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.

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.

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

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 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.

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

PubMed

Kanazawa, Ippei; Sugimoto, Toshitsugu

2013-11-01

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

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.

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

Mesenchymal stem cells for bone repair and metabolic bone diseases.

PubMed

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

2009-10-01

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

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.

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.

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'.

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.

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

[Metabolic bone disease osteomalacia].

PubMed

Reuss-Borst, M A

2014-05-01

Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

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.

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.

[Hearing and balance in metabolic bone diseases].

PubMed

Zatoński, Tomasz; Temporale, Hanna; Krecicki, Tomasz

2012-03-01

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

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.

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.

Is Bone Tissue Really Affected by Swimming? A Systematic Review

PubMed Central

Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

2013-01-01

Background Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. Aim This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. Methods A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. Results It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. Conclusion Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone. PMID:23950908

[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.

Metabolic Bone Diseases and Total Hip Arthroplasty: Preventing Complications.

PubMed

Moya-Angeler, Joaquin; Lane, Joseph M; Rodriguez, Jose A

2017-11-01

Metabolic bone diseases are a diverse group of conditions characterized by abnormalities in calcium metabolism and/or bone cell physiology. These unbalanced processes can eventually lead to bony deformities and altered joint biomechanics, resulting in degenerative joint disease. Not infrequently, patients with metabolic bone diseases have restricting hip joint pain that ultimately necessitates hip arthroplasty. To minimize complications, the surgeon must consider the particular characteristics of these patients. The surgical and medical management of patients with metabolic bone diseases undergoing hip arthroplasty requires appropriate preoperative diagnosis, careful attention to the technical challenges of surgery, and strategies to maximize the long-term results of the surgical intervention, such as the use of bone anabolic and anticatabolic agents.

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

Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

NASA Astrophysics Data System (ADS)

Fogelman, Ignac

Bone scan imaging with the current bone seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, has dramatically improved our ability to evaluate skeletal pathology. In this thesis, chapter 1 presents a review of the history of bone scanning, summarises present concepts as to the mechanism of uptake of bone seeking agents and briefly illustrates the role of bone scanning in clinical practice. In chapter 2 the applications of bone scan imaging and quantitative tracer techniques derived from the bone scan in the detection of metabolic bone disease are discussed. Since skeletal uptake of Tc-99m diphosphonate depends upon skeletal metabolism one might expect that the bone scan would be of considerable value in the assessment of metabolic bone disease. However in these disorders the whole skeleton is often diffusely involved by the metabolic process and simple visual inspection of the scan image may not reveal the uniformly increased uptake of tracer. Certain patterns of bone scan abnormality have, however, been reported in patients with primary hyperparathyroidism and renal osteo-dystrophy; the present studies extend these observations and introduce the concept of "metabolic features" which are often recognisable in conditions with generalised increased bone turnover. As an aid to systematic recognition of these features on a given bone scan image a semi-quantitative scoring system, the metabolic index, was introduced. The metabolic index allowed differentiation between various groups of patients with metabolic disorders and a control population. In addition, in a bone scan study of patients with acromegaly, it was found that the metabolic index correlated well with disease activity as measured by serum growth hormone levels. The metabolic index was, however, found to be a relatively insensitive means of identifying disease in individual patients. Patients with increased bone turnover will have an absolute increase in skeletal uptake of tracer. As a

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.

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

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.

[Serum sclerostin levels and metabolic bone diseases].

PubMed

Yamauchi, Mika; Sugimoto, Toshitsugu

2013-06-01

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

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.

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.

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

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

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.

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.

[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.

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.

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.

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

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.

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

PubMed

Ito, Akemi; Yajima, Aiji

2011-09-01

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

Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

PubMed

Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

2013-12-10

This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health.

Algorithm for employing physical forces in metabolic bone diseases.

PubMed

Massari, Leo

2011-04-01

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

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.

Clinical utility of bone turnover markers in the management of common metabolic bone diseases in adults.

PubMed

Glendenning, Paul; Chubb, S A Paul; Vasikaran, Samuel

2018-06-01

Bone turnover marker (BTMs) concentrations in blood and urine reflect bone-remodelling activity, and may be useful adjuncts in the diagnosis and management of metabolic bone diseases. Newer biomarkers, mainly bone regulatory proteins, are currently being investigated to elucidate their role in bone metabolism and disease and may in future be useful in clinical diagnosis and management of metabolic bone disease. BTM concentrations increase around menopause in women, and at a population level the degree of increase in BTMs reflect bone loss. However, lack of adequate data precludes their use in individual patients for fracture risk assessment in clinical practice. The rapid and large changes in BTMs following anti-resorptive and anabolic therapies for osteoporosis treatment indicate they may be useful for monitoring therapy in clinical practice. The offset of drug effect on BTMs could be helpful for adjudicating the duration of bisphosphonate drug holidays. BTMs may offer useful additional data in skeletal diseases that are typically characterised by increased bone remodelling: chronic kidney disease (CKD), primary hyperparathyroidism (PHPT) and Paget's disease. In CKD, bone specific alkaline phosphatase (bAP) is currently endorsed for use for the assessment of mineral bone disease. The role of BTMsin predicting the bone mineral density response to successful parathyroidectomy in PHPT shows some utility but the data are not consistent and studies are limited in size and/or duration. In Paget's disease of bone, BTMs are used to confirm diagnosis, evaluate extent of disease or degree of activity and for monitoring the response to bisphosphonate treatment. Whilst BTMs are currently used in specific clinical practice instances when investigating or managing metabolic bone disease, further data are needed to consolidate their clinical use where evidence of utility is limited. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

Leder, Benjamin Z; Finkelstein, Joel S

2005-12-01

-terminal propeptide of type 1 collagen), serum osteoprotegerin, and total body bone mineral density did not change. These data demonstrate that although short-term administration of anastrozole decreases serum estradiol levels in elderly men with mild hypogonadism, this intervention does not adversely affect bone metabolism over a 12-week period. This lack of an effect may be due to the concomitant increase in testosterone production, the relative modest effect on estradiol production, or a combination of both factors. These results suggest that anastrozole therapy is unlikely to have an adverse effect on bone metabolism when taken over extended periods and may prove to be a valuable method of normalizing testosterone production in older men.

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.

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-

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.

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.

Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

PubMed Central

Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

2013-01-01

This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

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

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.

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

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.

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.

Metabolic bone diseases during long-term total parenteral nutrition.

PubMed

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

2007-01-01

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

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.

Bone Metabolism in Anorexia Nervosa

PubMed Central

Fazeli, Pouneh K.; Klibanski, Anne

2014-01-01

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

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.

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 ...

Recent developments in metabolic bone diseases: a gnathic perspective.

PubMed

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

2014-12-01

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

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.

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.

Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

PubMed

Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

2013-05-15

This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption.

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.

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.

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.

[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.

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.

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

[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.

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

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.

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.

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.

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

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

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.

Gravity, calcium, and bone - Update, 1989

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Morey-Holton, Emily

1990-01-01

Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

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

The impact of microgravity on bone metabolism in vitro and in vivo.

PubMed

Loomer, P M

2001-01-01

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.

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

PubMed

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

2012-08-01

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

The effect of carprofen on selected markers of bone metabolism in dogs with chronic osteoarthritis.

PubMed

Liesegang, A; Limacher, S; Sobek, A

2007-08-01

The purpose of this study was to investigate the effect of the nonsteroidal anti-inflammatory drug carprofen on bone turnover and to monitor the progress of chronic osteoarthritic dogs by measuring different bone markers and radiographic evalutation of the corresponding joints. For this purpose 20 dogs of different ages and weight were devided into 2 groups. Ten dogs were assigned to Group R, treated with carprofen, and ten dogs to Group C, which had no treatment. Radiographs of the affected joints were reviewed initially and six months later at the end of the experiment. Blood was taken 8 times from each dog. Four bone markers (Osteocalcin (OC), bone-specific alkaline phosphatase (bAP), carboxyterminal telopeptide of type I collagen (ICTP), serum CrossLaps (CTX) as well as 1,25-(OH)2-Vitamin D and parathyroid hormone (PTH) were monitored for 6 months. No significant group effects on bone markers were notied. In Group R a decrease in ICTP concentrations during the first three months and a significant decrease in CTX concentrations in the first two months of the study were observed. The bone formation marker bAP revealed a significant decrease throughout the experiment. Three dogs of Group C and one dog of Group R showed osteoarthritic progression in the radiographs. The significant decrease of CTX indicates that carprofentreatment could have a retarding effect on the progression of osteoarthritis. Radiological findings suggest that carprofen may delay osteophyte formation. The monitoring of focal metabolic processes as in bone of a osteoarthrotic joint is difficult, since the bone mass is very active and metabolic processes may have an influence on the monitoring.

[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.

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.

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

PubMed

Eller-Vainicher, C; Bassotti, A; Imeraj, A; Cairoli, E; Ulivieri, F M; Cortini, F; Dubini, M; Marinelli, B; Spada, A; Chiodini, I

2016-08-01

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients. The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients. Fifty consecutive Caucasian patients, aged 30-50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects' calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed. Patients showed reduced BMD (Z-scores LS -0.45 ± 1.00, FN -0.56 ± 1.01, FT -0.58 ± 0.92) and TBS (1.299 ± 0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09 ± 1.22, FN 0.01 ± 0.97, FT 0.08 ± 0.89; TBS 1.382 ± 0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245 ± 0.138 vs 1.325 ± 0.086, p < 0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency. EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

Mineral metabolism in isolated mouse long bones: Opposite effects of microgravity on mineralization and resorption

NASA Technical Reports Server (NTRS)

Veldhuijzen, Jean Paul; Vanloon, Jack J. W. A.

1994-01-01

An experiment using isolated skeletal tissues under microgravity, is reported. Fetal mouse long bones (metatarsals) were cultured for 4 days in the Biorack facility of Spacelab during the IML-1 (International Microgravity Laboratory) mission of the Space Shuttle. Overall growth was not affected, however glucose consumption was significantly reduced under microgravity. Mineralization of the diaphysis was also strongly reduced under microgravity as compared to the on-board 1 g group. In contrast, mineral resorption by osteoclasts was signficantly increased. These results indicate that these fetal mouse long bones are a sensitive and useful model to further study the cellular mechanisms involved in the changed mineral metabolism of skeletal tissues under microgravity.

Maternal Nutrition during Pregnancy Affects Testicular and Bone Development, Glucose Metabolism and Response to Overnutrition in Weaned Horses Up to Two Years

PubMed Central

Mendoza, Luis; Peugnet, Pauline; Dubois, Cédric; Dahirel, Michèle; Lejeune, Jean-Philippe; Caudron, Isabelle; Guenon, Isabelle; Camous, Sylvaine; Tarrade, Anne; Wimel, Laurence; Serteyn, Didier; Bouraima-Lelong, Hélène; Chavatte-Palmer, Pascale

2017-01-01

Introduction Pregnant mares and post-weaning foals are often fed concentrates rich in soluble carbohydrates, together with forage. Recent studies suggest that the use of concentrates is linked to alterations of metabolism and the development of osteochondrosis in foals. The aim of this study was to determine if broodmare diet during gestation affects metabolism, osteoarticular status and growth of yearlings overfed from 20 to 24 months of age and/or sexual maturity in prepubertal colts. Material and methods Twenty-four saddlebred mares were fed forage only (n = 12, group F) or cracked barley and forage (n = 12, group B) from mid-gestation until foaling. Colts were gelded at 12 months of age. Between 20 and 24 months of age, all yearlings were overfed (+140% of requirements) using an automatic concentrate feeder. Offspring were monitored for growth between 6 and 24 months of age, glucose homeostasis was evaluated via modified frequently sampled intra veinous glucose tolerance test (FSIGT) at 19 and 24 months of age and osteoarticular status was investigated using radiographic examinations at 24 months of age. The structure and function of testicles from prepubertal colts were analyzed using stereology and RT-qPCR. Results Post-weaning weight growth was not different between groups. Testicular maturation was delayed in F colts compared to B colts at 12 months of age. From 19 months of age, the cannon bone was wider in B vs F yearlings. F yearlings were more insulin resistant at 19 months compared to B yearlings but B yearlings were affected more severely by overnutrition with reduced insulin sensitivity. The osteoarticular status at 24 months of age was not different between groups. Conclusion In conclusion, nutritional management of the pregnant broodmare and the growing foal may affect sexual maturity of colts and the metabolism of foals until 24 months of age. These effects may be deleterious for reproductive and sportive performances in older horses. PMID

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.

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.

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.

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

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.

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

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 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.

Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells.

PubMed

Sbaraglini, María Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond

2014-03-15

Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabolism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteocalcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and mineralization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro down-regulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells. Copyright © 2014 Elsevier B.V. All rights reserved.

[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.

Genetic manipulation of the ghrelin signaling system in male mice reveals bone compartment specificity of acylated and unacylated ghrelin in the regulation of bone remodeling

USDA-ARS?s Scientific Manuscript database

Ghrelin receptor-deficient (Ghsr-/-) mice that lack acylated ghrelin (AG) signaling retain a metabolic response to unacylated ghrelin (UAG). Recently, we showed that Ghsr-deficiency affects bone metabolism. The aim of this study was to further establish the impact of AG and UAG on bone metabolism. W...

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

Bone Health and Associated Metabolic Complications in Neuromuscular Diseases

PubMed Central

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

2014-01-01

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

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

Physical activity effects on bone metabolism.

PubMed

Smith, E L; Gilligan, C

1991-01-01

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

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..

Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India.

PubMed

Khandare, Arjun L; Gourineni, Shankar Rao; Validandi, Vakdevi

2017-10-23

A case-control study was undertaken among the school children aged 8-15 years to know the presence and severity of dental fluorosis, nutrition and kidney status, and thyroid function along with bone metabolic indicators in Doda district situated at high altitude where drinking water was contaminated and heat stress. This study included 824 participants with an age of 8-15 years. The results of the study reviled that dental fluorosis was significantly higher in affected than control area children. Urinary fluoride was significantly higher (p < 0.05) in affected children as compared to the control area school children. Nutritional status of affected children was lower than control area children. The chronic kidney damage (CKD) was higher in affected than control school children. Thyroid function was affected more in affected than control area schools. Serum creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH) 2 vitamin D, and osteocalcin were significantly higher in affected school children (p < 0.05) as compared to control school children, whereas there was no significant difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among the two groups. There was a significant decrease in thyroid-stimulating hormone (TSH) in the affected area school children compared to control. In conclusion, fluorotic area school children were more affected with dental fluorosis, kidney damage, along and some bone indicators as compared to control school children.

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.

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.

Genetic determinism of bone and mineral metabolism in meat-type chickens: A QTL mapping study.

PubMed

Mignon-Grasteau, Sandrine; Chantry-Darmon, Céline; Boscher, Marie-Yvonne; Sellier, Nadine; Chabault-Dhuit, Marie; Le Bihan-Duval, Elisabeth; Narcy, Agnès

2016-12-01

Skeletal integrity in meat-type chickens is affected by many factors including rapid growth rate, nutrition and genetics. To investigate the genetic basis of bone and mineral metabolism, a QTL detection study was conducted in an intercross between two lines of meat-type chickens divergently selected for their high (D +) or low (D -) digestive efficiency. Tibia size (length, diameter, volume) and ash content were determined at 3 weeks of age as well as phosphorus (P) retention and plasma concentration. Heritability of these traits and their genetic correlations with digestive efficiency were estimated. A QTL mapping study was performed using 3379 SNP markers. Tibia size, weight, ash content and breaking strength were highly heritable (0.42 to 0.61). Relative tibia diameter and volume as well as P retention were strongly and positively genetically correlated with digestive efficiency (0.57 to 0.80). A total of 35 QTL were identified (9 for tibia weight, 13 for tibia size, 5 for bone strength, 5 for bone mineralization, 2 for plasma P concentration and 1 for P retention). Six QTL were genome-wide significant, and 3 QTL for tibia relative volume, weight and ash weight on chromosome 6 were fixed, the positive allele coming from the D-line. For two QTL for ash content on chromosome 18 and relative tibia length on chromosome 26, the confidence intervals were small enough to identify potential candidate genes. These findings support the evidence of multiple genetic loci controlling bone and mineral metabolism. The identification of candidate genes may provide new perspectives in the understanding of bone regulation, even beyond avian species.

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.

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

[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.

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

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

[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.

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.

Factors affecting bone mineral density in multiple sclerosis patients

PubMed Central

Ayatollahi, Azin; Mohajeri-Tehrani, Mohammad Reza

2013-01-01

Background Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD). Methods 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years) participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA). The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS). The patient's quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29). Results Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI) of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs) pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001), but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL), disease duration and BMD of both site. Conclusion As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients’ treatment protocols

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.

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...

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.

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

Obesity is a concern for bone health with aging

PubMed Central

Shapses, Sue A.; Pop, L. Claudia; Wang, Yang

2017-01-01

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population. PMID:28385284

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.

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).

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.

High-fat Diet Decreases Cancellous Bone Mass But Has No Effect on Cortical Bone Mass in the Tibia in Mice

USDA-ARS?s Scientific Manuscript database

Introduction: Body mass has a positive effect on bone mineral density and the strength. Whether mass derived from an obesity condition is beneficial to bone has not been established; neither have the mechanism by which obesity affects bone metabolism. The aim of this study was to examine the effects...

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

[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.

Dietary protein level and source differentially affect bone metabolism, strength, and intestinal calcium transporter expression during ad libitum and food-restricted conditions in male rats

USDA-ARS?s Scientific Manuscript database

High protein diets may attenuate bone loss during energy restriction (ER). The objective of the current study was to determine whether high protein diets suppress bone turnover and improve bone quality in rats during ER and whether dietary protein source affects this relationship. Eighty 12-week o...

[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.

Effect of carbohydrate feeding on the bone metabolic response to running

PubMed Central

Varley, Ian; Jones, Thomas W.; James, Ruth M.; Tang, Jonathan C. Y.; Fraser, William D.; Greeves, Julie P.

2015-01-01

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass−1·h−1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover. PMID:26251510

Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism during Spaceflight and Recovery (Pro K)

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Zwart, S. R.; Shackelford, L.; Heer, M.

2009-01-01

Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

Stretching Your Energetic Budget: How Tendon Compliance Affects the Metabolic Cost of Running

PubMed Central

Uchida, Thomas K.; Hicks, Jennifer L.; Dembia, Christopher L.; Delp, Scott L.

2016-01-01

Muscles attach to bones via tendons that stretch and recoil, affecting muscle force generation and metabolic energy consumption. In this study, we investigated the effect of tendon compliance on the metabolic cost of running using a full-body musculoskeletal model with a detailed model of muscle energetics. We performed muscle-driven simulations of running at 2–5 m/s with tendon force–strain curves that produced between 1 and 10% strain when the muscles were developing maximum isometric force. We computed the average metabolic power consumed by each muscle when running at each speed and with each tendon compliance. Average whole-body metabolic power consumption increased as running speed increased, regardless of tendon compliance, and was lowest at each speed when tendon strain reached 2–3% as muscles were developing maximum isometric force. When running at 2 m/s, the soleus muscle consumed less metabolic power at high tendon compliance because the strain of the tendon allowed the muscle fibers to operate nearly isometrically during stance. In contrast, the medial and lateral gastrocnemii consumed less metabolic power at low tendon compliance because less compliant tendons allowed the muscle fibers to operate closer to their optimal lengths during stance. The software and simulations used in this study are freely available at simtk.org and enable examination of muscle energetics with unprecedented detail. PMID:26930416

Reproductive factors affecting the bone mineral density in postmenopausal women.

