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Sample records for abnormal bone turnover

  1. Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels.

    PubMed

    Pennisi, P; Signorelli, S S; Riccobene, S; Celotta, G; Di Pino, L; La Malfa, T; Fiore, C E

    2004-05-01

    Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score -1.71+/-1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score -2.5+/-0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3+/-3.1 vs 27.7+/-3.3 ng/ml, P<0.01, and 8.4+/-2.3 vs 12.5+/-1.4 microg/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9+/-138.9 vs 272.2+/-79.4 micro g/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5+/-1.07 vs 3.4+/-1.05 pmol/l, and 0.37+/-0.07 vs 0.36+/-0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG-RANKL system

  2. Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax

    PubMed Central

    Yu, Lixin; Hou, Shengcai; Hu, Bin; Zhao, Liqiang; Miao, Jinbai; Wang, Yang; Li, Tong; Zhang, Zhenkui; You, Bin; Pang, Baosen; Liang, Yufang; Zhao, Yi; Hao, Wei

    2016-01-01

    Background To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. Methods Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). Results Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. Conclusions It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in

  3. Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report.

    PubMed

    Kodama, Yasumitsu; Ogose, Akira; Oguri, Yoshimitsu; Ubaidus, Sobhan; Iizuka, Tateyuki; Takagi, Ritsuo

    2012-09-01

    A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

  4. Bone and bone turnover.

    PubMed

    Crofton, Patricia M

    2009-01-01

    Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

  5. Altered bone turnover during spaceflight

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Morey, E. R.; Liu, C.; Baylink, D. J.

    1982-01-01

    Modifications in calcium metabolism during spaceflight were studied, using parameters that reflect bone turnover. Bone formation rate, medullary area, bone length, bone density, pore size distribution, and differential bone cell number were evaluated in growing rate both immediately after and 25 days after orbital spaceflights aboard the Soviet biological satellites Cosmos 782 and 936. The primary effect of space flight on bone turnover was a reversible inhibition of bone formation at the periosteal surface. A simultaneous increase in the length of the periosteal arrest line suggests that bone formation ceased along corresponding portions of that surface. Possible reasons include increased secretion of glucocorticoids and mechanical unloading of the skeleton due to near-weightlessness, while starvation and immobilization are excluded as causes.

  6. Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

    SciTech Connect

    Porter, Daniel S.; Pienkowski, David; Faugere, Marie-Claude; Malluche, Hartmut H.

    2012-01-01

    Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bone with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.

  7. Supplementation of L-arginine prevents glucocorticoid-induced reduction of bone growth and bone turnover abnormalities in a growing rat model.

    PubMed

    Pennisi, Pietra; D'Alcamo, Maria Antonia; Leonetti, Concetta; Clementi, Anna; Cutuli, Vincenza Maria; Riccobene, Stefania; Parisi, Natalia; Fiore, Carmelo Erio

    2005-01-01

    The present study was designed to evaluate the effects of glucocorticoid (GC) treatment on bone turnover and bone mineral density in the growing rat. Because of the recent evidence that nitric oxide (NO) can counteract prednisolone-induced bone loss in mature rats, we examined the effect on bone of the NO donor L: -arginine in young male rats, in which bone mass is increased by the same biological mechanism as in children and adolescents. Thirty-six 10-week-old Sprague-Dawley male rats were assigned to six groups of six animals each, and treated for 4 weeks with either vehicle (once a week subcutaneous injection of 100 microl of sesame oil); prednisolone sodium succinate, 5 mg/kg, 5 days per week by intramuscular injection (i.m.); L-arginine, 10 mg/kg intraperitoneally (i.p.) once a day; N(G)-nitro-L-arginine methylester (L-NAME), 50 mg/kg subcutaneously once a day; prednisolone sodium succinate 5 mg/kg, 5 days per week i.m. +L-arginine 10 mg/kg i.p. once a day; or prednisolone sodium succinate, 5 mg/kg, 5 days per week i.m. +L-NAME 50 mg/kg subcutaneously once a day. Serum calcium, alkaline phosphatase (ALP), osteocalcin, and the C-terminal telopeptides of type I collagen (RatLaps) were measured at baseline conditions and after 2 and 4 weeks. Prior to treatment, and after 2 and 4 weeks, the whole body, vertebral, pelvic, and femoral bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) scanning. Prednisolone and prednisolone+L-NAME treated rats had significantly lower ALP and osteocalcin levels than controls at 2 and 4 weeks, and significantly higher levels of Rat-Laps than controls at 4 weeks. Prednisolone, L-NAME, and prednisolone+L-NAME produced a significant inhibition of bone accumulation and bone growth at all sites measured. Supplementation with L-arginine appeared to prevent the inhibition of bone growth and increase in bone resorption induced by prednisolone. These data would suggest, for the first time, that supplementation

