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.

[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.

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.

[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.

Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet.

PubMed

Barera, Graziano; Beccio, Sabrina; Proverbio, Maria Carla; Mora, Stefano

2004-01-01

A gluten-free diet (GFD) rapidly corrects the bone mineral deficit of children with untreated celiac disease. The mechanisms underlying such changes are still poorly understood. In a longitudinal study, we monitored changes in bone metabolism during consumption of a GFD. We studied 22 white patients with celiac disease (11 girls) aged 10.5 +/- 1.0 y at the time of diagnosis. We compared bone metabolism and bone mass values in these patients with those in 428 healthy white children aged 11.3 +/- 0.2 y. Bone-specific alkaline phosphatase (a bone formation index) and N-terminal telopeptide of type I collagen (NTx; a bone resorption marker) were measured at the time of diagnosis and after 2, 6, and 12 mo of the GFD. Bone mineral content was measured at the lumbar spine and for the whole skeleton. The bone mineral content of patients was significantly lower than that of control subjects at the time of diagnosis but not after 1 y of the GFD. Serum bone-specific alkaline phosphatase concentrations of patients were significantly lower than those of control subjects at the time of diagnosis (P = 0.0064) and increased gradually and significantly during the GFD (ANOVA F = 4.71; P = 0.024). Conversely, patients with untreated disease had significantly higher urinary concentrations of NTx than did healthy control subjects (P < 0.0001). Urinary concentrations of NTx were not significantly affected by treatment (P = 0.37). The rate of bone metabolism is altered in children with untreated celiac disease, and these alterations may be the cause of osteopathy. Remarkable changes occur after the initiation of a GFD, and they result in a more balanced equilibrium.

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

The role of leptin in regulating bone metabolism.

PubMed

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 the 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. Copyright © 2015. Published by Elsevier Inc.

Bone metabolism and arterial stiffness after renal transplantation.

PubMed

Cseprekál, Orsolya; Kis, Eva; Dégi, Arianna A; Kerti, Andrea; Szabó, Attila J; Reusz, György S

2014-01-01

To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial. Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx). Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r = -0.35; r = -0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of <24 months, PWV was correlated with BALP and beta-crosslaps (r=0.53; r = 0.69 respectively) while in the ≥24 months group, PWV was correlated with cholesterol (r=0.38). Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation.

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.

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 ...

The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.

PubMed

Cavalier, E; Bergmann, P; Bruyère, O; Delanaye, P; Durnez, A; Devogelaer, J-P; Ferrari, S L; Gielen, E; Goemaere, S; Kaufman, J-M; Toukap, A Nzeusseu; Reginster, J-Y; Rousseau, A-F; Rozenberg, S; Scheen, A J; Body, J-J

2016-07-01

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

Automated HPLC assay for urinary collagen cross-links: effect of age, menopause, and metabolic bone diseases.

PubMed

Kraenzlin, Marius E; Kraenzlin, Claude A; Meier, Christian; Giunta, Cecilia; Steinmann, Beat

2008-09-01

The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20-49 years. In men, cross-link values peaked at 20-29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%-60% at age 11-14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.

Calcium and Bone Metabolism Indices.

PubMed

Song, Lu

2017-01-01

Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) control calcium homeostasis, whereas PTH, 1,25(OH) 2 D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic

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.

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

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

PubMed

Langlois, M R; Delanghe, J R; Kaufman, J M; De Buyzere, M L; Van Hoecke, M J; Leroux-Roels, G G

1994-09-01

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

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

Uremic toxin and bone metabolism.

PubMed

Iwasaki, Yoshiko; Yamato, Hideyuki; Nii-Kono, Tomoko; Fujieda, Ayako; Uchida, Motoyuki; Hosokawa, Atsuko; Motojima, Masaru; Fukagawa, Masafumi

2006-01-01

Patients with end-stage renal disease (ESRD) develop various kinds of abnormalities in bone and mineral metabolism, widely known as renal osteodystrophy (ROD). Although the pathogenesis of ESRD may be similar in many patients, the response of the bone varies widely, ranging from high to low turnover. ROD is classified into several types, depending on the status of bone turnover, by histomorphometric analysis using bone biopsy samples [1,2]. In the mild type, bone metabolism is closest to that of persons with normal renal function. In osteitis fibrosa, bone turnover is abnormally activated. This is a condition of high-turnover bone. A portion of the calcified bone loses its lamellar structure and appears as woven bone. In the cortical bone also, bone resorption by osteoclasts is active, and a general picture of bone marrow tissue infiltration and the formation of cancellous bone can be observed. In osteomalacia, the bone surface is covered with uncalcified osteoid. This condition is induced by aluminum accumulation or vitamin D deficiency. The mixed type possesses characteristics of both osteitis fibrosa and osteomalacia. The bone turnover is so markedly accelerated that calcification of the osteoid cannot keep pace. In the adynamic bone type, bone resorption and bone formation are both lowered. While bone turnover is decreased, there is little osteoid. The existence of these various types probably accounts for the diversity in degree of renal impairment, serum parathyroid hormone (PTH) level, and serum vitamin D level in patients with ROD. However, all patients share a common factor, i.e., the presence of a uremic condition.

Bone mineral density and metabolic indices in hyperthyroidism.

PubMed

Al-Nuaim, A; El-Desouki, M; Sulimani, R; Mohammadiah, M

1991-09-01

Hyperthyroidism can alter bone metabolism by increasing both bone resorption and formation. The increase in bone resorption predominates, leading to a decrease in bone mass. To assess the effect of hyperthyroidism on bone and mineral metabolism, we measured bone density using single photon absorptiometry in 30 untreated hyperthyroid patients. Patients were categorized into three groups based on sex and alkaline phosphatase levels: 44 sex- and age-matched subjects were used as controls. Bone densities were significanlty lower in all patient groups compared with controls. Alkaline phosphatase was found to be a useful marker for assessing severity of bone disease in hyperthyroid patients as there is significant bone density among patients with higher alkaline phosphatase value. Hyperthyroidism should be considered in the differential diagnosis of unexplained alkaline phophatase activity.

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. Copyright 2010 Elsevier Inc. All rights reserved.

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.

Bone and vitamin D metabolism in HIV.

PubMed

Panayiotopoulos, Aristotle; Bhat, Nandini; Bhangoo, Amrit

2013-06-01

Human immunodeficiency virus (HIV) infection has progressed to a chronic disease and HIV positive individuals are living longer lives. This has lead to an increase in morbidity and mortality due to secondary issues, one being HIV bone disease. HIV infected pediatric and adult populations have a greater incidence in reduction of BMD as compared to the controls. Osteoporosis has been reported to be present in up to 15 % of HIV positive patients. We are starting to understand the mechanism behind the changes in HIV bone disease. Viral proteins interfere with osteoblastic activity either by direct interaction or by the inflammatory process that they induce. Anti-viral management, including highly active antiretroviral therapy (HAART), protease inhibitors, and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) also are involved in disrupting proper bone metabolism. Vitamin D levels have strong correlation with bone disease in HIV patients, and are dependent not only to chronic disease state, but interaction of pharmacologic management and inflammatory process as well. Work up of the secondary causes of osteopenia and osteoporosis should be undertaken in all patients. DEXA scan is recommended in all post-menopausal women with HIV, all HIV infected men 50 years of age or older and in those with a history of fragility fractures regardless of age or gender. Preventive measures include adequate nutrition, calcium and Vitamin D intake daily, muscle strengthening and balance exercises to increase BMD and reduce fractures. Bisphosphonates are considered to be the first line for the treatment of HIV associated bone disease. This review will describe how the balanced mechanism of bone metabolism is interrupted by the HIV infection itself, the complications that arise from HIV/AIDS, and its treatment options.

Regulation of Bone Metabolism by Serotonin.

PubMed

Lavoie, Brigitte; Lian, Jane B; Mawe, Gary M

2017-01-01

The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.

[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.

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.

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.

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.

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.

Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

PubMed Central

Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

2015-01-01

Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

Bone: from a reservoir of minerals to a regulator of energy metabolism

PubMed Central

Confavreux, Cyrille B

2011-01-01

Besides locomotion, organ protection, and calcium–phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease. PMID:21346725

Genetics of Paget's disease of bone

PubMed Central

Albagha, Omar ME

2015-01-01

Paget's disease of bone (PDB) is a common metabolic bone disease characterised by focal areas of increased bone turnover, which primarily affects people over the age of 55 years. Genetic factors have a fundamental role in the pathogenesis of PDB and are probably the main predisposing factor for the disease. The genetic contribution to PDB susceptibility ranges from rare pathogenic mutations in the single gene SQSTM1 to more common, small effect variants in at least seven genetic loci that predispose to the disease. These loci have additive effects on disease susceptibility and interact with SQSTM1 mutations to affect disease severity, making them a potentially useful tool in predicting disease risk and complication and in managing treatments. Many of these loci harbour genes that have important function in osteoclast differentiation such as CSF1, DCSTAMP and TNFRSF11A. Other susceptibility loci have highlighted new molecular pathways that have not been previously implicated in regulation of bone metabolism such as OPTN, which was recently found to negatively regulate osteoclast differentiation. PDB-susceptibility variants exert their effect either by affecting the protein coding sequence such as variants found in SQSTM1 and RIN3 or by influencing gene expression such as those found in OPTN and DCSTAMP. Epidemiological studies indicate that environmental triggers also have a key role in PDB and interact with genetic factors to influence manifestation and severity of the disease; however, further studies are needed to identify these triggers. PMID:26587225

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.

Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone

PubMed Central

Culbertson, Christopher D.; Kyker-Snowman, Kelly; Bushinsky, David A.

2012-01-01

Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality. PMID:22647635

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

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.

The impact of thyroid diseases on bone metabolism and fracture risk.

PubMed

Amashukeli, M; Giorgadze, E; Tsagareli, M; Nozadze, N; Jeiranashvili, N

2010-01-01

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. One of the leading causes of secondary osteoporosis are thyroid diseases; this fact carries special importance for Georgia because of thyroid disease prevalence in Georgian population. In the present article we discuss the mechanisms, by which thyroid hormones and thyroid stimulating hormone (TSH) act on bone. We also present the data of meta-analysis of large studies, which demonstrate the complex relationship between the thyroid diseases and bone mineral density as well as the fracture risk; namely by overt and subclinical thyrotoxicosis, hypothyroidism and the treatment with the suppressive doses of levothyroxine. Beside that, we review the related data and the possible reasons, why different treatment regimens of Grave's disease: conservative, operative and radioiodine are related to different fracture risks. Finally, we discuss briefly the practical aspects of the treatment of secondary osteoporosis, related with thyroid diseases.

Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study.

PubMed

Wada, Yasuyo; Hisamatsu, Tadakazu; Naganuma, Makoto; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Yajima, Tomoharu; Kouyama, Keisuke; Iwao, Yasushi; Ogata, Haruhiko; Hibi, Toshifumi; Abe, Takayuki; Kanai, Takanori

2015-12-01

Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Water restriction and bone metabolism in camels.

PubMed

Ben Goumi, M; Robins, S P; De La Farge, F; Coxam, V; Davicco, M J; Barlet, J P

1996-01-01

'Krafft disease', occurring in camels living in the very arid areas of North Africa, is characterized by spontaneous fractures of costal and/or appendicular bones. To better understand the mechanisms of this, we studied the influence of water restriction on plasma and urinary markers of bone metabolism in camels. Eight 2-year-old nonpregnant, nonlactating camels were studied at the research station of Laâyoune (Morocco). After a 10 day period of daily watering, five animals were watered only every 10th day over a 50 day period, then again watered daily for a final 10 day period (rehydration). The three control animals were watered daily throughout the whole experimental period (70 days). Each camel was fed a ration of straw, luceme hay and barley, resulting in a daily intake of 25 g calcium and 11 g phosphorus. Water restriction induced a decrease in daily urinary volume and an increase in plasma osmolality. These symptoms of dehydration were not associated with any significant change either in the markers of osteoblastic activity (plasma alkaline phosphatase activity and osteocalcine concentration) or in the markers of bone resorption (urinary excretion of calcium, hydroxyproline pyridinoline and deoxypyridinoline). Thus, in well-fed camels, water restriction did not affect bone metabolism. However, no conclusions were possible regarding the influence of dehydration or calcium and/or phosphorus deficiency in the etiology of 'Kraft disease'.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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%,more » 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).« less

Bone disease in thyrotoxicosis

PubMed Central

Reddy, P. Amaresh; Harinarayan, C. V.; Sachan, Alok; Suresh, V.; Rajagopal, G.

2012-01-01

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis. PMID:22561612

Bone disease in thyrotoxicosis.

PubMed

Reddy, P Amaresh; Harinarayan, C V; Sachan, Alok; Suresh, V; Rajagopal, G

2012-03-01

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis.

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

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.

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.

Disrupted Bone Metabolism in Long-Term Bedridden Patients.

PubMed

Eimori, Keiko; Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

Assessment of bone metabolism in premenopausal females with hyperthyroidism and hypothyroidism.

PubMed

Tuchendler, Dominika; Bolanowski, Marek

2013-01-01

Osteoporosis is one of the commonest metabolic diseases of bone. Its possible causes may include thyroid hormonal dysfunction. The objective of this study was to evaluate the effects of hyperthyroidism and hypothyroidism on osseous tissue metabolism in premenopausal women. 38 women with hyperthyroidism, 40 with hypothyroidism and 41 healthy women participated in this study. Initially after 6 and 12 months, each patient underwent selected hormonal, immunological and biochemical tests, measurement of concentrations of bone turnover markers and densitometry were also performed. On initial evaluation, lower cortical bone density was found in patients with hyperthyroidism (femoral neck). After 12 months, an increase in BMD was seen, but it was still lower than in the control group. Statistically significantly higher concentrations of bone turnover markers, decreasing from the sixth month of treatment, were noted only in the group with hyperthyroidism. Statistically significant differences were not noted in the femoral neck nor in the lumbar spine BMD in patients with hypothyroidism. Hyperthyroidism poses a negative effect on bone metabolism. Hypothyroidism in premenopausal females does not have any influence on bone density.

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.

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.

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

Paget's disease of bone resembling bone metastasis from gastric cancer.

PubMed

Shimoyama, Yasuyuki; Kusano, Motoyasu; Shimoda, Yoko; Ishihara, Shingo; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Sano, Takaaki; Hirato, Junko; Mori, Masatomo

2011-08-01

A 74-year-old man had an endoscopic type 0'-IIc tumor in the upper gastric body on the greater curvature and biopsy showed the tumor to be a well-differentiated adenocarcinoma (Group 5). He was referred to us for endoscopic submucosal dissection (ESD). Endoscopy revealed fold convergency, fold swelling, and fusion of the fold, indicating tumor invasion into the submucosa, which was outside the indications for ESD. In addition, there was an increase of serum bone-type alkaline phosphatase (ALP-III and ALP-IV) and urinary cross-linked N-terminal telopeptide of type I collagen (a bone metabolism marker), while (18)F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left pelvis and Th10, suggesting bone metastases. We first diagnosed gastric cancer with bone metastases; however, the symptoms suggested pathological bone fracture and no bone pain. Therefore, a computed tomography-guided aspiration bone biopsy was performed to exclude the possibility of Paget's disease of bone. Biopsy specimens revealed no tumor and a mosaic pattern. No increased uptake of (18)F-FAMT (L-[3-(18)F] α-methyltyrosine) supported a diagnosis of no bone metastases from gastric cancer. We finally diagnosed gastric cancer accompanied by Paget's disease of bone and performed a laparoscopy-assisted proximal gastrectomy. The pathological diagnosis was U less 0-IIb, and U post 0-IIc ypT1a (M) N0H0P0M0 yp stage IA. In gastric cancer patients with suspected bone metastasis, we also need to consider Paget's disease of bone.

Disrupted Bone Metabolism in Long-Term Bedridden Patients

PubMed Central

Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Background Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. Methods This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. Results The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Conclusions Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients. PMID:27275738

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

Metabolic analysis of osteoarthritis subchondral bone based on UPLC/Q-TOF-MS.

PubMed

Yang, Gang; Zhang, Hua; Chen, Tingmei; Zhu, Weiwen; Ding, Shijia; Xu, Kaiming; Xu, Zhongwei; Guo, Yanlei; Zhang, Jian

2016-06-01

Osteoarthritis (OA), one of the most widespread musculoskeletal joint diseases among the aged, is characterized by the progressive loss of articular cartilage and continuous changes in subchondral bone. The exact pathogenesis of osteoarthritis is not completely clear. In this work, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) in combination with multivariate statistical analysis was applied to analyze the metabolic profiling of subchondral bone from 42 primary osteoarthritis patients. This paper described a modified two-step method for extracting the metabolites of subchondral bone from primary osteoarthritis patients. Finally, 68 metabolites were identified to be significantly changed in the sclerotic subchondral bone compared with the non-sclerotic subchondral bone. Taurine and hypotaurine metabolism and beta-alanine metabolism were probably relevant to the sclerosis of subchondral bone. Taurine, L-carnitine, and glycerophospholipids played a vital regulation role in the pathological process of sclerotic subchondral bone. In the sclerotic process, beta-alanine and L-carnitine might be related to the increase of energy consumption. In addition, our findings suggested that the intra-cellular environment of sclerotic subchondral bone might be more acidotic and hypoxic compared with the non-sclerotic subchondral bone. In conclusion, this study provided a new insight into the pathogenesis of subchondral bone sclerosis. Our results indicated that metabolomics could serve as a promising approach for elucidating the pathogenesis of subchondral bone sclerosis in primary osteoarthritis. Graphical Abstract Metabolic analysis of osteoarthritis subchondral bone.

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

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.

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

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. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

Abnormalities in biomarkers of mineral and bone metabolism in kidney donors.

PubMed

Kasiske, Bertram L; Kumar, Rajiv; Kimmel, Paul L; Pesavento, Todd E; Kalil, Roberto S; Kraus, Edward S; Rabb, Hamid; Posselt, Andrew M; Anderson-Haag, Teresa L; Steffes, Michael W; Israni, Ajay K; Snyder, Jon J; Singh, Ravinder J; Weir, Matthew R

2016-10-01

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease.

PubMed

Chavassieux, P; Seeman, E; Delmas, P D

2007-04-01

Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.

Influence on bone metabolism of dietary trace elements, protein, fat, carbohydrates, and vitamins.

PubMed

Sarazin, M; Alexandre, C; Thomas, T

2000-01-01

Osteoporosis is a multifactorial disease driven primarily by the genetic factors that control bone metabolism. Among environmental factors, diet may play a key role, affording a target for low-cost intervention. Calcium and vitamin D are well known to affect bone metabolism. Other nutrients may influence bone mass changes; for instance, a number of trace elements and vitamins other than vitamin D are essential to many of the steps of bone metabolism. A wide variety of foods provide these nutrients, and in industrialized countries deficiencies are more often due to idiosyncratic eating habits than to cultural influences. Both culture and vogue influence the amount of carbohydrate, fat, and protein in the typical diet. In children, the current trend is to reduce protein and to increase carbohydrate and fat. Data from epidemiological and animal studies suggest that this may adversely affect bone mass and the fracture risk.

Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis.