PubMed

Ozdemir, Ferda; Demirbag, Derya; Rodoplu, Meliha

2005-03-01

Osteoporosis has been defined as a metabolic bone disease characterized by a loss of bone mineral density (BMD) greater than 2.5 standard deviations below young adult peak bone mass or the presence of fracture. By considering that some factors related to female reproductive system might influence the ultimate risk of osteoporosis, we aimed to investigate if a relationship exists between the present BMD of postmenopausal women with their past and present reproductive characteristics. The present study focused on how BMD could be affected by the following factors in postmenopausal women, such as age at menarche, age at first pregnancy, the number of pregnancies and total breast-feeding time. We reviewed detailed demographic history of 303 postmenopausal women. According to the results of the present study, a negative correlation was found between the number of parities and BMD. The BMD values decreased as the number of pregnancies increased. When the BMD values for lumbar vertebrae 2 and Ward's triangle were investigated, it was observed that a significant difference exists between the women with no child birth and those with more than five parities. There was a significant relationship between age at first pregnancy and BMD values at the lumbar vertebrae 2 and Ward's triangle. Women who had five or more abortions were found to have significantly lower spine BMD values compared to women who had no abortions or women who had one or two abortions. These findings indicate that the increased risk of osteoporosis is associated with the increased number of pregnancies and abortions and higher age at first pregnancy.

Metabolism, obesity and the metabolic syndrome.

PubMed

Persson, Pontus B; Bondke Persson, Anja

2018-05-13

The current obesity epidemic has not only spread from Western to developing economies, but is affecting ever younger individuals. While oftentimes blamed on a slow metabolism or a hereditary component, one might consider whether family recipes and dietary habits are hereditary to a much higher degree than slow metabolism or big bones could ever be. Education is critical, so how do we explain metabolism to a layman, e.g. a parent of an obese child? - Metabolism denotes all the processes, which turn nutrients from our food into energy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

Obesity is a concern for bone health with aging.

PubMed

Shapses, Sue A; Pop, L Claudia; Wang, Yang

2017-03-01

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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 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.

SILICON AND BONE HEALTH

PubMed Central

JUGDAOHSINGH, R.

2009-01-01

Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which presently in the UK results in over 200,000 fractures annually at a cost of over one billion pounds. Figures are set to increase worldwide. Understanding the factors which affect bone metabolism is thus of primary importance in order to establish preventative measures or treatments for this condition. Nutrition is an important determinant of bone health, but the effects of the individual nutrients and minerals, other than calcium, is little understood. Accumulating evidence over the last 30 years strongly suggest that dietary silicon is beneficial to bone and connective tissue health and we recently reported strong positive associations between dietary Si intake and bone mineral density in US and UK cohorts. The exact biological role(s) of silicon in bone health is still not clear, although a number of possible mechanisms have been suggested, including the synthesis of collagen and/or its stabilization, and matrix mineralization. This review gives an overview of this naturally occurring dietary element, its metabolism and the evidence of its potential role in bone health. PMID:17435952

[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.

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.

Does fetal smoke exposure affect childhood bone mass? The Generation R Study.

PubMed

Heppe, D H M; Medina-Gomez, C; Hofman, A; Rivadeneira, F; Jaddoe, V W V

2015-04-01

We assessed the intrauterine influence of maternal smoking on childhood bone mass by comparing parental prenatal and postnatal smoking habits. We observed higher bone mass in children exposed to maternal smoking, explained by higher body weight. Maternal smoking or related lifestyle factors may affect childhood weight gain rather than skeletal growth. Maternal smoking during pregnancy may adversely affect bone health in later life. By comparing the associations of maternal and paternal smoking and of prenatal and postnatal exposure with childhood bone measures, we aimed to explore whether the suggested association could be explained by fetal programming or reflects confounding by familial factors. In 5565 mothers, fathers and children participating in a population-based prospective cohort study, parental smoking habits during pregnancy and current household smoking habits were assessed by postal questionnaires. Total body bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DXA) at the median age of 6.0 years (IQR 0.37). In confounder-adjusted models, maternal smoking during pregnancy was associated with a higher BMC of 11.6 g (95 % confidence interval (CI) 5.6, 17.5), a larger BA of 9.7 cm(2) (95 % CI 3.0, 16.4), a higher BMD of 6.7 g/cm(2) (95 % CI 2.4, 11.0) and a higher BMC of 5.4 g (95 % CI 1.3, 9.6) adjusted for BA of the child. Current weight turned out to mediate these associations. Among mothers who did not smoke, paternal smoking did not show evident associations with childhood bone measures. Also, household smoking practices during childhood were not associated with childhood bone measures. Our results do not support the hypothesis of fetal smoke exposure affecting childhood bone mass via intrauterine mechanisms. Maternal smoking or related lifestyle factors may affect childhood weight gain rather than skeletal growth.

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.

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.

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.

Variations in Urine Calcium Isotope: Composition Reflect Changes in Bone Mineral Balance in Humans

NASA Technical Reports Server (NTRS)

Skulan, Joseph; Anbar, Ariel; Bullen, Thomas; Puzas, J. Edward; Shackelford, Linda; Smith, Scott M.

2004-01-01

Changes in bone mineral balance cause rapid and systematic changes in the calcium isotope composition of human urine. Urine from subjects in a 17 week bed rest study was analyzed for calcium isotopic composition. Comparison of isotopic data with measurements of bone mineral density and metabolic markers of bone metabolism indicates the calcium isotope composition of urine reflects changes in bone mineral balance. Urine calcium isotope composition probably is affected by both bone metabolism and renal processes. Calcium isotope. analysis of urine and other tissues may provide information on bone mineral balance that is in important respects better than that available from other techniques, and illustrates the usefulness of applying geochemical techniques to biomedical problems.

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

A study of stress-free living bone and its application to space flight

NASA Technical Reports Server (NTRS)

Leblanc, A.; Spira, M.

1983-01-01

Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

[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

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.

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.

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.

Influence of calcium and phosphorus feeding on markers of bone metabolism in transition cows.

PubMed

Moreira, V R; Zeringue, L K; Williams, C C; Leonardi, C; McCormick, M E

2009-10-01

A study was carried out to verify the effect of Ca and P levels on production, digestibility, and serum bone metabolism biomarkers in dairy cows. Fifty-two nonlactating multiparous cows (>or=3 lactations) were confined in a free-stall barn approximately 20 d before calving. A standard close-up diet was fed to cows once daily until d 2 postpartum. Cows were randomly assigned to 1 of 4 dietary treatments arranged in a 2 x 2 factorial approach averaging 0.64% Ca for high Ca (HCa), 0.46% Ca for low Ca (LCa), 0.47% P for high P (HP), and 0.38% P for low P (LP) on a dry matter basis. Experimental diets were fed twice daily from 3 d in milk (DIM) until 31 DIM. Intake and milk yield were recorded daily. Milk samples were collected on d 28, 29, and 30 postpartum for components analyses. Blood samples were drawn 10 d before expected calving, at calving, and at 15 and 30 DIM for serum analyses of osteocalcin, a biomarker of bone accretion, and pyridinoline, a biomarker of bone resorption. Total fecal collection was conducted when cows in a block averaged 20 DIM. Intake and production traits were not significantly affected by any of the dietary treatments. Cows averaged nearly 21 kg/d dry matter intake and 44 kg/d milk yield from 6 to 31 DIM. There were no significant differences across treatments in body weight or body condition score loss. Phosphorus intake, P fecal output, P digestibility, and P apparent absorption were affected by dietary P content. Calcium intake was higher with HCa, but Ca fecal output, digestibility, and apparent absorption showed an interaction between dietary Ca and dietary P. Calcium fecal output was 100.6 g/d for cows fed HCaHP, intermediate for cows on the HCaLP diet (89 g/d), and similar among cows fed the 2 LCa diets (70 g/d with LCaHP and 75 with LCaLP). There was no significant effect of Ca or P on osteocalcin measurements. Pyridinoline concentrations were affected by dietary Ca levels and tended to have a significant dietary Ca x dietary P

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.

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.

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.

Factors affecting bone mineral density in postmenopausal women.

PubMed

Heidari, Behzad; Hosseini, Reza; Javadian, Yahya; Bijani, Ali; Sateri, Mohammad Hassan; Nouroddini, Haj Ghorban

2015-01-01

This study aimed to determine the relationship between bone mineral density (BMD) and demographic, biochemical, and clinical features according to BMD measurement sites. The results indicated that BMD correlates negatively with menopause duration, parity, and history of fractures but positively correlates with obesity, physical activity, education, and serum ferritin. Osteoporosis (OP) is an important cause of morbidity and mortality in the elderly people. The impacts of various factors on bone mineral density (BMD) differ across diverse population. We hypothesized that the influences of factors which affect BMD vary according to BMD measurement sites. The aim of this study was to determine the relationship between BMD in the femoral neck (FN) and lumbar spine (LS) with some common clinical, demographic, and biochemical parameters in postmenopausal women. In this cross-sectional case-control study, all postmenopausal women of the Amirkola Health and Ageing Project (AHAP) who performed bone densitometry were included. BMD at FN and LS was measured by DXA method. Data regarding clinical, demographic, and biochemical characteristics were provided. OP was diagnosed by the International Society for Clinical Densitometry criteria. Pearson correlation and multivariate regression analyses with simultaneous adjustment were performed to determine relationship. Five hundred thirty-seven women with mean age of 67.9 ± 6.7 years and mean menopause duration (MD) of 15.8 ± 5.1 years were studied. MD correlated negatively with FN-BMD and LS-BMD g/cm(2) (r = -0.405, p = 0.001 and r = -0.217, p = 0.001). Body mass index (BMI) correlated positively with FN and LS-BMD g/cm(2) (r = 0.397, p = 0.001 and r = 0.311, p = 0.001). The association of MD with risk of FN-OP was stronger than LS-OP. Obesity and metabolic syndrome (MS) and higher serum ferritin reduced the risk of OP at both LS and FN similarly, whereas the impacts of parity, prior fracture, high level of education, and physical

Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial.

PubMed

Vianna, Andre Gustavo Daher; de Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Borba, Victoria Zeghbi Cochenski; Barreto, Fellype de Carvalho

2017-01-01

Several antidiabetic therapies affect bone metabolism. Sulfonylureas have the lowest impact on bone among oral antidiabetics. The objective of this study is to compare the effects of vildagliptin and gliclazide modified release (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with uncontrolled type 2 diabetes (T2D). Forty-two postmenopausal women with uncontrolled T2D were randomly allocated into vildagliptin or gliclazide MR (control) groups. The primary endpoint was the change in the BTMs in months 6 and 12 compared with the baseline. The secondary endpoint was the variation in the BMD, which was assessed via dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and total hip at baseline and month 12. After a 12-month treatment, the BTM serum carboxy-terminal telopeptide of type 1 collagen increased 0.001 ± 0.153 ng/mL in the vildagliptin group versus 0.008 ± 0.060 ng/mL in the gliclazide MR group ( p  = 0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen type I and urinary amino-terminal telopeptide of type 1 collagen remained stable in both groups, and there was no statistically significant difference between the effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD did not change in the vildagliptin or gliclazide MR groups after a 12-month treatment (0.000 ± 0.025 g/cm 2 versus -0.008 ± 0.036, respectively, p  = 0.434). Furthermore, there was a similar lack of change in the femoral neck and total hip BMD values in both treatments. Bone turnover markers and BMD remained unchanged after a 12-month treatment in both groups, which suggests that vildagliptin has the same safety profile as gliclazide MR on bone metabolism. Trial Registration ClinicalTrials.gov number NCT01679899.

Developing bones are differentially affected by compromised skeletal muscle formation

PubMed Central

Nowlan, Niamh C.; Bourdon, Céline; Dumas, Gérard; Tajbakhsh, Shahragim; Prendergast, Patrick J.; Murphy, Paula

2010-01-01

Mechanical forces are essential for normal adult bone function and repair, but the impact of prenatal muscle contractions on bone development remains to be explored in depth in mammalian model systems. In this study, we analyze skeletogenesis in two ‘muscleless’ mouse mutant models in which the formation of skeletal muscle development is disrupted; Myf5nlacZ/nlacZ:MyoD−/− and Pax3Sp/Sp (Splotch). Ossification centers were found to be differentially affected in the muscleless limbs, with significant decreases in bone formation in the scapula, humerus, ulna and femur, but not in the tibia. In the scapula and humerus, the morphologies of ossification centers were abnormal in muscleless limbs. Histology of the humerus revealed a decreased extent of the hypertrophic zone in mutant limbs but no change in the shape of this region. The elbow joint was also found to be clearly affected with a dramatic reduction in the joint line, while no abnormalities were evident in the knee. The humeral deltoid tuberosity was significantly reduced in size in the Myf5nlacZ/nlacZ:MyoD−/− mutants while a change in shape but not in size was found in the humeral tuberosities of the Pax3Sp/Sp mutants. We also examined skeletal development in a ‘reduced muscle’ model, the Myf5nlacZ/+:MyoD−/− mutant, in which skeletal muscle forms but with reduced muscle mass. The reduced muscle phenotype appeared to have an intermediate effect on skeletal development, with reduced bone formation in the scapula and humerus compared to controls, but not in other rudiments. In summary, we have demonstrated that skeletal development is differentially affected by the lack of skeletal muscle, with certain rudiments and joints being more severely affected than others. These findings indicate that the response of skeletal progenitor cells to biophysical stimuli may depend upon their location in the embryonic limb, implying a complex interaction between mechanical forces and location

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

PubMed

Singh, Lakshman; Tyagi, Sonia; Myers, Damian; Duque, Gustavo

2018-04-01

Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

Effects of a metabolic syndrome induced by a fructose-rich diet on bone metabolism in rats.

PubMed

Felice, Juan Ignacio; Gangoiti, María Virginia; Molinuevo, María Silvina; McCarthy, Antonio Desmond; Cortizo, Ana María

2014-02-01

The aims of this study were: first, to evaluate the possible effects of a fructose rich diet (FRD)-induced metabolic syndrome (MS) on different aspects of long bone histomorphometry in young male rats; second, to investigate the effects of this diet on bone tissue regeneration; and third, to correlate these morphometric alterations with changes in the osteogenic/adipogenic potential and expression of specific transcription factors, of marrow stromal cells (MSC) isolated from rats with fructose-induced MS. MS was induced in rats by treatment with a FRD for 28 days. Halfway through treatment, a parietal wound was made and bone healing was evaluated 14 days later. After treatments, histomorphometric analysis was performed in dissected femoral and parietal bones. MSC were isolated from the femora of control or fructose-treated rats and differentiated either to osteoblasts (evaluated by type 1 collagen, Alkaline phosphatase and extracellular nodule mineralization) or to adipocytes (evaluated by intracellular triglyceride accumulation). Expression of Runx2 and PPARγ was assessed by Western blot. Fructose-induced MS induced deleterious effects on femoral metaphysis microarchitecture and impaired bone regeneration. Fructose treatment decreased the osteogenic potential of MSC and Runx2 expression. In addition, it increased the adipogenic commitment of MSC and PPARγ expression. Fructose-induced MS is associated with deleterious effects on bone microarchitecture and with a decrease in bone repair. These alterations could be due to a deviation in the adipogenic/osteogenic commitment of MSC, probably by modulation of the Runx2/PPARγ ratio. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture.

PubMed

Sanz-Salvador, Lucía; García-Pérez, Miguel Ángel; Tarín, Juan J; Cano, Antonio

2015-02-01

Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use. © 2015 European Society of Endocrinology.

Constitutional bone impairment in Noonan syndrome.

PubMed

Baldassarre, Giuseppina; Mussa, Alessandro; Carli, Diana; Molinatto, Cristina; Ferrero, Giovanni Battista

2017-03-01

Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism. In this study, we investigated the bone quality assessed by phalangeal quantitative ultrasound (QUS) and the metabolic bone profiling in a group of patients with NS, to determine whether low bone mineralization is primary or secondary to NS characteristics. Thirty-five patients were enrolled, including 20 males (55.6%) and 15 females (44.5%) aged 1.0-17.8 years (mean 6.4 ± 4.5, median 4.9 years). Each patients was submitted to clinical examination, estimation of the bone age, laboratory assays, and QUS assessment. Twenty-five percent of the cohort shows reduced QUS values for their age based on bone transmission time. Bone measurement were adjusted for multiple factors frequently observed in NS patients, such as growth retardation, delayed bone age, retarded puberty, and reduced body mass index, potentially affecting bone quality or its appraisal. In spite of the correction attempts, QUS measurement indicates that bone impairment persists in nearly 15% of the cohort studied. Our results indicate that bone impairment in NS is likely primary and not secondary to any of the phenotypic traits of NS, nor consistent with metabolic disturbances. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth.

PubMed

Uchimura, Tomoya; Hollander, Judith M; Nakamura, Daisy S; Liu, Zhiyi; Rosen, Clifford J; Georgakoudi, Irene; Zeng, Li

2017-10-01

Postnatal bone growth involves a dramatic increase in length and girth. Intriguingly, this period of growth is independent of growth hormone and the underlying mechanism is poorly understood. Recently, an IGF2 mutation was identified in humans with early postnatal growth restriction. Here, we show that IGF2 is essential for longitudinal and appositional murine postnatal bone development, which involves proper timing of chondrocyte maturation and perichondrial cell differentiation and survival. Importantly, the Igf2 null mouse model does not represent a simple delay of growth but instead uncoordinated growth plate development. Furthermore, biochemical and two-photon imaging analyses identified elevated and imbalanced glucose metabolism in the Igf2 null mouse. Attenuation of glycolysis rescued the mutant phenotype of premature cartilage maturation, thereby indicating that IGF2 controls bone growth by regulating glucose metabolism in chondrocytes. This work links glucose metabolism with cartilage development and provides insight into the fundamental understanding of human growth abnormalities. © 2017. Published by The Company of Biologists Ltd.

Insulin resistance and bone: a biological partnership.

PubMed

Conte, Caterina; Epstein, Solomon; Napoli, Nicola

2018-04-01

Despite a clear association between type 2 diabetes (T2D) and fracture risk, the pathogenesis of bone fragility in T2D has not been clearly elucidated. Insulin resistance is the primary defect in T2D. Insulin signalling regulates both bone formation and bone resorption, but whether insulin resistance can affect bone has not been established. On the other hand, evidence exists that bone might play a role in the regulation of glucose metabolism. This article reviews the available experimental and clinical evidence on the interplay between bone and insulin resistance. Interestingly, a bilateral relationship between bone and insulin resistance seems to exist that unites them in a biological partnership.

Bone Metabolism on ISS Missions

NASA Technical Reports Server (NTRS)

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

2014-01-01

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

Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).

PubMed

Krupski, W; Tatara, M R; Charuta, A; Brodzki, A; Szpetnar, M; Jóźwik, A; Strzałkowska, N; Poławska, E; Łuszczewska-Sierakowska, I

2018-06-01

1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT.

PubMed

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases.

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

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

NASA Technical Reports Server (NTRS)

Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

1996-01-01

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

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.

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.

Influence of high-altitude grazing on bone metabolism of growing sheep.

PubMed

Liesegang, A; Hüttenmoser, D; Risteli, J; Leiber, F; Kreuzer, M; Wanner, M

2013-02-01

The objective of this study was to identify the effect of high alpine grazing, associated with varying pasture grass qualities and more pronounced exercise on typically steep slopes, on bone metabolism by improving bone density and enhancing bone turnover in growing sheep. Twenty-four 5-month-old sheep were randomly assigned to two groups. One group was kept at high altitude (HA; 2000-2200 m a.s.l.) for 3 months, and the other group (C; control) remained in the lowlands (400 m a.s.l.). Both groups were kept in grazing pastures with access to good-quality swards. Before the start of the experiment, blood samples were taken, the sheep were weighed, and the left metatarsus of each animal was analysed by quantitative computer tomography. After 1 month, blood samples were taken and body weight was measured, followed by biweekly sampling. Finally, the animals were slaughtered, and the bones were collected for analysis of various bone parameters. Body weight development did not differ between the groups. Concentrations of 25-OH-Vitamin D, carboxy-terminal telopeptide of type I collagen and activities of bone-specific alkaline phosphatase were always higher in the HA group than in the C group, except on the last two sampling dates. Bone mineral content and density increased in both groups during the experiment, but more intensively in the HA group. In addition, the cortical thickness of the HA group increased. The present study demonstrates an increase in bone turnover and mineral content of the bones of the growing sheep grazing in high alpine pastures. The factors associated with HA grazing, therefore, clearly seem to improve bone composition. © 2011 Blackwell Verlag GmbH.

