005). The implication of these results is that patellofemoral pain may be related to bone metabolic activity at the patellofemoral joint. PMID:21812024

  4. Effects of dietary bread crust Maillard reaction products on calcium and bone metabolism in rats.

    PubMed

    Roncero-Ramos, Irene; Delgado-Andrade, Cristina; Haro, Ana; Ruiz-Roca, Beatriz; Morales, Francisco J; Navarro, María Pilar

    2013-06-01

    Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism.

  5. Effects of a prolonged submersion on bone strength and metabolism in young healthy submariners.

    PubMed

    Luria, Tal; Matsliah, Yinnon; Adir, Yochai; Josephy, Noam; Moran, Daniel S; Evans, Rachel K; Abramovich, Amir; Eliakim, Alon; Nemet, Dan

    2010-01-01

    Submariners taking part in prolonged missions are exposed to environmental factors that may adversely affect bone health. Among these, relatively high levels of CO(2), lack of sunlight exposure affecting vitamin D metabolism, limited physical activity, and altered dietary habits. The aims of this study were to examine the effect of a prolonged submersion (30 days) on changes in bone strength using quantitative bone speed of sound and in markers of bone metabolism that include bone turnover (BAP, PINP, TRAP5b, and CTx) and endocrine regulators (serum calcium, PTH, and 25[OH]D) in a group of 32 young healthy male submariners. The prolonged submersion led to increases in body weight and BMI and to a decrease in fitness level. There was a significant decrease in bone strength following the submersion. Speed of sound exhibited continued decline at 4 weeks after return to shore and returned to baseline levels at the 6-month follow-up. There was a significant increase in circulating calcium level. PTH and 25(OH)D levels decreased significantly. Significant decreases were observed in both TRAP5b and CTx levels, markers of bone resorption, as well as in N-terminal propeptide of type I collagen (PINP), a bone formation marker. Prolonged submersion led to a significant decrease in bone strength, accompanied by an overall decrease in bone metabolism. Bone strength was regained only 6 months after return to shore. Prevention and/or rehabilitation programs should be developed following periods of relative disuse even for young submariners. The effects of repeated prolonged submersions on bone health are yet to be determined.

  6. Determinants of quality of life in Paget's disease of bone.

    PubMed

    Castro, Gláucio Ricardo Werner de; Castro, Silvania Ana Fernandes de; Pereira, Ivanio Alves; Zimmermann, Adriana Fontes; Toscano, Maria Amazile; Neves, Fabricio Souza; Scottini, Maria Aparecida; Paupitz, Juliane; Rosa, Julia Salvan da; Buss, Ziliani; Fröde, Tânia Silvia

    2017-09-26

    To evaluate the parameters associated with quality of life in patients with Paget's disease of bone. Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment. Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status. The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status. The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.

  7. Metabolic Syndrome: Nonalcoholic Fatty Liver Disease.

    PubMed

    Williams, Tracy

    2015-08-01

    Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  8. Novel microinjector for carrying bone substitutes for bone regeneration in periodontal diseases.

    PubMed

    Tsai, Hsiao-Cheng; Li, Yi-Chen; Young, Tai-Horng; Chen, Min-Huey

    2016-01-01

    Traditionally, guide bone regeneration (GBR) was a widely used method for repairing bone lost from periodontal disease. There were some disadvantages associated with the GBR method, such as the need for a stable barrier membrane and a new creative cavity during the surgical process. To address these disadvantages, the purpose of this study was to evaluate a novel microinjector developed for dental applications. The microinjector was designed to carry bone graft substitutes to restore bone defects for bone regeneration in periodontal diseases. The device would be used to replace the GBR method. In this study, the injected force and ejected volume of substitutes (including air, water, and ethanol) were defined by Hooke's law (n = 3). The optimal particle size of bone graft substitutes was determined by measuring the recycle ratio of bone graft substitutes from the microinjector (n = 3). Furthermore, a novel agarose gel model was used to evaluate the feasibility of the microinjector. The current study found that the injected force was less than 0.4 N for obtaining the ejected volume of approximately 2 mL, and when the particle size of tricalcium phosphate (TCP) was smaller than 0.5 mm, 80% TCP could be ejected from the microinjector. Furthermore, by using an agarose model to simulate the periodontal soft tissue, it was also found that bone graft substitutes could be easily injected into the gel. The results confirmed the feasibility of this novel microinjector for dental applications to carry bone graft substitutes for the restoration of bone defects of periodontal disease. Copyright © 2015. Published by Elsevier B.V.