PubMed

Turner, Justine; Pellerin, Genevieve; Mager, Diana

2009-11-01

: Given dietary gluten exposure, growing children with celiac disease may experience malabsorption of nutrients, negatively affecting bone health. The purpose of this study was to determine the prevalence of low bone mass in children with celiac disease, according to the presence of symptoms at diagnosis. : A retrospective chart review of the Stollery Children's Hospital Celiac Clinic charts (April 1989-September 2007) was conducted. Bone mineral density (BMD) of the spine was measured using dual energy x-ray absorptiometry. Demographics, symptoms at presentation, and anthropometric and biochemical data relevant to bone health were recorded. : Seventy-four children (9.6 +/- 3.7 years; range 3.3-16.0 years) were included. Lumbar BMD z scores more than or equal to -1 were observed in 58 cases (65%), z scores below -1 but above -2 were observed in 14 cases (19%) and z scores less than or equal to -2 were observed in 12 cases (16%). There was no significant difference in mean lumbar BMD z scores between symptomatic and asymptomatic children (P = 0.34). When adjusted for bone age and bone surface area, BMD lumbar z score was inversely correlated with age at diagnosis (P < 0.05). : An equivalent reduction in spine bone mass was observed in children with celiac disease at diagnosis regardless of the presence of symptoms. Delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis. Appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health.

Zoledronic acid in pediatric metabolic bone disorders.

PubMed

Bowden, Sasigarn A; Mahan, John D

2017-10-01

Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted.

Zoledronic acid in pediatric metabolic bone disorders

PubMed Central

Mahan, John D.

2017-01-01

Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted. PMID:29184807

Bone metabolism in galactosemia.

PubMed

Panis, B; Forget, P Ph; van Kroonenburgh, M J P G; Vermeer, C; Menheere, P P; Nieman, F H; Rubio-Gozalbo, M E

2004-10-01

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.

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

2017-12-01

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.

Does methamphetamine affect bone metabolism?

PubMed

Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

2014-05-07

There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might

[Homeostasis and Disorder of Musculoskeletal System.Molecular mechanism of bone metabolism and future therapeutic strategies.

PubMed

Nakashima, Tomoki

Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells. An imbalance of this process is often linked to various bone diseases. Thus, the elucidation of the molecular mechanisms involved in bone remodeling is critical for a deeper understanding of the maintenance of healthy skeleton and bone disease.

[Obesity and bone metabolism].

PubMed

Holecki, Michał; Zahorska-Markiewicz, Barbara; Wiecek, Andrzej; Nieszporek, Teresa; Zak-Gołab, Agnieszka

2008-01-01

Both bone and adipose tissue change their size, shape and distribution during the whole human being's life. Many factors, including genetic factors, hormones and activity of nervous system are responsible for these changes. It is generally accepted that obesity has a protective effect on bone tissue. On the other hand some authors present an opposite results--the lack of beneficial effect of obesity on development of osteoporosis fractures. The aim of this article was to present and discuss the relations between adipose tissue and bone metabolism.

Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

PubMed Central

Luce, Vincenza; Ventura, Annamaria; Colucci, Silvia; Cavallo, Luciano; Grano, Maria

2015-01-01

Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteoprotegerin, in the regulation of insulin function and glucose metabolism. PMID:25873957

Metabolic and biochemical considerations of bone.

PubMed

Lutwak, L

1975-01-01

Recognition of the dynamic aspects of bone metabolism can lead to a unified concept involving endocrine and nutritional influences. Although most hormones can influence bone metabolism directly or indirectly, the principal ones involved in skeletal metabolism are parathyroid hormone, calcitonin and 1,25-dihydroxy-vitamin D. The actions of parathyroid hormone and 1,25-dihydroxy-vitamin D result in elevations of circulating extracellular fluid calcium concentration through actions directly on bone, intestine, and kidney. Calcitonin leads to decreases in calcium concentration, primarily by action on bone and kidney. The absorption and retention of calcium by the organism is further influenced by the dietary content of calcium, phosphorus, protein, and fluoride. Chronic dietary deficiencies of calcium and excesses of phosphorus may lead to chronic nutritional secondary hyperparathyroidism with resulting skeletal demineralization. In both experimental animals and in man, the earliest manifestation of this condition may be demineralization of the jaw with resultant paradentosis. Experimental studies in animals and in man have shown that this form of demineralization may be completely reversed by increasing dietary calcium and decreasing dietary phosphrous.

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.

Clinical relevance of changes in bone metabolism in inflammatory bowel disease

PubMed Central

Miheller, Pal; Lőrinczy, Katalin; Lakatos, Peter Laszlo

2010-01-01

Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous risk factors have to be considered, and these factors should be weighed properly to help in the identification of the appropriate patients for screening. In this editorial, the authors aim to highlight the most important clinical aspects of the epidemiology, prevention, diagnosis and treatment of IBD-related bone loss. PMID:21105186

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. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

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

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

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.

Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

PubMed

Suchacki, Karla J; Cawthorn, William P

2018-01-01

The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

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.

Bone-Immune Cell Crosstalk: Bone Diseases

PubMed Central

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

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. PMID:26000310

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.

[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.

Sphingolipid metabolism diseases.

PubMed

Kolter, Thomas; Sandhoff, Konrad

2006-12-01

Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

The Central Nervous System and Bone Metabolism: An Evolving Story.

PubMed

Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

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

The Metabolic Microenvironment Steers Bone Tissue Regeneration.

PubMed

Loeffler, Julia; Duda, Georg N; Sass, F Andrea; Dienelt, Anke

2018-02-01

Over the past years, basic findings in cancer research have revealed metabolic symbiosis between different cell types to cope with high energy demands under limited nutrient availability. Although this also applies to regenerating tissues with disrupted physiological nutrient and oxygen supply, the impact of this metabolic cooperation and metabolic reprogramming on cellular development, fate, and function during tissue regeneration has widely been neglected so far. With this review, we aim to provide a schematic overview on metabolic links that have a high potential to drive tissue regeneration. As bone is, aside from liver, the only tissue that can regenerate without excessive scar tissue formation, we will use bone healing as an exemplarily model system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Short-term variability in biomarkers of bone metabolism in sheep.

PubMed

Sousa, Cristina P; de Azevedo, Jorge T; Reis, Rui L; Gomes, Manuela E; Dias, Isabel R

2014-01-01

Changes in bone remodeling during pathological states and during their treatment can be assessed noninvasively by measuring biomarkers of bone metabolism. Their application is limited, however, by the potential biological variability in the levels of these biomarkers over time. To determine the short-term variability in biomarkers of bone metabolism in adult sheep, the authors measured serum levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N-terminal propeptide of type-III procollagen (PIIINP), deoxypyridinoline (DPD), tartrate-resistant acid phosphatase (TRAP), calcium and phosphorus intermittently over a 12-week period. There were significant differences in mean ALP activity and in phosphorus concentrations over time, but all other biomarkers showed no significant short-term variability. The results suggest that biomarkers of bone metabolism in sheep, especially the bone resorption marker DPD and the bone formation marker BALP, can be used reliably to detect changes in bone cellular activity.

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...

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

Bone Metabolism of the Patient with a Malignant Melanoma during the Entry Examination and the Check-up of Whole-body Bone Scintigraphy.

PubMed

Weissensteiner, Jaroslav; Babušíková, Eva

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

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. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis

PubMed Central

2014-01-01

Introduction 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. Methods 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. Results 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. Conclusions 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

Metabolic Syndrome and Periodontal Disease Progression in Men

PubMed Central

Kaye, E.K.; Chen, N.; Cabral, H.J.; Vokonas, P.; Garcia, R.I.

2016-01-01

Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study’s aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (≥5 mm), clinical attachment loss (≥5 mm), mobility (≥0.5 mm), and alveolar bone loss (≥40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ≥5 mm (1.37; 1.14 to 1.65), clinical attachment loss ≥5 mm (1.19; 1.00 to 1.41), alveolar bone loss ≥40% (1.25; 1.00 to 1.56), and tooth mobility ≥0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that

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

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

Synthesis and in vitro evaluation of bone-seeking superparamagnetic iron oxide nanoparticles as contrast agents for imaging bone metabolic activity.

PubMed

Panahifar, Arash; Mahmoudi, Morteza; Doschak, Michael R

2013-06-12

In this article, we report the synthesis and in vitro evaluation of a new class of nonionizing bone-targeting contrast agents based on bisphosphonate-conjugated superparamagnetic iron oxide nanoparticles (SPIONs), for use in imaging of bone turnover with magnetic resonance imaging (MRI). Similar to bone-targeting (99m)Technetium medronate, our novel contrast agent uses bisphosphonates to impart bone-seeking properties, but replaces the former radioisotope with nonionizing SPIONs which enables their subsequent detection using MRI. Our reported method is relatively simple, quick and cost-effective and results in BP-SPIONs with a final nanoparticle size of 17 nm under electron microscopy technique (i.e., TEM). In-vitro binding studies of our novel bone tracer have shown selective binding affinity (around 65%) for hydroxyapatite, the principal mineral of bone. Bone-targeting SPIONs offer the potential for use as nonionizing MRI contrast agents capable of imaging dynamic bone turnover, for use in the diagnosis and monitoring of metabolic bone diseases and related bone pathology.

Bone loss in Crohn's disease: exercise as a potential countermeasure.

PubMed

Lee, Naomi; Radford-Smith, Graham; Taaffe, Dennis R

2005-12-01

Crohn's disease (CD) is associated with a number of secondary conditions including osteoporosis, which increases the risk of bone fracture. The cause of metabolic bone disease in this population is believed to be multifactorial and may include the disease itself and associated inflammation, high-dose corticosteroid use, weight loss and malabsorption, a lack of exercise and physical activity, and an underlying genetic predisposition to bone loss. Reduced bone mineral density has been reported in between 5% to 80% of CD sufferers, although it is generally believed that approximately 40% of patients suffer from osteopenia and 15% from osteoporosis. Recent studies suggest a small but significantly increased risk of fracture compared with healthy controls and, perhaps, sufferers of other gastrointestinal disorders such as ulcerative colitis. The role of physical activity and exercise in the prevention and treatment of CD-related bone loss has received little attention, despite the benefits of specific exercises being well documented in healthy populations. This article reviews the prevalence of and risk factors for low bone mass in CD patients and examines various treatments for osteoporosis in these patients, with a particular focus on physical activity.

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. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Chronic Inhibition of ERK1/2 Signaling Improves Disordered Bone and Mineral Metabolism in Hypophosphatemic (Hyp) Mice

PubMed Central

Zhang, Martin Y. H.; Ranch, Daniel; Pereira, Renata C.; Armbrecht, Harvey J.; Portale, Anthony A.

2012-01-01

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)2D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)2D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)2D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)2D metabolism and bone mineralization. PMID:22334725

Chronic inhibition of ERK1/2 signaling improves disordered bone and mineral metabolism in hypophosphatemic (Hyp) mice.

PubMed

Zhang, Martin Y H; Ranch, Daniel; Pereira, Renata C; Armbrecht, Harvey J; Portale, Anthony A; Perwad, Farzana

2012-04-01

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)₂D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)₂D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)₂D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)₂D metabolism and bone mineralization.

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

Bone metabolism in cow milk allergic children.

PubMed

Jakusova, Lubica; Jesenak, Milos; Schudichova, Jela; Banovcin, Peter

2013-07-01

Children with cow milk allergy are suspected to develop calcium metabolism disturbances. We observed increased markers of bone turnover in these children. Children with cow milk allergy are more prone to develop the disturbances of the bone mineralization even in the first year of life.

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.

Gonadal steroids and bone metabolism in men.

PubMed

Leder, Benjamin

2007-06-01

Over the past decade, our increasing awareness of the clinical importance of osteoporosis in men has stimulated intense interest in trying to better understand male skeletal physiology and pathophysiology. The present review focuses on a major focus of research in this area, namely the attempt to define the influence and therapeutic potential of gonadal steroids in male bone metabolism. Building on previous work defining the relative roles of androgens and estrogens in the developing male skeleton and in maintaining normal bone turnover, recent studies have begun to define these issues from epidemiologic, physiologic and therapeutic perspectives. With access to data from large prospectively defined populations of men, investigators are confirming and challenging existing hypotheses and forwarding new concepts. Clinical trials have expanded beyond standard androgen replacement studies to explore more complex hormonal interventions. Physiologic investigation has continued to probe the mechanisms underlying the differential and independent roles of androgens and estrogens in male bone metabolism. Recent work has added significantly to our understanding of the role of gonadal steroids in male skeletal physiology. Nonetheless, further research is necessary to build on these initial human studies and to capitalize on rapidly emerging advances in our understanding of the basic biology of bone metabolism.

[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.

Muscle-Bone Interactions in Pediatric Bone Diseases.

PubMed

Veilleux, Louis-Nicolas; Rauch, Frank

2017-10-01

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

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-

The consequences of pediatric renal transplantation on bone metabolism and growth.

PubMed

Bacchetta, Justine; Ranchin, Bruno; Demède, Delphine; Allard, Lise

2013-10-01

During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).

Bone Marrow Diseases

MedlinePlus

Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

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.

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.

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

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.

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.

[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.

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)

Oral Health and Bone Disease

MedlinePlus

... Oral Health and Bone Disease Oral Health and Bone Disease Osteoporosis and tooth loss are health concerns ... for Healthy Bones Resources For Your Information Skeletal Bone Density and Dental Concerns The portion of the ...

[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.

Epigenetics of bone diseases.

PubMed

Michou, Laetitia

2017-12-12

Histone deacetylation, DNA methylation, and micro-RNAs (miRNAs) are the three main epigenetic mechanisms that regulate gene expression. All the physiological processes involved in bone remodeling are tightly regulated by epigenetic factors. This review discusses the main epigenetic modifications seen in tumoral and non-tumoral bone diseases, with emphasis on miRNAs. The role for epigenetic modifications of gene expression in the most common bone diseases is illustrated by drawing on the latest publications in the field. In multifactorial bone diseases such as osteoporosis, many epigenetic biomarkers, either alone or in combination, have been associated with bone mineral density or suggested to predict osteoporotic fractures. In addition, treatments designed to modulate bone remodeling by selectively targeting the function of specific miRNAs are being evaluated. Advances in the understanding of epigenetic regulation shed new light on the pathophysiology of other non-tumoral bone diseases, including genetic conditions inherited on a Mendelian basis. Finally, in the area of primary and metastatic bone tumors, the last few years have witnessed considerable progress in elucidating the epigenetic regulation of oncogenesis and its local interactions with bone tissue. These new data may allow the development of epigenetic outcome predictors, which are in very high demand, and of innovative therapeutic agents acting via miRNA modulation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

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.

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

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.

Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture.

PubMed

Bours, Sandrine P G; van Geel, Tineke A C M; Geusens, Piet P M M; Janssen, Marcel J W; Janzing, Heinrich M J; Hoffland, Ge A; Willems, Paul C; van den Bergh, Joop P W

2011-05-01

Previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB) are frequently found in patients with osteoporosis, but the prevalence in patients at the time they present with a clinical fracture is unknown. All consecutive patients with a recent clinical vertebral or nonvertebral fracture, who were able and willing to be investigated (n = 626: 482 women, 144 men, age range 50-97 yr) had bone mineral density and laboratory investigations (serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, TSH, free T(4), serum and urine protein electrophoresis, and in men also serum testosterone). Known SECOB contributors were present in 23.0% of patients and newly diagnosed SECOB contributors in 26.5%: monoclonal proteinemia (14 of 626), renal insufficiency grade III or greater (54 of 626), primary (17 of 626) and secondary (64 of 626) hyperparathyroidism, hyperthyroidism (39 of 626), and hypogonadism in men (12 of 144). Newly diagnosed SECOBs, serum 25-hydroxyvitamin D less than 50 nmol/liter (in 63.9%), and dietary calcium intake less than 1200 mg/d (in 90.6%) were found at any age, in both sexes, after any fracture (except SECOB in men with finger and toe fractures) and at any level of bone mineral density. At presentation with a fracture, 26.5% of patients have previously unknown contributors to SECOB, which are treatable or need follow-up, and more than 90% of patients have an inadequate vitamin D status and/or calcium intake. Systematic screening of patients with a recent fracture identifies those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present.

Relationship between metabolic syndrome and its components with bone densitometry in postmenopausal women.

PubMed

Abbasi, Mahnaz; Farzam, Seyed Amir; Mamaghani, Zahra; Yazdi, Zohreh

2017-11-01

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.

Pain and Paget's Disease of Bone

MedlinePlus

... Disease of Bone Pain and Paget’s Disease of Bone Types of Pain Paget’s disease can cause several ... Last Reviewed 2015-05 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, ...

The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor.

PubMed

Ma, Xiaohong; He, Liqun

2018-06-24

Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been used for nourish kidney essence improve bone malnutrition of renal bone disease by regulating the metabolism of calcium and phosphorus and participating in osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were significantly decreased, while the serum calcium level was significantly increased, and the Cbfa1 protein level was significantly decreased and FGF23 protein level was significantly increased by Zuogui pill treatment. Compared with model rats, the BMD of rat was significantly increased by Zuogui pill treatment. Histological analysis revealed that the kidney injury of rats with CKD was significantly reduced by zuogui pill treatment. Compared with model rats, the CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and NaPiIIa protein level were significantly decreased in the kidney by zuogui pill treatment. We inferred that zuogui pill exhibited potential therapeutic effects on CKD-MBD in the rats by regulating bone metabolism and nourish kidney. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

HYPERCALCURIA AND METABOLIC BONE DISEASE

PubMed Central

Rosenberg, Milton L.

1954-01-01

Hypercalcuria leading to nephrocalcinosis and nephrolithiasis may be secondary to a number of causes. In most instances, the history, physical examination, a few simple laboratory tests and x-ray study of the bones will reveal the true primary diagnosis. Specific treatment, if instituted early, will result in a satisfactory response and prevent the progression of renal complications. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:13209371

[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.

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders.

PubMed

Bover, Jordi; Ureña, Pablo; Aguilar, Armando; Mazzaferro, Sandro; Benito, Silvia; López-Báez, Víctor; Ramos, Alejandra; daSilva, Iara; Cozzolino, Mario

2018-02-14

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

PubMed

Johnsson, Martin; Jonsson, Kenneth B; Andersson, Leif; Jensen, Per; Wright, Dominic

2015-05-01

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.

Bone metabolism in anorexia nervosa and hypothalamic amenorrhea.

PubMed

Chou, Sharon H; Mantzoros, Christos

2018-03-01

Anorexia nervosa (AN) and hypothalamic amenorrhea (HA) are states of chronic energy deprivation associated with severely compromised bone health. Poor bone accrual during adolescence followed by increased bone loss results in lifelong low bone density, degraded bone architecture, and higher risk of fractures, despite recovery from AN/HA. Amenorrhea is only one of several compensatory responses to the negative energy balance. Other hypothalamic-pituitary hormones are affected and contribute to bone deficits, including activation of hypothalamic-pituitary-adrenal axis and growth hormone resistance. Adipokines, particularly leptin, provide information on fat/energy stores, and gut hormones play a role in the regulation of appetite and food intake. Alterations in all these hormones influence bone metabolism. Restricted in scope, current pharmacologic approaches to improve bone health have had overall limited success. Copyright © 2017 Elsevier Inc. All rights reserved.

[Secondary osteoporosis or secondary contributors to bone loss in fracture. Endocrinological aspects of bone metabolism].

PubMed

Fukumoto, Seiji

2013-09-01

Bone works to play essential roles in mineral metabolism and hematopoiesis as well as to support our body and protect internal organs as a hard tissue. In order to accomplish these multiple functions, bone needs to communicate with other organs. Endocrine system functions as one of the communication pathways between bone and other organs. It has been known that bone is a target organ of many hormones. In addition, it has been established that bone itself produces hormones and works as an endocrine organ.

Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes.