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

Effects of manganese deficiency on serum hormones and biochemical markers of bone metabolism in chicks.

PubMed

Zhaojun, Wang; Lin, Wang; Zhenyong, Wang; Jian, Wang; Ran, Liu

2013-05-01

In order to investigate the effect of manganese (Mn) deficiency on bone metabolism in chicks, ninety 1-day-old male Arbor Acre chicks were randomly divided into 3 groups and each group were given a diet having a different concentration of Mn (60 mg kg(-1), control group; 40 mg kg(-1), Mn-deficient group I; 8.7 mg kg(-1), Mn-deficient group II). The serum was collected at 42 days old. Tests were performed to evaluate the changes in the levels of PTH, CT, ALP, TrACP, HOP TNF-alpha, OC, Mn and Ca in the serum of the chicks and the results showed that the levels of CT, ALP, TrACP, HOP, and Mn decreased markedly (P < 0.05), while PTH, Ca, and TNF-alpha increased markedly (P < 0.05) due to manganese deficiency in the diet, which indicates that Mn deficiency results in disorder of bone regulatory hormones and enzymes of bone metabolism in the serum.

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

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT

PubMed Central

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Summary Introduction Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Methods Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Results Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. Discussion CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases. PMID:28740526

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.

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.

Control of bone and fat mass by oxytocin.

PubMed

Amri, Ez-Zoubir; Pisani, Didier F

2016-11-01

Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass, and an increase in fat accumulation. It is established that both obesity and osteoporosis are affected by genetic and environmental factors, bone remodeling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone family and regulates the function of peripheral target organs, its circulating levels decreased with age. Nowadays, it is well established that OT plays an important role in the control of bone and fat mass and their metabolism. Of note, OT and oxytocin receptor knock out mice develop bone defects and late-onset obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis and obesity as well as associated metabolic disorders such as type 2 diabetes and cardiovascular diseases. In this review, we will discuss findings regarding the OT effects on bone and fat mass.

The relationship between glucose metabolism, metabolic syndrome, and bone-specific alkaline phosphatase: a structural equation modeling approach.

PubMed

Cheung, Ching-Lung; Tan, Kathryn C B; Lam, Karen S L; Cheung, Bernard M Y

2013-09-01

Serum alkaline phosphatase plays a role in vascular calcification. It is found in various tissues, whereas bone-specific alkaline phosphatase (BAP) more specifically reflects mineral metabolism. The relationship of serum alkaline phosphatase (total and bone-specific) with diabetes and metabolic syndrome (MetS), 2 major risk factors of vascular calcification, is largely unknown. We aimed to investigate the relationships between glucose metabolism, components of the MetS, and alkaline phosphatase. This was a cross-sectional study of a nationally representative sample of the U.S. population in 1999 through 2004. Participants were 3773 nondiabetic participants of the National Health and Nutrition Examination Survey 1999-2004. We measured serum BAP and total alkaline phosphatase. In multivariable linear regression, updated homeostasis model assessment (HOMA2) for insulin resistance (β = 0.068), HOMA2 for β-cell function (β = 0.081), insulin (β = 0.065), mean arterial pressure (β = 0.15), and high-density lipoprotein (HDL)-cholesterol (β = 0.209) were positively associated with BAP, whereas HOMA2 for insulin sensitivity (β = -0.065) was negatively associated with BAP. On the other hand, only mean arterial pressure and HDL-cholesterol were significantly associated with total alkaline phosphatase. Moreover, a structural equation model revealed that hypertension, low HDL, and insulin resistance had significant direct effects on serum BAP levels, whereas obesity and inflammation might have indirect effects on serum BAP levels. The overall model showed very good fit to the data (comparative fit index = 0.995, root mean square error of approximation = 0.037, and standardized root mean square residual = 0.006). Glucose metabolism and MetS are significantly related to serum BAP levels. How BAP mediates vascular calcification in diabetes and MetS warrants further studies.

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.

Association between metabolic syndrome and bone fractures: a meta-analysis of observational studies.

PubMed

Sun, Kan; Liu, Jianmin; Lu, Nan; Sun, Hanxiao; Ning, Guang

2014-02-09

Emerging epidemiological evidence suggest an association between metabolic syndrome and fractures. However, whether metabolic syndrome is an independent risk or protective factor of fractures remains controversial. Our goal is to provide a quantitative assessment of the association between metabolic syndrome and bone fractures by conducting a meta-analysis of observational studies. The PubMed and Embase database were searched through to March 2013 to identify studies that met pre-established inclusion criteria. Reference lists of retrieved articles were also reviewed. Summary effect estimates with 95% confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies. Eight epidemiologic studies involving 39,938 participants were included in the meta-analysis. In overall analysis, metabolic syndrome was not associated with prevalent fractures [pooled odds ratio (OR) 0.93, 95% CI 0.84 - 1.03] in cross-sectional studies or incident fractures [pooled relative risk (RR) 0.88, 95% CI 0.37 - 2.12] in prospective cohort studies. No evidence of heterogeneity was found in cross-sectional studies (p = 0.786, I2 = 0.0%). A substantial heterogeneity was detected in cohort studies (p = 0.001, I2 = 85.7%). No indication of significant publication bias was found either from Begg's test or Egger's test. Estimates of total effects were substantially consistent in the sensitivity and stratification analyses. The present meta-analysis of observational studies suggests that the metabolic syndrome has no explicit effect on bone fractures.

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.

[Long-term effects of 7-year growth hormone substitution on bone metabolism, bone density, and bone quality in growth hormone-deficient adults].

PubMed

Wilhelm, Birgit; Kann, Peter Herbert

2004-10-15

Subnormal bone mineral density (BMD) and increased fracture risk are described in patients with growth hormone deficiency (GHD). Growth hormone (GH) has been reported to have beneficial effects on bone in GHD. The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism, BMD, and bone quality in patients with GHD. 20 adult patients with GHD (eleven male, nine female, mean age 42.5 years) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week. After 6 months all patients received GH. After a 1-year double-blind, placebo-controlled study the patients were followed for another 72 months in an open study. The patients were compared to 20 age- und sex-matched healthy controls. Bone turnover was determined by ICTP (type I collagen carboxyterminal cross-linked telopeptide) as parameter of bone resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker of bone formation. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA). Apparent phalangeal ultrasound transmission velocity (APU) was assessed as parameter of bone quality independent of BMD. At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls. During the 1st year of GH replacement therapy BMD decreased, followed by a continuous increase in BMD (about 12%) up to 60 months which remained unchanged thereafter, building up a plateau. After 72 months no significant difference between the patients and the healthy controls could be detected. Concerning parameters of bone turnover, first ICTP as marker of bone resorption showed a significant increase, later on the marker of bone formation increased as well. APU decreased during the first 6 months of treatment, but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study. BMD

Bone health in Down syndrome.

PubMed

García-Hoyos, Marta; Riancho, José Antonio; Valero, Carmen

2017-07-21

Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm 2 ) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm 3 ), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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.

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.

Effects of atorvastatin on bone mineral density (BMD) and bone metabolism in elderly males with osteopenia and mild dyslipidemia: a 1-year randomized trial.

PubMed

Chen, Zhi-guo; Cai, Hua-jie; Jin, Xian; Lu, Jin-hua; Wang, Jing; Fang, Ning-yuan

2014-01-01

We explored the effects of atorvastatin on BMD and biochemical markers of bone metabolism in a 1-year, prospective, randomized controlled study. 64 male patients with osteopenia and mild dyslipidemia (mean age 80.1±6.6 years) were randomized to a 1-year atorvastatin treatment or control. BMD of hip and lumbar spine was measured with dual-energy X-ray absorptionmetry (DXA). Bone metabolic markers including resorption markers β-c-terminal telopeptide of type I collagen (CTx), formative markers osteocalcin (OC), 25-hydroxyvitamin D (25(OH)D) were measured with electrochemiluminescence immunoassay (ECLIA). Other bone metabolism markers including intact parathyroid hormone (iPTH) and testosterone were measured with chemiluminescence enzyme immunoassay (CLEIA). Levels of serum lipid and biochemical parameters were measured with automatic biochemical analyzer. All the parameters were recorded at baseline, and at 6 and 12 months, respectively. Compared with the control group, the atorvastatin treatment group showed significant reduction of triglyceride (TG, P<0.01) and low-density lipoprotein cholesterol (LDL-C, P<0.01). At 12 month, total hip BMD in atorvastatin group was significantly higher (P<0.01) compared with the control group, while there were no similar effect on femoral neck or lumbar spine between the two groups (P=0.48 and 0.53 respectively). Meanwhile, CTx significantly reduced in atorvastatin treatment group (P<0.001) compared with baseline. Our findings suggest that in elderly male patients with osteopenia and mild dyslipidemia, therapeutic doses of atorvastatin were associated with positive effects on BMD, probably mediated by suppressed bone resorption. Copyright © 2014. Published by Elsevier Ireland Ltd.

Abutment Disconnection/Reconnection Affects Peri-implant Marginal Bone Levels: A Meta-Analysis.

PubMed

Koutouzis, Theofilos; Gholami, Fatemeh; Reynolds, John; Lundgren, Tord; Kotsakis, Georgios A

Preclinical and clinical studies have shown that marginal bone loss can be secondary to repeated disconnection and reconnection of abutments that affect the peri-implant mucosal seal. The aim of this systematic review and meta-analysis was to evaluate the impact of abutment disconnections/reconnections on peri-implant marginal bone level changes. To address this question, two reviewers independently performed an electronic search of three major databases up to October 2015 complemented by manual searches. Eligible articles were selected on the basis of prespecified inclusion and exclusion criteria after a two-phase search strategy and assessed for risk of bias. A random-effects meta-analysis was performed for marginal bone loss. The authors initially identified 392 titles and abstracts. After evaluation, seven controlled clinical studies were included. Qualitative assessment of the articles revealed a trend toward protective marginal bone level preservation for implants with final abutment placement (FAP) at the time of implant placement compared with implants for which there were multiple abutment placements (MAP). The FAP group exhibited a marginal bone level change ranging from 0.08 to 0.34 mm, whereas the MAP group exhibited a marginal bone level change ranging from 0.09 to 0.55 mm. Meta-analysis of the seven studies reporting on 396 implants showed significantly greater bone loss in cases of multiple abutment disconnections/reconnections. The weighted mean difference in marginal bone loss was 0.19 mm (95% confidence interval, 0.06-0.32 mm), favoring bone preservation in the FAP group. Within the limitations of this meta-analysis, abutment disconnection and reconnection significantly affected peri-implant marginal bone levels. These findings pave the way for revisiting current restorative protocols at the restorative treatment planning stage to prevent incipient marginal bone loss.

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.

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.

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

PubMed

Tirabassi, G; delli Muti, N; Gioia, A; Biagioli, A; Lenzi, A; Balercia, G

2014-04-01

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption.

PubMed

Wongdee, Kannikar; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-01-01

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D 3 , and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism.

PubMed

Hansen, Morten S S; Tencerova, Michaela; Frølich, Jacob; Kassem, Moustapha; Frost, Morten

2018-01-01

The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

A New Insight to Bone Turnover: Role of ω-3 Polyunsaturated Fatty Acids

PubMed Central

López-Frías, Magdalena; López-Aliaga, Inmaculada; Ochoa, Julio J.

2013-01-01

Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor κ β (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ω-3 PUFA supplementation plays a major role in bone health. PMID:24302863

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

A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.

PubMed

Smith, Brenda J; Bu, So Young; Wang, Yan; Rendina, Elizabeth; Lim, Yin F; Marlow, Denver; Clarke, Stephen L; Cullen, Diane M; Lucas, Edralin A

2014-01-01

Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone

Weight loss and bone mineral density.

PubMed

Hunter, Gary R; Plaisance, Eric P; Fisher, Gordon

2014-10-01

Despite evidence that energy deficit produces multiple physiological and metabolic benefits, clinicians are often reluctant to prescribe weight loss in older individuals or those with low bone mineral density (BMD), fearing BMD will be decreased. Confusion exists concerning the effects that weight loss has on bone health. Bone density is more closely associated with lean mass than total body mass and fat mass. Although rapid or large weight loss is often associated with loss of bone density, slower or smaller weight loss is much less apt to adversely affect BMD, especially when it is accompanied with high intensity resistance and/or impact loading training. Maintenance of calcium and vitamin D intake seems to positively affect BMD during weight loss. Although dual energy X-ray absorptiometry is normally used to evaluate bone density, it may overestimate BMD loss following massive weight loss. Volumetric quantitative computed tomography may be more accurate for tracking bone density changes following large weight loss. Moderate weight loss does not necessarily compromise bone health, especially when exercise training is involved. Training strategies that include heavy resistance training and high impact loading that occur with jump training may be especially productive in maintaining, or even increasing bone density with weight loss.

Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

PubMed Central

Zheng, Junke; Lu, Zhigang; Kocabas, Fatih; Böttcher, Ralph T.; Costell, Mercedes; Kang, Xunlei; Liu, Xiaoye; DeBerardinis, Ralph J.; Wang, Qianming; Chen, Guo-Qiang

2014-01-01

How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-l-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow. PMID:24385538

A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

PubMed

Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

2017-06-01

Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effects of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in osteopenia women.

PubMed

Kim, Chang Sun; Kim, Ji Yeon; Kim, Hyo Jin

2014-03-01

The purpose of this study was to examine the effect of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in elderly osteopenia women. We selected 11 people of elderly osteopenia women and loaded a single bout pilates exercise about RPE 10-14 level. The blood samples were collected before, immediately after and 60 minute after pilates exercise, then examined calcium metabolic markers in serum and extracted peripheral blood mononuclear cell (PBMC) from whole blood and confirmed mRNA expression of bone metabolic cytokines from PBMC. To clarify the changes during exercise, we designed repeated measure ANOVA as the control group to perform blood sampling without exercise. As a result, serum P showed significant interaction effect between group and time (p<.001), the pilates exercise group decreased about 9% at immediately after exercise and 13% during recovery after exercise (p<.05), while the control group showed a tendency to increase. Serum CK also showed a significant interaction between group and time (p<.05), the pilates group significantly increased at immediately after exercise and during recovery after exercise (p<.05) but the control group didn't have changes. TNF-α and IL-6 mRNA expression in PBMC was significantly increased in the pilates group (p<.01, p<.05), although INF-γ mRNA expression didn't show statistically significant difference, it tended to increase in the pilates group (NS). These results suggested that a single bout pilates exercise of elderly osteopenia women cause hypophosphatemia with temporary muscle damage, and it leading high turnover bone metabolic state with to activate both of bone formation and bone resorption.

The effects of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in osteopenia women

PubMed Central

Kim, Chang Sun; Kim, Ji Yeon; Kim, Hyo Jin

2014-01-01

[Purpose] The purpose of this study was to examine the effect of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in elderly osteopenia women. [Methods] We selected 11 people of elderly osteopenia women and loaded a single bout pilates exercise about RPE 10-14 level. The blood samples were collected before, immediately after and 60 minute after pilates exercise, then examined calcium metabolic markers in serum and extracted peripheral blood mononuclear cell (PBMC) from whole blood and confirmed mRNA expression of bone metabolic cytokines from PBMC. To clarify the changes during exercise, we designed repeated measure ANOVA as the control group to perform blood sampling without exercise. [Results] As a result, serum P showed significant interaction effect between group and time (p<.001), the pilates exercise group decreased about 9% at immediately after exercise and 13% during recovery after exercise (p<.05), while the control group showed a tendency to increase. Serum CK also showed a significant interaction between group and time (p<.05), the pilates group significantly increased at immediately after exercise and during recovery after exercise (p<.05) but the control group didn’t have changes. TNF-α and IL-6 mRNA expression in PBMC was significantly increased in the pilates group (p<.01, p<.05), although INF-γ mRNA expression didn’t show statistically significant difference, it tended to increase in the pilates group (NS). [Conclusion] These results suggested that a single bout pilates exercise of elderly osteopenia women cause hypophosphatemia with temporary muscle damage, and it leading high turnover bone metabolic state with to activate both of bone formation and bone resorption. PMID:25566441

Multiple fractures and impaired bone metabolism in Wolfram syndrome: a case report.

PubMed

Catalano, Antonino; Bellone, Federica; Cicala, Giuseppe; Giandalia, Annalisa; Morabito, Nunziata; Cucinotta, Domenico; Russo, Giuseppina Tiziana

2017-01-01

Wolfram Syndrome (WS) is a rare and lethal disease characterized by optic atrophy, diabetes mellitus, diabetes insipidus, and hearing loss. To date, osteoporotic related fractures have not been reported in affected patients. Here, we describe the case of a man affected by WS complicated by several bone fragility fractures. A 50-year-old Caucasian man was hospitalized because of tibia and fibula fractures. His clinical features included diabetes mellitus, diabetes insipidus, optic atrophy and deafness that were consistent with an unrecognized WS diagnosis, which was confirmed by the identification of a specific mutation in gene WFS1 encoding wolframin. Bone mineral density by phalangeal quantitative ultrasound demonstrated severe osteoporosis, with high serum levels of surrogate markers of bone turn-over. Previously unidentified rib fractures were also detected. To the best of our knowledge, this is the first report of osteoporotic related fractures in a patient affected by WS. Although no effective treatments are currently available to delay the progression of the disease, this case report suggests to evaluate fracture risk in the diagnostic work-up of WS.

Bone marrow adipocytes: a neglected target tissue for growth hormone.

PubMed

Gevers, Evelien F; Loveridge, Nigel; Robinson, Iain C A F

2002-10-01

Bone marrow (BM) contains numerous adipocytes. These share a common precursor with osteoblasts and chondrocytes, but their function is unknown. It is unclear what regulates the differentiation of these three different cell types, though their subsequent metabolic activity is under hormonal regulation. GH and estrogen stimulate bone growth and mineralization, by direct effects on chondrocytes and osteoblasts. GH also stimulates lipolysis in subcutaneous and visceral adipocytes. However, adipocytes in BM have largely been ignored as potential targets for GH or estrogen action. We have addressed this by measuring BM adipocyte number, perimeter and area as well as bone area and osteoblast activity in GH-deficient dwarf (dw/dw), normal, or ovariectomized (Ovx) rats, with or without GH, IGF-1, PTH, or estrogen treatment or high fat feeding. Marrow adipocyte numbers were increased 5-fold (P < 0.001) in dw/dw rats, and cell size was also increased by 20%. These values returned toward normal in dw/dw rats given GH but not when given IGF-1. Cancellous bone area and osteoblast number were significantly (P < 0.005) lower in dw/dw rats, though alkaline phosphatase (ALP) activity in individual osteoblasts was unchanged. GH treatment increased % osteoblast covered bone surface without affecting individual cell ALP activity. Ovariectomy in normal or dw/dw rats had no affect on marrow adipocyte number nor size, although estrogen treatment in ovariectomized (Ovx) normal rats did increase adipocyte number. Ovx decreased tibial cancellous bone area in normal rats (64%; P < 0.05) and decreased osteoblast ALP-activity (P < 0.01) but did not affect the percentage of osteoblast-covered bone surface. Estrogen replacement reversed these changes. While treatment with PTH by continuous sc infusion decreased cancellous bone (P < 0.05) and high fat feeding increased the size of BM adipocytes (P < 0.01), they did not affect BM adipocyte number. These results suggest that GH has a specific action

VDR deficiency affects alveolar bone and cementum apposition in mice.