  8. Bone turnover in malnourished children.

    PubMed

    Branca, F; Robins, S P; Ferro-Luzzi, A; Golden, M H

    Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of collagen that are located mainly in bone and cartilage. When bone matrix is resorbed these cross-links are quantitatively excreted in the urine and therefore represent specific markers. We have measured the urinary excretion rate of PYD and DPD in 46 severely malnourished boys to assess their skeletal turnover and to relate this to their subsequent rate of growth. The children were aged 13 months (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4 (0.8) Z-score. PYD excretion when malnourished and after "recovery" was 11.2 (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3) nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross-links did not change with recovery. These data show that cartilage and bone turnover is much lower in the malnourished than in the recovered child. There was no difference in the degree of depression of turnover between the children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during recovery was significantly related to cross-link excretion, age, and weight-for-height on admission. These three factors accounted for 44% of the variance in the height velocity of the children. PYD and DPD excretion rate could be used to assess therapeutic interventions designed to alleviate stunting. PMID:1361595

  9. Chronic erythroid hyperplasia and accelerated bone turnover.

    PubMed

    Weinstein, R S; Lutcher, C L

    Bone atrophy is generally thought to be the etiology of the decreased skeletal mass and fractures found in patients with ineffective hematopoiesis and associated erythroid hyperplasia. A bone biopsy from a patient with chronic erythroid hyperplasia and diffuse cortical osteopenia revealed a normal trabecular bone volume, excess osteoid, numerous osteoblasts, and increased osteoclastic resorptive surface. The increased fractional labeled surfaces and widely spaced double tetracycline labels indicated accelerated bone turnover, despite demonstrable iron deposits at the calcification front and cement lines and a low serum level of 25-hydroxyvitamin D. The relationship between the expanded marrow space and trabecular bone suggests that local marrow factors may be responsible for the rapid bone remodeling.

  10. [Clinical evaluation for abnormalities of bone and mineral metabolism in ESKD].

    PubMed

    Yano, Shozo

    2016-09-01

    In patients with end-stage kidney disease(ESKD), bone disorders are characterized by cortical porosity and by abnormal turnover of bone metabolism:adynamic(low turnover)bone disease and high turnover bone due to various degrees of secondary hyperparathyroidism. Abnormalities of bone metabolism are generally assessed by interview, X-ray, bone mineral density(BMD), serum phosphorus, calcium, and parathyroid hormone levels, and bone metabolic markers. Recent clinical studies have demonstrated that high turnover bone representing elevated bone metabolic markers and low BMD are independent risks of bone fractures as well as mortality among this population. Treatment of bone disorders in ESKD patients should be aiming at the normalization of mineral metabolism and the maintenance and/or improvement of BMD. PMID:27561341

  11. Bone turnover markers: use in osteoporosis.

    PubMed

    Naylor, Kim; Eastell, Richard

    2012-07-01

    Biochemical markers of bone turnover (bone turnover markers, BTMs) can be used to study changes in bone remodelling in osteoporosis. Investigators and clinicians should be aware of the appropriate sample collection and storage conditions for optimum measurements of these markers. Improvements in the variability of BTM measurements have resulted from the development of assays for automated analysers, and from international consensus regarding their use. Appropriate reference intervals should be used for the optimum interpretation of results. BTMs can provide information that is useful for the management of patients with osteoporosis, for both the initial clinical assessment and for guiding and monitoring of treatment. BTMs are clinically useful to determine possible causes of secondary osteoporosis by identifying patients with high bone turnover and rapid bone loss. In the follow-up of treatment response, BTM levels respond rapidly to both anabolic and antiresorptive treatments. BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose; they are also potentially useful as surrogate biomarkers for fracture.

  12. Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats.