PubMed

Ogata, Makiko; Ide, Risa; Takizawa, Miho; Tanaka, Mizuho; Tetsuo, Tamaki; Sato, Asako; Iwasaki, Naoko; Uchigata, Yasuko

2015-01-01

Diabetes is a risk factor for osteoporosis, and glycemic control is critical during osteoporosis treatment in patients with type 2 diabetes (T2D). However, diabetic therapies have potentially adverse effects on bone metabolism. Additionally, biomarkers for bone metabolism are directly affected by drug therapies for osteoporosis. This study examined resting energy expenditure (REE) and respiratory quotient (RQ) as indices of bone metabolism in postmenopausal Japanese women with T2D. Forty-six postmenopausal Japanese women with T2D were examined. Procollagen type 1 N-terminal propeptide (P1NP, a fasting serum bone formation marker) and carboxy-terminal collagen cross-links-1 (CTX-1, a resorption marker) were evaluated, along with intact parathyroid hormone, 25-hydroxyvitamin D (25[OH]D), urine microalbumin, motor nerve conduction velocity, sensory nerve conduction velocity, R-R interval, body composition, REE, RQ, and bone mineral density at the nondominant distal radius. The mean T-score was low with high variance (-1.7 ± 1.6), and 18 patients (39%) met the criteria for osteoporosis. REE was positively correlated with body mass index (β = 0.517; r(2) = 0.250), serum calcium (β = 0.624; r(2) = 0.200), glycated hemoglobin A1C for the previous 6 mo (β = 0.395; r(2) = 0.137), and the serum P1NP/CTX-1 ratio (β = 0.380; r(2) = 0.144). RQ was positively correlated with serum 25(OH)D (β = 0.387; r(2) = 0.131). The basal metabolic rate and diabetic pathophysiology are interrelated with bone turnover. Copyright © 2015 Elsevier Inc. All rights reserved.

Bone Disease in Axial Spondyloarthritis.

PubMed

Van Mechelen, Margot; Gulino, Giulia Rossana; de Vlam, Kurt; Lories, Rik

2018-05-01

Axial spondyloarthritis is a chronic inflammatory skeletal disorder with an important burden of disease, affecting the spine and sacroiliac joints and typically presenting in young adults. Ankylosing spondylitis, diagnosed by the presence of structural changes to the skeleton, is the prototype of this disease group. Bone disease in axial spondyloarthritis is a complex phenomenon with the coexistence of bone loss and new bone formation, both contributing to the morbidity of the disease, in addition to pain caused by inflammation. The skeletal structural changes respectively lead to increased fracture risk and to permanent disability caused by ankylosis of the sacroiliac joints and the spine. The mechanism of this new bone formation leading to ankylosis is insufficiently known. The process appears to originate from entheses, specialized structures that provide a transition zone in which tendon and ligaments insert into the underlying bone. Growth factor signaling pathways such as bone morphogenetic proteins, Wnts, and Hedgehogs have been identified as molecular drivers of new bone formation, but the relationship between inflammation and activation of these pathways remains debated. Long-standing control of inflammation appears necessary to avoid ankylosis. Recent evidence and concepts suggest an important role for biomechanical factors in both the onset and progression of the disease. With regard to new bone formation, these processes can be understood as ectopic repair responses secondary to inflammation-induced bone loss and instability. In this review, we discuss the clinical implications of the skeletal changes as well as the underlying molecular mechanisms, the relation between inflammation and new bone formation, and the potential role of biomechanical stress.

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.

Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

PubMed

Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

2004-10-15

Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

Bone metabolism markers and vitamin D in adolescent cyclists.

PubMed

Olmedillas, Hugo; Gonzalez-Agüero, Alejandro; Rapún-López, Marta; Gracia-Marco, Luis; Gomez-Cabello, Alba; Pradas de la Fuente, Francisco; Moreno, Luís A; Casajús, José A; Vicente-Rodríguez, Germán

2018-02-03

This study aimed to describe bone metabolic activity in adolescent competitive cyclists compared to age-matched controls. The main result is that younger subjects present a higher bone turnover than the older ones. Moreover, cyclists under the age of 17 have higher scores on all markers than age-matched controls. The purpose of this study was to describe bone metabolic activity in adolescent competitive cyclists compared to age-matched controls. Twenty-two male adolescent cyclists between 14 and 20 years (y) and 20 age-matched controls participated in this study. Serum osteocalcin (OC), aminoterminal propeptide of type I procollagen (PINP), and β-isomerized C-telopeptides (β-CTX) were analyzed by electrochemiluminescence immunoassay (ECLIA); plasma 25 hydroxyvitamin D [25(OH)D] was analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of variance revealed no significant differences in bone metabolism markers and vitamin D between cyclists and controls. Cyclists over 17 y had a significantly lower concentration in bone formation and resorption biochemical markers compared to cyclists under 17 y (all P < 0.05). Moreover, controls over 17 y presented lower concentration for PINP (P < 0.05) compared to their peers under 17 y. Comparisons between cyclists and controls under 17 y revealed higher concentrations of OC and PINP (P < 0.05) in cyclists. Group interaction by age was found for OC, PINP, and β-CTX (P < 0.01). Cyclists over 17 y had higher concentrations of [25(OH)D] (P < 0.05) than age-matched controls. The present results support the idea that cycling during adolescence may be associated to a decrease in bone turnover that may affect bone health later in life.

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.

A study of changes in bone metabolism in cases of gender identity disorder.

PubMed

Miyajima, Tsuyoshi; Kim, Yoon Taek; Oda, Hiromi

2012-07-01

The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.

Bone and mineral metabolism in adult celiac disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caraceni, M.P.; Molteni, N.; Bardella, M.T.

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 significantmore » 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.« less

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

PubMed

Kawarazaki, Hiroo; Shibagaki, Yugo; Kido, Ryo; Nakajima, Ichiro; Fuchinoue, Shohei; Ando, Katsuyuki; Fujita, Toshiro; Fukagawa, Masafumi; Teraoka, Satoshi; Fukumoto, Seiji

2012-07-01

While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

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.

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism.

PubMed

Kakareko, Katarzyna; Rydzewska-Rosolowska, Alicja; Brzosko, Szymon; Gozdzikiewicz-Lapinska, Joanna; Koc-Zorawska, Ewa; Samocik, Pawel; Kozlowski, Robert; Mysliwiec, Michal; Naumnik, Beata; Hryszko, Tomasz

2017-04-01

Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels. This is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [β-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days). Twenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m 2 ). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9-831.2) vs. 583.0 (411.7-752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8-103.3) vs. 77.1 (60.5-109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4-0.64) vs. 0.59 (0.46-0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8-31.4) vs. 17.9 (15.0-22.0) U/l, p < 0.0001 and 3.3 (3.0-3.7) vs. 2.8 (2.3-3.2) U/l, p < 0.001, respectively]. Nephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.

[Morphological analysis of bone dynamics and metabolic bone disease. Effect of loading on bone tissue].

PubMed

Sakai, Akinori

2011-04-01

We developed a voluntarily climbing animal model to investigate the effect of skeletal loading on bone tissue. At the cross section of the mid-femur, climbing exercise increases outer diameter and area of cortical bone. The mechanical strength of the femur is increased. This change of cortical volume and structure is more marked in anti-gravity exercise, such as climbing and jumping, than aerobic exercise. At the bone marrow area, climbing exercise increases trabecular bone volume and osteoblast number, while it decreases fat volume and adipocyte number. Skeletal loading promotes differentiation from mesenchymal stem cells to osteoblasts and suppresses that to adipocytes by facilitating the signal through PTH÷PTHrP receptor.

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.

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 ...

Bone metabolism and renal stone risk during International Space Station missions.

PubMed

Smith, Scott M; Heer, Martina; Shackelford, Linda C; Sibonga, Jean D; Spatz, Jordan; Pietrzyk, Robert A; Hudson, Edgar K; Zwart, Sara R

2015-12-01

Bone loss and renal stone risk are longstanding concerns for astronauts. Bone resorption brought on by spaceflight elevates urinary calcium and the risk of renal stone formation. Loss of bone calcium leads to concerns about fracture risk and increased long-term risk of osteoporosis. Bone metabolism involves many factors and is interconnected with muscle metabolism and diet. We report here bone biochemistry and renal stone risk data from astronauts on 4- to 6-month International Space Station missions. All had access to a type of resistive exercise countermeasure hardware, either the Advanced Resistance Exercise Device (ARED) or the Interim Resistance Exercise Device (iRED). A subset of the ARED group also tested the bisphosphonate alendronate as a potential anti-resorptive countermeasure (Bis+ARED). While some of the basic bone marker data have been published, we provide here a more comprehensive evaluation of bone biochemistry with a larger group of astronauts. Regardless of exercise, the risk of renal stone formation increased during spaceflight. A key factor in this increase was urine volume, which was lower during flight in all groups at all time points. Thus, the easiest way to mitigate renal stone risk is to increase fluid consumption. ARED use increased bone formation without changing bone resorption, and mitigated a drop in parathyroid hormone in iRED astronauts. Sclerostin, an osteocyte-derived negative regulator of bone formation, increased 10-15% in both groups of astronauts who used the ARED (p<0.06). IGF-1, which regulates bone growth and formation, increased during flight in all 3 groups (p<0.001). Our results are consistent with the growing body of literature showing that the hyper-resorptive state of bone that is brought on by spaceflight can be countered pharmacologically or mitigated through an exercise-induced increase in bone formation, with nutritional support. Key questions remain about the effect of exercise-induced alterations in bone

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis*

PubMed Central

Zhang, Ying; Zheng, Yu-xin; Zhu, Jun-ming; Zhang, Jian-min; Zheng, Zhe

2015-01-01

Objective: The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods: 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. Results: 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. Conclusions: Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children. PMID:26160719

How Is Paget's Disease of Bone Diagnosed?

MedlinePlus

... of Bone Diagnosed? How Is Paget’s Disease of Bone Diagnosed? Symptoms of Paget’s Disease Many people with ... Last Reviewed 2015-05 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, ...

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.

Rapamycin and the transcription factor C/EBPbeta as a switch in osteoclast differentiation: implications for lytic bone diseases.

PubMed

Smink, Jeske J; Leutz, Achim

2010-03-01

Lytic bone diseases and in particular osteoporosis are common age-related diseases characterized by enhanced bone fragility due to loss of bone density. Increasingly, osteoporosis poses a major global health-care problem due to the growth of the elderly population. Recently, it was found that the gene regulatory transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) is involved in bone metabolism. C/EBPbeta occurs as different protein isoforms of variable amino terminal length, and regulation of the C/EBPbeta isoform ratio balance was found to represent an important factor in osteoclast differentiation and bone homeostasis. Interestingly, adjustment of the C/EBPbeta isoform ratio by the process of translational control is downstream of the mammalian target of rapamycin kinase (mTOR), a sensor of the nutritional status and a target of immunosuppressive and anticancer drugs. The findings imply that modulating the process of translational control of C/EBPbeta isoform expression could represent a novel therapeutic approach in osteolytic bone diseases, including cancer and infection-induced bone loss.

The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease.

PubMed

Iijima, Hideki; Shinzaki, Shinichiro; Takehara, Tetsuo

2012-11-01

This review summarizes the recent literature about the roles of vitamins D and K in bone metabolism and immunity-mediated inflammatory processes in inflammatory bowel diseases (IBDs). The levels of vitamins D and K are lower than normal in patients with IBD, especially in Crohn's disease. Although vitamins D and K are important for the maintenance of bone mineral density in non-IBD patients, an association between vitamins D or K and bone metabolism is not apparent in IBD patients. Recent studies showed that vitamins D and K are suggested to have immune-suppressive effects, both in animal models of colitis and human trials. In particular, vitamin D suppresses dendritic and T-cell functions by inhibiting the production of proinflammatory cytokines. Insufficiency of vitamin D is associated with the activated phenotype of IBD. Vitamins D and K potentially contribute to the maintenance of bone health in IBD, but this effect may be diminished by other factors such as steroid use, reduced exposure to sunlight, and inflammatory cytokines. Vitamin D and possibly vitamin K are suggested to be involved in the suppression of immune-mediated inflammation and modulation of disease activity.

Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review of Literature.

PubMed

Gupta, Monica; Singhal, Lalita; Kumar, Akshay

2018-06-01

Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.

[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.

[Regression analysis of serum bone metabolic markers and traditional Chinese medicine syndromes in patients with CKD-MBD].

PubMed

Yang, Hai-Ming; Meng, Xian-Jie; Wu, Wei; Liu, Ying-Lu; Zhai, Xiao-Juan

2017-10-01

To analyze the interdependent relationship between serum bone metabolic markers and traditional Chinese medicine (TCM) syndromes in patients with chronic kidney disease (stages 3 and 4)-related mineral and bone disorder (CKD-MBD), in order to provide the objective basis for exploring the rules of TCM syndrome differentiation in patients with CKD-MBD. The retrospective survey was conducted to collect 105 cases with CKD (stages 3 and 4)-MBD. General clinical indexes, frequency of TCM syndromes and distribution of TCM syndrome type were investigated. Furthermore, serum bone metabolic markers, including calcium (Ca2+), phosphonium (P3+), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), procollagen type 1 amino-N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) were analyzed, respectively. Meanwhile, bone mineral density (BMD) was assessed. And then, the multivariate regression analysis was performed for serum bone metabolic markers and TCM syndromes. The results showed that the general clinical features of the 105 patients included old age, hypertension, fracture, loss of bone mass and mild abnormalities of serum bone metabolic markers. High-frequency TCM syndromes were related to Yang deficiency in Spleen and Kidney, Qi deficiency in Spleen and Kidney and blood stasis. Moreover, Yang deficiency in Spleen and Kidney and blood stasis were found as the most frequent characteristics of the distribution of TCM syndromes type. The clinical characteristics of patients with the syndrome type of Yang deficiency in Spleen and Kidney were probably old age, increase in TCM syndrome scores and abnormalities in iPTH and P1NP. In addition, the interdependent relationship between abnormality in Ca2+ and syndromes of hair loss, tooth shake and sexual dysfunction, abnormality in P3+ and syndromes of aches in waist and knees, abnormality in iPTH and syndromes of soreness and weakness in waist and knees, lassitude, fatigue and extreme chilliness, abnormality in ALP and

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.

Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania.

PubMed

Lerchbaum, E; Schwetz, V; Nauck, M; Völzke, H; Wallaschofski, H; Hannemann, A

2015-05-01

Accumulating evidence demonstrates an important interaction between bone and energy metabolism. We aimed to study the associations of three bone turnover markers (BTM: osteocalcin, beta-crosslaps, procollagen type 1 N-terminal propeptide) as well as of 25-hydroxyvitamin D and parathyroid hormone with metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM) in a large population-based cohort. This cross-sectional study comprised 2671 adult men and women participating in the first follow-up of the population-based Study of Health in Pomerania (SHIP-1). Multivariable logistic regression analyses were performed to assess sex-specific associations between the BTMs, 25-hydroxyvitamin D or parathyroid hormone and metabolic disease. All models were adjusted for age, body mass index, smoking status, physical activity, estimated glomerular filtration rate and month of blood sampling. The models for women were further adjusted for menopausal status. Higher BTM or 25-hydroxyvitamin D concentrations were associated with significantly lower odds for metabolic disease, while there was no association between parathyroid hormone and MetS or T2DM. Our results contribute to the accumulating evidence of a cross-sectional association between high BTM or 25-hydroxyvitamin D concentrations and a lower prevalence of MetS or T2DM. Further research is necessary to evaluate the mechanisms underlying these results. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

The evaluation of bone metabolism in children with renal transplantation.

PubMed

Büyükkaragöz, Bahar; Bakkaloglu, Sevcan A; Kandur, Yaşar; Isiyel, Emel; Akcaboy, Meltem; Buyan, Necla; Hasanoglu, Enver

2015-06-01

This study aims to evaluate BMD and bone biomarkers and to investigate the effects of immunosuppressives on bone disease after RTx. Thirty-three RTR aged 16.7 ± 3.7 yr and healthy controls (n = 32) were enrolled. There was no difference between pre-RTx BMD and BMD at the time of study (45.9 ± 30.9 months after RTx), while both values were lower than controls (p < 0.01 and p < 0.05, respectively). Worst BMD scores were obtained at sixth month after RTx (-0.2 ± 0.9) and best at fourth year (1.4 ± 1.3). 25-hydroxy-(OH) vitamin D and OPG were higher in RTR (p < 0.001). BMD z scores negatively correlated with OPG and cumulative CS doses at the time of study (r = -0.344, p < 0.05 and r = -0.371, p < 0.05, respectively). Regression analysis revealed OPG as the only predictor of BMD (β -0.78, 95% CI -0.004 to -0.013, p < 0.001). The increase in OPG, a significant predictor of BMD, could either be secondary to graft dysfunction or for protection against bone loss. CS doses should be minimized to avoid their untoward effects on bone metabolism. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Negative correlation between bone mineral density and TSH receptor antibodies in long-term euthyroid postmenopausal women with treated Graves’ disease

PubMed Central

2013-01-01

Background Thyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves’ disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over. The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves’ disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb. Methods Cross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves’ disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured. Results Only euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves’ disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves’ disease. In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = −0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01). Conclusions In euthyroid women with a history of Graves’ hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this

Bone metabolism of male rats chronically exposed to cadmium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brzoska, Malgorzata M.; 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)more » 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.« less

Classical metaphyseal lesions thought to be pathognomonic of child abuse are often artifacts or indicative of metabolic bone disease.

PubMed

Miller, Marvin; Mirkin, L David

2018-06-01

The objective of the present study was to review the histopathology in the original articles by authors Kleinman and Marks that described the specificity of the classical metaphyseal lesion for child abuse and to determine if there were any oversights in the authors' analysis. We reviewed the histopathology of the original studies that equated the classical metaphyseal lesion with child abuse. We compared this with the histopathology of metaphyseal fractures caused by known accidental, severe trauma in children and reviewed the histopathology of artifacts that can sometimes be produced in bone histology preparations. Acute classical metaphyseal lesions showed no hemorrhage, and the chronic classical metaphyseal showed islands of cartilage proliferation at the metaphyses and growth plate, findings consistent with rickets and other metabolic bone disorders. Some of the acute metaphyseal lesions were consistent with artifacts. We believe the original studies that equate the classical metaphyseal lesion with child abuse are flawed. The most compelling observation that challenges the histopathology of the classical metaphyseal lesion as being a fracture is the absence of hemorrhage in the acute classical metaphyseal lesion. We hypothesize that some of the classical metaphyseal lesions were artifacts or represent metabolic bone disorders that were not considered and that these two non-traumatic explanations may have been the basis of the abnormal bone findings. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of low gravity on calcium metabolism and bone formation (L-7)

NASA Technical Reports Server (NTRS)

Suda, Tatsuo

1993-01-01

Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

[Black bone disease of the skull and facial bones].

PubMed

Laure, B; Petraud, A; Sury, F; Bayol, J-C; Marquet-Van Der Mee, N; de Pinieux, G; Goga, D

2009-11-01

We report the case of a patient with a craniofacial black bone disease. This was discovered accidentally during a coronal approach. A 38-year-old patient was referred to our unit for facial palsy having appeared 10 years before. Rehabilitation of the facial palsy was performed with a lengthening temporal myoplasty and lengthening of the upper eyelid elevator. An unusual black color of the skull was observed at incision of the coronal approach. Subperiostal dissection of skull and malars confirmed the presence of a black bone disease. A postoperative history revealed minocycline intake (200mg per day) during 3 years. This craniofacial black bone disease was caused by minocycline intake. The originality of this case is to see directly the entire craniofacial skeleton black. This abnormal pigmentation may affect various organs or tissues. Bone pigmentation is irreversible unlike that of the mouth mucosa or of the skin. This abnormal pigmentation is usually discovered accidentally.

Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease.

PubMed

Tomaschitz, Andreas; Ritz, Eberhard; Pieske, Burkert; Rus-Machan, Jutta; Kienreich, Katharina; Verheyen, Nicolas; Gaksch, Martin; Grübler, Martin; Fahrleitner-Pammer, Astrid; Mrak, Peter; Toplak, Hermann; Kraigher-Krainer, Elisabeth; März, Winfried; Pilz, Stefan

2014-01-01

Inappropriate aldosterone and parathyroid hormone (PTH) secretion is strongly linked with development and progression of cardiovascular (CV) disease. Accumulating evidence suggests a bidirectional interplay between parathyroid hormone and aldosterone. This interaction may lead to a disproportionally increased risk of CV damage, metabolic and bone diseases. This review focuses on mechanisms underlying the mutual interplay between aldosterone and PTH as well as their potential impact on CV, metabolic and bone health. PTH stimulates aldosterone secretion by increasing the calcium concentration in the cells of the adrenal zona glomerulosa as a result of binding to the PTH/PTH-rP receptor and indirectly by potentiating angiotensin 2 induced effects. This may explain why after parathyroidectomy lower aldosterone levels are seen in parallel with improved cardiovascular outcomes. Aldosterone mediated effects are inappropriately pronounced in conditions such as chronic heart failure, excess dietary salt intake (relative aldosterone excess) and primary aldosteronism. PTH is increased as a result of (1) the MR (mineralocorticoid receptor) mediated calciuretic and magnesiuretic effects with a trend of hypocalcemia and hypomagnesemia; the resulting secondary hyperparathyroidism causes myocardial fibrosis and disturbed bone metabolism; and (2) direct effects of aldosterone on parathyroid cells via binding to the MR. This adverse sequence is interrupted by mineralocorticoid receptor blockade and adrenalectomy. Hyperaldosteronism due to klotho deficiency results in vascular calcification, which can be mitigated by spironolactone treatment. In view of the documented reciprocal interaction between aldosterone and PTH as well as the potentially ensuing target organ damage, studies are needed to evaluate diagnostic and therapeutic strategies to address this increasingly recognized pathophysiological phenomenon. © 2013.

The relationship between low bone mass and metabolic syndrome in Korean women.

PubMed

Hwang, D-K; Choi, H-J

2010-03-01

We examined the relationship between low bond mass and metabolic syndrome in 2,475 Korean women. After adjustment for all covariates, mean vertebral BMD was significantly lower in women with metabolic syndrome. Moreover, age and weight adjusted vertebral BMD was significantly decreased with additional components of the metabolic syndrome. Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and metabolic syndrome. It has been suggested that proinflammatory cytokines and low-grade systemic inflammation activate bone resorption and may lead to reduced bone mineral density (BMD). The objective of this study was to determine the relationship between low bone mass and metabolic syndrome in Korean women. This is a cross-sectional study of 2,548 women aged 18 years and over who had visited the Health Promotion Center. Physical examination and laboratory tests were performed. Vertebral BMD was measured using dual-energy X-ray absorptiometry. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III criteria. Among 2,475 women, 511 (21.0%) women had metabolic syndrome. Women with abdominal obesity or hypertriglyceridemia had significantly lower vertebral BMD than women without respective components after adjustment for age, weight, and height. After adjustment for all covariates, mean vertebral BMD was significantly lower in women with metabolic syndrome (p = 0.031). Moreover, age- and weight-adjusted vertebral BMD were significantly decreased with additional components of the metabolic syndrome (p = 0.004). These findings suggest that metabolic syndrome might be another risk factor for osteoporosis and related fractures.

Evolution of bone disease after kidney transplantation: A prospective histomorphometric analysis of trabecular and cortical bone.

PubMed

Carvalho, Catarina; Magalhães, Juliana; Pereira, Luciano; Simões-Silva, Liliana; Castro-Ferreira, Inês; Frazão, João Miguel

2016-01-01

Post-transplant bone disease results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. Bone biopsy remains the gold-standard diagnostic tool. We aimed to prospectively evaluate trabecular and cortical bone by histomorphometry after kidney transplantation. Seven patients, willing to perform follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and trans-iliac bone biopsy were performed within the first 2 months after renal transplantation and repeated after 2-5 years of follow-up. Follow-up biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91 ± 0.81 to 0.47 ± 0.12%, P = 0.036), osteoblasts number/bone surface (0.45 (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 ± 2.02 to 2.22 ± 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81, 2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation (351.65 ± 135.04 to 541.79 ± 151.91 μm, P = 0.024) in follow-up biopsy suggest loss in bone quantity. We found no significant differences in cortical analysis, except a reduction in external cortical osteonal eroded surface (5.76 (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent results. The results show a reduction in bone activity, suggesting increased risk of adynamic bone and loss of bone volume. Cortical bone seems less affected by post-transplant biological changes in the first years after kidney transplantation. © 2015 Asian Pacific Society of Nephrology.

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

Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism.

PubMed

Gutiérrez, Orlando M; Luzuriaga-McPherson, Alexandra; Lin, Yiming; Gilbert, Linda C; Ha, Shin-Woo; Beck, George R

2015-11-01

Phosphorus-based food additives can substantially increase total phosphorus intake per day, but the effect of these additives on endocrine factors regulating bone and mineral metabolism is unclear. This study aimed to examine the effect of phosphorus additives on markers of bone and mineral metabolism. Design and Setting, and Participants: This was a feeding study of 10 healthy individuals fed a diet providing ∼1000 mg of phosphorus/d using foods known to be free of phosphorus additives for 1 week (low-additive diet), immediately followed by a diet containing identical food items; however, the foods contained phosphorus additives (additive-enhanced diet). Parallel studies were conducted in animals fed low- (0.2%) and high- (1.8%) phosphorus diets for 5 or 15 weeks. The changes in markers of mineral metabolism after each diet period were measured. Participants were 32 ± 8 years old, 30% male, and 70% black. The measured phosphorus content of the additive-enhanced diet was 606 ± 125 mg higher than the low-additive diet (P < .001). After 1 week of the low-additive diet, consuming the additive-enhanced diet for 1 week significantly increased circulating fibroblast growth factor 23 (FGF23), osteopontin, and osteocalcin concentrations by 23, 10, and 11%, respectively, and decreased mean sclerostin concentrations (P < .05 for all). Similarly, high-phosphorus diets in mice significantly increased blood FGF23, osteopontin and osteocalcin, lowered sclerostin, and decreased bone mineral density (P < .05 for all). The enhanced phosphorus content of processed foods can disturb bone and mineral metabolism in humans. The results of the animal studies suggest that this may compromise bone health.

What Is Paget's Disease of Bone?

MedlinePlus

... for the Public What Is Paget’s Disease of Bone? Fast Facts: An Easy-to-Read Series of ... and Other Related Conditions: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, ...

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.

Development, regulation, metabolism and function of bone marrow adipose tissues.

PubMed

Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

2018-05-01

Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.

PubMed

Shin, Bae Kun; Kang, Suna; Kim, Da Sol; Park, Sunmin

2018-02-01

Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly

[Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].

PubMed

Aguilar Del Rey, Francisco Javier; García Portales, Rosa; Haro Liger, Manuel; Rodríguez Andreu, José; Casals Sánchez, José Luis; Pérez González, Rita

2016-07-15

To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

[Genetic basis for skeletal disease. Dental management of patients with bone diseases].

PubMed

Shintani, Seikou; Ooshima, Takashi

2010-08-01

Malformation of teeth can be found in patients with bone diseases, which was induced when the disease occurred during the tooth formation. The tooth malformation shows typical manifestations of the disease, which may demonstrate the occurrence of the bone disease. In this article, dental management of the patients with bone diseases such as X-linked hypophosphatemic rickets, osteogenesis imperfecta, and hypophosphatasia was presented.

Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density.

PubMed

Klaus, J; Reinshagen, M; Adler, G; Boehm, Bo; von Tirpitz, C

2008-10-23

Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

Pediatric inflammatory bowel disease and bone health.

PubMed

Mascarenhas, Maria R; Thayu, Meena

2010-08-01

Childhood and adolescence are important periods for bone development. Any disease that affects bone health has the potential to affect the bones not only in the short term but also later in life. Bone health abnormalities in patients with inflammatory bowel disease are being increasingly recognized. Screening the at-risk patient is important so that appropriate treatments can be instituted. Treatment options are limited to vitamin D and calcium supplementation, control of underlying disease activity, and appropriate physical activity. The role of bisphosphonates in these patients needs to be better studied, and treatment with bisphosphonates may be considered for some patients in consultation with a bone health expert.

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

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.

Fracture risk and bone mineral density in metabolic syndrome: a meta-analysis.

PubMed

Esposito, Katherine; Chiodini, Paolo; Capuano, Annalisa; Colao, Annamaria; Giugliano, Dario

2013-08-01

The risk of bone fractures in subjects with the metabolic syndrome is unknown. We did a meta-analysis to assess the association between metabolic syndrome, risk of fractures, and bone mineral density (BMD). We did searches on electronic databases (Medline, Scopus, and ISI Web of Knowledge) until December 2012 and searched reports to identify studies in humans on bone fractures and BMD at different sites. Two independent reviewers collected the relevant reports. We did random-effects meta-analyses to determine the risk of fractures and BMD values associated with metabolic syndrome. A total of 17 studies, with 35 datasets, were included. In 10 articles (14 datasets) including 1350 incident and 1628 prevalent fractures, metabolic syndrome was associated with a reduced fracture risk (risk ratio = 0.85, 95% confidence interval, 0.71-1.00; high heterogeneity: I(2) = 55%, P = .006). Omission of 2 outlier studies resulted in a significant negative association (risk ratio = 0.85, P = .012; I(2) = 34%, P = .130). Most of the reduced fracture risk was seen in cohort studies (18% reduced risk), suggesting a direction of causality; sex, site of fracture, and definition of the syndrome did not affect the estimates. In 16 articles, including 29 341 subjects, there was no difference in spine, femoral neck, or calcaneus BMD values between subjects with or without metabolic syndrome; mean differences ranged from 0.001 to 0.012 g/cm(2) (P > .10). This article shows a reduced risk of bone fractures associated with metabolic syndrome, without modification of BMD. The clinical significance of these findings remains uncertain and should be addressed in future prospective studies.

[Aging and homeostasis. Management of disorders in bone and calcium metabolism associated with ageing.

PubMed

Takeuchi, Yasuhiro

Disorders in bone and calcium metabolism associated with aging are based on secondary hyperparathyroidism due to impaired intestinal calcium absorption caused by insufficient vitamin D actions and augmented bone resorption due to sex hormone deficiency. Both of them are involved in the development of osteoporosis that increases risk of fractures. Therefore, the most important thing for management of disorders in bone and calcium metabolism associated with aging is to prevent fractures with appropriate drugs for osteoporosis.

Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer.

PubMed

Zidan, Jamal; Keidar, Zohar; Basher, Walid; Israel, Ora

2004-01-01

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoral neck after 12 mo treatment with tamoxifen (p = 0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p < or = 0.01). TSH and PTH levels were increased (p < or = 0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen's effect on bone mineral density.

Cellular Mechanisms of Multiple Myeloma Bone Disease

PubMed Central

Oranger, Angela; Carbone, Claudia; Izzo, Maddalena; Grano, Maria

2013-01-01

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and decreased osteoblast differentiation. A dysregulated production of numerous cytokines that can contribute to the uncoupling of bone cell activity is well documented in the bone marrow microenvironment of MM patients. These molecules are produced not only by malignant plasma cells, that directly contribute to MM bone disease, but also by bone, immune, and stromal cells interacting with each other in the bone microenvironment. This review focuses on the current knowledge of MM bone disease biology, with particular regard on the role of bone and immune cells in producing cytokines critical for malignant plasma cell proliferation as well as in osteolysis development. Therefore, the understanding of MM pathogenesis could be useful to the discovery of novel agents that will be able to both restore bone remodelling and reduce tumor burden. PMID:23818912

Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men.

PubMed

Leder, Benjamin Z; Finkelstein, Joel S

2005-12-01

Both estrogens and androgens play important roles in skeletal development and maintenance in men. The relative importance of estrogens and androgens in male bone metabolism, however, remains undefined. Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men. Currently, anastrozole is being investigated as a potential agent for the treatment of hypogonadism in aging men. Because anastrozole lowers estrogen levels and raises androgen levels, its effect on bone metabolism is difficult to predict. To assess the effects of anastrozole on bone turnover, we randomized 37 elderly (ages 62-74) mildly hypogonadal men (serum testosterone <350 ng/dl) to receive either anastrozole 1 mg daily (n=12), anastrozole 1 mg twice weekly (n=11), or daily placebo (n=14) for 12 weeks. Serum gonadal steroid levels, serum and urine biochemical markers of bone turnover, serum osteoprotegerin, and total body bone mineral density were measured at baseline and week 12. Mean serum levels of total and bioavailable testosterone increased substantially in both treated groups. Specifically, mean +/- SD bioavailable testosterone levels increased from 99+/-31 ng/dl to 207+/-65 ng/dl in the group receiving 1 mg of anastrozole daily and from 115+/-37 ng/dl to 178+/-55 ng/dl in the subjects receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both groups). Serum estradiol levels decreased modestly in both treated groups (from 26+/-8 pg/ml to 17+/-6 pg/ml in the daily treatment group and from 27+/-8 pg/ml to 17+/-5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both groups). Despite these hormonal changes, no increases in biochemical markers of bone resorption were observed. Specifically, mean serum N-telopeptide and urinary deoxypyridinoline concentrations remained stable in both treated groups over the 12-week treatment period. Similarly, serum biochemical markers of bone formation (osteocalcin and amino

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

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats.

PubMed

Zivna, Helena; Gradošová, Iveta; Zivny, Pavel; Cermakova, Eva; Palicka, Vladimir

2018-06-13

Spontaneously hypertensive rats (SHR) represent a model of essential hypertension. We studied the effect of amlodipine (AML) on bone markers, bone mineral density (BMD), and biomechanical properties of osteopenic bone induced by orchidectomy in male SHR. Rats were allocated to 3 groups and were sacrificed after 12 weeks: sham-operated control; orchidectomised control; and orchidectomised receiving a diet supplemented with AML. Indicators of bone turnover were assessed in bone homogenate, BMD was measured by dual energy X-ray absorptiometry, and the femurs were subjected to biomechanical testing. Long-term AML administration does not have a negative impact on bone metabolism and density in male SHR. © 2018 S. Karger AG, Basel.

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

Effects of electromagnetic pulse on bone metabolism of mice in vivo.

PubMed

Li, Kang-Chu; Ma, Shi-Rong; Ding, Gui-Rong; Guo, Yao; Guo, Guo-Zhen

2009-12-01

To study the effects of electromagnetic pulse (EMP) on bone metabolism of mice in vivo. Twenty-four male BALB/c mice were divided into a control group and 2 experimental groups (n=8). The whole-body of mice in experimental groups were exposed to 50 kV/m and 400kV/m EMP, 400 pulses daily for 7 consecutive days at 2 seconds intervals. Alkaline phosphotase (ALP) activity, serum calcium concentration and osteocalcin level and trabecular bone volume (BV/TV, %) were measured immediately after EMP exposure by biochemical, ELISA and morphological methods. The ALP activity, serum calcium concentration and osteocalcin level and BV/TV in experimental groups remained unchanged after EMP exposure. Conclusion Under our experimental conditions, EMP exposure cannot affect bone metabolism of mice in vivo.

Cross-talk of MicroRNA and hydrogen sulfide: A novel therapeutic approach for bone diseases

PubMed Central

Zhai, Yuankun; Tyagi, Suresh C.; Tyagi, Neetu

2017-01-01

Bone homeostasis requires a balance between the bone formation of osteoblasts and bone resorption of osteoclasts to maintain ideal bone mass and bone quality. An imbalance in bone remodeling processes results in bone metabolic disorders such as osteoporosis. Hydrogen sulfide (H2S), a gasotransmitter, has attracted the focus of many researchers due to its multiple physiological functions. It has been implicated in anti-inflammatory, vasodilatory, angiogenic, cytoprotective, anti-oxidative and anti-apoptotic mechanisms. H2S has also been shown to exert osteoprotective activity through its anti-inflammatory and anti-oxidative effects. However, the underlying molecular mechanisms by which H2S mitigates bone diseases are not completely understood. Experimental evidence suggests that H2S may regulate signaling pathways by directly influencing a gene in the cascade or interacting with some other gasotransmitter (carbon monoxide or nitric oxide) or both. MicroRNAs (miRNAs) are short non-coding RNAs which regulate gene expression by targeting, binding and suppressing mRNAs; thus controlling cell fate. Certainly, bone remodeling is also regulated by miRNAs expression and has been reported in many studies. MicroRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new possibility for exploring the H2S-microRNA crosstalk in bone diseases. However, the relationship between miRNAs, bone development, and H2S is still not well explained. This review focuses on miRNAs and their roles in regulating bone remodeling and possible mechanisms behind H2S mediated bone loss inhibition, H2S-miRNAs crosstalk in relation to the pathophysiology of bone remodeling, and future perspectives for miRNA-H2S as a therapeutic agent for bone diseases. PMID:28618652

Cross-talk of MicroRNA and hydrogen sulfide: A novel therapeutic approach for bone diseases.

PubMed

Zhai, Yuankun; Tyagi, Suresh C; Tyagi, Neetu

2017-08-01

Bone homeostasis requires a balance between the bone formation of osteoblasts and bone resorption of osteoclasts to maintain ideal bone mass and bone quality. An imbalance in bone remodeling processes results in bone metabolic disorders such as osteoporosis. Hydrogen sulfide (H 2 S), a gasotransmitter, has attracted the focus of many researchers due to its multiple physiological functions. It has been implicated in anti-inflammatory, vasodilatory, angiogenic, cytoprotective, anti-oxidative and anti-apoptotic mechanisms. H 2 S has also been shown to exert osteoprotective activity through its anti-inflammatory and anti-oxidative effects. However, the underlying molecular mechanisms by which H 2 S mitigates bone diseases are not completely understood. Experimental evidence suggests that H 2 S may regulate signaling pathways by directly influencing a gene in the cascade or interacting with some other gasotransmitter (carbon monoxide or nitric oxide) or both. MicroRNAs (miRNAs) are short non-coding RNAs which regulate gene expression by targeting, binding and suppressing mRNAs; thus controlling cell fate. Certainly, bone remodeling is also regulated by miRNAs expression and has been reported in many studies. MicroRNAs also regulate H 2 S biosynthesis. The inter-regulation of microRNAs and H 2 S opens a new possibility for exploring the H 2 S-microRNA crosstalk in bone diseases. However, the relationship between miRNAs, bone development, and H 2 S is still not well explained. This review focuses on miRNAs and their roles in regulating bone remodeling and possible mechanisms behind H 2 S mediated bone loss inhibition, H 2 S-miRNAs crosstalk in relation to the pathophysiology of bone remodeling, and future perspectives for miRNA-H 2 S as a therapeutic agent for bone diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

PubMed

Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

2007-03-01

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

PubMed Central

Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

1975-01-01

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs.

PubMed

Seymour, Roger S; Smith, Sarah L; White, Craig R; Henderson, Donald M; Schwarz-Wings, Daniela

2012-02-07

The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs

PubMed Central

Seymour, Roger S.; Smith, Sarah L.; White, Craig R.; Henderson, Donald M.; Schwarz-Wings, Daniela

2012-01-01

The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat. PMID:21733896

Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism.