  9. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

    PubMed Central

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. PMID:23836972

  10. [Evidences of physical agents action on bone metabolism and their potential clinical use].

    PubMed

    Lirani, Ana Paula R; Lazaretti-Castro, Marise

    2005-12-01

    The action of physical agents such as low level laser therapy, low-intensity pulsed ultrasound and electrical and electromagnetic fields on bone have been often studied, showing that they are able to promote osteogenesis, accelerate fracture consolidation and augment bone mass. The use of these therapeutic modalities was first based on the finding that bone is a piezoelectric material, that means it can generate polarization when deformed, transforming mechanical energy into electric energy, and this has widen therapeutic possibilities to bony tissue. The present work aims to present evidences of physiologic effects and mechanisms of action of these physical agents on bone metabolism, based on articles published in international scientific literature.

  11. Phosphatidylethanolamine Metabolism in Health and Disease

    PubMed Central

    Calzada, Elizabeth; Onguka, Ouma; Claypool, Steven M.

    2016-01-01

    Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid in eukaryotic cells. The existence of four only partially redundant biochemical pathways that produce PE, highlights the importance of this essential phospholipid. The CDP-ethanolamine and phosphatidylserine decarboxylase pathways occur in different subcellular compartments and are the main sources of PE in cells. Mammalian development fails upon ablation of either pathway. Once made, PE has diverse cellular functions that include serving as a precursor for phosphatidylcholine and a substrate for important posttranslational modifications, influencing membrane topology, and promoting cell and organelle membrane fusion, oxidative phosphorylation, mitochondrial biogenesis, and autophagy. The importance of PE metabolism in mammalian health has recently emerged following its association with Alzheimer's disease, Parkinson's disease, nonalcoholic liver disease, and the virulence of certain pathogenic organisms. PMID:26811286

  12. Polyamine metabolism in Menkes kinky hair disease.

    PubMed

    Rennert, O M; Chan, W Y; Hidalgo, H; Cushing, W; Griesmann, G

    1980-05-09

    Clinical investigations of the urinary excretion of putrescine and the polyamines spermidine and spermine in a patient with Menkes kinky hair disease are reported. This disorder, characterized by intra- and extracellular copper deficiency, is associated with significant depression of diamine oxidase and monoamine oxidase activity. Urinary excretion of diamine and polyamines, monitored over a 2-month interval in a 4-month old patient with Menkes kinky hair disease, documented a 3- to 10-fold increase in the excretion of free putrescine, spermidine and spermine as well as the conjugated derivatives of putrescine and spermidine. These observations suggest that abnormalities in diamine and polyamine concentration occur in disease states in which the metabolic transformation of these compounds is impaired.

  13. Zoledronic acid in the management of metastatic bone disease.

    PubMed

    Santini, Daniele; Fratto, Maria Elisabetta; Vincenzi, Bruno; Galluzzo, Sara; Tonini, Giuseppe

    2006-12-01

    Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. Moreover, in vivo preclinical and preliminary clinical data suggest that bisphosphonates may prevent cancer treatment-induced bone loss and the onset of malignant bone disease in patients with early-stage cancer. This comprehensive review critically reports the several preclinical evidences of action of bisphosphonates on osteoclasts, lymphocytes and tumour cells. In addition, all the clinical trials evaluating the effects of principal bisphosphonates on skeletal disease progression in patients with breast cancer, prostate cancer, non-small cell lung cancer and other cancers have been reported. Of the available bisphosphonates, intravenous zoledronic acid has demonstrated the broadest clinical activity and is actually approved for the treatment of bone metastases from any solid tumour in many countries. Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. This issue and the other topics relating to the safety of bisphosphonates are discussed in this review.

  14. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lip