    PubMed

    Hirata, Junya; Hirai, Kazuya; Asai, Hirobumi; Matsumoto, Chiho; Inada, Masaki; Miyaura, Chisato; Yamato, Hideyuki; Watanabe-Akanuma, Mie

    2015-10-01

    Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation-related parameters and bone resorption-related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation-related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH. PMID:26112820

  13. Association of bone mineral density with biochemical markers of bone turnover in hemodialysis children

    PubMed Central

    Hajizadeh, Niloofar; Mehrkash, Mehryar; Fahimi, Daryoosh; Qorbani, Mostafa; Shafa, Nina

    2016-01-01

    Introduction: Although some descriptive and cross-sectional studies have been reported about bone mass in chronic kidney disease (CKD) children, only a few studies investigated markers of bone turnover and the bone mass measurements. Objectives: The aim of this study was to evaluate the association between bone mineral density (BMD) and biochemical markers of bone turnover in hemodialysis (HD) children. Patients and Methods: The children who had received dialysis for at least the preceding 6‐month were included. BMD was measured for total body, the lumbar spine and the femoral neck and the blood samples were tested to assess biochemical bone turnover markers. Results: The study group was comprised of 27 patients with CKD, 9 males (33%) and 18 females (67%) with the mean±SD age of the subjects 14.9±4.5 years. Positive significant correlations of parathyroid hormone (PTH) with total body bone densitometry Z-score, lumbar spine and femoral neck Z-score(r=0.43, P=0.06; r=0.41, P=0.08 and r=0.45, P=0.05, respectively) was noted. In addition, positive significant correlations calcium and total body, lumbar spine and femoral neck Z-score (r=0.52, P=0.02; r=0.28, P=0.23 and r=0.36, P=0.12, respectively) was seen. Interestingly, a positive significant correlation between alkaline phosphatase (ALP) and lumbar spine Z-score was found (r=0.46, P=0.04), while the correlation of this parameter with total body and femoral neck Z-score was not significant (P>0.05). Conclusion: In our study, majority of patients with CKD had low level of BMD. In addition, lower levels of calcium (Ca), phosphorus (P), PTH and 25 (OH) vitamins D in patients with abnormal BMD Z-scores were detected. PMID:27689118

  14. Association of bone mineral density with biochemical markers of bone turnover in hemodialysis children

    PubMed Central

    Hajizadeh, Niloofar; Mehrkash, Mehryar; Fahimi, Daryoosh; Qorbani, Mostafa; Shafa, Nina

    2016-01-01

    Introduction: Although some descriptive and cross-sectional studies have been reported about bone mass in chronic kidney disease (CKD) children, only a few studies investigated markers of bone turnover and the bone mass measurements. Objectives: The aim of this study was to evaluate the association between bone mineral density (BMD) and biochemical markers of bone turnover in hemodialysis (HD) children. Patients and Methods: The children who had received dialysis for at least the preceding 6‐month were included. BMD was measured for total body, the lumbar spine and the femoral neck and the blood samples were tested to assess biochemical bone turnover markers. Results: The study group was comprised of 27 patients with CKD, 9 males (33%) and 18 females (67%) with the mean±SD age of the subjects 14.9±4.5 years. Positive significant correlations of parathyroid hormone (PTH) with total body bone densitometry Z-score, lumbar spine and femoral neck Z-score(r=0.43, P=0.06; r=0.41, P=0.08 and r=0.45, P=0.05, respectively) was noted. In addition, positive significant correlations calcium and total body, lumbar spine and femoral neck Z-score (r=0.52, P=0.02; r=0.28, P=0.23 and r=0.36, P=0.12, respectively) was seen. Interestingly, a positive significant correlation between alkaline phosphatase (ALP) and lumbar spine Z-score was found (r=0.46, P=0.04), while the correlation of this parameter with total body and femoral neck Z-score was not significant (P>0.05). Conclusion: In our study, majority of patients with CKD had low level of BMD. In addition, lower levels of calcium (Ca), phosphorus (P), PTH and 25 (OH) vitamins D in patients with abnormal BMD Z-scores were detected.