PubMed

Zhang, Xueming; Rahemtulla, Firoz; Zhang, Ping; Thomas, Huw F

2011-07-01

To compare the mineralisation density (MD), morphology and histology of alveolar bone and cementum amongst VDR +/+, VDR -/-, and VDR -/- groups supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25% phosphorous. Four groups of mice (6 mice/group) were identified by genotyping: VDR +/+ mice (VDR wild type), VDR -/- mice (VDR deficient), VDR -/- offsprings derived from VDR -/- parents receiving a supplemental diet (early rescued), and VDR -/- mice fed with a supplemental diet beginning at age one month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was used to compare MD and morphology of alveolar bone and cementum. H-E and Toluidine blue staining was used to examine the ultrastructure of the alveolar bone and cementum at matched locations. In VDR -/- group, alveolar bone and cementum failed to mineralise normally. Early rescue increased MD of alveolar bone in VDR -/- mice with excessive alveolar bone formation, but which not observed in late rescue group. MD and morphology of cementum-dentine complex in both early and late rescue groups were comparable with VDR +/+ group when feeding with high-calcium rescue diet. VDR affects alveolar bone mineralisation and formation systemically and locally. However, cementum apposition and mineralisation is mainly regulated by calcium concentrations in serum. Copyright © 2010 Elsevier Ltd. All rights reserved.

Correlates of bone quality in older persons

PubMed Central

Lauretani, F.; Bandinelli, S.; Russo, C.R.; Maggio, M.; Di Iorio, A.; Cherubini, A.; Maggio, D.; Ceda, G.P.; Valenti, G.; Guralnik, J.M.; Ferrucci, L.

2009-01-01

Purpose of the study In a population-based sample of older persons, we studied the relationship between tibial bone density and geometry and factors potentially affecting osteoporosis. Methods Of the 1260 participants aged 65 years or older eligible for the InCHIANTI study, 1155 received an interview and 915 (79.2%) had complete data on tibial QCTscans and other variables used in the analysis presented here. The final study population included 807 persons (372 men and 435 women, age range 65–96 years) after exclusion of participants affected by bone diseases or treated with drugs that interfere with bone metabolism. Results In both sexes, calf cross-sectional muscle area (CSMA) was significantly and independently associated with total bone cross-sectional area (tCSA) and cortical bone cross-sectional area (cCSA) but not with trabecular or cortical volumetric bone mineral density (vBMD). Bioavailable testosterone (Bio-T) was independently associated with both trabecular and cortical vBMD in both sexes. In women, independently of confounders, 25(OH)-vitamin D was positively associated with tCSA and cortical vBMD, while PTH was negatively associated with cortical vBMD. IL-1 beta was negatively correlated with cortical vBMD in women, while TNF-alpha was associated with enhanced bone geometrical adaptation in men. Conclusions Physiological parameters that are generically considered risk factors for osteoporosis were associated with specific bone parameters assessed by tibial QCT. Factors known to be associated with increased bone reabsorption, such as 25(OH)-vitamin D, PTH and Bio-T, affected mainly volumetric BMD, while factors associated with bone mechanical stimulation, such as CSMA, affected primarily bone geometry. Our results also suggested that pro-inflammatory cytokines might be considered as markers of bone resorption. PMID:16709469

The effect of topiramate and lamotrigine on rat bone mass, structure and metabolism.

PubMed

Simko, Julius; Fekete, Sona; Gradosova, Iveta; Malakova, Jana; Zivna, Helena; Valis, Martin; Palicka, Vladimir; Zivny, Pavel

2014-05-15

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome.

PubMed

Aoki, Motokuni; Kawahata, Hirohisa; Sotobayashi, Daisuke; Yu, Hisahiro; Moriguchi, Atsushi; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

2015-08-01

Although recent studies suggest that several antihypertensive drugs could reduce the risk of bone fracture, it is still unclear how these drugs act on bone remodeling, especially in elderly women with severe osteoporosis with disuse syndrome. In the present study, we investigated the effects of a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) on bone metabolism in elderly bedridden women with hypertension and disuse syndrome. Elderly bedridden women (aged >75 years) receiving antihypertensive therapy treated with CCB were recruited in the present study. The participants were divided into two groups--CCB group and ARB group--and followed up to 12 months. Markers of bone resorption were markedly increased, suggesting accelerated bone resorption in the participants of the present study. In the follow-up period, the patients treated with a CCB showed a significant decrease in bone mineral density in a time-dependent manner, accompanied by a significant increase in bone resorption markers, whereas treatment with olmesartan inhibited bone loss, associated with attenuation of increased bone resorption markers. Bone mineral density of femoral neck in the CCB group was significantly lower than that in the ARB group at 6 months. The present study showed inhibitory effects of an ARB on bone resorption in hypertensive patients with accelerated bone resorption, such as elderly bedridden women, and indicated an important role of the renin-angiotensin system in bone metabolism. In elderly hypertensive patients, ARB might be expected to have additional beneficial potential to maintain bone health in bedridden patients. © 2014 Japan Geriatrics Society.

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

[Effect of milk product with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women: randomized trial].

PubMed

García-Martín, Antonia; Quesada Charneco, Miguel; Alvárez Guisado, Alejandro; Jiménez Moleón, José Juan; Fonollá Joya, Juristo; Muñoz-Torres, Manuel

2012-02-04

To analyze the effects of nutritional intervention with a milk product enriched with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women. We performed a double-blind controlled randomized trial in ninety-nine postmenopausal women. Group S women (n=48) were randomized to consume milk product enriched with soy isoflavone (50 mg/day) while group C (n=51) consumed product control for 12 months. Parameters of quality of life (Cervantes scale), markers of bone metabolism and bone mass estimated by ultrasound of the calcaneus (QUS) were evaluated. Overall, there was an improvement in the domains menopause (P=.015) and vasomotor symptoms (P<.001). S group emphasized the assessment of vasomotor symptoms (P=.001) and differed positively from group C in health (P=.019), sex (P=.021) and partner (P=.002). Serum levels TRAP (P<.001) and OPG (P=.007) decreased and concentrations of 25-OH-vitamin D increased (P<.001) without differences between groups. In the assessment of QUS, there was an increase in estimated bone mineral density in group S (P=.040), whereas in group C there were no significant differences. Daily consumption of these milk products increases levels of 25-OH-vitamin D and decreases bone metabolism markers. Additional supplementation with soy isoflavones seems to improve quality of life and bone mass in Spanish postmenopausal women. Copyright © 2010 Elsevier España, S.L. All rights reserved.

The impact of diabetes and diabetes medications on bone health.

PubMed

Gilbert, Matthew P; Pratley, Richard E

2015-04-01

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures despite increased body weight and normal or higher bone mineral density. The mechanisms by which T2DM increases skeletal fragility are unclear. It is likely that a combination of factors, including a greater risk of falling, regional osteopenia, and impaired bone quality, contributes to the increased fracture risk. Drugs for the treatment of T2DM may also impact on the risk for fractures. For example, thiazolidinediones accelerate bone loss and increase the risk of fractures, particularly in older women. In contrast, metformin and sulfonylureas do not appear to have a negative effect on bone health and may, in fact, protect against fragility fracture. Animal models indicate a potential role for incretin hormones in bone metabolism, but there are only limited data on the impact of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 agonists on bone health in humans. Animal models also have demonstrated a role for amylin in bone metabolism, but clinical trials in patients with type 1 diabetes with an amylin analog (pramlintide) have not shown a significant impact on bone metabolism. The effects of insulin treatment on fracture risk are inconsistent with some studies showing an increased risk and others showing no effect. Finally, although there is limited information on the latest class of medications for the treatment of T2DM, the sodium-glucose co-transporter-2 inhibitors, these drugs do not seem to increase fracture risk. Because diabetes is an increasingly common chronic condition that can affect patients for many decades, further research into the effects of agents for the treatment of T2DM on bone metabolism is warranted. In this review, the physiological mechanisms and clinical impact of diabetes treatments on bone health and fracture risk in patients with T2DM are described.

The Factors Affecting Bone Density in Cirrhosis

PubMed Central

Hajiabbasi, Asghar; Shafaghi, Afshin; Fayazi, Haniyeh Sadat; Shenavar Masooleh, Irandokht; Hedayati Emami, Mohammad Hassan; Ghavidel Parsa, Pooneh; Amir Maafi, Alireza

2015-01-01

Background: Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients. Objectives: We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it. Patients and Methods: In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant. Results: A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m2 were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower

Positive affect predicts cerebral glucose metabolism in late middle-aged adults

PubMed Central

Nicholas, Christopher R.; Hoscheidt, Siobhan M.; Clark, Lindsay R.; Racine, Annie M.; Berman, Sara E.; Koscik, Rebecca L.; Maritza Dowling, N.; Asthana, Sanjay; Christian, Bradley T.; Sager, Mark A.

2017-01-01

Abstract Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family history of Alzheimer’s disease, APOE ε4 status and interval between visits, positive affect was associated with greater cerebral glucose metabolism across para-/limbic, frontal, temporal and parietal regions. Our findings provide evidence that positive affect in late midlife is associated with greater brain health in regions involved in affective processing and also known to be susceptible to early neuropathological processes. The current findings may have implications for interventions aimed at increasing positive affect to attenuate early neuropathological changes in at-risk individuals. PMID:28402542

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats.

PubMed

Glorie, Lorenzo; Behets, Geert J; Baerts, Lesley; De Meester, Ingrid; D'Haese, Patrick C; Verhulst, Anja

2014-09-01

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management. Copyright © 2014 the American Physiological Society.

An Evaluation of Select Physical Activity Exercise Classes on Bone Metabolism.

PubMed

Stone, Tori M; Wingo, Jonathan E; Young, John C; Navalta, James W

2018-01-01

Weight-bearing physical activity can optimize bone mass early in life and prevent the development of osteoporosis. However, less is known about the potential benefits of non-weight-bearing activities. The purpose of this study was to assess the efficacy of structured physical activity classes on bone metabolism. Twenty-eight premenopausal women, aged 18-35 years who were either enrolled in a yoga class (n=14) or cardio-kickboxing class (n=14) voluntarily consented to participate. Both classes were introductory classes meeting twice per week for 50 min per session for 12 weeks. Anteroposterior spine (L1-L4), hip (dual femur), and total body bone mineral density (BMD) was measured in both groups pre and post intervention using dual-energy X-ray absorptiometry (DXA). Pre and post blood samples were drawn for measurement of serum osteocalcin (OC) by enzyme-linked immunosorbent assay (ELISA) in each group. Baseline subject characteristics including age, height, weight, body fat percentage, and lean body mass did not differ between groups. BMD levels did not increase but were held stable over the course of the intervention. Yoga increased OC by 68% (P < 0.001) and cardio-kickboxing increased OC by 67% (P < 0.001) over the course of the 12-week classes. While 12 weeks of yoga and cardio-kickboxing were insufficient to induce BMD changes, OC levels reflect the bone formation process was initiated, but not yet complete. Increased OC levels suggest the selected physical activity classes provided enough of a stimulus to precipitate a future response of bone growth, assuming exercise training remains constant.

Effect of modified alkaline supplementation on bone metabolic turnover in rats.

PubMed

Chui, D H; Marotta, F; Liu, T; Minelli, E; Yadav, H; Signorelli, P; Lorenzetti, A; Jain, S

2008-01-01

This study aims to determine the effects of a high protein diet and alkaline supplementation on bone metabolic turnover in rats. Eight-week-old male Sprague-Dawley rats were investigated by bone status, including bone mineral density (BMD) and biomechanical markers from blood and urine. Thirty rats were randomly divided into three groups and treated for 8 weeks as follows: baseline control group (n. 10, C), high-protein supplemented diet group (n. 10, chronic acidosis, CA group) and supplemented chronic acidosis (n.10, SCA). Diet-treated rats were fed an acidic high-protein diet and the supplementation consisted in a modified alkaline formula (Basenpulver, NaMed, Italy). At the end of the experimental period, the rats were sacrificed, blood samples were drawn and femur and tibia were removed for analysis of bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA). In the CA group, 24-hour urinary calcium (Ca) and phosphorus (P) excretion were increased 2.1-fold (p<0.05 vs normal diet controls) as well as kidney weight. However, serum Ca and P concentration, as well as urinary Dpd excretion were not significantly changed. Femural and tibial BMD was significantly decreased in the CA group (p<0.05), but alkaline supplementation prevented such phenomenon (p<0.05 vs CA). These results suggest that blood Ca and P concentrations in chronic acidosis condition during the 12-week supplementation might be maintained by hypercalciuria and hyperphosphaturia at the expenses of bone structure. However, modified alkaline supplementation is able to prevent such derangements.

Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

NASA Technical Reports Server (NTRS)

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

2006-01-01

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

PubMed Central

Palermo, Andrea; Tuccinardi, Dario; Defeudis, Giuseppe; Watanabe, Mikiko; D’Onofrio, Luca; Lauria Pantano, Angelo; Napoli, Nicola; Pozzilli, Paolo; Manfrini, Silvia

2016-01-01

Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic. PMID:27240395

Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure.

PubMed

Scholz-Ahrens, Katharina E; Ade, Peter; Marten, Berit; Weber, Petra; Timm, Wolfram; Açil, Yahya; Glüer, Claus-C; Schrezenmeir, Jürgen

2007-03-01

Several studies in animals and humans have shown positive effects of nondigestible oligosaccharides (NDO) on mineral absorption and metabolism and bone composition and architecture. These include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharide, and also resistant starches, sugar alcohols, and difructose anhydride. A positive outcome of dietary prebiotics is promoted by a high dietary calcium content up to a threshold level and an optimum amount and composition of supplemented prebiotics. There might be an optimum composition of fructooligosaccharides with different chain lengths (synergy products). The efficacy of dietary prebiotics depends on chronological age, physiological age, menopausal status, and calcium absorption capacity. There is evidence for an independent probiotic effect on facilitating mineral absorption. Synbiotics, i.e., a combination of probiotics and prebiotics, can induce additional effects. Whether a low content of habitual NDO would augment the effect of dietary prebiotics or synbiotics remains to be studied. The underlying mechanisms are manifold: increased solubility of minerals because of increased bacterial production of short-chain fatty acids, which is promoted by the greater supply of substrate; an enlargement of the absorption surface by promoting proliferation of enterocytes mediated by bacterial fermentation products, predominantly lactate and butyrate; increased expression of calcium-binding proteins; improvement of gut health; degradation of mineral complexing phytic acid; release of bone-modulating factors such as phytoestrogens from foods; stabilization of the intestinal flora and ecology, also in the presence of antibiotics; stabilization of the intestinal mucus; and impact of modulating growth factors such as polyamines. In conclusion, prebiotics are the most promising but also best investigated substances with respect to a bone-health-promoting potential, compared with probiotics

Midlife women, bone health, vegetables, herbs and fruit study. The Scarborough Fair study protocol.

PubMed

Gunn, Caroline A; Weber, Janet L; Kruger, Marlena C

2013-01-10

Bone loss is accelerated in middle aged women but increased fruit/vegetable intake positively affects bone health by provision of micronutrients essential for bone formation, buffer precursors which reduce acid load and phytochemicals affecting inflammation and oxidative stress. Animal studies demonstrated bone resorption inhibiting properties of specific vegetables, fruit and herbs a decade ago. To increase fruit/vegetable intake in post menopausal women to 9 servings/day using a food specific approach to significantly reduce dietary acid load and include specific vegetables, fruit and herbs with bone resorbing inhibiting properties to assess effect on bone turnover, metabolic and inflammatory markers. The Scarborough Fair Study is a randomised active comparator controlled multi centre trial. It aimed to increase fruit and vegetable intake in 100 post menopausal women from ≤ 5 servings/day to ≥ 9 servings/day for 3 months. The women in the dietary intervention were randomly assigned to one of the two arms of the study. Both groups consumed ≥ 9 servings/day of fruit/vegetables and selected herbs but the diet of each group emphasised different fruit/vegetables/herbs with one group (B) selecting from a range of vegetables, fruit and culinary herbs with bone resorbing inhibiting properties. 50 women formed a negative control group (Group C usual diet). Primary outcome variables were plasma bone markers assessed at baseline, 6 weeks and 12 weeks. Secondary outcome variables were plasma inflammation and metabolic markers and urinary electrolytes (calcium, magnesium, potassium and sodium) assessed at baseline and 12 weeks. Dietary intake and urine pH change also were outcome variables. The dietary change was calculated with 3 day diet diaries and a 24 hour recall. Intervention participants kept a twice weekly record of fruit, vegetable and herb intake and urine pH. This study will provide information on midlife women's bone health and how a dietary intervention

Altered thermogenesis and impaired bone remodeling in Misty mice.

PubMed

Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E; Bornstein, Sheila A; Le, Phuong; Kawai, Masanobu; Lotinun, Sutada; Horowitz, Mark C; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2013-09-01

Fat mass may be modulated by the number of brown-like adipocytes in white adipose tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic energy metabolism and, with age, bone remodeling becomes uncoupled and brown adipose tissue (BAT) function declines. To test the interaction between BAT and bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We found that Misty mice have accelerated age-related trabecular bone loss and impaired brown fat function (including reduced temperature, lower expression of Pgc1a, and less sympathetic innervation compared to wild-type (+/ +)). Despite reduced BAT function, Misty mice had normal core body temperature, suggesting heat is produced from other sources. Indeed, upon acute cold exposure (4°C for 6 hours), inguinal WAT from Misty mice compensated for BAT dysfunction by increasing expression of Acadl, Pgc1a, Dio2, and other thermogenic genes. Interestingly, acute cold exposure also decreased Runx2 and increased Rankl expression in Misty bone, but only Runx2 was decreased in wild-type. Browning of WAT is under the control of the sympathetic nervous system (SNS) and, if present at room temperature, could impact bone metabolism. To test whether SNS activity could be responsible for accelerated trabecular bone loss, we treated wild-type and Misty mice with the β-blocker, propranolol. As predicted, propranolol slowed trabecular bone volume/total volume (BV/TV) loss in the distal femur of Misty mice without affecting wild-type. Finally, the Misty mutation (a truncation of DOCK7) also has a significant cell-autonomous role. We found DOCK7 expression in whole bone and osteoblasts. Primary osteoblast differentiation from Misty calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling. Despite the multifaceted effects of the Misty mutation, we have shown that impaired brown fat function leads to altered SNS activity and bone loss, and for the first time that cold

[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.

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.

Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density.