PubMed

Cao, Yixuan; Wang, Yongqiang; Sprangers, Sara; Picavet, Daisy I; Glogauer, Michael; McCulloch, Christopher A; Everts, Vincent

2017-08-01

Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP + osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm 2 ; p < 0.05), as were nuclear size and the surface area of cytoplasm. The nuclei of adseverin null osteoclasts exhibited more heterochromatin (31 ± 3%) than wild-type cells (8 ± 1%), suggesting that adseverin affects cell differentiation. The data indicate that in healthy, developing tissues, adseverin contributes to the regulation of osteoclast structure but not to bone metabolism in vivo.

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.

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.

[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.

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

MedlinePlus

... and Osteoarthritis: Different Yet Related Paget’s Disease of Bone and Osteoarthritis: Different Yet Related Paget’s disease and ... about Paget’s disease , contact: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones. ...

Metabolically healthy/unhealthy components may modify bone mineral density in obese people.

PubMed

Mirzababaei, Atieh; Mirzaei, Khadijeh; Khorrami-Nezhad, Leila; Maghbooli, Zhila; Keshavarz, Seyed Ali

2017-10-29

Link between obesity and bone health is controversial. It seems that maybe the difference in metabolic status leads to this difference. We studied relation between metabolically healthy/unhealthy components with bone mineral density. Results showed metabolically unhealthy obesity (MUHO) phenotypes have better bone status at hip site than metabolically healthy obesity (MHO). Also, component metabolic can effect on BMD in different sites. This cross-sectional study aimed to compare total BMD and L-L4 BMD in MHO and MUHO base on Karelis criteria. We enrolled 272 Iranian obese women and men (BMI ≥ 30). According to Karelis criteria, the participants were grouped base to MHO and MUHO. The body composition and BMD were assessed for all cases. Serum HDL-C, LDL-C, total cholesterol, triglyceride (TG), fasting blood glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP) levels were quantified by ELISA method. Our results demonstrate MUHO phenotype have high total BMD more than MHO (P = 0.01, CI = 0.12 to 0.21). Also, the results of logistic regression analysis showed MUHO have strongly associated with total BMD (β = -0.42, CI = - 0.31 to - 0.04, P = 0.009), but did not affected L2-L4 BMD (β = - 0.09, CI = - 0.14 to 0.08, P = 0.578); this represents that there was discordance in MUHO subjects. Our evidence implicated that HOMA-IR, high level serum TG, hs-CRP, and low level serum HDL had mediatory effect on relationship between obesity and high BMD at the hip region in MUHO subjects (P < 0.05). Present evidence indicates that, could be a novel link between difference in MUH phenotype and MH phenotype with bone status. Also, component metabolic can effect on BMD in different sites.

Dietary Sodium Effects on Bone Loss and Calcium Metabolism During Bed Rest

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Arnaud, Sara B.; Abrams, Steven A.; Paloski, W. H. (Technical Monitor)

2000-01-01

The acceleration of age-related bone loss is one of the most detrimental effects of space flight. The ability to understand and counteract this loss will be critical for crew health and safety during and after long-duration missions. Studies in healthy ambulatory individuals have linked high salt (sodium) diets, hypercalciuria, and increased renal stone risk. Dietary salt may modulate bone loss through changes in calcium metabolism and the calcium endocrine system. The research proposed here will determine the role of dietary salt in the loss of bone during simulated space flight. Calcium metabolism will be determined through calcium kinetics studies, endocrine and biochemical measurements; and estimates of the mass, distribution and mechanical properties of bone, in subjects fed low (100 mmol sodium/day) or high (250 mmol sodium/day) levels of dietary salt during 28 days of headdown tilt bedrest. This research addresses the role of dietary salt in the loss of bone and calcium in space flight, and integrates the changes in calcium metabolism with those occurring in other physiologic systems. These data will be critical for both countermeasure development, and in determination of nutritional requirements for extended-duration space flight. The potential countermeasures resulting from this research will reduce health risks due to acceleration of age-related osteoporosis and increased risk of renal stone formation..

[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.

Martial Arts and Metabolic Diseases.

PubMed

Hamasaki, Hidetaka

2016-05-09

Different forms of martial arts are practiced worldwide, each with various intensities of physical activity. These disciplines are potentially an effective exercise therapy for metabolic diseases. Tai chi is the most well-studied style of martial arts and has shown evidence of its effect on metabolic diseases; however, little evidence is available regarding the association between other styles of martial arts and metabolic health. To summarize and evaluate the effects of martial arts on metabolic diseases, eligible articles were searched by using Pubmed. To date, systematic reviews provide no definite conclusion on the effectiveness of tai chi for treating metabolic diseases because of a small numbers of subjects, short durations of clinical trials, and some biases involved in testing. However, there are several clinical studies on subjects with metabolic diseases, which show that tai chi improves obesity, glycemic control, blood pressure control, and lipid profiles. Currently, some limited evidence suggests that other martial arts, such as kung fu and karate, may be beneficial for body composition, glycemic control, and arterial stiffness. To clarify the effectiveness of martial arts for treating metabolic diseases, well-designed prospective studies, preferably with a larger number of subjects and of longer duration, are warranted.

Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.

PubMed

Rowe, Peter S N

2012-01-01

More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500

β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease

PubMed Central

2015-01-01

The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p < 0.05). β-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease (p < 0.05). Furthermore, treatment with β-glucans reduced the expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin expression in animals with diabetes and periodontal disease (p < 0.05). It was concluded that treatment with β-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease. PMID:26291983

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.

[The biological role of exosomes in bone remodeling and bone diseases.

PubMed

Urabe, Fumihiko; Yoshioka, Yusuke; Ochiya, Takahiro

Exosomes are about 100nm membrane vesicles, and released from almost all cell types. They carry and transfer a wide variety of molecules, such as mRNAs, microRNAs, proteins, and lipids, as modulators of intercellular communication. Various studies have shown that this exosome-mediated intercellular communication lead to proliferation, invasion and metastasis of cancer cells. In addition to that, emerging data suggest that exosomes are also involved in physiological processes of bone remodeling and bone diseases. Increasing understanding of the working mechanism of exosomes will provide us with new therapeutic and diagnostic opportunities. Here we summarize the current research on exosomes in bone remodeling and bone diseases.

The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease.

PubMed

Oksztulska-Kolanek, Ewa; Znorko, Beata; Michałowska, Małgorzata; Pawlak, Krystyna

2016-01-01

Mineral metabolism disturbances are common in chronic kidney disease (CKD) and have been classified as a new clinical entity, also known as CKD-mineral and bone disorders (CKD-MBD). A decrease in the bone strength, whose clinical manifestation is a tendency for fracture, has been recognized as an important component of CKD-MBD. Because of ethical issues, measurements of the bone strength in the human body are usually limited to noninvasive techniques, such as radiography, dual-energy X-ray absorptiometry and the assays of bone turnover biomarkers. However, it has been postulated recently that the evidence concerning bone strength based solely on the determination of the bone quantity may be insufficient and that bone quality should also be examined. In this regard, an animal model of CKD can represent an experimental tool to test the effectiveness of new therapeutic strategies. Despite the many available methods that are used to diagnose metabolic bone disorders and predict fracture risk especially in small rodents with CKD, it turns out that the most appropriate are biomechanical tests, which can provide information about the structural and material properties of bone. The present review summarizes and discusses the principles for carrying out selected biomechanical tests (3-point bending test and compression test) and their application in clinical practice. © 2015 S. Karger AG, Basel.

Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism.

PubMed

Wan Hasan, Wan Nuraini; Chin, Kok-Yong; Jolly, James Jam; Abd Ghafar, Norzana; Soelaiman, Ima Nirwana

2018-04-23

Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling. This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential. Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans. mevalonate pathway can be exploited to develop effective antiosteoporosis agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

High-fat diets affect energy and bone metabolism in growing rats.

PubMed

Macri, Elisa V; Gonzales Chaves, Macarena M; Rodriguez, Patricia N; Mandalunis, Patricia; Zeni, Susana; Lifshitz, Fima; Friedman, Silvia M

2012-06-01

High-fat diets are usually associated with greater weight (W) gain and body fat (BF). However, it is still unclear whether the type and amount of fat consumed influence BF. Additionally, dietary fat intake may also have consequences on skeletal health. To evaluate in healthy growing rats the effects of high-fat diets and type of dietary fat intake (saturated or vegetable oils) on energy and bone metabolism. At weaning, male Wistar rats (n = 50) were fed either a control diet (C; fat = 7% w/w) or a high-fat diet (20% w/w) containing either: soybean oil, corn oil (CO), linseed oil (LO), or beef tallow (BT) for 8 weeks. Zoometric parameters, BF, food intake and digestibility, and total and bone alkaline phosphatase (b-AP) were assessed. Total skeleton bone mineral density (BMD) and content (BMC), BMC/W, spine BMD, and bone volume (static-histomorphometry) were measured. Animals fed BT diet achieved lower W versus C. Rats fed high-fat vegetable oil diets showed similar effects on the zoometric parameters but differed in BF. BT showed the lowest lipid digestibility and BMC. In contrast, high vegetable oil diets produced no significant differences in BMC, BMC/W, BMD, spine BMD, and bone volume. Marked differences were observed for LO and BT groups in b-AP and CO and BT groups in bone volume. BT diet rich in saturated fatty acids had decreased digestibility and adversely affected energy and bone metabolisms, in growing healthy male rats. There were no changes in zoometric and bone parameters among rats fed high vegetable oil diets.

Martial Arts and Metabolic Diseases

PubMed Central

Hamasaki, Hidetaka

2016-01-01

Different forms of martial arts are practiced worldwide, each with various intensities of physical activity. These disciplines are potentially an effective exercise therapy for metabolic diseases. Tai chi is the most well-studied style of martial arts and has shown evidence of its effect on metabolic diseases; however, little evidence is available regarding the association between other styles of martial arts and metabolic health. To summarize and evaluate the effects of martial arts on metabolic diseases, eligible articles were searched by using Pubmed. To date, systematic reviews provide no definite conclusion on the effectiveness of tai chi for treating metabolic diseases because of a small numbers of subjects, short durations of clinical trials, and some biases involved in testing. However, there are several clinical studies on subjects with metabolic diseases, which show that tai chi improves obesity, glycemic control, blood pressure control, and lipid profiles. Currently, some limited evidence suggests that other martial arts, such as kung fu and karate, may be beneficial for body composition, glycemic control, and arterial stiffness. To clarify the effectiveness of martial arts for treating metabolic diseases, well-designed prospective studies, preferably with a larger number of subjects and of longer duration, are warranted. PMID:29910276

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.

Bone Cell Bioenergetics and Skeletal Energy Homeostasis

PubMed Central

Riddle, Ryan C.; Clemens, Thomas L.

2017-01-01

The rising incidence of metabolic diseases worldwide has prompted renewed interest in the study of intermediary metabolism and cellular bioenergetics. The application of modern biochemical methods for quantitating fuel substrate metabolism with advanced mouse genetic approaches has greatly increased understanding of the mechanisms that integrate energy metabolism in the whole organism. Examination of the intermediary metabolism of skeletal cells has been sparked by a series of unanticipated observations in genetically modified mice that suggest the existence of novel endocrine pathways through which bone cells communicate their energy status to other centers of metabolic control. The recognition of this expanded role of the skeleton has in turn led to new lines of inquiry directed at defining the fuel requirements and bioenergetic properties of bone cells. This article provides a comprehensive review of historical and contemporary studies on the metabolic properties of bone cells and the mechanisms that control energy substrate utilization and bioenergetics. Special attention is devoted to identifying gaps in our current understanding of this new area of skeletal biology that will require additional research to better define the physiological significance of skeletal cell bioenergetics in human health and disease. PMID:28202599

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. 2016 BMJ Publishing Group Ltd.

[Effects of the combined calcitonin and sodium etidronate therapy in Paget's disease of bone].

PubMed

Nuti, R; Turchetti, V; Righi, G; Vattimo, A

1982-03-03

The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.

Circular RNAs and hereditary bone diseases.

PubMed

Zhai, Naixiang; Lu, Yanqin; Wang, Yanzhou; Ren, Xiuzhi; Han, Jinxiang

2018-02-01

Circular RNA (circRNA) is a non-linear form of RNA derived from exonic, intronic, and exon-intron gene regions. circRNAs are characterized by covalent closed loops, highly stable nuclease resistance, and specific expression in species and developmental stages. CircRNA molecules have been identified as playing roles in the regulation of cell transcription, transcriptional expression after translation, interactions with microRNAs, and protein coding. A high stability and tissue- and disease-specific expression allow circRNAs to serve as potential biomarkers both for diseases and prognosis. CircRNAs function in bone remodeling by directly participating in bone-related signaling pathways and by forming the circRNA-miRNA-mRNA axis. Studies have seldom reported on the low incidence of circRNAs in genetic bone disorders. The current study reviews the characteristics of circRNAs and recent research on their role in rare hereditary bone diseases.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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. Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density ( a BMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). MetS was present in 975 men (31.2 %). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine a BMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip a BMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models. Men with MetS have higher a BMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and

The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.

PubMed

Jiang, Jun; Boyle, Leryn J; Mikus, Catherine R; Oberlin, Douglas J; Fletcher, Justin A; Thyfault, John P; Hinton, Pamela S

2014-11-01

Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small

Effects of short-term step aerobics exercise on bone metabolism and functional fitness in postmenopausal women with low bone mass.

PubMed

Wen, H J; Huang, T H; Li, T L; Chong, P N; Ang, B S

2017-02-01

Measurement of bone turnover markers is an alternative way to determine the effects of exercise on bone health. A 10-week group-based step aerobics exercise significantly improved functional fitness in postmenopausal women with low bone mass, and showed a positive trend in reducing resorption activity via bone turnover markers. The major goal of this study was to determine the effects of short-term group-based step aerobics (GBSA) exercise on the bone metabolism, bone mineral density (BMD), and functional fitness of postmenopausal women (PMW) with low bone mass. Forty-eight PMW (aged 58.2 ± 3.5 years) with low bone mass (lumbar spine BMD T-score of -2.00 ± 0.67) were recruited and randomly assigned to an exercise group (EG) or to a control group (CG). Participants from the EG attended a progressive 10-week GBSA exercise at an intensity of 75-85 % of heart rate reserve, 90 min per session, and three sessions per week. Serum bone metabolic markers (C-terminal telopeptide of type 1 collagen [CTX] and osteocalcin), BMD, and functional fitness components were measured before and after the training program. Mixed-models repeated measures method was used to compare differences between the groups (α = 0.05). After the 10-week intervention period, there was no significant exercise program by time interaction for CTX; however, the percent change for CTX was significantly different between the groups (EG = -13.1 ± 24.4 % vs. CG = 11.0 ± 51.5 %, P < 0.05). While there was no significant change of osteocalcin in both groups. As expected, there was no significant change of BMD in both groups. In addition, the functional fitness components in the EG were significantly improved, as demonstrated by substantial enhancement in both lower- and upper-limb muscular strength and cardiovascular endurance (P < 0.05). The current short-term GBSA exercise benefited to bone metabolism and general health by significantly reduced bone resorption activity and improved

The conclusiveness of less-invasive imaging techniques (computer tomography, X-ray) with regard to their identification of bone diseases in a primate model (Callithrix jacchus).

PubMed

Grohmann, J; Taetzner, S; Theuss, T; Kuehnel, F; Buchwald, U; Einspanier, A

2012-04-01

Although common marmosets seem to be appropriate animal models to examine bone diseases, no data about the conclusiveness of less-invasive techniques are available. Therefore, the aim was to combine different techniques to analyse changes in bone metabolism of common marmosets with bone diseases. Five monkeys were examined by X-ray, computer tomography (CT), histology and immunohistochemistry (IHC). Monkeys with lowest bone mineral density (BMD) showed increased bone marrow, decreased cancellous bone and decreased contrast in X-ray. Highest alkaline phosphatase (AP)-levels were detected in bones with low elastic modulus. Expression of osteopontin (OPN), osteocalcin (OC) and runt-related transcriptions factor 2 (RUNX 2) was detected in bones with high modulus. No expression was present in bones with lower modulus. Collagen type I and V were found in every bone. In conclusion, CT, X-ray and AP are useful techniques to detect bone diseases in common marmosets. These observations could be confirmed by IHC. © 2012 John Wiley & Sons A/S.

Prevalence of Vitamin D Deficiency and Its Association With Metabolic Disease in Korean Orthopedic Patients.

PubMed

Kim, Ki-Tack; Kang, Kyung-Chung; Shin, Dong-Eun; Lee, Sang-Hoon; Lee, Jung-Hee; Kwon, Tae-Yoon

2015-10-01

Vitamin D is considered essential for bone and muscle health, and some studies have demonstrated the positive effects of vitamin D on metabolic diseases and cancer. Nevertheless, a high prevalence of vitamin D deficiency has been reported in various populations, regardless of country or race. However, no studies regarding the prevalence of vitamin D deficiency in Korean orthopedic patients currently exist. This cross-sectional study included 272 male and 937 female patients aged 50 years and older who were consecutively admitted to the authors' orthopedic department. Vitamin D (25-hydroxy vitamin D), bone turnover markers (osteocalcin, c-telopeptide), and bone mineral density were measured. The prevalence of vitamin D deficiency and its association with other factors were evaluated. Mean patient age was 67.2 ± 8.9 years, and mean level of vitamin D was 16.1 ± 9.1 ng/mL. Overall, 91.2% of patients had deficient (<20 ng/mL; 70.6%) or insufficient (20-30 ng/mL; 20.6%) levels of vitamin D. Vitamin D level did not vary by age group or sex. The level of vitamin D was significantly associated with osteocalcin, c-telopeptide, calcium, alkaline phosphatase, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glucose (P<.01). Vitamin D level in Korean orthopedic patients of this region was extremely low, regardless of sex and age. Although vitamin D was not directly associated with bone mineral density, there were significant associations between vitamin D and other factors related to bone health and metabolic diseases. Copyright 2015, SLACK Incorporated.

Effect of simulated weightlessness and chronic 1,25-dihydroxyvitamin D administration on bone metabolism

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Globus, R. K.; Levens, M. J.; Wronski, T. J.; Morey-Holton, E.

1985-01-01

Weightlessness, as experienced during space flight, and simulated weightlessness induce osteopenia. Using the suspended rat model to simulate weightlessness, a reduction in total tibia Ca and bone formation rate at the tibiofibular junction as well as an inhibition of Ca-45 and H-3-proline uptake by bone within 5-7 days of skeletal unloading was observed. Between days 7 and 15 of unloading, uptake of Ca-45 and H-3-proline, and bone formation rate return to normal, although total bone Ca remains abnormally low. To examine the relationship between these characteristic changes in bone metabolism induced by skeletal unloading and vitamin D metabolism, the serum concentrations of 25-hydroxyvitamin D (25-OH-D), 24, 25-dihydroxyvitamin D (24,25(OH)2D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) at various times after skeletal unloading were measured. The effect of chronic infusion of 1,25(OH)2D3 on the bone changes associated with unloading was also determined.

Neuronal hypothalamic regulation of body metabolism and bone density is galanin dependent.