PubMed

Tsentidis, Charalampos; Gourgiotis, Dimitrios; Kossiva, Lydia; Marmarinos, Antonios; Doulgeraki, Artemis; Karavanaki, Kyriaki

2016-06-01

Sclerostin is an inhibitor of the Wnt/beta-catenin bone metabolic pathway. Increased sclerostin levels and reduced bone mineral density (BMD) have been documented in adult patients with diabetes mellitus (DM), predominantly in those with type 2 diabetes mellitus (T2DM). No relative data exist on childhood type 1 diabetes mellitus (T1DM). Our objective was to study plasma sclerostin in T1DM children and adolescents and controls and its correlations with metabolic bone markers and BMD. This was a cross-sectional study that was conducted at an outpatient clinical center. Forty T1DM children and adolescents were evaluated (mean ± SD age: 13.04 ± 3.53 yr, T1DM duration: 5.15 ± 3.33 yr), along with 40 healthy matched controls (age 12.99 ± 3.3 yr). Sclerostin, soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL), osteoprotegerin, osteocalcin, C-telopeptide crosslinks, electrolytes, parathyroid hormone (PTH), and total 25(OH)D were measured. Lumbar and subcranial total body BMD were evaluated with dual energy X-ray absorptiometry (DXA). Sclerostin levels demonstrated a Gaussian distribution, with no significant difference between patients and controls (51.56 ± 12.05 vs. 50.98 ± 13.55 pmol/L, p = 0.84). Significantly lower values were found in girls and prepubertal children. Sclerostin values were significantly and gradually increased in children through pubertal Tanner stages 1-3, were reduced at stage 4 and increased again at pubertal stage 5. Sclerostin levels were positively correlated with logCTX (logarithm of C-terminal telopeptide crosslinks of type I collagen), logOsteocalcin (logarithm of Osteocalcin), magnesium, total body, and L1-L4 BMD z-score. T1DM patients had similar levels of sclerostin with controls. Sclerostin correlated with bone resorption and formation markers and also with bone mass indices, gender, and pubertal stage. The decrease in sclerostin values observed in pubertal stage 4 adolescents coincides with the concurrent growth

The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism.

PubMed

Sodi, R; Hazell, M J; Durham, B H; Rees, C; Ranganath, L R; Fraser, W D

2009-09-01

There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. We observed a positive correlation between BMI and BMD (r=0.44, p<0.001). When normalised for BMI, total-, HMW-adiponectin concentrations and HMW/total-adiponectin ratio were significantly lower in obese compared to lean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, p<0.001). Our data suggests that there is no significant difference in the circulating concentration of fasting early morning total- or HMW-adiponectin in post-menopausal women with or without osteoporosis. The correlation between HMW/total-adiponectin ratio and OPG may indicate that adiponectin could influence bone metabolism by altering osteoblast production of OPG thereby affecting osteoclasts mediated bone resorption.

Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide

NASA Astrophysics Data System (ADS)

Fei, Fan; Lee, Keith M.; McCarry, Brian E.; Bowdish, Dawn M. E.

2016-03-01

Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6-8 wk) and old (18-22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age.

Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study.

PubMed

Tenta, Roxane; Moschonis, George; Koutsilieris, Michael; Manios, Yannis

2011-08-01

To assess the effectiveness of a dietary intervention combined with fortified dairy products on bone metabolism and bone mass indices in postmenopausal women. Forty postmenopausal women (55-65 years old) were equally randomized into a dietary group (DG), receiving daily and for 30 months, 1,200 mg of calcium and 7.5 μg of vitamin D(3) for the first 12 months that increased to 22.5 μg for the remaining 18 months of intervention through fortified dairy products; and a control group (CG). Differences in the changes of bone metabolism and bone mass indices were examined with repeated measures ANOVA. A significant increase was observed for PTH levels only in the CG during the first six winter months of intervention (p = 0.049). After 30 months of intervention, during winter, serum 25(OH)D significantly decreased in the CG while remained in the same high levels as in the summer period in the DG. Serum RANKL levels decreased significantly in the DG compared with the increase in the CG during the 30-month intervention period (p = 0.005). Serum CTx decreased significantly in the DG after six (-0.08; -0.12 to -0.03) and 12 (-0.03; -0.08 to -0.02) months of intervention. Finally, the DG had more favorable changes in total body BMD than the CG (p < 0.001). Increasing dietary intake of calcium and vitamin D in osteopenic postmenopausal women appears to be effective in producing favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules.

Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice.

PubMed

Synhaeve, Nicholas; Wade-Gueye, Ndéye Marième; Musilli, Stefania; Stefani, Johanna; Grandcolas, Line; Gruel, Gaëtan; Souidi, Maâmar; Dublineau, Isabelle; Bertho, Jean-Marc

2014-01-01

The aim of this work was to delineate the effects of chronic ingestion of strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l(-1) of (90) Sr two weeks before mating. Offspring were then continuously contaminated with (90) Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20 weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in (90) Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C-telopeptide of collagen in the plasma of (90) Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of (90) Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis. Copyright © 2012 John Wiley & Sons, Ltd.

Endothelial Barrier and Metabolism: New Kids on the Block Regulating Bone Marrow Vascular Niches.

PubMed

Harjes, Ulrike; Verfaillie, Catherine; Carmeliet, Peter

2016-05-09

The vasculature of the bone marrow remains poorly characterized, yet crucial to maintain hematopoiesis and retain stem cells in a quiescent state. A recent study by Itkin et al. (2016) in Nature reports how vascular barrier integrity and endothelial cell metabolism regulate hematopoietic stem cell quiescence and leukocyte trafficking. Copyright © 2016 Elsevier Inc. All rights reserved.

Gallium modulates osteoclastic bone resorption in vitro without affecting osteoblasts

PubMed Central

Verron, Elise; Masson, Martial; Khoshniat, Solmaz; Duplomb, Laurence; Wittrant, Yohann; Baud'huin, Marc; Badran, Zahi; Bujoli, Bruno; Janvier, Pascal; Scimeca, Jean-Claude; Bouler, Jean-Michel; Guicheux, Jérôme

2010-01-01

Background and purpose: Gallium (Ga) has been shown to be effective in the treatment of disorders associated with accelerated bone loss, including cancer-related hypercalcemia and Paget's disease. These clinical applications suggest that Ga could reduce bone resorption. However, few studies have studied the effects of Ga on osteoclastic resorption. Here, we have explored the effects of Ga on bone cells in vitro. Experimental approach: In different osteoclastic models [osteoclasts isolated from long bones of neonatal rabbits (RBC), murine RAW 264.7 cells and human CD14-positive cells], we have performed resorption activity tests, staining for tartrate resistant acid phosphatase (TRAP), real-time polymerase chain reaction analysis, viability and apoptotic assays. We also evaluated the effect of Ga on osteoblasts in terms of proliferation, viability and activity by using an osteoblastic cell line (MC3T3-E1) and primary mouse osteoblasts. Key results: Gallium dose-dependently (0–100 µM) inhibited the in vitro resorption activity of RBC and induced a significant decrease in the expression level of transcripts coding for osteoclastic markers in RAW 264.7 cells. Ga also dramatically reduced the formation of TRAP-positive multinucleated cells. Ga down-regulated in a dose-dependant manner the expression of the transcription factor NFATc1. However, Ga did not affect the viability or activity of primary and MC3T3-E1 osteoblasts. Conclusions and implications: Gallium exhibits a dose-dependent anti-osteoclastic effect by reducing in vitro osteoclastic resorption, differentiation and formation without negatively affecting osteoblasts. We provide evidence that this inhibitory mechanism involves down-regulation of NFATc1 expression, a master regulator of RANK-induced osteoclastic differentiation. PMID:20397300

Marrow Adipose Tissue in Older Men: Association with Visceral and Subcutaneous Fat, Bone Volume, Metabolism, and Inflammation.

PubMed

Bani Hassan, Ebrahim; Demontiero, Oddom; Vogrin, Sara; Ng, Alvin; Duque, Gustavo

2018-03-26

Marrow (MAT) and subcutaneous (SAT) adipose tissues display different metabolic profiles and varying associations with aging, bone density, and fracture risk. Using a non-invasive imaging methodology, we aimed to investigate the associations between MAT, SAT, and visceral fat (VAT) with bone volume, bone remodeling markers, insulin resistance, and circulating inflammatory mediators in a population of older men. In this cross-sectional study, 96 healthy men (mean age 67 ± 5.5) were assessed for anthropometric parameters, body composition, serum biochemistry, and inflammatory panel. Using single-energy computed tomography images, MAT (in L2 and L3 and both hips), VAT, and SAT (at the level of L2-L3 and L4-L5) were measured employing Slice-O-Matic software (Tomovision), which enables specific tissue demarcation applying previously reported Hounsfield unit thresholds. MAT volume was similar in all anatomical sites and independent of BMI. In all femoral regions of interest (ROIs) there was a strong negative association between bone and MAT volumes (r = - 0.840 to - 0.972, p < 0.001), with location-dependent variations in the lumbar spine. Unlike VAT and SAT, no associations between MAT and serum glucose, inflammatory markers or insulin resistance indicators were found. Bone decline occurred without red marrow expansion; thus lost bone was mainly (if not exclusively) replaced by MAT. In conclusion, strong inverse correlations between MAT and bone mass, which have been previously observed in women, were also confirmed in older men. However, MAT volume in all ROIs was interrelated and unlike women, mainly independent of VAT or SAT. The lack of strong association between MAT vs VAT/SAT, and its discordant associations with metabolic and inflammatory mediators provide further evidence on MAT's distinct attributes in older men.

Birth weight and adult bone metabolism are unrelated: results from birth weight-discordant monozygotic twins.

PubMed

Frost, Morten; Petersen, Inge; Andersen, Thomas L; Langdahl, Bente L; Buhl, Thora; Christiansen, Lene; Brixen, Kim; Christensen, Kaare

2013-12-01

Low birth weight (BW) has been associated with poor bone health in adulthood. The aim of this study was to investigate the association between BW and bone mass and metabolism in adult BW-discordant monozygotic (MZ) twins. A total of 153 BW-extremely discordant MZ twin pairs were recruited from the Danish Twin Registry. Serum vitamin D (25-hydroxyvitamin D [25OHD]) and bone turnover markers (BTMs) amino-terminal propeptide of type I procollagen (P1NP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), and cross-linked C-telopeptide (CTX) were quantified. Femoral neck (FN), total hip (TH), lumbar spine (LS), and whole-body (WB) bone mineral density (BMD) (ie, FN-BMD, TH-BMD, LS-BMD, and WB-BMD, respectively) were measured using dual-energy X-ray absorptiometry (DXA). Twins were studied as single individuals using regression analyses with or without adjustment for height, weight, age, sex, and intrapair correlation. Within-pair differences were assessed using Student's t test and fixed-regression models. BW was not associated with BTMs, LS-BMD, TH-BMD, FN-BMD, or WB-BMD, but BW was associated with WB-BMC, and WB-Area after adjustments. Compared to the co-twin, twins with the highest BW were heavier and taller in adulthood (mean differences ± SD): 3.0 ± 10.5 kg; 1.6 ± 2.6 cm; both p < 0.001). Within-pair analyses showed that LS-BMD, TH-BMD, and FN-BMD tended to be higher in twins with highest BW (for all: mean difference 0.01 ± 0.1 g/cm(2) ; p = 0.08, 0.05, and 0.10, respectively). No difference was observed after adjustment for adult body size. Intrapair differences in BW were not associated with differences in any of the biochemical parameters or BMD. Small differences between twins in BMD were explained by dissimilarities in body size. These results suggest that BW and adult bone metabolism are unrelated. © 2013 American Society for Bone and Mineral Research.

In vitro and in vivo evidence for orphan nuclear receptor RORα function in bone metabolism

PubMed Central

Meyer, Thomas; Kneissel, Michaela; Mariani, Jean; Fournier, Brigitte

2000-01-01

Bone is a major target site for steroid hormone action. Steroid hormones like cortisol, vitamin D, and estradiol are responsible for principal events associated with bone formation and resorption. Over the past decade, new members of the nuclear hormone gene family have been identified that lack known ligands. These orphan receptors can be used to uncover signaling molecules that regulate yet unidentified physiological networks. In the present study the function of retinoic acid receptor-related orphan receptor (ROR) α in bone metabolism has been examined. We showed that RORα and RORγ, but not RORβ, are expressed in mesenchymal stem cells derived from bone marrow. Interestingly, for RORα we observed an increased messenger signal expression between control cells and cells undergoing osteogenic differentiation. Furthermore, the direct activation of mouse bone sialoprotein by RORα, typically 7-fold, has been shown. In contrast, transient overexpression of RORα overrides the activation of the osteocalcin promoter by 1α,25-dihydroxyvitamin D3. In addition, we have investigated bone mass parameters and bone geometry in the mouse mutant staggerer (sg/sg), a mouse strain that carries a deletion within the RORα gene. Homozygote mutants have thin long bones compared with the heterozygote animals and wild-type littermates. More interestingly, the bones of the sg/sg animals are osteopenic as indicated by the comparison of bone mineral contents of sg/sg animals to the heterozygote and wild-type animals. We conclude that these in vitro and in vivo results suggest a function for RORα in bone biology. RORα most likely acts by direct modulation of a bone matrix component. PMID:10900268

Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study.

PubMed

Zhang, Jing; Li, Tingting; Xu, Liangzhi; Li, Wenjuan; Cheng, Meng; Zhuang, Jing; Chen, Yan; Xu, Wenming

2013-08-01

Leptin may be a potential option in preventing osteoporosis for menopausal women. The objective of this study is to explore the molecular mechanism of leptin on bone metabolism in osteoblast. Primary osteoblasts were isolated from parietal bone of adult female rats. mRNA level of OB-Rb in osteoblasts was inhibited by siRNA to block leptin signal transmission. The whole genome expression was tested by using gene chip to preliminarily explore the molecular mechanism of leptin in regulating osteoblast activity. The optimal concentration of siRNA was 25 nM, resulting in a maximal inhibition of OB-Rb mRNA. Ossification (p < 0.05) and bone mineralization (p = 0.0001) were downregulated by inhibiting leptin signal transmission, while bone resorption (p = 0.007), osteoblast differentiation (p = 0.026) and negative regulation of bone remodeling (p = 0.004) were upregulated. The expressions of some genes were regulated by OB-Rb siRNA. The expressions of alkaline phosphatase (p = 0.014) and osteocalcin (p = 0.002) were reduced, while that of vascular endothelial growth factor A (p = 0.0076) and IL-6 (p = 0.021) were increased. In a model of osteoblast, leptin positively promotes ossification through multiple ways including bone mineralization, remodeling, resorption and osteoblast differentiation, but which way plays the most critical role is not discussed in this study and needs to be clarified in future.

Boning up on DPP4, DPP4 substrates, and DPP4-adipokine interactions: Logical reasoning and known facts about bone related effects of DPP4 inhibitors.

PubMed

Glorie, Lorenzo; D'Haese, Patrick C; Verhulst, Anja

2016-11-01

Dipeptidyl peptidase 4 (DPP4) is a conserved exopeptidase with an important function in protein regulation. The activity of DPP4, an enzyme which can either be anchored to the plasma membrane or circulate free in the extracellular compartment, affects the glucose metabolism, cellular signaling, migration and differentiation, oxidative stress and the immune system. DPP4 is also expressed on the surface of osteoblasts, osteoclasts and osteocytes, and was found to play a role in collagen metabolism. Many substrates of DPP4 have an established role in bone metabolism, among which are incretins, gastrointestinal peptides and neuropeptides. In general, their effects favor bone formation, but some effects are complex and have not been completely elucidated. DPP4 and some of its substrates are known to interact with adipokines, playing an essential role in the energy metabolism. The prolongation of the half-life of incretins through DPP4 inhibition led to the development of these inhibitors to improve glucose tolerance in diabetes. Current literature indicates that the inhibition of DPP4 activity might also result in a beneficial effect on the bone metabolism, but the long-term effect of DPP4 inhibition on fracture outcome has not been entirely established. Diabetic as well as postmenopausal osteoporosis is associated with an increased activity of DPP4, as well as a shift in the expression levels of DPP4 substrates, their receptors, and adipokines. The interactions between these factors and their relationship in bone metabolism are therefore an interesting field of study. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical factors affecting pathological fracture and healing of unicameral bone cysts

PubMed Central

2014-01-01

Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

Clinical factors affecting pathological fracture and healing of unicameral bone cysts.

PubMed

Urakawa, Hiroshi; Tsukushi, Satoshi; Hosono, Kozo; Sugiura, Hideshi; Yamada, Kenji; Yamada, Yoshihisa; Kozawa, Eiji; Arai, Eisuke; Futamura, Naohisa; Ishiguro, Naoki; Nishida, Yoshihiro

2014-05-17

Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery.

Altered thermogenesis and impaired bone remodeling in Misty mice

PubMed Central

Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E; Bornstein, Sheila A; Le, Phuong; Kawai, Masanobu; Lotinun, Sutada; Horowitz, Mark C; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2013-01-01

Fat mass may be modulated by the number of brown-like adipocytes in white adipose tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic energy metabolism and, with age, bone remodeling becomes uncoupled and brown adipose tissue (BAT) function declines. To test the interaction between BAT and bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We found that Misty mice have accelerated age-related trabecular bone loss and impaired brown fat function (including reduced temperature, lower expression of Pgc1a and less sympathetic innervation compared to wildtype (+/+)). Despite reduced BAT function, Misty mice had normal core body temperature, suggesting heat is produced from other sources. Indeed, upon acute cold exposure (4°C for 6 hr), inguinal WAT from Misty mice compensated for BAT dysfunction by increasing expression of Acadl, Pgc1a, Dio2 and other thermogenic genes. Interestingly, acute cold exposure also decreased Runx2 and increased Rankl expression in Misty bone, but only Runx2 was decreased in wildtype. Browning of WAT is under the control of the sympathetic nervous system (SNS) and, if present at room temperature, could impact bone metabolism. To test whether SNS activity could be responsible for accelerated trabecular bone loss, we treated wildtype and Misty mice with the β-blocker, propranolol. As predicted, propranolol slowed trabecular BV/TV loss in the distal femur of Misty mice without affecting wildtype. Finally, the Misty mutation (a truncation of DOCK7) also has a significant cell-autonomous role. We found DOCK7 expression in whole bone and osteoblasts. Primary osteoblast differentiation from Misty calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling. Despite the multifaceted effects of the Misty mutation, we have shown that impaired brown fat function leads to altered SNS activity and bone loss, and for the first time that cold exposure negatively affects bone remodeling

Second hand tobacco smoke adversely affects the bone of immature rats

PubMed Central

Rosa, Rodrigo César; Pereira, Sângela Cunha; Cardoso, Fabrizio Antônio Gomide; Caetano, Abadio Gonçalves; de Santiago, Hildemberg Agostinho Rocha; Volpon, José Batista

2017-01-01

OBJECTIVES: To evaluate the influence of secondhand cigarette smoke exposure on longitudinal growth of the tibia of growing rats and some parameters of bone quality. METHODS: Forty female rats were randomly divided into four groups: control: rats were sham exposed; 30 days: rats were exposed to tobacco smoke for 30 days; 45 days: rats were exposed to tobacco smoke for 45 days; and 60 days: rats were exposed to tobacco smoke for 60 days. Blood samples were collected to evaluate the levels of cotinine and alkaline phosphatase. Both tibias were dissected and weighed; the lengths were measured, and the bones were then stored in a freezer for analysis of bone mineral content and mechanical resistance (maximal load and stiffness). RESULTS: Exposure of rats to tobacco smoke significantly compromised bone health, suggesting that the harmful effects may be time dependent. Harmful effects on bone growth were detected and were more pronounced at 60-day follow-ups with a 41.8% reduction in alkaline phosphatase levels (p<0.01) and a decrease of 11.25% in tibia length (p<0.001). Furthermore, a 41.5% decrease in bone mineral density was observed (p<0.001), leading to a 42.8% reduction in maximum strength (p<0.001) and a 56.7% reduction in stiffness (p<0.001). CONCLUSION: Second hand cigarette smoke exposure in rats affected bones that were weaker, deforming them and making them osteopenic. Additionally, the long bone was shorter, suggesting interference with growth. Such events seem to be related to time of exposure. PMID:29319726

Second hand tobacco smoke adversely affects the bone of immature rats.

PubMed

Rosa, Rodrigo César; Pereira, Sângela Cunha; Cardoso, Fabrizio Antônio Gomide; Caetano, Abadio Gonçalves; Santiago, Hildemberg Agostinho Rocha de; Volpon, José Batista

2017-12-01

To evaluate the influence of secondhand cigarette smoke exposure on longitudinal growth of the tibia of growing rats and some parameters of bone quality. Forty female rats were randomly divided into four groups: control: rats were sham exposed; 30 days: rats were exposed to tobacco smoke for 30 days; 45 days: rats were exposed to tobacco smoke for 45 days; and 60 days: rats were exposed to tobacco smoke for 60 days. Blood samples were collected to evaluate the levels of cotinine and alkaline phosphatase. Both tibias were dissected and weighed; the lengths were measured, and the bones were then stored in a freezer for analysis of bone mineral content and mechanical resistance (maximal load and stiffness). Exposure of rats to tobacco smoke significantly compromised bone health, suggesting that the harmful effects may be time dependent. Harmful effects on bone growth were detected and were more pronounced at 60-day follow-ups with a 41.8% reduction in alkaline phosphatase levels (p<0.01) and a decrease of 11.25% in tibia length (p<0.001). Furthermore, a 41.5% decrease in bone mineral density was observed (p<0.001), leading to a 42.8% reduction in maximum strength (p<0.001) and a 56.7% reduction in stiffness (p<0.001). Second hand cigarette smoke exposure in rats affected bones that were weaker, deforming them and making them osteopenic. Additionally, the long bone was shorter, suggesting interference with growth. Such events seem to be related to time of exposure.

The gut microbiota regulates bone mass in mice

PubMed Central

Sjögren, Klara; Engdahl, Cecilia; Henning, Petra; Lerner, Ulf H; Tremaroli, Valentina; Lagerquist, Marie K; Bäckhed, Fredrik; Ohlsson, Claes

2012-01-01

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4+ T cells and CD11b+/GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis. © 2012 American Society for Bone and Mineral Research. PMID:22407806

Effects of seasonal vitamin D deficiency and respiratory acidosis on bone metabolism markers in submarine crewmembers during prolonged patrols.

PubMed

Holy, Xavier; Collombet, Jean-Marc; Labarthe, Frédéric; Granger-Veyron, Nicolas; Bégot, Laurent

2012-02-01

The aim of the study was to determine the seasonal influence of vitamin D status on bone metabolism in French submariners over a 2-mo patrol. Blood samples were collected as follows: prepatrol and patrol days 20, 41, and 58 on crewmembers from both a winter (WP; n = 20) and a summer patrol (SP; n = 20), respectively. Vitamin D status was evaluated for WP and SP. Moreover, extended parameters for acid-base balance (Pco(2), pH, and bicarbonate), bone metabolism (bone alkaline phosphatase and COOH-terminal telopeptide of type I collagen), and mineral homeostasis (parathyroid hormone, ionized calcium and phosphorus) were scrutinized. As expected, SP vitamin D status was higher than WP vitamin D status, regardless of the considered experimental time. A mild chronic respiratory acidosis (CRA) was identified in both SP and WP submariners, up to patrol day 41. Such an occurrence paired up with an altered bone remodeling coupling (decreased bone alkaline phosphatase-to-COOH-terminal telopeptide of type I collagen ratio). At the end of the patrol (day 58), a partial compensation of CRA episode, combined with a recovered normal bone remodeling coupling, was observed in SP, not, however, in WP submariners. The mild CRA episode displayed over the initial 41-day submersion period was mainly induced by a hypercapnia resulting from the submarine-enriched CO(2) level. The correlated impaired bone remodeling may imply a physiological attempt to compensate this acidosis via bone buffering. On patrol day 58, the discrepancy observed in terms of CRA compensation between SP and WP may result from the seasonal influence on vitamin D status.

Complete metabolic remission with Gefitinib in a hemodialysis patient with bone metastases from non-small cell lung cancer.

PubMed

Del Conte, Alessandro; Minatel, Emilio; Schinella, Domenico; Baresic, Tanja; Basso, Stefano M M; Lumachi, Franco

2014-01-01

Gefitinib is highly active in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating mutation of the epidermal growth factor receptor (EGFR) gene. The feasibility and the degree of response to treatment with gefitinib in patients with chronic renal failure (CRF) undergoing hemodialysis has not yet been fully described in literature. We describe the case of a 70-year-old man with CRF undergoing hemodialysis three times-a-week who developed vertebral and rib bone metastasis three years after lobectomy. The bone biopsy confirmed the pulmonary origin and pyrosequencing analysis revealed deletion in E746-E750 of exon 19. We started daily administration of 250 mg gefitinib with no changes in the hemodialysis schedule. Gefitinib was well-tolerated without any adverse event. After three months, the (18)F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) showed complete metabolic remission of bone lesions. The patient is still under treatment and maintains response (30 months to date). To our knowledge, this is the first description of complete metabolic remission in this type of patient. In conclusion, gefitinib has been safely administered to a patient with NSCLC with EGFR-activating mutation undergoing chronic hemodialysis and its use has achieved an excellent and prolonged response on bone metastases.

Bone Density and Dental External Apical Root Resorption

PubMed Central

Iglesias-Linares, Alejandro; Morford, Lorri Ann

2016-01-01

When orthodontic patients desire shorter treatment times with aesthetic results and long-term stability, it is important for the orthodontist to understand the potential limitations and problems that may arise during standard and/or technology-assisted accelerated treatment. Bone density plays an important role in facilitating orthodontic tooth movement (OTM), such that reductions in bone density can significantly increase movement velocity. Lifestyle, genetic background, environmental factors and disease status all can influence a patients’ overall health and bone density. In some individuals, these factors may create specific conditions that influence systemic-wide bone metabolism. Both genetic variation and the onset of a bone-related disease can influence systemic bone density and local bone density, such as is observed in the mandible and maxilla. These types of localized density changes can affect the rate of OTM and may also influence the risk of unwanted outcomes, i.e., the occurrence of dental external apical root resorption (EARR). PMID:27766484

Studies of Intercellular Communication and Intracellular Metabolic Responses by Bone Cells to Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Doty, Stephen B.

1997-01-01

Spaceflight affects the weight bearing skeletal tissues by reducing the rate of new bone formation. This effect on the long bones of flown rats has been quantitated but the effect at the cellular level and the mechanism(s) involved are not understood. We are applying electron microscopy, coupled with histochemistry and immunocytochemistry to determine the cellular functions most affected by spaceflight. The emphasis for study of these samples from SLS-1, a 9-day mission, is on the histochemical and structural changes of the endosteal and perivascular osteoblasts found in diaphyseal bone of femur and tibia. Work is still in progress but some findings are described: (1) An expected decrease in alkaline phosphatase activity in osteoblasts from flight animals, but an increase in enzyme activity in the stromal stem cells adjacent to the osteoblast. (2) An increase in osteoclastic TRAP activity in the trabecular bone region in response to spaceflight. (3) A large increase in procollagen containing secretory granules in osteoblasts in the recovery group, and a significant decrease in granule numbers in the flight group.

Exploring the Bone Proteome to Help Explain Altered Bone Remodeling and Preservation of Bone Architecture and Strength in Hibernating Marmots.

PubMed

Doherty, Alison H; Roteliuk, Danielle M; Gookin, Sara E; McGrew, Ashley K; Broccardo, Carolyn J; Condon, Keith W; Prenni, Jessica E; Wojda, Samantha J; Florant, Gregory L; Donahue, Seth W

2016-01-01

Periods of physical inactivity increase bone resorption and cause bone loss and increased fracture risk. However, hibernating bears, marmots, and woodchucks maintain bone structure and strength, despite being physically inactive for prolonged periods annually. We tested the hypothesis that bone turnover rates would decrease and bone structural and mechanical properties would be preserved in hibernating marmots (Marmota flaviventris). Femurs and tibias were collected from marmots during hibernation and in the summer following hibernation. Bone remodeling was significantly altered in cortical and trabecular bone during hibernation with suppressed formation and no change in resorption, unlike the increased bone resorption that occurs during disuse in humans and other animals. Trabecular bone architecture and cortical bone geometrical and mechanical properties were not different between hibernating and active marmots, but bone marrow adiposity was significantly greater in hibernators. Of the 506 proteins identified in marmot bone, 40 were significantly different in abundance between active and hibernating marmots. Monoaglycerol lipase, which plays an important role in fatty acid metabolism and the endocannabinoid system, was 98-fold higher in hibernating marmots compared with summer marmots and may play a role in regulating the changes in bone and fat metabolism that occur during hibernation.

High prevalence of hypogonadism and associated impaired metabolic and bone mineral status in subfertile men.

PubMed

Bobjer, Johannes; Bogefors, Karolina; Isaksson, Sigrid; Leijonhufvud, Irene; Åkesson, Kristina; Giwercman, Yvonne Lundberg; Giwercman, Aleksander

2016-08-01

It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was therefore to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men. Cross-sectional case-control study. Men from infertile couples (n = 192); 18-50 years; sperm concentration <20 × 10(6) /ml and population-based age-matched controls (n = 199). Blood sampling, anthropometrics, blood pressure, ankle-brachial index and assessment by dual-energy X-ray absorptiometry were undertaken. Odds ratios of biochemical hypogonadism (total testosterone <8·0 nmol/l and/or luteinizing hormone ≥8·6 IU/l and/or ongoing androgen replacement therapy) were calculated. Serum concentrations of sex hormones, lipids, glucose, insulin and HbA1c were assessed and bone mineral density (BMD) evaluated. Compared to controls, the risk of hypogonadism was increased among subfertile men (OR 10; 95% CI, 5·1, 22), being highest in those with nonobstructive azoospermia. Hypogonadal men had higher HbA1c concentration (mean diff. 2·8 mmol/mol; 95% CI, 0·64, 4·9; P = 0·011) and lower lumbar spine BMD (mean diff. 0·05 g/cm(2) ; 95% CI, 0·01, 0·10; P = 0·032) compared to eugonadal subfertile men, even more pronounced in subfertile men with subnormal testosterone levels. Young subfertile men have 10 times increased OR of hypogonadism, which is linked to increased HbA1c and decreased bone mineralization. Endocrine assessment and, if needed, measures to prevent metabolic sequelae and osteoporosis should be included in the routine management of men from infertile couples. © 2016 John Wiley & Sons Ltd.

Influence of different calcium concentrations in the diet on bone metabolism in growing dairy goats and sheep.

PubMed

Liesegang, A; Risteli, J

2005-01-01

The purpose of this study was to investigate, if different Ca concentrations in diets have an influence on bone mineral metabolism in growing goats and sheep. Twelve growing goats and sheep were divided into two groups. The two control groups received 6.1 g calcium/day (nG) and 6.7 g calcium/day (nS) for goat and sheep respectively. The other two groups were fed 17.7 g calcium/day (hG) and 18.5 g calcium/day (hS). Blood samples were taken 2, 4, 5 and 6 weeks after the start of the experiment. In serum Ca and vitamin D were determined and bone metabolism was measured using crosslinked carboxyterminal telopeptide of type I collagen (ICTP), crosslaps, bone-specific alkaline phosphatase and osteocalcin (OC). Bone mineral density (BMD) was quantified using quantitative computed tomography. Bone resorption marker (ICTP) concentrations were significantly different between both groups control sheep/control goat and hS/hG, but no significant differences were evident in the different feeding groups within one species. OC concentrations showed a similar course to ICTP. The goats had significantly higher concentrations compared with sheep. The 1,25 dihydroxyvitamin D (VITD) concentrations in both hCa groups were significantly lower than in the control groups. BMD increased in the hCa groups compared with the control groups with the time, but significant differences were only evident in sheep in week 2. The hCa diet did not induce differences between the groups within one species for all bone markers. The control Ca diet seems to improve the active Ca absorption via VITD whereas the hCa diet leads to a higher amount of Ca apparently digested. Higher BMD was only observed in group hS compared with nS.

Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism.

PubMed

Philbrick, Kenneth A; Wong, Carmen P; Branscum, Adam J; Turner, Russell T; Iwaniec, Urszula T

2017-03-01

Leptin, the protein product of the ob gene, is essential for normal bone growth, maturation and turnover. Peripheral actions of leptin occur at lower serum levels of the hormone than central actions because entry of leptin into the central nervous system (CNS) is limited due to its saturable transport across the blood-brain barrier (BBB). We performed a study in mice to model the impact of leptin production associated with different levels of adiposity on bone formation and compared the response with well-established centrally mediated actions of the hormone on energy metabolism. Leptin was infused (0, 4, 12, 40, 140 or 400 ng/h) for 12 days into 6-week-old female ob/ob mice (n = 8/group) using sc-implanted osmotic pumps. Treatment resulted in a dose-associated increase in serum leptin. Bone formation parameters were increased at EC 50 infusion rates of 7-17 ng/h, whereas higher levels (EC 50 , 40-80 ng/h) were required to similarly influence indices of energy metabolism. We then analyzed gene expression in tibia and hypothalamus at dose rates of 0, 12 and 140 ng/h; the latter dose resulted in serum leptin levels similar to WT mice. Infusion with 12 ng/h leptin increased the expression of genes associated with Jak/Stat signaling and bone formation in tibia with minimal effect on Jak/Stat signaling and neurotransmitters in hypothalamus. The results suggest that leptin acts peripherally to couple bone acquisition to energy availability and that limited transport across the BBB insures that the growth-promoting actions of peripheral leptin are not curtailed by the hormone's CNS-mediated anorexigenic actions. © 2017 Society for Endocrinology.

Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

PubMed

Delgado-Lista, Javier; Perez-Martinez, Pablo; Solivera, Juan; Garcia-Rios, Antonio; Perez-Caballero, A I; Lovegrove, Julie A; Drevon, Christian A; Defoort, Catherine; Blaak, Ellen E; Dembinska-Kieć, Aldona; Risérus, Ulf; Herruzo-Gomez, Ezequiel; Camargo, Antonio; Ordovas, Jose M; Roche, Helen; Lopez-Miranda, José

2014-02-01

Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

Biochemical Assessment of Bone Health in Working Obese Egyptian Females with Metabolic Syndrome; the Effect of Weight Loss by Natural Dietary Therapies

PubMed Central

Moaty, Maha I. A.; Fouad, Suzanne; Shebini, Salwa M. El; Kazem, Yusr I.; Tapozada, Salwa T.

2015-01-01

AIM: To investigate the relation between bone parameters and the metabolic syndrome criteria, before and after the administration of two different natural dietary supplements in middle aged working obese Egyptian women suffering from metabolic syndrome (MetS). SUBJECTS AND METHODS: Fifty eight middle aged obese female volunteers suffering from metabolic syndrome were divided into two groups. During the first period, group (A) consumed a low caloric diet and nutritional supplement consisting of doum flour biscuits, while group (B) consumed whole meal wheat flour biscuit with the same instructions. During the second period, both supplements were omitted. Assessment of blood pressure, relevant anthropometric parameters, lipid accumulation product, fasting blood glucose, uric acid, 25 hydroxy vitamin D (25 (OH) D), parathyroid hormone (PTH) and bone-specific alkaline phosphatase were performed. RESULTS: Data showed that although both supplements improved the MetS criteria and the bone health parameters, the supplement containing the doum flour proved to be more effective. CONCLUSION: These results confirm the benefit of doum in improving bone health parameter [25 (OH) D/PTH axis] in the MetS patients, beside the MetS criteria. So, we can conclude that natural effective supplements lead towards the optimization of biochemical parameters in favor of a healthy outcome. PMID:27275291

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.

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.

Early changes in parameters of bone and mineral metabolism during therapy for hyper- and hypothyroidism.

PubMed

Sabuncu, T; Aksoy, N; Arikan, E; Ugur, B; Tasan, E; Hatemi, H

2001-01-01

The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n= 38), 2) Hyperthyroid patients treated for three months (n=21), 3) Untreated hypothyroid patients (n=27), 4) Hypothyroid patients treated for three months (n= 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P < 0.001 and P = 0.02, respectively). These results suggest that both bone formation and resorption markers increase in hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

PubMed Central

Houdek, Devon

2017-01-01

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed. PMID:28408926

Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

PubMed

Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

2016-10-01

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

Metabolic Features of Multiple Myeloma.

PubMed

El Arfani, Chaima; De Veirman, Kim; Maes, Ken; De Bruyne, Elke; Menu, Eline

2018-04-14

Cancer is known for its cellular changes contributing to tumour growth and cell proliferation. As part of these changes, metabolic rearrangements are identified in several cancers, including multiple myeloma (MM), which is a condition whereby malignant plasma cells accumulate in the bone marrow (BM). These metabolic changes consist of generation, inhibition and accumulation of metabolites and metabolic shifts in MM cells. Changes in the BM micro-environment could be the reason for such adjustments. Enhancement of glycolysis and glutaminolysis is found in MM cells compared to healthy cells. Metabolites and enzymes can be upregulated or downregulated and play a crucial role in drug resistance. Therefore, this review will focus on changes in glucose and glutamine metabolism linked with the emergence of drug resistance. Moreover, metabolites do not only affect other metabolic components to benefit cancer development; they also interfere with transcription factors involved in proliferation and apoptotic regulation.

Reheating of soy oil is detrimental to bone metabolism in oestrogen deficient rats.

PubMed

Ima-Nirwana, S; Ahmad, S Nazrun; Yee, L J; Loh, H C; Yew, S F; Norazlina, M; Abdul, M T Gapor; Kamsiah, J

2007-03-01

The short-term and long- term effects of heated soy oil on bone metabolism in ovariectomised Sprague-Dawley rats were studied. Three-month-old female rats, were divided into five groups: normal control (NC); ovariectomised control (OVXC); ovariectomised and fed rat chow with added fresh soybean oil (SOF) or once-heated soy oil (SO1) or five-times-heated soy oil (SO5). Short-term parameters measured after one month were serum interleukin-6 (IL-6) and osteocalcin. Long-term parameters measured after six months were the structural bone histomorphometrical parameters. Vitamin E content in the soy oil subjected to the different heating treatments were also measured. Rats in the SO5 group had higher levels of IL-6 after one month compared to the other four groups. Osteocalcin levels in the SO1 and SO5 groups remained high after treatment, while those in the NC and SOF groups declined. After six months, bone mass declined in the SO5 group. Vitamin E assay in the oils showed that levels of alpha-tocopherol decreased after heating the oil once and five times, while levels of gamma- and delta-tocopherols only declined after heating five times. Repeated heating of soy oil destroyed the tocopherols causing raised serum IL-6 and osteocalcin levels, leading to increased bone resorption and osteoporosis in the long term.

Bone Metabolism in Adolescent Athletes With Amenorrhea, Athletes With Eumenorrhea, and Control Subjects

PubMed Central

Christo, Karla; Prabhakaran, Rajani; Lamparello, Brooke; Cord, Jennalee; Miller, Karen K.; Goldstein, Mark A.; Gupta, Nupur; Herzog, David B.; Klibanski, Anne; Misra, Madhusmita

2011-01-01

OBJECTIVE We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. METHODS In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. RESULTS Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. CONCLUSIONS Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass. PMID:18519482

Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1

PubMed Central

Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

2009-01-01

Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H+-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium ± the OGR1 inhibitor CuCl2. CuCl2 decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Cai. Perfusion with MET induced a rapid, flow-independent, increase in Cai in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Cai in response to H+, we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Cai in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Cai in response to MET and is a prime candidate for an osteoblast proton sensor. PMID:18847331

Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.

PubMed

Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

2009-02-01

Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H(+)-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium +/- the OGR1 inhibitor CuCl(2). CuCl(2) decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Ca(i). Perfusion with MET induced a rapid, flow-independent, increase in Ca(i) in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Ca(i) in response to H(+), we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Ca(i) in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Ca(i) in response to MET and is a prime candidate for an osteoblast proton sensor.

[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

Evaluation of the parameters affecting bone temperature during drilling using a three-dimensional dynamic elastoplastic finite element model.