PubMed

Idelevich, Anna; Sato, Kazusa; Nagano, Kenichi; Rowe, Glenn; Gori, Francesca; Baron, Roland

2018-06-01

In the brain, the ventral hypothalamus (VHT) regulates energy and bone metabolism. Whether this regulation uses the same or different neuronal circuits is unknown. Alteration of AP1 signaling in the VHT increases energy expenditure, glucose utilization, and bone density, yet the specific neurons responsible for each or all of these phenotypes are not identified. Using neuron-specific, genetically targeted AP1 alterations as a tool in adult mice, we found that agouti-related peptide-expressing (AgRP-expressing) or proopiomelanocortin-expressing (POMC-expressing) neurons, predominantly present in the arcuate nucleus (ARC) within the VHT, stimulate whole-body energy expenditure, glucose utilization, and bone formation and density, although their effects on bone resorption differed. In contrast, AP1 alterations in steroidogenic factor 1-expressing (SF1-expressing) neurons, present in the ventromedial hypothalamus (VMH), increase energy but decrease bone density, suggesting that these effects are independent. Altered AP1 signaling also increased the level of the neuromediator galanin in the hypothalamus. Global galanin deletion (VHT galanin silencing using shRNA) or pharmacological galanin receptor blockade counteracted the observed effects on energy and bone. Thus, AP1 antagonism reveals that AgRP- and POMC-expressing neurons can stimulate body metabolism and increase bone density, with galanin acting as a central downstream effector. The results obtained with SF1-expressing neurons, however, indicate that bone homeostasis is not always dictated by the global energy status, and vice versa.

Aesculin modulates bone metabolism by suppressing receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and transduction signals.

PubMed

Zhao, Xiao-Li; Chen, Lin-Feng; Wang, Zhen

2017-06-17

Aesculin (AES), a coumarin compound derived from Aesculus hippocasanum L, is reported to exert protective role against inflammatory diseases, gastric disease and cancer. However, direct effect of AES in bone metabolism is deficient. In this study, we examined the effects of AES on osteoclast (OC) differentiation in receptor activator of NF-κB ligand (RANKL)-induced RAW264.7 cells. AES inhibits the OC differentiation in both dose- and time-dependent manner within non-toxic concentrations, as analyzed by Tartrate Resistant Acid Phosphatase (TRAP) staining. The actin ring formation manifesting OC function is also decreased by AES. Moreover, expressions of osteoclastogenesis related genes Trap, Atp6v0d2, Cathepsin K and Mmp-9 are decreased upon AES treatment. Mechanistically, AES attenuates the activation of MAPKs and NF-κB activity upon RANKL induction, thus leading to the reduction of Nfatc1 mRNA expression. Moreover, AES inhibits Rank expression, and RANK overexpression markedly decreases AES's effect on OC differentiation and NF-κB activity. Consistently, AES protects against bone mass loss in the ovariectomized and dexamethasone treated rat osteoporosis model. Taken together, our data demonstrate that AES can modulate bone metabolism by suppressing osteoclastogenesis and related transduction signals. AES therefore could be a promising agent for the treatment of osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

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...

Facts a New Patient Needs to Know about Paget's Disease of Bone

MedlinePlus

... Patient Needs to Know About Paget’s Disease of Bone What Is Paget’s Disease of Bone? Paget’s disease of bone causes bones to grow ... Paget’s disease. These include: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones. ...

Comparative effect of soy protein, soy isoflavones, and 17beta-estradiol on bone metabolism in adult ovariectomized rats.

PubMed

Cai, David J; Zhao, Yongdong; Glasier, Jennifer; Cullen, Diane; Barnes, Stephen; Turner, Charles H; Wastney, Meryl; Weaver, Connie M

2005-05-01

This study provided a comprehensive investigation on the effect of soy protein and soy isoflavones on both calcium and bone metabolism in virgin adult rats. The measurements included bone histology, calcium kinetic modeling, calcium balance, bone densitometry, and whole body densitometry. Results confirmed the bone-preserving effect of estrogen but did not support a bone-sparing role of soy isoflavones. Several animal and short-term human studies have indicated that soy protein isolate enriched with isoflavones may be used as an alternative therapy to estrogen replacement therapy. However, none of the previous studies have investigated this estrogenic effect on both calcium and bone metabolism in animals or humans, which is essential in ascertaining the mode of action of isoflavones. This study was designed to determine the effects of soy protein versus isoflavones on calcium and bone metabolism in an ovariectomized rat model. Unmated 6-month-old ovariectomized and sham-operated female Sprague-Dawley rats were randomly assigned to nine groups (16 rats/group) and pair-fed soy- or casein-based diets with or without isoflavones for 8 weeks. A reference group was administered estrogen through subcutaneous implants (20-35 pg/liter plasma). Bone densitometry, histomorphometry, and mechanical testing were used to study bone metabolism and quality. Calcium metabolism was studied using calcium tracer balance and kinetics. After ovariectomy, estrogen prevented bone loss in trabecular bone and suppressed formation on both trabecular and cortical bone surfaces. Isoflavones given as enriched soy protein isolate or supplements did not prevent trabecular bone loss. Combining isoflavones with estrogen had no additional benefits over estrogen alone. There were no differences in response to isoflavones caused by protein source. None of the treatments significantly affected either total Ca balance or (45)Ca absorption. However, soy protein showed significant effects on reducing

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.

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.

[Impact of thyroid diseases on bone].

PubMed

Tsourdi, E; Lademann, F; Siggelkow, H

2018-05-09

Thyroid hormones are key regulators of skeletal development in childhood and bone homeostasis in adulthood, and thyroid diseases have been associated with increased osteoporotic fractures. Hypothyroidism in children leads to an impaired skeletal maturation and mineralization, but an adequate and timely substitution with thyroid hormones stimulates bone growth. Conversely, hyperthyroidism at a young age accelerates skeletal development, but may also cause short stature because of a premature fusion of the growth plates. Hypothyroidism in adults causes an increase in the duration of the remodeling cycle and, thus, leads to low bone turnover and enhanced mineralization, but an association with a higher fracture risk is less well established. In adults, a surplus of thyroid hormones enhances bone turnover, mostly due to an increased bone resorption driven by osteoclasts. Thus, hyperthyroidism is a well-recognized cause of high-bone turnover secondary osteoporosis, resulting in an increased susceptibility to fragility fractures. Subclinical hyperthyroidism, especially resulting from endogenous disease, also has an adverse effect on bone mineral density and is associated with fractures. In most patients with overt or subclinical hyperthyroidism restoration of the euthyroid status reverses bone loss. In postmenopausal women who receive thyroid-stimulating hormone suppression therapy because of thyroid cancer, antiresorptive treatments may be indicated. Overall, extensive data support the importance of a euthyroid status for bone mineral accrual and growth in childhood as well as maintenance of bone health in adulthood.

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

PubMed

Lamb, Joseph J; Holick, Michael F; Lerman, Robert H; Konda, Veera R; Minich, Deanna M; Desai, Anuradha; Chen, Tai C; Austin, Melissa; Kornberg, Jacob; Chang, Jyh-Lurn; Hsi, Alex; Bland, Jeffrey S; Tripp, Matthew L

2011-05-01

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D₃, and 500 μg vitamin K₁ twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P < .001) in serum osteocalcin (indicative of bone turnover), whereas the placebo arm exhibited a 21% increase (P = .003). Serum 25-hydroxyvitamin D increased 23% (P = .001) in the intervention arm and decreased 12% (P = .03) in the placebo arm. The between-arm differences for osteocalcin and 25-hydroxyvitamin D were statistically significant. Serum insulin-like growth factor I was statistically increased in both arms, but the between-arm differences were not statistically significant. Subanalysis showed that among those in the highest tertile of baseline insulin-like growth factor I, the intervention arm exhibited a significant increase in amino-terminal propeptide of type I collagen, whereas the placebo arm showed a significant decrease at 14 weeks. Treatment with rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

PubMed

Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

2012-03-01

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

PubMed Central

Locatelli, Vittorio; Bianchi, Vittorio E.

2014-01-01

Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. PMID:25147565

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

PubMed Central

Thompson, Wesley K.; McEvoy, Linda K.; Schork, Andrew J.; Zuber, Verena; LeBlanc, Marissa; Bettella, Francesco; Mills, Ian G.; Desikan, Rahul S.; Djurovic, Srdjan; Gautvik, Kaare M.; Dale, Anders M.; Andreassen, Ole A.

2015-01-01

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. PMID:26695485

Microbiota and metabolic diseases.

PubMed

Pascale, Alessia; Marchesi, Nicoletta; Marelli, Cristina; Coppola, Adriana; Luzi, Livio; Govoni, Stefano; Giustina, Andrea; Gazzaruso, Carmine

2018-05-02

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

Transcriptional control of Sost in bone [Transcriptional control of Sclerostin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sebastian, Aimy; Loots, Gabriela G.

Sclerostin is an osteocyte derived negative regulator of bone formation. A highly specific expression pattern and the exclusive bone phenotype have made Sclerostin an attractive target for therapeutic intervention in treating metabolic bone diseases such as osteoporosis and in facilitating fracture repair. Understanding the molecular mechanisms that regulate Sclerostin transcription is of great interest as it may unveil new avenues for therapeutic approaches. Such studies may also elucidate how various signaling pathways intersect to modulate bone metabolism. Furthermore we review the current understanding of the upstream molecular mechanisms that regulate Sost/SOST transcription, in bone.

Transcriptional control of Sost in bone [Transcriptional control of Sclerostin

DOE PAGES

Sebastian, Aimy; Loots, Gabriela G.

2016-10-19

Sclerostin is an osteocyte derived negative regulator of bone formation. A highly specific expression pattern and the exclusive bone phenotype have made Sclerostin an attractive target for therapeutic intervention in treating metabolic bone diseases such as osteoporosis and in facilitating fracture repair. Understanding the molecular mechanisms that regulate Sclerostin transcription is of great interest as it may unveil new avenues for therapeutic approaches. Such studies may also elucidate how various signaling pathways intersect to modulate bone metabolism. Furthermore we review the current understanding of the upstream molecular mechanisms that regulate Sost/SOST transcription, in bone.

[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.

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

Sclerostin and bone metabolism markers in hyperthyroidism before treatment and interrelations between them.

PubMed

Sarıtekin, İlker; Açıkgöz, Şerefden; Bayraktaroğlu, Taner; Kuzu, Fatih; Can, Murat; Güven, Berrak; Mungan, Görkem; Büyükuysal, Çağatay; Sarıkaya, Selda

2017-01-01

Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with Wnt signal pathway and it has been reported that increased thyroid hormones in hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk of bone fractures by stimulating the bone loss in adults. The aim of this study was to examine the sclerostin serum levels, the relation between sclerostin and thyroid hormones as well as the biochemical markers of the bone metabolism in patients with hyperthyroidism (including multinodular goiter and Graves' disease), whose treatments have not started yet. No difference was found in the serum sclerostin levels between the hyperthyroidism group (n=24) and the control group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary phosphorus excretion were found to be higher in the hyperthyroid group than in the control group (p<0.001, p=0.009). A positive correlation was determined between the sclerostin and bone alkaline phosphatase levels (p<0.001); a negative correlation between the osteocalcin and thyroid stimulating hormone (TSH) (p<0.05); a positive correlation between the osteocalcin and thyroid hormones (FT 3 ,FT 4 ) (p<0.001); and a positive correlation between the deoxypyridinoline and hydroxyproline (p<0.001). No correlation was determined between sclerostin and TSH,FT 3 ,FT 4 (p>0.05). Therefore, we consider that a long-term study that covers the pre-post treatment stages of hyperthyroidism, including both the destruction and construction of the skeleton would be more enlightening. Moreover, the assessment of the synthesis of sclerostin in the bone tissue and in the serum level might show differences.

Machine learning based analytics of micro-MRI trabecular bone microarchitecture and texture in type 1 Gaucher disease.

PubMed

Sharma, Gulshan B; Robertson, Douglas D; Laney, Dawn A; Gambello, Michael J; Terk, Michael

2016-06-14

Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study.

PubMed

Kryskiewicz, Edyta; Pawlowska, Joanna; Pludowski, Pawel; Ismail, Hor; Karczmarewicz, Elzbieta; Teisseyre, Mikolaj; Skorupa, Ewa; Ryzko, Jozef; Kalicinski, Piotr; Socha, Jerzy; Lorenc, Roman S

2012-01-01

Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively

Value of Osteoblast-Derived Exosomes in Bone Diseases.

PubMed

Ge, Min; Wu, Yingzhi; Ke, Ronghu; Cai, Tianyi; Yang, Junyi; Mu, Xiongzheng

2017-06-01

The authors' purpose is to reveal the value of osteoblast-derived exosomes in bone diseases. Microvesicles from supernatants of mouse Mc3t3 were isolated by ultracentrifugation and then the authors presented the protein profile by proteomics analysis. The authors detected a total number of 1536 proteins by mass spectrometry and found 172 proteins overlap with bone database. The Ingenuity Pathway Analysis shows network of "Skeletal and Muscular System Development and Function, Developmental Disorder, Hereditary Disorder" and pathway about osteogenesis. EFNB1 and transforming growth factor beta receptor 3 in the network, LRP6, bone morphogenetic protein receptor type-1, and SMURF1 in the pathway seemed to be valuable in the exosome research of related bone disease. The authors' study unveiled the content of osteoblast-derived exosome and discussed valuable protein in it which might provide novel prospective in bone diseases research.

Bone marrow derived stem cells in joint and bone diseases: a concise review.

PubMed

Marmotti, Antonio; de Girolamo, Laura; Bonasia, Davide Edoardo; Bruzzone, Matteo; Mattia, Silvia; Rossi, Roberto; Montaruli, Angela; Dettoni, Federico; Castoldi, Filippo; Peretti, Giuseppe

2014-09-01

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the

Protective effect of egg yolk peptide on bone metabolism.

PubMed

Kim, Hye Kyung; Lee, Sena; Leem, Kang-Hyun

2011-03-01

Osteoporosis is a major health problem worldwide, and most current therapy used in osteoporosis treatment acts by either increasing bone formation or decreasing bone resorption. However, the adverse effects of these therapies may preclude their long-term use. We examined the effects of egg yolk water-soluble peptide (YPEP) on bone metabolism as an alternative to current therapeutic agents in ovariectomized (OVX) rats. In the first step, the in vitro effects of YPEP on bone loss were determined. The proliferation, collagen content, and alkaline phosphatase activity of preosteoblastic MC3T3-E1 cells and osteoclastogenesis from bone marrow-derived precursor cells were measured. The in vivo experiment confirmed the positive effect of YPEP on bone tissue. Three-month-old female Sprague-Dawley rats were either sham operated or ovariectomized and fed commercial chow diet or 0.1% YPEP-supplemented diet for 3 month. YPEP increased preosteoblastic MC3T3-E1 cell proliferation and alkaline phosphatase activity in a dose-dependent manner. Collagen content was also increased by YPEP treatment. Furthermore, YPEP potently suppressed osteoclastogenesis from bone marrow-derived precursor cells. YPEP (100 μg/mL) abolished the formation of osteoclasts positive for tartrate-resistant acid phosphatase. OVX rats supplemented with YPEP showed an osteoprotective effect, as the bone mineral density and cortical thickness in the tibia were increased compared with the OVX controls. Moreover, histological data indicate that YPEP prevented the cancellous bone loss induced by ovariectomy. None of these protective effects were observed in casein-treated rats. The present study suggests that YPEP is a promising alternative to current therapeutic agents for the management of osteoporosis.

Bisphosphonates in chronic kidney disease; balancing potential benefits and adverse effects on bone and soft tissue.

PubMed

Toussaint, Nigel D; Elder, Grahame J; Kerr, Peter G

2009-01-01

Cardiovascular disease is highly prevalent in chronic kidney disease (CKD) and is often associated with increased vascular stiffness and calcification. Recent studies have suggested a complex interaction between vascular calcification and abnormalities of bone and mineral metabolism, with an inverse relationship between arterial calcification and bone mineral density (BMD). Although osteoporosis is recognized and treated in CKD 1 to 3, the interpretation of BMD levels in the osteoporotic range is controversial in CKD 4, 5, and 5D when renal osteodystrophy is generally present. In addition, there is a paucity of data for patients with CKD mineral and bone disorder (MBD), because studies using bisphosphonates in postmenopausal and glucocorticoid-induced osteoporosis have generally excluded patients with significant CKD. For these patients, treatment of low BMD using standard therapies for osteoporosis is not without potential for harm due to the possibility of worsening low bone turnover, osteomalacia, mixed uraemic osteodystrophy, and of exacerbated hyperparathyroidism; and bisphosphonates should only be used selectively and with caution. Some experimental and clinical studies have also suggested that bisphosphonates may reduce progression of extra-osseous calcification and inhibit the development of atherosclerosis. The authors review the potential benefits and risks associated with bisphosphonate use for bone protection in CKD, and assess their effect on vascular calcification and atherosclerosis.

How rare bone diseases have informed our knowledge of complex diseases.

PubMed

Johnson, Mark L

2016-01-01

Rare bone diseases, generally defined as monogenic traits with either autosomal recessive or dominant patterns of inheritance, have provided a rich database of genes and associated pathways over the past 2-3 decades. The molecular genetic dissection of these bone diseases has yielded some major surprises in terms of the causal genes and/or involved pathways. The discovery of genes/pathways involved in diseases such as osteopetrosis, osteosclerosis, osteogenesis imperfecta and many other rare bone diseases have all accelerated our understanding of complex traits. Importantly these discoveries have provided either direct validation for a specific gene embedded in a group of genes within an interval identified through a complex trait genome-wide association study (GWAS) or based upon the pathway associated with a monogenic trait gene, provided a means to prioritize a large number of genes for functional validation studies. In some instances GWAS studies have yielded candidate genes that fall within linkage intervals associated with monogenic traits and resulted in the identification of causal mutations in those rare diseases. Driving all of this discovery is a complement of technologies such as genome sequencing, bioinformatics and advanced statistical analysis methods that have accelerated genetic dissection and greatly reduced the cost. Thus, rare bone disorders in partnership with GWAS have brought us to the brink of a new era of personalized genomic medicine in which the prevention and management of complex diseases will be driven by the molecular understanding of each individuals contributing genetic risks for disease.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

PubMed Central

Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi

2014-01-01

Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857

Central Depletion of Brain-Derived Neurotrophic Factor in Mice Results in High Bone Mass and Metabolic Phenotype

PubMed Central

Zayzafoon, M.; Rymaszewski, M.; Heiny, J.; Rios, M.; Hauschka, P. V.

2012-01-01

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal differentiation/survival, the regulation of food intake, and the pathobiology of obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether central BDNF affects bone mass in vivo is not known. We therefore examined bone mass and energy use in brain-targeted BDNF conditional knockout mice (Bdnf2lox/2lox/93). The deletion of BDNF in the brain led to a metabolic phenotype characterized by hyperphagia, obesity, and increased abdominal white adipose tissue. Central BDNF deletion produces a marked skeletal phenotype characterized by increased femur length, elevated whole bone mineral density, and bone mineral content. The skeletal changes are developmentally regulated and appear concurrently with the metabolic phenotype, suggesting that the metabolic and skeletal actions of BDNF are linked. The increased bone development is evident in both the cortical and trabecular regions. Compared with control, Bdnf2lox/2lox/93 mice show greater trabecular bone volume (+50% for distal femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal and metabolic phenotypes were gender dependent, with female being more affected than male mice. However, uncoupling protein-1 expression in brown fat, a marker of sympathetic tone, was not different between genotypes. We show that deletion of central BDNF expression in mice results in increased bone mass and white adipose tissue, with no significant changes in sympathetic signaling or peripheral serotonin, associated with hyperphagia, obesity, and leptin resistance. PMID:23011922

Bone mineral status and metabolism in patients with Williams-Beuren syndrome.