PubMed

Chen, Yung-Chuan; Tu, Yuan-Kun; Zhuang, Jun-Yan; Tsai, Yi-Jung; Yen, Cheng-Yo; Hsiao, Chih-Kun

2017-11-01

A three-dimensional dynamic elastoplastic finite element model was constructed and experimentally validated and was used to investigate the parameters which influence bone temperature during drilling, including the drill speed, feeding force, drill bit diameter, and bone density. Results showed the proposed three-dimensional dynamic elastoplastic finite element model can effectively simulate the temperature elevation during bone drilling. The bone temperature rise decreased with an increase in feeding force and drill speed, however, increased with the diameter of drill bit or bone density. The temperature distribution is significantly affected by the drilling duration; a lower drilling speed reduced the exposure duration, decreases the region of the thermally affected zone. The constructed model could be applied for analyzing the influence parameters during bone drilling to reduce the risk of thermal necrosis. It may provide important information for the design of drill bits and surgical drilling powers.

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.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

PubMed

Tack, Lloyd J W; Craen, Margarita; Lapauw, Bruno; Goemaere, Stefan; Toye, Kaatje; Kaufman, Jean-Marc; Vandewalle, Sara; T'Sjoen, Guy; Zmierczak, Hans-Georg; Cools, Martine

2018-06-01

Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma.

PubMed

Kim, Mee Kyoung; Yun, Kyung-Jin; Kim, Min-Hee; Lim, Dong-Jun; Kwon, Hyuk-Sang; Song, Ki-Ho; Kang, Moo-Il; Baek, Ki Hyun

2015-02-01

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were -0.88, -1.3 and -0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine -2.1%, femoral neck -2.2%, and hip -2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Long-term supplementation with young coconut juice does not prevent bone loss but rather alleviates body weight gain in ovariectomized rats.

PubMed

Matsushita, Hiroshi; Minami, Akira; Kanazawa, Hiroaki; Suzuki, Takashi; Subhadhirasakul, Sanan; Watanabe, Kazushi; Wakatsuki, Akihiko

2017-05-01

Young coconut ( Cocos nucifera Linn.) juice (YCJ) has traditionally been consumed to alleviate symptoms associated with the menopause. Recently, the authors demonstrated that short-term (6-week) YCJ supplementation to ovariectomized rats resulted in increased bone mass and bone formation parameter, suggesting that YCJ consumption has a positive effect on bone metabolism and may represent an intervention to help slow the bone loss during menopause transition. The present study sought to determine how long-term (12-week) YCJ supplementation affects bone metabolism in ovariectomized rats, to investigate whether such supplementation may be helpful to in osteoporosis treatment. Ten-week-old female Wistar rats were subjected to either a sham operation (Sham) or bilateral ovariectomy (Ovx). The Ovx+YCJ group received 5X-concentrated YCJ at a dose of 15 ml/kg/day for 12 weeks. Rats in the Ovx group had significantly lower femur bone mineral density than those in the Sham group. YCJ supplementation did not significantly affect this difference. However, YCJ prevented the increase in bone area of the mid third of the femur, a site high in cortical bone, and body weight gain observed following Ovx. Our findings indicate that long-term YCJ intake does not alter bone loss, but rather alleviates body weight gain following menopause.

Calcium homeostasis and bone metabolic responses to protein diets and energy restriction: a randomized control trial

USDA-ARS?s Scientific Manuscript database

Despite some beneficial effects on bone, high protein diets are conventionally considered a primary dietary risk factor for osteoporosis and bone fracture due to the acid load associated with protein catabolism. To test the hypothesis that high dietary protein diets do not negatively affect calcium ...

GSK-3β Function in Bone Regulates Skeletal Development, Whole-Body Metabolism, and Male Life Span

PubMed Central

Gillespie, J. R.; Bush, J. R.; Bell, G. I.; Aubrey, L. A.; Dupuis, H.; Ferron, M.; Kream, B.; DiMattia, G.; Patel, S.; Woodgett, J. R.; Karsenty, G.; Hess, D. A.; Beier, F.

2016-01-01

Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in peri-natal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3β in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died after weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type 2 diabetes. Our data suggest that skeletal-specific deletion of GSK-3β affects global metabolism and sensitizes male mice to developing type 2 diabetes. PMID:23904355

Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

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

Chen, Y.-J.; Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan

2005-11-15

Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses ofmore » CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.« less

Kinetic aspects of bone mineral metabolism

NASA Technical Reports Server (NTRS)

Palmer, H. E.

1973-01-01

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

Change of urinary fluoride and bone metabolism indicators in the endemic fluorosis areas of southern china after supplying low fluoride public water

PubMed Central

2013-01-01

Background Few studies have evaluated health impacts, especially biomarker changes, following implementation of a new environmental policy. This study examined changes in water fluoride, urinary fluoride (UF), and bone metabolism indicators in children after supplying low fluoride public water in endemic fluorosis areas of Southern China. We also assessed the relationship between UF and serum osteocalcin (BGP), calcitonin (CT), alkaline phosphatase (ALP), and bone mineral density to identify the most sensitive bone metabolism indicators related to fluoride exposure. Methods Four fluorosis-endemic villages (intervention villages) in Guangdong, China were randomly selected to receive low-fluoride water. One non-endemic fluorosis village with similar socio-economic status, living conditions, and health care access, was selected as the control group. 120 children aged 6-12 years old were randomly chosen from local schools in each village for the study. Water and urinary fluoride content as well as serum BGP, CT, ALP and bone mineral density were measured by the standard methods and compared between the children residing in the intervention villages and the control village. Benchmark dose (BMD) and benchmark dose lower limit (BMDL) were calculated for each bone damage indicator. Results Our study found that after water source change, fluoride concentrations in drinking water in all intervention villages (A-D) were significantly reduced to 0.11 mg/l, similar to that in the control village (E). Except for Village A where water change has only been taken place for 6 years, urinary fluoride concentrations in children of the intervention villages were lower or comparable to those in the control village after 10 years of supplying new public water. The values of almost all bone indicators in children living in Villages B-D and ALP in Village A were either lower or similar to those in the control village after the intervention. CT and BGP are sensitive bone metabolism

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...

Cardiac metabolic pathways affected in the mouse model of barth syndrome.

PubMed

Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

2015-01-01

Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients

PubMed Central

Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov NCT02361372 PMID:26655888

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

PubMed

Tu, Min-Yu; Chen, Hsiao-Ling; Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. ClinicalTrials.gov NCT02361372.

[Effect of ultraviolet irradiation through glass on the level of 25-hydroxy vitamin D and bone metabolism in rats].

PubMed

Wu, Wei; Wang, Shu-Rong; Zhang, Wei

2009-02-01

Some research has shown that there is a dose-dependent relationship between ultraviolet B (UVB) and serum levels of 25-hydroxy vitamin D[25-(OH)D]\\. Vitamin D is correlated with bone metabolism. This study aimed to explore the effect of UVB irradiation through glass on serum levels of 25-(OH)D and bone metabolism in rats. Wistar rats were fed with vitamin D deficient diet and randomly divided into three groups: no UVB exposure, direct UVB exposure (160 min/d) and indirect UVB exposure (through glass) (160 min/d). By 21 days after exposure, bone mineral density (BMD) and serum levels of 25-(OH)D, parathyroid hormone (PTH), osteocalcin (OC), bone alkaline phosphatase (BALP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) were measured. BMD (0.036+/-0.002 g/cm2) in the indirect UVB exposure group was significantly higher than that in the no UVB exposure group (0.029+/-0.002 g/cm2) (<0.01). Serum ICTP level in the indirect UVB exposure group was significantly lower than that in the no UVB exposure group (0.181+/-0.067 microg/L vs 0.194+/-0.066 microg/L; <0.01). Serum levels of PTH, 25-(OH)D, BALP and OC in the indirect UVB exposure group were not significantly different from those in the no UVB exposure group. Compared with the direct UVB exposure group, serum levels of OC (0.559+/-0.067 ng/mL vs 0.278+/-0.067 ng/mL; <0.05) and PTH (0.181+/-0.067 microg/L vs 0.109+/-0.067 microg/L; <0.05) in the indirect UVB exposure group significantly increased, while serum levels of 25-(OH)D significantly decreased (28.67+/-1.35 nmol/L vs 34.69+/-4.30 nmol/L; <0.01). There were no significant differences in BMD and serum levels of BALP and ICTP between the indirect UVB exposure and the direct UVB exposure groups. UVB irradiation through glass cannot elevate serum levels of 25-(OH)D, but can decrease bone turnover rate and increase BMD. The effect of UVB irradiation through glass on bone metabolism is similar to that of direct UVB irradiation.

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

[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.

Alterations in markers of bone metabolism and adipokines following a 3-month lifestyle intervention induced weight loss in obese prepubertal children.

PubMed

Gajewska, J; Weker, H; Ambroszkiewicz, J; Szamotulska, K; Chełchowska, M; Franek, E; Laskowska-Klita, T

2013-08-01

Adipokines may influence bone metabolism in children, but this phenomenon is not well understood. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. We determined serum leptin, soluble leptin receptor (sOB-R), adiponectin, BALP (bone alkaline phosphatase), CTX-I (C-terminal telopeptide of type I collagen), body composition and bone mineral density (by dual-energy X-ray absorptiometry) in 100 obese prepubertal children before and after 3 months of lifestyle intervention (low-energy diet, physical activity). The control group consisted of 70 non-obese children. Obese children had higher BALP activity by about 20% (p<0.001) and similar value of CTX-I compared with non-obese children. After weight loss (-0.96 BMI-SDS mean change), the BALP value in obese patients decreased (p<0.001), whereas CTX-I concentration was unchanged. Changes in BALP were positively correlated with changes in BMI (Body Mass Index) (r=0.352, p<0.001), but not associated with adipokine levels. Trend analysis using SDS-BMI subgroups showed that greater reduction of body mass was associated with a greater decrease of BALP (p=0.035) and leptin values (p<0.001), as well as a greater increase of sOB-R (p<0.003). Obesity during the prepubertal period is associated with an alteration in the adipokines profile and greater whole-body bone mass as a result of increased bone formation rather than reduced bone resorption. Changes in bone metabolism during lifestyle intervention seem to be related to weight loss but not to changes in adipokines. Further studies should elucidate the influence of long-term therapy on bone mass in childhood. © Georg Thieme Verlag KG Stuttgart · New York.

Factors affecting the pullout strength of cancellous bone screws.

PubMed

Chapman, J R; Harrington, R M; Lee, K M; Anderson, P A; Tencer, A F; Kowalski, D

1996-08-01

Screws placed into cancellous bone in orthopedic surgical applications, such as fixation of fractures of the femoral neck or the lumbar spine, can be subjected to high loads. Screw pullout is a possibility, especially if low density osteoporotic bone is encountered. The overall goal of this study was to determine how screw thread geometry, tapping, and cannulation affect the holding power of screws in cancellous bone and determine whether current designs achieve maximum purchase strength. Twelve types of commercially available cannulated and noncannulated cancellous bone screws were tested for pullout strength in rigid unicellular polyurethane foams of apparent densities and shear strengths within the range reported for human cancellous bone. The experimentally derived pullout strength was compared to a predicted shear failure force of the internal threads formed in the polyurethane foam. Screws embedded in porous materials pullout by shearing the internal threads in the porous material. Experimental pullout force was highly correlated to the predicted shear failure force (slope = 1.05, R2 = 0.947) demonstrating that it is controlled by the major diameter of the screw, the length of engagement of the thread, the shear strength of the material into which the screw is embedded, and a thread shape factor (TSF) which accounts for screw thread depth and pitch. The average TSF for cannulated screws was 17 percent lower than that of noncannulated cancellous screws, and the pullout force was correspondingly less. Increasing the TSF, a result of decreasing thread pitch or increasing thread depth, increases screw purchase strength in porous materials. Tapping was found to reduce pullout force by an average of 8 percent compared with nontapped holes (p = 0.0001). Tapping in porous materials decreases screw pullout strength because the removal of material by the tap enlarges hole volume by an average of 27 percent, in effect decreasing the depth and shear area of the internal

Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism.

PubMed

Simsek, Gönül; Karter, Yesari; Aydin, Seval; Uzun, Hafize

2003-12-31

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not

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.

Do increased drilling speed and depth affect bone viability at implant site?

PubMed

Tabrizi, Reza; Nazhvanai, Ali Dehghani; Farahmand, Mohammad Mahdi; Pourali, Sara Yasour; Hosseinpour, Sepanta

2017-01-01

The aim of this study was to assess the effect of increasing the drilling speed and depth during implant site preparation on bone viability. In this prospective cohort study, participants were divided into four groups based on the speed and depth of drilling at the first molar site in the mandible. Participants underwent drilling at Group 1: 1000 rpm and 10 mm depth, Group 2: 1500 rpm and 10 mm, Group 3: 1000 rpm and 13 mm, and Group 4: 1500 rpm and 13 mm. Obtained specimens were assessed histologically to the qualitative measurement of bone viability, and the percentage of vital bone were evaluated by histomorphometric analysis. ANOVA was used to compare age and the mean percentage of vital bone and Tukey's test as post hoc was applied for pairwise comparison of groups. A total of 100 participants were studied in four groups (25 subjects in each group). Histological evaluation revealed a low level of bone viability maintenance in all groups. Histomorphometric analysis showed the mean percentage of vital bone was 9.5 ± 3.91% in Group 1, 8.86 ± 3.84% in Group 2, 8.32 ± 3.80% in Group 3, and 4.27 ± 3.22% in Group 4. A significant difference was noted in the mean percentage of bone viability among the four groups ( P = 0.001). It seems that increasing the drilling speed or depth during dental implant site preparation does not affect the mean percentage of cell viability, while the increase in both depth and speed may decrease the percentage of viable cells.

The association between bone health indicated by calcaneal quantitative ultrasound and metabolic syndrome in Malaysian men.

PubMed

Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Ahmad, Fairus; Mohd Ramli, Elvy Suhana; Aminuddin, Amilia; Wan Ngah, Wan Zurinah

2015-01-01

Previous studies on the relationship between bone health and metabolic syndrome (MS) have revealed heterogeneous results. There are limited studies employing bone quantitative ultrasonometry in evaluating this relationship. This study aimed to determine the relationship between MS and bone health in a group of Malaysian middle-aged and elderly men using bone quantitative ultrasonometry. This cross-sectional study recruited 309 free living Chinese and Malay men aged 40 years and above residing in Klang Valley, Malaysia. Their demographic and anthropometric data were collected. Their calcaneal speed of sound (SOS) was measured using a CM-200 bone ultrasonometer. Their blood was collected for the evaluation of lipid profile, total testosterone and sex hormone-binding globulin. The joint interim MS definition was used for the classification of subjects. Multiple linear regression analysis was used to assess the association between SOS and indicators of MS and the presence of MS, with suitable adjustment for confounders. There was no significant difference in SOS value between MS and non-MS subjects (p > 0.05). The SOS values among subjects with different MS scores did not differ significantly (p > 0.05). There were no significant associations between SOS values and indicators of MS or the presence of MS (p > 0.05). The relationship between bone health and MS is not significant in Malaysian middle-aged and elderly men. A longitudinal study should be conducted to evaluate the association between bone loss and MS to confirm this finding.

Dietary magnesium reduction to 25% of nutrient requirement disrupts bone and mineral metabolism in the rat.

PubMed

Rude, Robert K; Gruber, Helen E; Norton, H James; Wei, Livia Y; Frausto, Angelica; Kilburn, Jeremy

2005-08-01

Low dietary magnesium (Mg) may be a risk factor for osteoporosis. In animals, severe Mg deficiency (0.04% of nutrient requirement [NR]) results in bone loss. We have also found that a more moderate dietary Mg restriction (10% of NR) also resulted in loss of bone. We now report the effect of Mg intake of 25% NR on bone and mineral metabolism in the rat. Serum Mg, Ca, PTH, 1,25(OH)2-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured at 2, 4, and 6 months in control and Mg-deficient animals. Femurs and tibias were collected for mineral content, micro-computerized tomography, histomorphometry, and immunocytochemical localization. Profound Mg deficiency developed as assessed by marked hypomagnesemia and 27% reduction in bone Mg content. Serum calcium was not significantly different between groups. Mg depletion resulted in a significantly lower serum PTH concentrations. Serum 1,25(OH)2-vitamin D was also significantly lower. No difference was noted in markers of bone turnover. Histomorphometry and micro-computerized tomography demonstrated decreased bone volume and trabecular thickness. No difference was observed for osteoclast or osteoblast number. Inflammatory cytokines may contribute to bone loss. We found that immunocytochemical localization of TNFalpha in osteoclasts was increased 138-150%. This increase in TNFalpha may be due to increased substance P as it was found to be elevated from 179% to 432%. These data demonstrate that Mg intake of 25% NR in the rat causes lower bone mass which may be related to increased release of substance P and TNFalpha.

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.

Gravity, Calcium, And Bone: Update, 1989

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Morey-Holton, Emily

1992-01-01

Report reviews short-term flight and ground-based experiments on effects of 1 g and 0 g on skeletal adaptation, calcium metabolism, and growth processes. Results indicate two principal components of calcium metabolism-calcium endocrine system and bone - respond within days to changes in orientation of body in gravitation and to weightlessness. Effects of spaceflight or bed rest on biomechanics of bones more severe than on total body bone mass.

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats.

PubMed

Nagura, Nana; Komatsu, Jun; Iwase, Hideaki; Hosoda, Hiroshi; Ohbayashi, Osamu; Nagaoka, Isao; Kaneko, Kazuo

2015-05-01

The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts.

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats

PubMed Central

NAGURA, NANA; KOMATSU, JUN; IWASE, HIDEAKI; HOSODA, HIROSHI; OHBAYASHI, OSAMU; NAGAOKA, ISAO; KANEKO, KAZUO

2015-01-01

The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts. PMID:26137225

Mineral balance and bone turnover in adolescents with anorexia nervosa.

PubMed

Abrams, S A; Silber, T J; Esteban, N V; Vieira, N E; Stuff, J E; Meyers, R; Majd, M; Yergey, A L

1993-08-01

We evaluated seven female adolescents with anorexia nervosa to determine whether calcium metabolism was affected by their disorder. We measured calcium absorption, urinary calcium excretion, and calcium kinetics, using a dual-tracer, stable-isotope technique during the first weeks of an inpatient nutritional rehabilitation program. Results were compared with those from a control group of seven healthy adolescent girls of similar ages. The percentage of absorption of calcium was lower in subjects with anorexia nervosa than in control subjects (16.2% +/- 6.3% vs 24.6% +/- 7.2%; p < 0.05). Urinary calcium excretion was greater in subjects with anorexia nervosa than in control subjects (6.4 +/- 2.5 vs 1.6 +/- 0.7 mg.kg-1 x day-1; p < 0.01) and was associated with bone resorption rather than calcium hyper-absorption. Calcium kinetic studies demonstrated a decreased rate of bone formation and an increased rate of bone resorption. These results suggest marked abnormalities in mineral metabolism in patients with anorexia nervosa. From these results, we hypothesize that improvement in bone mineralization during recovery from anorexia nervosa will require resolution of hormonal abnormalities, including hypercortisolism, in addition to increased calcium intake.

Reduced energy availability: implications for bone health in physically active populations.

PubMed

Papageorgiou, Maria; Dolan, Eimear; Elliott-Sale, Kirsty J; Sale, Craig

2018-04-01

The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Quantitative trait locus on chromosome X affects bone loss after maturation in mice.