PubMed

Stagi, Stefano; Manoni, Cristina; Scalini, Perla; Chiarelli, Francesco; Verrotti, Alberto; Cecchi, Cecilia; Lapi, Elisabetta; Giglio, Sabrina; Romano, Silvia; de Martino, Maurizio

2016-07-01

To evaluate bone mineral status and metabolism in a cohort of patients with Williams-Beuren syndrome (WBS). Thirty-one children (15 females, 16 males; mean age 9.6±2.74 years) and 10 young adults (6 females, 4 males; mean age 21.4±5.11 years) with WBS were cross-sectionally evaluated and compared with two age-, sex-, and body-size-matched paediatric (155 subjects, 75 females and 80 males; mean age 9.7±2.93 years) and adult (50 subjects, 30 females and 20 males; mean age 22.3±5.42 years) healthy controls. We evaluated ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels, and urinary deoxypyridinoline concentrations. We also calculated the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) z-scores. WBS patients showed a significantly reduced AD-SoS z-score (p <0.001) and BTT z-score (p <0.001) compared with the controls. This finding persisted when we divided the sample into paediatric and adult patients. WBS patients also had significantly higher ionised (p <0.001) and total calcium (p <0.001) levels as well as higher PTH levels (p <0.001) compared with the controls. Furthermore, WBS children and adolescents had significantly lower serum osteocalcin levels (p <0.001) and urinary deoxypyridinoline concentrations (p <0.001) than controls. WBS subjects exhibit a significant reduction in bone mineral status and impaired bone metabolism. These findings point to the need for close monitoring of WBS patients.

Aneurysmal bone cyst: a hereditary disease?

PubMed

Leithner, Andreas; Machacek, Felix; Haas, Oskar A; Lang, Susanna; Ritschl, Peter; Radl, Roman; Windhager, Reinhard

2004-05-01

Recent genetic and immunohistochemical studies propose that the primary aneurysmal bone cyst is a tumour and not a reactive tumour-simulating lesion. Based on a familial case of aneurysmal bone cyst the authors contacted 135 patients with this disease. Sixty-eight females and 67 males (median age 14 years; range 2-73 years) were asked if other family members had bone lesions. One hundred and seven patients (79%) denied having other family members with lesions, 23 patients (17%) did not answer, and five patients (4%) gave evidence of other bone lesions in the family. These data indicate that a predisposing genetic defect could be part of a multifactorial pathogenesis in the development of some aneurysmal bone cysts.

Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease.

PubMed

Dumas, Marc-Emmanuel; Kinross, James; Nicholson, Jeremy K

2014-01-01

Metabolic syndrome, a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease, is becoming an increasing global health concern. Insulin resistance is often associated with metabolic syndrome and also typical hepatic manifestations such as nonalcoholic fatty liver disease. Profiling of metabolic products (metabolic phenotyping or metabotyping) has provided new insights into metabolic syndrome and nonalcoholic fatty liver disease. Data from nuclear magnetic resonance spectroscopy and mass spectrometry combined with statistical modeling and top-down systems biology have allowed us to analyze and interpret metabolic signatures in terms of metabolic pathways and protein interaction networks and to identify the genomic and metagenomic determinants of metabolism. For example, metabolic phenotyping has shown that relationships between host cells and the microbiome affect development of the metabolic syndrome and fatty liver disease. We review recent developments in metabolic phenotyping and systems biology technologies and how these methodologies have provided insights into the mechanisms of metabolic syndrome and nonalcoholic fatty liver disease. We discuss emerging areas of research in this field and outline our vision for how metabolic phenotyping could be used to study metabolic syndrome and fatty liver disease. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Uncoupling Protein 2 and Metabolic Diseases

PubMed Central

Sreedhar, Annapoorna; Zhao, Yunfeng

2017-01-01

Mitochondria are fascinating organelles involved in various cellular-metabolic activities that are integral for mammalian development. Although they perform diverse, yet interconnected functions, mitochondria are remarkably regulated by complex signaling networks. Therefore, it is not surprising that mitochondrial dysfunction is involved in plethora of diseases, including neurodegenerative and metabolic disorders. One of the many factors that lead to mitochondrial-associated metabolic diseases is the uncoupling protein-2, a family of mitochondrial anion proteins present in the inner mitochondrial membrane. Since their discovery, uncoupling proteins have attracted considerable attention due to their involvement in mitochondrial-mediated oxidative stress and energy metabolism. This review attempts to provide a summary of recent developments in the field of uncoupling protein 2 relating to mitochondrial associated metabolic diseases. PMID:28351676

Bone: best papers of the year 2017.

PubMed

Laurent, Michaël R

2018-03-15

An overview of selected papers related to bone published in 2017 is provided. This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year. A PubMed search using the keyword "bone" and articles published in 2017. Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation. Other selected articles cover effectiveness of bisphosphonates and changes in mineralization after long-term use, new guidelines for glucocorticoid- and aromatase inhibitor-induced osteoporosis, increasing use of high-dose vitamin D supplements despite lack of evidence for their widespread high-dose use, and cardiovascular safety concerns surrounding the use of calcium supplements. Other topics discussed are effects of diabetes on bone health, reciprocal crosstalk between bone cells and adipose tissue, and resistance exercise training to prevent bone loss and sarcopenia. These papers offer a hopeful outlook for a better treatment and management of patients with osteoporosis and other metabolic bone diseases anno 2018.

Effects of the two types of anorexia nervosa (binge eating/purging and restrictive) on bone metabolism in female patients.

PubMed

Maïmoun, Laurent; Guillaume, Sébastien; Lefebvre, Patrick; Bertet, Helena; Seneque, Maude; Philibert, Pascal; Picot, Marie-Christine; Dupuy, Anne-Marie; Paris, Françoise; Gaspari, Laura; Ben Bouallègue, Fayçal; Courtet, Philippe; Mariano-Goulart, Denis; Renard, Eric; Sultan, Charles

2018-06-01

This study compared the profiles of the two types of anorexia nervosa (AN; restrictive: AN-R, and binge eating/purging: AN-BP) in terms of body composition, gynaecological status, disease history and the potential effects on bone metabolism. Two hundred and eighty-six women with AN (21.8 ± 6.5 years; 204 AN-R and 82 AN-BP) and 130 age-matched controls (CON; 22.6 ± 6.8 years) were enrolled. Areal bone mineral density (aBMD) was determined using DXA and resting energy expenditure (REE) was indirectly assessed using calorimetry. Markers of bone formation (osteocalcin [OC], procollagen type I N-terminal propeptide [PINP] and resorption (type I-C telopeptide breakdown products [CTX]) and leptin were concomitantly evaluated. Anorexia nervosa patients presented an alteration in aBMD and bone turnover. When compared according to type, AN-BP were older than AN-R and showed less severe undernutrition, lower CTx levels, longer duration of AN, and higher REE levels and aBMD at radius and lumbar spine. After adjustment for age, weight and hormonal contraceptive use, the aBMD and CTx differences disappeared. In both AN groups, aBMD was positively correlated with anthropometric parameters and negatively correlated with durations of AN and amenorrhoea, the bone formation markers (OC and PINP) and the leptin/fat mass ratio. REE was positively correlated with aBMD in AN-R patients only. This study shows the profiles of AN patients according to AN type. However, the impact of the profile characteristics on bone status, although significant, was minor and disappeared after multiple adjustments. The positive correlation between REE and aBMD reinforces the concept that energy disposal and bone metabolism are strongly interdependent. © 2018 John Wiley & Sons Ltd.

[Clinical practice guidelines for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Bone Metabolism Working Group of the Spanish Society of Endocrinology].

PubMed

Reyes García, Rebeca; Jódar Gimeno, Esteban; García Martín, Antonia; Romero Muñoz, Manuel; Gómez Sáez, José Manuel; Luque Fernández, Inés; Varsavsky, Mariela; Guadalix Iglesias, Sonsoles; Cano Rodriguez, Isidoro; Ballesteros Pomar, María Dolores; Vidal Casariego, Alfonso; Rozas Moreno, Pedro; Cortés Berdonces, María; Fernández García, Diego; Calleja Canelas, Amparo; Palma Moya, Mercedes; Martínez Díaz-Guerra, Guillermo; Jimenez Moleón, José J; Muñoz Torres, Manuel

2012-03-01

To provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist. Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group. The document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rignell-Hydbom, A., E-mail: anna.rignell-hydbom@med.lu.se; Skerfving, S.; Lundh, T.

Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed inmore » serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p,p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other.« less

Effects of dexamethasone, celecoxib, and methotrexate on the histology and metabolism of bone tissue in healthy Sprague Dawley rats.

PubMed

Liu, Yanzhi; Cui, Yang; Chen, Yan; Gao, Xiang; Su, Yanjie; Cui, Liao

2015-01-01

To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats. Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1) control (saline, daily); 2) dexamethasone (2 mg/kg, twice weekly); 3) celecoxib (50 mg/kg, daily); and 4) methotrexate (0.5 mg/kg, twice weekly). The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses. The following results were obtained: 1) dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2) celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3) methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats. This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats. The results indicate that the three antiarthritics have varying degrees of side effects on bone metabolism, and these findings will help physicians to learn more about the potential effects of antiarthritics on bone metabolism.

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

Prediction and Informative Risk Factor Selection of Bone Diseases.

PubMed

Li, Hui; Li, Xiaoyi; Ramanathan, Murali; Zhang, Aidong

2015-01-01

With the booming of healthcare industry and the overwhelming amount of electronic health records (EHRs) shared by healthcare institutions and practitioners, we take advantage of EHR data to develop an effective disease risk management model that not only models the progression of the disease, but also predicts the risk of the disease for early disease control or prevention. Existing models for answering these questions usually fall into two categories: the expert knowledge based model or the handcrafted feature set based model. To fully utilize the whole EHR data, we will build a framework to construct an integrated representation of features from all available risk factors in the EHR data and use these integrated features to effectively predict osteoporosis and bone fractures. We will also develop a framework for informative risk factor selection of bone diseases. A pair of models for two contrast cohorts (e.g., diseased patients versus non-diseased patients) will be established to discriminate their characteristics and find the most informative risk factors. Several empirical results on a real bone disease data set show that the proposed framework can successfully predict bone diseases and select informative risk factors that are beneficial and useful to guide clinical decisions.

Frequency of low bone mineral density in Saudi patients with inflammatory bowel disease.

PubMed

Ismail, Mona H; Al-Elq, Abdulmohsen H; Al-Jarodi, Mahdi E; Azzam, Nahla A; Aljebreen, Abdulrahman M; Al-Momen, Sami A; Bseiso, Bahaa F; Al-Mulhim, Fatma A; Alquorain, Abdulaziz

2012-01-01

Metabolic bone disease is common in patients with inflammatory bowel disease (IBD). Our aim was to determine the frequency of bone loss among Saudi patients with IBD and possible contributing risk factors. We retrospectively reviewed Saudi patients with IBD, between 18 and 70 years of age, who had bone mass density (BMD) determined by dual-energy X-ray absorptiometry scanning at one of three hospitals in the Kingdom of Saudi Arabia from 2001 to 2008. Case notes and BMDs results were carefully reviewed for demographic and clinical data. Low bone mass, osteopenia, and osteoporosis were defined according to the WHO guidelines. Predictive factors for BMD were analyzed using group comparisons and stepwise regression analyses. Ninety-five patients were included; 46% had Crohn's disease (CD) and 54% had ulcerative colitis (UC). The average age was 30.9±11.6 years. Using T-scores, the frequency of osteopenia was 44.2%, and the frequency of osteoporosis was 30.5% at both lumbar spine and proximal femur. Only 25.3% of patients exhibited a BMD within the normal range. Our results revealed a positive correlation between the Z-score in both the lumbar spine and the proximal femur and body mass index (BMI) (P=0.042 and P=0.018, respectively). On regression analysis BMI, age, and calcium supplementation were found to be the most important independent predictors of BMD. Saudi patients with IBD are at an increased risk of low BMD and the frequency of decreased BMD in Saudi patients with CD and UC were similar. BMI and age were the most important independent predictors of low BMD.

Osteoporosis: Modern Paradigms for Last Century's Bones.

PubMed

Kruger, Marlena C; Wolber, Frances M

2016-06-17

The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss.

PubMed

Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc; Moriarty, Tara J

2017-02-01

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. Copyright © 2017 Tang et al.

Bone effects of biologic drugs in rheumatoid arthritis.

PubMed

Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

2013-01-01

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

PubMed

Rodrigues Neto Angéloco, Larissa; Arces de Souza, Gabriela Cristina; Almeida Romão, Elen; Garcia Chiarello, Paula

2018-05-01

The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effects of Artemisia Princeps Supplementation on Bone Metabolism in Ovariectomized Rats.

PubMed

Cho, H-J; Kim, J-W; Ju, S-Y; Park, Y-K

2016-01-01

The aim of this study was to investigate the effects of Artemisia princeps (AP) extract on bone metabolism and its potential role in the prevention of osteoporosis in ovariectomized rats. Twenty-six female Sprague-Dawley rats were divided into five groups and treated as follows: sham-operated control group (SHAM); ovariectomized control group (OVX), ovariectomized group treated by gavage with 10 mg/kg/day alendronate (ALEN); ovariectomized group treated by gavage with 100 mg/kg/day Artemisia princeps (AP100); ovariectomized group treated by gavage with 300 mg/kg/day Artemisia princeps (AP300). Treatment of ovariectomized rats with AP extracts for 15 weeks prevented the reduction in bone thickness and trabecular bone mineral density caused by urinary Ca and Cr excretion, and also prevented the increase in bone turnover by maintaining the serum Ca/P ratio. As a result, the microarchitecture of the trabecular bone and cortical bone after ovariectomy was markedly improved by administration of AP extracts. In conclusion, AP prevented bone loss and osteoclast activity associated with high bone turnover in ovariectomized rats by controlling the serum Ca/P ratio and through anti-inflammatory and anti-oxidant properties. Our data implicate AP as a promising therapeutic option for the improvement of postmenopausal osteoporosis.

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

NASA Technical Reports Server (NTRS)

Morukov, B. V.; Zaychik, V. YE.; Ivanov, V. M.; Orlov, O. I.

1988-01-01

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

The dental implications of bisphosphonates and bone disease.

PubMed

Cheng, A; Mavrokokki, A; Carter, G; Stein, B; Fazzalari, N L; Wilson, D F; Goss, A N

2005-12-01

In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients.

Bone as an ion exchange system: evidence for a link between mechanotransduction and metabolic needs.

PubMed

Rubinacci, A; Covini, M; Bisogni, C; Villa, I; Galli, M; Palumbo, C; Ferretti, M; Muglia, M A; Marotti, G

2002-04-01

To detect whether the mutual interaction occurring between the osteocytes-bone lining cells system (OBLCS) and the bone extracellular fluid (BECF) is affected by load through a modification of the BECF-extracellular fluid (ECF; systemic extracellular fluid) gradient, mice metatarsal bones immersed in ECF were subjected ex vivo to a 2-min cyclic axial load of different amplitudes and frequencies. The electric (ionic) currents at the bone surface were measured by a vibrating probe after having exposed BECF to ECF through a transcortical hole. The application of different loads and different frequencies increased the ionic current in a dose-dependent manner. The postload current density subsequently decayed following an exponential pattern. Postload increment's amplitude and decay were dependent on bone viability. Dummy and static loads did not induce current density modifications. Because BECF is perturbed by loading, it is conceivable that OBLCS tends to restore BECF preload conditions by controlling ion fluxes at the bone-plasma interface to fulfill metabolic needs. Because the electric current reflects the integrated activity of OBLCS, its evaluation in transgenic mice engineered to possess genetic lesions in channels or matrix constituents could be helpful in the characterization of the mechanical and metabolic functions of bone.

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.

Temporary brittle bone disease: fractures in medical care.

PubMed

Paterson, Colin R

2009-12-01

Temporary brittle bone disease is the name given to a syndrome first reported in 1990, in which fractures occur in infants in the first year of life. The fractures include rib fractures and metaphyseal fractures which are mostly asymptomatic. The radiological features of this disorder mimic those often ascribed to typical non-accidental injury. The subject has been controversial, some authors suggesting that the disorder does not exist. This study reports five infants with typical features of temporary brittle bone disease in whom all or most of the fractures took place while in hospital. A non-accidental cause can be eliminated with some confidence, and these cases provide evidence in support of the existence of temporary brittle bone disease.

HIV and Bone Metabolism

PubMed Central

Ofotokun, Ighovwerha; Weitzmann, M. Neale

2013-01-01

The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the “immuno-skeletal interface.” Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART. PMID:21616037

Destructive bone disease in early syphilis.

PubMed

Dismukes, W E; Delgado, D G; Mallernee, S V; Myers, T C

1976-12-06

Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis. A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling. Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease. Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms.

The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves' Disease.

PubMed

Cho, Sun Wook; Bae, Jae Hyun; Noh, Gyeong Woon; Kim, Ye An; Moon, Min Kyong; Park, Kyoung Un; Song, Junghan; Yi, Ka Hee; Park, Do Joon; Chung, June-Key; Cho, Bo Youn; Park, Young Joo

2015-01-01

Osteoporosis-related fractures are one of the complications of Graves' disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves' disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves' disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves' disease.

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

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

Effects of ipriflavone on caged layer bone metabolism in vitro and in vivo.

PubMed

Yao, J; Zhang, J; Hou, J-F

2007-03-01

The effects of ipriflavone on caged layer bone metabolism were examined in vitro and in vivo. Ipriflavone at 10(-8) M stimulated the activity of osteoblasts cultured from embryonic chick calvariae, and 10(-9) to 10(-7) M inhibited osteoclasts from chick tibias and humeri. Ipriflavone concentrations of 10(-4) and 10(-5) M inhibited osteoblast activity. These results suggest that ipriflavone influences bone metabolism by regulating the functional balance between osteoblasts and osteoclasts. Based on these in vitro experiments, in vivo studies were conducted to further clarify the effects of ipriflavone. Five hundred 58-wk-old ISA caged layers were divided into 5 groups that were fed diets containing 0, 15, 25, 50, and 100 ppm of ipriflavone. The experiment lasted 70 d. Egg production increased in hens fed 25 ppm and decreased in hens fed 50 and 100 ppm when compared with the controls and hens fed 15 ppm (P < 0.05). Egg weight, shell quality, BW, and serum P, Ca, estrogen, and bone mineral content were not affected by inclusion of ipriflavone in the diet. Hens consuming 25 ppm of ipriflavone had greater serum alkaline phosphatase and bone gla-protein levels than controls. Adding 25 ppm of ipriflavone to the feed appears to be close to an ideal level for clinical treatment of osteoporosis because of improved egg production while maintaining bone mineral content.

Osteomalacia in Crohn's disease.

PubMed

Dedeoglu, Meryem; Garip, Yesim; Bodur, Hatice

2014-01-01

Osteomalacia is a metabolic bone disorder characterized by impaired mineralization of the bone matrix. Vitamin D deficiency due to malabsorption syndromes may cause osteomalacia. This is a case of a patient with a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease who was admitted to our outpatient clinic with symptoms of osteomalacia. Osteomalacia is a metabolic bone disease characterized by an impaired mineralization of the bone matrix, frequently caused by disorders in vitamin D or phosphate metabolism. Vitamin D deficiency due to malabsorption syndromes (e.g., Crohn's disease, ulcerative colitis, celiac disease, and jejuno-ileal bypass for obesity) may cause osteomalacia. A 43-year-old male presented with fatigue, low back pain, and morning stiffness. He had a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease. Laboratory findings revealed low serum calcium, low 25-hydroxy vitamin D3, normal phosphorus, elevated parathyroid hormone, and alkaline phosphatase levels. Radiographs revealed grade IV sacroiliitis and Looser zones. He was diagnosed with osteomalacia due to the malabsorption of vitamin D. His symptoms and signs were relieved with supplements of vitamin D and calcium. Osteomalacia should be considered in differential diagnosis when assessing low back pain in the patients with chronic inflammatory bowel disease. Vitamin D deficiency should be treated with vitamin D supplementation in patients with Crohn's disease to prevent osteomalacia.

The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

NASA Astrophysics Data System (ADS)

Parkman, Robertson

1986-06-01

Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

The use of Na-22 as a tracer for long-term bone mineral turnover studies.

NASA Technical Reports Server (NTRS)

Palmer, H. E.; Rieksts, G. A.; Palmer, R. F.; Gillis, M. F.

1979-01-01

Sodium-22 has been 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 Na-22, which is released through the metabolic turnover of the bone. The Na-22 not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high, but nontoxic levels of NaCl. The Na-22 tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

Clinical-laboratory findings of bone metabolism in healthy premature and full-term neonates: preliminary results

PubMed Central

Dokos, Charalampos; Tsakalidis, Christos; Manaridou, Kyriakoula; Karayianni, Paraskevi; Kyrkos, Ioannis; Roussos, Israel

2017-01-01

Summary Premature infants are a major risk group for bone metabolic disorders. The purpose of this study is to clarify certain aspects of bone metabolism in healthy preterm and full-term neonates. Forty neonates (20 preterm and 20 full-term) were the material of the study. For each neonate demographic data (gender, gestational week) and anthropometric data (body weight) were recorded. Blood samples were collected and biochemical markers of bone metabolism (serum ALP, Ca, P, Mg) were immediately estimated. According to the results there is a statistically significant difference in average ALP of preterm neonates compared to full term neonates. Slightly higher values of Ca, P, Mg occurred in premature neonates while there was a statistically significant difference in the weeks of gestation and body weights between the two groups. It is typical in premature neonates the decrease in levels of ALP by the weeks of gestation and the stable levels of Ca. Gestational week seems to positively affect P and Mg levels in preterm neonates. Conclusively from our study’s results arises that the week of gestation and not so much the body weight influence the alterations of bone biochemical biomarkers in healthy premature newborns. It seems that very premature neonates have high levels of serum ALP in decompensation of lower levels of Mg and P from all the newborns in this study. Therefore in very premature neonates, it is recommended to estimate serum ALP, Mg and P for assessment of bone turnover. PMID:29263727

Clinical-laboratory findings of bone metabolism in healthy premature and full-term neonates: preliminary results.

PubMed

Dokos, Charalampos; Tsakalidis, Christos; Manaridou, Kyriakoula; Karayianni, Paraskevi; Kyrkos, Ioannis; Roussos, Israel

2017-01-01

Premature infants are a major risk group for bone metabolic disorders. The purpose of this study is to clarify certain aspects of bone metabolism in healthy preterm and full-term neonates. Forty neonates (20 preterm and 20 full-term) were the material of the study. For each neonate demographic data (gender, gestational week) and anthropometric data (body weight) were recorded. Blood samples were collected and biochemical markers of bone metabolism (serum ALP, Ca, P, Mg) were immediately estimated. According to the results there is a statistically significant difference in average ALP of preterm neonates compared to full term neonates. Slightly higher values of Ca, P, Mg occurred in premature neonates while there was a statistically significant difference in the weeks of gestation and body weights between the two groups. It is typical in premature neonates the decrease in levels of ALP by the weeks of gestation and the stable levels of Ca. Gestational week seems to positively affect P and Mg levels in preterm neonates. Conclusively from our study's results arises that the week of gestation and not so much the body weight influence the alterations of bone biochemical biomarkers in healthy premature newborns. It seems that very premature neonates have high levels of serum ALP in decompensation of lower levels of Mg and P from all the newborns in this study. Therefore in very premature neonates, it is recommended to estimate serum ALP, Mg and P for assessment of bone turnover.

Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site.

PubMed

Tamimi, Faleh; Torres, Jesus; Al-Abedalla, Khadijeh; Lopez-Cabarcos, Enrique; Alkhraisat, Mohammad H; Bassett, David C; Gbureck, Uwe; Barralet, Jake E

2014-07-01

Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics have the capacity to conduct bone augmentation. However, there is heterogeneity in the graft behaviour in vivo that seems to correlate with the host anatomy. In this study, we sought to investigate the metabolic activity of the regenerated bone in monolithic monetite onlays by using positron emission tomography-computed tomography (PET-CT) in rats. This information was used to optimize the design of monetite onlays with different macroporous architecture that were then fabricated using a 3D-printing technique. In vivo, bone augmentation was attempted with these customized onlays in rabbits. PET-CT findings demonstrated that bone metabolism in the calvarial bone showed higher activity in the inferior and lateral areas of the onlays. Histological observations revealed higher bone volume (up to 47%), less heterogeneity and more implant osseointegration (up to 38%) in the augmented bone with the customized monetite onlays. Our results demonstrated for the first time that it is possible to achieve osseointegration of dental implants in bone augmented with 3D-printed synthetic onlays. It was also observed that designing the macropore geometry according to the bone metabolic activity was a key parameter in increasing the volume of bone augmented within monetite onlays. Copyright © 2014 Elsevier Ltd. All rights reserved.

IL-20 bone diseases involvement and therapeutic target potential.

PubMed

Wang, Hsiao-Hsuan; Hsu, Yu-Hsiang; Chang, Ming-Shi

2018-04-24

Millions of people around the world suffer from bone disorders, likes osteoporosis, rheumatoid arthritis (RA), and cancer-induced osteolysis. In general, the bone remodeling balance is determined by osteoclasts and osteoblasts, respectively responsible for bone resorption and bone formation. Excessive inflammation disturbs the activities of these two kinds of cells, typically resulting in the bone loss. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, cancer, liver fibrosis, and RA. IL-20 has an important role in the regulation of osteoclastogenesis and osteoblastogenesis and is upregulated in several bone-related diseases. The anti-IL-20 monoclonal antibody treatment has a therapeutic potential in several experimental disease models including ovariectomy-induced osteoporosis, cancer-induced osteolysis, and bone fracture. This review article provides an overview describing the IL-20's biological functions in the common bone disorders and thus providing a novel therapeutic strategy in the future.

[Insights into cystic fibrosis-related bone disease].

PubMed

Braun, C; Bacchetta, J; Reix, P

2016-08-01

With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effects of alkylphenols on bone metabolism in vivo and in vitro.

PubMed

Hagiwara, Hiromi; Sugizaki, Toshinori; Tsukamoto, Yu; Senoh, Emi; Goto, Tadashi; Ishihara, Yoko

2008-09-01

Alkylphenols are endocrine disruptors that show estrogen-like effects in various wildlife species. However, little information is available about the action of these chemicals on bone metabolism. We investigated the effects of alkylphenols, such as nonylphenol (NP) and octylphenol (OP), on the formation of bone using several culture systems for osteoclasts and osteoblasts, as well as in vivo experiments. NP and OP dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) in cocultures of mouse spleen cells or mouse bone marrow cells with ST2 cells. However, beta-estradiol at 10(-9)M to 10(-6)M did not affect this process. In contrast, neither compound affected the proliferation and differentiation of rat calvarial osteoblast-like cells (ROB cells). When NP or OP (0.1mg/kg body weight) was administered subcutaneously to pregnant mice at 10 days, 12 days and 14 days post-coitus, fetuses at 17.5 days post-coitus showed stimulation of sternebrae bone calcification. Our findings suggest that alkylphenols have critical effects on the formation of bone by non-estrogenic effects.

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. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Molecular Differences in Hepatic Metabolism between AA Broiler and Big Bone Chickens: A Proteomic Study.

PubMed

Zheng, Aijuan; Chang, Wenhuan; Liu, Guohua; Yue, Ying; Li, Jianke; Zhang, Shu; Cai, Huiyi; Yang, Aijun; Chen, Zhimin

2016-01-01

Identifying the metabolic differences in the livers of modern broilers and local chicken breeds is important for understanding their biological characteristics, and many proteomic changes in their livers are not well characterized. We therefore analyzed the hepatic protein profiles of a commercial breed, Arbor Acres (AA) broilers, and a local dual purpose breed, Big Bone chickens, using two-dimensional electrophoresis combined with liquid chromatography-chip/electrospray ionization-quadruple time-of-flight/mass spectrometry (LC-MS/MS). A total of 145 proteins were identified as having differential abundance in the two breeds at three growth stages. Among them, 49, 63 and 54 belonged to 2, 4, and 6 weeks of age, respectively. The higher abundance proteins in AA broilers were related to the energy production pathways suggesting enhanced energy metabolism and lipid biosynthesis. In contrast, the higher abundance proteins in Big Bone chickens showed enhanced lipid degradation, resulting in a reduction in the abdominal fat percentage. Along with the decrease in fat deposition, flavor substance synthesis in the meat of the Big Bone chickens may be improved by enhanced abundance of proteins involved in glycine metabolism. In addition, the identified proteins in nucleotide metabolism, antioxidants, cell structure, protein folding and transporters may be critically important for immune defense, gene transcription and other biological processes in the two breeds. These results indicate that selection pressure may have shaped the two lines differently resulting in different hepatic metabolic capacities and extensive metabolic differences in the liver. The results from this study may help provide the theoretical basis for chicken breeding.

Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice

PubMed Central

Wu, Yuwei; Tu, Qisheng; Valverde, Paloma; Zhang, Jin; Murray, Dana; Dong, Lily Q.; Cheng, Jessica; Jiang, Hua; Rios, Maribel; Morgan, Elise; Tang, Zhihui

2014-01-01

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor-1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC. PMID:24780611

Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice.

PubMed

Wu, Yuwei; Tu, Qisheng; Valverde, Paloma; Zhang, Jin; Murray, Dana; Dong, Lily Q; Cheng, Jessica; Jiang, Hua; Rios, Maribel; Morgan, Elise; Tang, Zhihui; Chen, Jake

2014-06-15

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor-1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC. Copyright © 2014 the American Physiological Society.

Effects of 1.8 GHz radiofrequency field on microstructure and bone metabolism of femur in mice.

PubMed

Guo, Ling; Zhang, Jun-Ping; Zhang, Ke-Ying; Wang, Huan-Bo; Wang, Huan; An, Guang-Zhou; Zhou, Yan; Meng, Guo-Lin; Ding, Gui-Rong

2018-04-30

To investigate the effects of 1.8 GHz radiofrequency (RF) field on bone microstructure and metabolism of femur in mice, C57BL/6 mice (male, age 4 weeks) were whole-body exposed or sham exposed to 1.8 GHz RF field. Specific absorption rates of whole body and bone were approximately 2.70 and 1.14 W/kg (6 h/day for 28 days). After exposure, microstructure and morphology of femur were observed by microcomputed tomography (micro-CT), Hematoxylin and Eosin (HE) and Masson staining. Subsequently, bone parameters were calculated directly from the reconstructed images, including structure model index, bone mineral density, trabecular bone volume/total volume, connectivity density, trabecular number, trabecular thickness, and trabecular separation. Biomarkers that reflect bone metabolism, such as serum total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRACP-5b), were determined by biochemical assay methods. Micro-CT and histology results showed that there was no significant change in bone microstructure and the above parameters in RF group, compared with sham group. The activity of serum ALP and BALP increased 29.47% and 16.82%, respectively, in RF group, compared with sham group (P < 0.05). In addition, there were no significant differences in the activity of serum TRACP-5b between RF group and sham group. In brief, under present experimental conditions, we did not find support for an effect of 1.8 GHz RF field on bone microstructure; however, it might promote metabolic function of osteoblasts in mice. Bioelectromagnetics. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Atlas of computerized blood flow analysis in bone disease.

PubMed

Gandsman, E J; Deutsch, S D; Tyson, I B

1983-11-01

The role of computerized blood flow analysis in routine bone scanning is reviewed. Cases illustrating the technique include proven diagnoses of toxic synovitis, Legg-Perthes disease, arthritis, avascular necrosis of the hip, fractures, benign and malignant tumors, Paget's disease, cellulitis, osteomyelitis, and shin splints. Several examples also show the use of the technique in monitoring treatment. The use of quantitative data from the blood flow, bone uptake phase, and static images suggests specific diagnostic patterns for each of the diseases presented in this atlas. Thus, this technique enables increased accuracy in the interpretation of the radionuclide bone scan.

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments.

PubMed

Kwakwa, Kristin A; Vanderburgh, Joseph P; Guelcher, Scott A; Sterling, Julie A

2017-08-01

Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes.

Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation

PubMed Central

Guimaro, Maria C.; Alves, Rozeneide M.; Rose, Ester; Sousa, Alessandro O.; de Cássia Rosa, Ana; Hecht, Mariana M.; Sousa, Marcelo V.; Andrade, Rafael R.; Vital, Tamires; Plachy, Jiří; Nitz, Nadjar; Hejnar, Jiří; Gomes, Clever C.; L. Teixeira, Antonio R.

2014-01-01

Background Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. Methods/Principal Findings To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. Conclusions/Significance Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. PMID:25521296

Fat, Sugar, and Bone Health: A Complex Relationship

PubMed Central

Tian, Li; Yu, Xijie

2017-01-01

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation

Fat, Sugar, and Bone Health: A Complex Relationship.

PubMed

Tian, Li; Yu, Xijie

2017-05-17

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation

Strontium-85 Scanning of Suspected Bone Disease

PubMed Central

Parsons, Victor; Williams, Margery; Hill, David; Frost, Pamela; Lapham, Avril

1969-01-01

Strontium-85 scanning of suspected bone lesions in 81 patients has added to the criteria for the diagnosis of malignant and other lesions of bone. Of 46 patients with a previous history of malignant disease and skeletal symptoms negative radiological findings were recorded in 19, but nine of these had positive scans, eight of which when followed up over periods of up to four years proved to be metastatic. A similar prevalence of positive scans occurred in patients without a previous history of malignancy. Because of the anatomical localization of lesions made possible by this technique a tissue diagnosis was made in six patients, while fields of radiotherapy were altered in another seven. This technique can improve the management of patients with suspected bone disease. PMID:5761888

Cat-scratch disease and bone scintigraphy.

PubMed

Ismaili-Alaoui, Nadia; Vuong, Valerie; Marcu-Marin, M; Sergent-Alaoui, Aline; Chevallier, Bertrand; de Labriolle-Vaylet, Claire

2012-08-01

Cat-scratch disease is a bacterial infection caused by Bartonella henselae. Bone involvement is rare. We describe the case of a 7-year-old boy with a systemic form of the disease. He presented with a 15-day history of fever, altered general condition, weight loss and cough, associated with back pain, and right-sided coxalgia. Bone scintigraphy with Tc-99m hydroxymethylene diphosphonate showed spinal involvement, the iliac crest, the right ankle, and the right first metatarsal. Magnetic resonance imaging confirmed these locations. He was positive for anti-Bartonella henselae. The fever regressed before treatment with rifampicin began, and he made a full recovery.

Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents.

PubMed

Silva, Carla C; Goldberg, Tamara B L; Nga, Hong S; Kurokawa, Cilmery S; Capela, Renata C; Teixeira, Altamir S; Dalmas, José C

2011-01-01

To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m(2)), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm(2)) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus.

PubMed

Campistol, Josep M; Holt, David W; Epstein, Solomon; Gioud-Paquet, Martine; Rutault, Karine; Burke, James T

2005-09-01

Sirolimus is a new immunosuppressive agent used as treatment to prevent acute renal allograft rejection. One of the complications of renal transplantation and subsequent long-term immunosuppression is bone loss associated with osteoporosis and consequent fracture. Two open-label, randomized, phase 2 studies comparing sirolimus versus cyclosporine (CsA) included indices of bone metabolism as secondary end-points. Markers of bone turnover, serum osteocalcin and urinary N-telopeptides, were measured over a 1-year period in 115 patients receiving either CsA or sirolimus as a primary therapy in combination with azathioprine and glucocorticoids (study A) or mycophenolate mofetil (MMF) and glucocorticoids (study B). Urinary excretion of N-telopeptides and the concentrations of serum osteocalcin were consistently higher in the CsA-treated patients and significantly different at week 24 for N-telopeptides and at weeks 12, 24, and 52 for osteocalcin. In conclusion, future trials are warranted to test whether a sirolimus-based regimen conserves bone mineral density compared with a CsA-based regimen.

[An in vitro method for studying the metabolism of young bone matrix].

PubMed

Bonneton, C; Guest, M; Delbarre, F

1977-07-04

A method for studying in vitro bone resorption by the use of 35S labeled injection was investigated. Various substances (papaine) and hormones (calcitonin, vitamin D analogues) were tested and their effects on 35S and 45Ca metabolism were compared.

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

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.

[Investigation of adolescents' bone metabolism in the western part of Transdanubia].

PubMed

Csákváry, Violetta; Puskás, Tamás; Bödecs, Tamás; Lôcsei, Zoltán; Oroszlán, György; Kovács, L Gábor; Toldy, Erzsébet

2009-10-25

Childhood reference range based on the age is not available in Hungary, therefore the diagnosis and therapy of bone metabolic diseases of childhood are subject to difficulties. The aim of this work is to provide information about the adolescents' results of bone mineral density and bone biomarkers. Measurements were performed in 169 healthy adolescents (98 girls, 71 boys, age: 17.0+/-1.2 years). Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine were measured using Double X-ray Absorptiometry (DXA, LUNAR, GE Health Care, USA) and Z-score values were analyzed using different reference population. In the serum, bone biomarkers osteocalcin (OC) and beta-crosslaps (beta-Cl) were measured by a fully automated, electrochemiluminescence immunoassay method (Elecsys-2010, Roche). Data were analyzed according to gender and the Tanner stage and grade system. Associations between body mass index (BMI), calcium intake, consumption of soft drinks and coke, and physical exercise were investigated. BMC values for both age groups were significantly elevated in boys of the Tanner stage V. (15-16 years: 62.9+/-14.3 g; 17-19 years: 69.8+/-9.3g) than in girls (58.1+/-10.4; 61.6+/-8.5 g) (p<0.001). BMD values were higher in girls, than in boys (1.17+/-0.12 g/cm 2 vs. 1.13+/-0.11 g/cm 2) (p<0.05). OC and beta-Cl levels showed negative correlation with age in both gender (p<0.01), while OC and beta-Cl levels were higher in boys, than in girls (p<0.001). Elevation of BMC and BMD values were associated with increase of BMI in both gender (p<0.05), but the biomarkers in thin girls were higher, than in overweight girls (p<0.05). Authors obtained excellent correlations between the BMD-Z-score values compared to the German standard and to their own population (girls: r=0.97, boys: 0.88), but the absolute values significantly differed from one another. 80% of adolescents are on a diet with insufficient calcium intake, while 38% of them do not play sport regularly

Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model

PubMed Central

Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A.; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B.; Isales, Carlos; Caldwell, R. William; Fulzele, Sadanand

2016-01-01

A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of L-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of L-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. PMID:26704078

Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

PubMed

Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

2015-05-01

The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

PubMed Central

Kwakwa, Kristin A.; Vanderburgh, Joseph P.; Guelcher, Scott A.

2018-01-01

Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes. PMID:28646444

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.

Metabolic brain networks in aging and preclinical Alzheimer's disease.

PubMed

Arnemann, Katelyn L; Stöber, Franziska; Narayan, Sharada; Rabinovici, Gil D; Jagust, William J

2018-01-01

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69-89) compared to young adults (N = 17, ages 20-30) and patients with Alzheimer's disease (N = 22, ages 69-89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease.

Calcium metabolism in health and disease.

PubMed

Peacock, Munro

2010-01-01

This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

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. Copyright © 2012 Elsevier Inc. All rights reserved.