PubMed

Okudaira, Shuzo; Shimizu, Motoyuki; Otsuki, Bungo; Nakanishi, Rika; Ohta, Akira; Higuchi, Keiichi; Hosokawa, Masanori; Tsuboyama, Tadao; Nakamura, Takashi

2010-09-01

Genetic programming is known to affect the peak bone mass and bone loss after maturation. However, little is known about how polymorphic genes on chromosome X (Chr X) modulate bone loss after maturation. We previously reported a quantitative trait locus (QTL) on Chr X, designated Pbd3, which had a suggestive linkage to bone mass, in male SAMP2 and SAMP6 mice. In this study, we aimed to clarify the effects of Pbd3 on the skeletal phenotype. We generated a congenic strain, P2.P6-X, carrying a 45.6-cM SAMP6-derived Chr X interval on a SAMP2 genetic background. The effects of Pbd3 on the bone phenotype were determined by microcomputed tomography (microCT), whole-body dual-energy X-ray absorptiometry (DXA), serum bone turnover markers, and histomorphometric parameters. Both the bone area fraction (BA/TA) on microCT and whole-body DXA revealed reduced bone loss in P2.P6-X compared with that in SAMP2. The serum concentrations of bone turnover markers at 4 months of age were significantly lower in P2.P6-X than in SAMP2, but did not differ at 8 months of age. These results were observed in female mice, but not in male mice. In conclusion, a QTL within a segregated 45.6-cM interval on Chr X is sex-specifically related to the rate of bone loss after maturation.

Quantitative MRI and spectroscopy of bone marrow

PubMed Central

Ruschke, Stefan; Dieckmeyer, Michael; Diefenbach, Maximilian; Franz, Daniela; Gersing, Alexandra S.; Krug, Roland; Baum, Thomas

2017-01-01

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332–353. PMID:28570033

Long-term effects of intermittent equine parathyroid hormone fragment (ePTH-1-37) administration on bone metabolism in healthy horses.

PubMed

Weisrock, Katharina U; Winkelsett, Sarah; Martin-Rosset, William; Forssmann, Wolf-Georg; Parvizi, Nahid; Coenen, Manfred; Vervuert, Ingrid

2011-11-01

Intermittent administration of parathyroid hormone (PTH) is an anabolic therapy for osteoporotic conditions in humans. This study evaluated the effects of equine PTH fragment (ePTH-1-37) administration on bone metabolism in 12 healthy horses. Six horses each were treated once daily for 120days with subcutaneous injections of 0.5μg/kg ePTH-1-37 or placebo. Blood was collected to determine ionized calcium (Ca(++)), total Ca (Ca(T)), inorganic phosphorus, serum equine osteocalcin (eOC), carboxy-terminal telopeptide of type I collagen (ICTP), bone-specific alkaline phosphatase, and carboxy-terminal cross-linked telopeptide of type I collagen. Bone mineral density (BMD) was determined with dual X-ray absorptiometry of the metacarpus and calcaneus. Significantly higher blood Ca(++) and plasma Ca(T) concentrations were measured 5h after ePTH-1-37 administration compared to placebo. Higher serum eOC concentrations were found for ePTH-1-37 treatment at days 90 (P<0.05) and 120 (P=0.05). Significantly higher serum ICTP levels were observed with ePTH-1-37 treatment at days 60 and 90. For both study groups, BMD increased significantly in the calcaneus. Long-term use of ePTH-1-37 seemed to have no negative effects on bone metabolism in healthy horses. The absence of undesirable side effects is the premise to ensure safety for further clinical investigations in horses with increased bone resorption processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Which metabolic imaging, besides bone scan with 99mTc-phosphonates, for detecting and evaluating bone metastases in prostatic cancer patients? An open discussion.

PubMed

Bombardieri, E; Setti, L; Kirienko, M; Antunovic, L; Guglielmo, P; Ciocia, G

2015-12-01

Prostate cancer bone metastases occur frequently in advanced cancer and this is matter of particular attention, due to the great impact on patient's management and considering that a lot of new emerging therapeutic options have been recently introduced. Imaging bone metastases is essential to localize lesions, to establish their size and number, to study characteristics and changes during therapy. Besides radiological imaging, nuclear medicine modalities can image their features and offer additional information about their metabolic behaviour. They can be classified according to physical characteristics, type of detection, mechanism of uptake, availability for daily use. The physiopathology of metastases formation and the mechanisms of tracer uptake are essential to understand the interpretation of nuclear medicine images. Therefore, radiopharmaceuticals for bone metastases can be classified in agents targeting bone (99mTc-phosphonates, 18F-fluoride) and those targeting prostatic cancer cells (18F-fluoromethylcholine, 11C-choline, 18F-fluorodeoxyglucose). The modalities using the first group of tracers are planar bone scan, SPECT or SPECT/CT with 99mTc-diphosphonates, and 18F-fluoride PET/CT, while the modalities using the second group include 18F/11C-choline derivatives PET/CT, 18F-FDG PET/CT and PET/CT scans with several other radiopharmaceuticals described in the literature, such as 18F/11C-acetate derivatives, 18F-fluoro-5α-dihydrotestosterone (FDHT), 18F-anti-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), 18F-2'-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) and 68Ga-labeled-prostate specific membrane antigen (PMSA) PET/TC. However, since data on clinical validation for these last novel modalities are not conclusive and/or are not still sufficient in number, at present they can be still considered as promising tools under evaluation. The present paper considers the nuclear modalities today available for the clinical routine. This overview wants

Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro.

PubMed

Seebach, Caroline; Schultheiss, Judith; Wilhelm, Kerstin; Frank, Johannes; Henrich, Dirk

2010-07-01

Various synthetic bone-graft substitutes are used commercially as osteoconductive scaffolds in the treatment of bone defects and fractures. The role of bone-graft substitutes is changing from osteoconductive conduits for growth to an delivery system for biologic fracture treatments. Achieving optimal bone regeneration requires biologics (e.g. MSC) and using the correct scaffold incorporated into a local environment for bone regeneration. The need for an unlimited supply with high quality bone-graft substitutes continue to find alternatives for bone replacement surgery. This in vitro study investigates cell seeding efficiency, metabolism, gene expression and growth behaviour of MSC sown on six commercially clinical available bone-graft substitutes in order to define their biological properties: synthetic silicate-substituted porous hydroxyapatite (Actifuse ABX), synthetic alpha-TCP (Biobase), synthetic beta-TCP (Vitoss), synthetic beta-TCP (Chronos), processed human cancellous allograft (Tutoplast) and processed bovines hydroxyapatite ceramic (Cerabone). 250,000 MSC derived from human bone marrow (n=4) were seeded onto the scaffolds, respectively. On days 2, 6 and 10 the adherence of MSC (fluorescence microscopy) and cellular activity (MTT assay) were analysed. Osteogenic gene expression (cbfa-1) was analysed by RT-PCR and scanning electron microscopy was performed. The highest number of adhering cells was found on Tutoplast (e.g. day 6: 110.0+/-24.0 cells/microscopic field; p<0.05) followed by Chronos (47.5+/-19.5, p<0.05), Actifuse ABX (19.1+/-4.4), Biobase (15.7+/-9.9), Vitoss (8.8+/-8.7) and Cerabone (8.1+/-2.2). MSC seeded onto Tutoplast showed highest metabolic activity and gene expression of cbfa-1. These data are confirmed by scanning electron microscopy. The cell shapes varied from round-shaped cells to wide spread cells and cell clusters, depending on the bone-graft substitutes. Processed human cancellous allograft is a well-structured and biocompatible

Non-reproductive Effects of Anovulation: Bone Metabolism in the Luteal Phase of Premenopausal Women Differs between Ovulatory and Anovulatory Cycles.

PubMed

Niethammer, B; Körner, C; Schmidmayr, M; Luppa, P B; Seifert-Klauss, V R

2015-12-01

Introduction: Several authors have linked subclinical ovulatory disturbances in normal length menstrual cycles to premenopausal fracture risk and bone changes. This study systematically examined the influence of ovulation and anovulation on the bone metabolism of premenopausal women. Participants and Methods: In 176 cycles in healthy premenopausal women, FSH, 17β-estradiol (E2) and progesterone (P4) as well as bone alkalic phosphatase (BAP), pyridinoline (PYD) and C-terminal crosslinks (CTX) were measured during the follicular and during the luteal phase. The probability and timing of ovulation was self-assessed by a monitoring device. In addition, bone density of the lumbar spine was measured by quantitative computed tomography (QCT) at baseline and at the end of the study. Analysis was restricted to blood samples taken more than three days before the following menstruation. Results: 118 cycles out of the 176 collected cycles were complete with blood samples taken within the correct time interval. Of these, 56.8 % were ovulatory by two criteria (ovulation symbol shown on the monitor display and LP progesterone > 6 ng/ml), 33.1 % were possibly ovulatory by one criterion (ovulation symbol shown on the monitor display or LP progesterone > 6 ng/ml), and 10.2 % were anovulatory by both criteria). Ovulation in the previous cycle and in the same cycle did not significantly influence the mean absolute concentrations of the bone markers. However, bone formation (BAP) was higher in the luteal phase of ovulatory cycles than in anovulatory cycles (n. s.) and the relative changes within one cycle were significantly different for bone resorption (CTX) during ovulatory vs. anovulatory cycles (p < 0.01). In 68 pairs of cycles following each other directly, both ovulation in the previous cycle and ovulation in the present cycle influenced CTX, but not the differences of other bone markers. Conclusion: Ovulatory cycles reduce bone resorption in their luteal

Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation.

PubMed

Tangpricha, Vin; Luo, Menghua; Fernández-Estívariz, Concepción; Gu, Li H; Bazargan, Niloofar; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Galloway, John R; Leader, Lorraine M; Ziegler, Thomas R

2006-01-01

Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD

Prebiotics and Bone.

PubMed

Whisner, Corrie M; Weaver, Connie M

2017-01-01

Recent advancements in food science have resulted in the extraction and synthesis of novel dietary fibers or prebiotics. Subsequently, great interest has emerged in developing strategies to improve metabolic conditions like osteoporosis by modulating the intestinal microbiome with fiber. Prebiotics have been shown to increase calcium absorption in the lower gut of both animals and humans as well as improve measures of bone mineral density and strength in rodent models. Fewer data are available in humans, but data from growing children and postmenopausal women suggest that prebiotics have both short- and long-term effects that beneficially affect bone turnover and mineral accretion in the skeleton. Currently, the exact mechanism by which these products elicit their effects on bone is poorly understood, but emerging data suggest that the gut microbiota may be involved in one or more direct and indirect pathways. The most well-accepted mechanism is through microbial fermentation of prebiotics which results in the production of short-chain fatty acids and a concomitant decrease in pH which increases the bioavailability of calcium in the colon. While other mechanisms may be eliciting a prebiotic effect on bone, the current data suggest that novel dietary fibers may be an affordable and effective method of maximizing mineral accretion in growing children and preventing bone loss in later years when osteoporosis is a greater risk. This chapter will discuss the dynamic role of prebiotics in bone health by discussing the current state of the art, addressing gaps in knowledge and their role in public health.

Cola beverage consumption delays alveolar bone healing: a histometric study in rats.

PubMed

Teófilo, Juliana Mazzonetto; Leonel, Daniel Vilela; Lamano, Teresa

2010-01-01

Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group) or tap water (control group) ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01). Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

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

An evaluation of the effect of age and the peri-parturient period on bone metabolism in dairy cows as measured by serum bone-specific alkaline phosphatase activity and urinary deoxypyridinoline concentration.

PubMed

Sato, Reiichiro; Onda, Ken; Kato, Hajime; Ochiai, Hideharu; Kawai, Kazuhiro; Iriki, Tsunenori; Kaneko, Kazuyuki; Yamazaki, Yukio; Wada, Yasunori

2013-08-01

Various biochemical markers help to evaluate the state of bone turnover in humans and could be used during the peri-parturient period in dairy cows when calcium (Ca) metabolism changes dramatically. To investigate this, the peri-partum characteristics of serum bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were investigated. Both serum BAP activity and urinary DPD concentrations were increased and demonstrated wide variability in younger animals, and these findings were consistent with other bone turnover markers. Around the time of parturition, serum Ca concentration and serum BAP activity in multiparous cows were significantly lower than in primiparous cows, but urinary DPD concentration was unchanged. The use of BAP as a bone formation marker appears to be valuable for evaluating bone remodelling status in cows, but the specificity of the test needs to be confirmed. The DPD/BAP ratio around parturition demonstrated a clear difference in bone turnover status between the two parity groups with multiparous cows demonstrating increased signs of bone resorption compared with primiparous cows, corresponding to the Ca requirement for milk production. In future studies, the applicability of the ratio of bone resorption marker to bone formation marker should be evaluated for bone turnover assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

PubMed

Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

2016-05-01

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. © 2016 Poultry Science Association Inc.

Flavanol plasma bioavailability is affected by metabolic syndrome in rats.

PubMed

Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

2017-09-15

Flavanols, which exert several health benefits, are metabolized after ingestion. Factors such as the host physiological condition could affect the metabolism and bioavailability of flavanols, influencing their bioactivities. This study aimed to qualitatively evaluate whether a pathological state influenced flavanol plasma bioavailability. Standard and cafeteria (CAF) diet fed rats, a robust model of metabolic syndrome (MeS), were administered 1000mg/kg of flavanol enriched grape seed polyphenol extract (GSPE). Flavanols and their metabolites were quantified by HPLC-MS/MS in plasma before and at 2, 4, 7, 24, and 48h after GSPE ingestion. Results showed that in CAF administered rats the maximum time of plasma flavanol concentration was delayed and these animals presented higher levels of plasma phase-II metabolites as well as altered microbial metabolites. In conclusion, this study demonstrated that MeS pathological state modified flavanol bioavailability, supporting the hypothesis that flavanol metabolism, and therefore flavanol functionality, depend on the organism's state of health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of electromagnetic radiation exposure on bone mineral density, thyroid, and oxidative stress index in electrical workers

PubMed Central

Kunt, Halil; Şentürk, İhsan; Gönül, Yücel; Korkmaz, Mehmet; Ahsen, Ahmet; Hazman, Ömer; Bal, Ahmet; Genç, Abdurrahman; Songur, Ahmet

2016-01-01

Background In the literature, some articles report that the incidence of numerous diseases increases among the individuals who live around high-voltage electric transmission lines (HVETL) or are exposed vocationally. However, it was not investigated whether HVETL affect bone metabolism, oxidative stress, and the prevalence of thyroid nodule. Methods Dual-energy X-ray absorptiometry (DEXA) bone density measurements, serum free triiodothyronine (FT3), free thyroxine (FT4), RANK, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), phosphor, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were analyzed to investigate this effect. Results Bone mineral density levels of L1–L4 vertebrae and femur were observed significantly lower in the electrical workers. ALP, phosphor, RANK, RANKL, TOS, OSI, and anteroposterior diameter of the left thyroid lobe levels were significantly higher, and OPG, TAS, and FT4 levels were detected significantly lower in the study group when compared with the control group. Conclusion Consequently, it was observed that the balance between construction and destruction in the bone metabolism of the electrical workers who were employed in HVETL replaced toward destruction and led to a decrease in OPG levels and an increase in RANK and RANKL levels. In line with the previous studies, long-term exposure to an electromagnetic field causes disorders in many organs and systems. Thus, it is considered that long-term exposure to an electromagnetic field affects bone and thyroid metabolism and also increases OSI by increasing the TOS and decreasing the antioxidant status. PMID:26929645

Osteoimmunology: Influence of the Immune System on Bone Regeneration and Consumption.

PubMed

Limmer, Andreas; Wirtz, Dieter C

2017-06-01

Background Stimulating bone regeneration is a central aim in orthopaedic and trauma surgery. Although the replacement of bone with artificial materials like cement or apatite helps to keep up bone stability, new bone often cannot be regenerated. Increasing research efforts have led to the clinical application of growth factors stimulating bone growth (e.g. bone morphogenic protein, BMP) and inhibitors preventing bone consumption (e.g. RANKL blocking antibodies). These factors mostly concentrate on stimulating osteoblast or preventing osteoclast activity. Current Situation It is widely accepted that osteoblasts and osteoclasts are central players in bone regeneration. This concept assumes that osteoblasts are responsible for bone growth while osteoclasts cause bone consumption by secreting matrix-degrading enzymes such as cathepsin K and matrix metalloproteinases (MMP). However, according to new research results, bone growth or consumption are not regulated by single cell types. It is rather the interaction of various cell types that regulates bone metabolism. While factors secreted by osteoblasts are essential for osteoclast differentiation and activation, factors secreted by activated osteoclasts are essential for osteoblast activity. In addition, recent research results imply that the influence of the immune system on bone metabolism has long been neglected. Factors secreted by macrophages or T cells strongly influence bone growth or degradation, depending on the bone microenvironment. Infections, sterile inflammation or tumour metastases not only affect bone cells directly, but also influence immune cells such as T cells indirectly. Furthermore, immune cells and bone are mechanistically regulated by similar factors such as cytokines, chemokines and transcription factors, suggesting that the definition of bone and immune cells has to be thought over. Outlook Bone and the immune system are regulated by similar mechanisms. These newly identified similarities

The influence of vegan diet on bone mineral density and biochemical bone turnover markers.

PubMed

Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Chełchowska, Magdalena; Franek, Edward; Laskowska-Klita, Teresa

2010-01-01

Vegetarian diets can be healthy when they are well balanced and if a variety of foods is consumed. However, elimination of animal products from the diet (vegan diets) decreases the intake of some essential nutrients and may influence the bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of the study was to assess the effect of vegan diet on bone density (BMD) density and serum concentrations of bone metabolism markers. We examined a family on vegan diet which consisted of parents and two children. Dietary constituents were analysed using a nutritional program. Total and regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of calcium and phosphate in serum obtained from fasting patients were determined by colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and bone turnover markers by specific enzyme immunoassays. In studied vegans, the dietary intake of phosphate was adequate while calcium and vitamin D were below the recommended range. Concentrations of calcium, phosphate and bone turnover markers in the serum of all subjects were within the physiological range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0). Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to -1.7 in children. Our results suggest that an inadequate dietary intake of calcium and vitamin D may impair the bone turnover rate and cause a decrease in bone mineral density in vegans. The parameters of bone density and bone metabolism should be monitored in vegans, especially children, in order to prevent bone abnormalities.

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

A fluorescence spotlight on the clockwork development and metabolism of bone.

PubMed

Iimura, Tadahiro; Nakane, Ayako; Sugiyama, Mayu; Sato, Hiroki; Makino, Yuji; Watanabe, Takashi; Takagi, Yuzo; Numano, Rika; Yamaguchi, Akira

2012-05-01

Biological phenomena that exhibit periodic activity are often referred as biorhythms or biological clocks. Among these, circadian rhythms, cyclic patterns reflecting a 24-h cycle, are the most obvious in many physiological activities including bone growth and metabolism. In the late 1990s, several clock genes were isolated and their primary structures and functions were identified. The feedback loop model of transcriptional factors was proposed to work as a circadian core oscillator not only in the suprachiasmatic nuclei of the anterior hypothalamus, which is recognized as the mammalian central clock, but also in various peripheral tissues including cartilage and bone. Looking back to embryonic development, the fundamental architecture of skeletal patterning is regulated by ultradian clocks that are defined as biorhythms that cycle more than once every 24 h. As post-genomic approaches, transcriptome analysis by micro-array and bioimaging assays to detect luminescent and fluorescent signals have been exploited to uncover a more comprehensive set of genes and spatio-temporal regulation of the clockwork machinery in animal models. In this review paper, we provide an overview of topics related to these molecular clocks in skeletal biology and medicine, and discuss how fluorescence imaging approaches can contribute to widening our views of this realm of biomedical science.

Bone and fat connection in aging bone.

PubMed

Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

Plasminogen activator inhibitor-1 deficiency ameliorates insulin resistance and hyperlipidemia but not bone loss in obese female mice.