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

    PubMed

    Hamed, Sherifa A

    2016-01-01

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

  16. Bone Turnover Markers and Osteoprotegerin in Uncomplicated Pregnancy

    PubMed Central

    Styczynska, Hanna; Sobanska, Izabela; Pater, Agnieszka; Pollak, Joanna; Mankowska, Aneta

    2009-01-01

    Although calcium metabolism during pregnancy is well described the mechanisms involved in bone metabolism are not quite clear. Increase of osteoprotegerin (OPG) with elevated bone turnover is supposed to be a homeostatic mechanism limiting bone loss. The aim of the study was to assess bone turnover in pregnancy in relation to serum osteoprotegerin level. Osteocalcin (OC), beta-crosslaps (CTx), OPG, vitamin 25 OH D3, parathormone (PTH), and calcium (Ca) were determined in 30 healthy women at 1st and at 3rd trimester of pregnancy and 27 healthy age-matched non pregnant women. In pregnant women average OPG, CTx and serum calcium concentrations were found to be highly elevated. During pregnancy OPG and bone resorption significantly rised whereas only slight increase in OC level was found with concomitant decrease in serum calcium. OPG correlated positively with OC and Ca only at 1st trimester. Serum CTx and OPG at 1st trimester seemed to be the only parameters to differentiate between elevated and normal bone turnover among pregnant women. In pregnancy bone turnover increases mainly due to enhanced bone resorption. The determination of osteocalcin at the beginning of pregnancy seems to be of limited clinical use, whereas measuring bone resorption markers such as CTx and/or osteoprotegerin may have a good predictive value for later pregnancy-associated bone loss.

  17. [Bone turnover and mineralization in patients with kidney failure].

    PubMed

    James, Junichiro

    2016-09-01

    Bone remodeling is a device to accomplish "the buffering of the extracellular fluid mineral", which is one of the two major physiological functions of bone. Bone turnover is a term to express the frequency of bone remodeling, and its last step is calcification. When remodeling is induced, at first a large amount of mineral is released from bone to extracellular fluid transiently, and thereafter mineral is slowly and steadily drawn into bone. The extracellular minerals, especially calcium, are maintained by this repetition. When kidney is injured, bone turnover takes a wide spectrum from remarkably high cases to low cases. Primary calcification also shows marked individual differences. The classic renal bone diseases 5 classification clearly categorizes these disease condition, which is synonymous with renal osteodystrophy today. PMID:27561340

  18. Bone marrow ablation demonstrates that estrogen plays an important role in osteogenesis and bone turnover via an antioxidative mechanism.

    PubMed

    Shi, Chunmin; Wu, Jun; Yan, Quanquan; Wang, Rong; Miao, Dengshun

    2015-10-01

    To assess the effect of estrogen deficiency on osteogenesis and bone turnover in vivo, 8-week-old mice were sham-operated or bilaterally ovariectomized (OVX), and after 8 weeks, mechanical bone marrow ablation (BMX) was performed and newly formed bone tissue was analyzed from 6 days to 2 weeks after BMX. Our results demonstrated that OVX mice following BMX displayed 2 reversed phase changes, one phase observed at 6 and 8 days after BMX delayed osteogenesis accompanied by a delay in osteoclastogenesis, and the other phase observed at 12 and 14 days after BMX increased osteoblastic activity and osteoclastic activity. Furthermore, we asked whether impaired osteogenesis caused by estrogen deficiency was associated with increased oxidative stress, and oxidative stress parameters were examined in bone tissue from sham-operated and OVX mice and OVX mice were administrated with antioxidant N-acetyl-l-cysteine (NAC) or vehicle after BMX. Results demonstrated that estrogen deficiency induced oxidative stress in mouse bone tissue with reduced antioxidase levels and activity, whereas NAC administration almost rescued the abnormalities in osteogenesis and bone turnover caused by OVX. Results from this study indicate that estrogen deficiency resulted in primarily impaired osteogenesis and subsequently accelerated bone turnover by increasing oxidative stress and oxidative stress promises to be an effective target in the process of treatment of postmenopausal osteoporosis. PMID:26036172

  19. Mice transgenic for HTLV-I LTR-tax exhibit tax expression in bone, skeletal alterations, and high bone turnover.

    PubMed

    Ruddle, N H; Li, C B; Horne, W C; Santiago, P; Troiano, N; Jay, G; Horowitz, M; Baron, R

    1993-11-01

    HTLV-I infection can result in adult T cell leukemia with accompanying hypercalcemia and increased bone resorption. A viral etiology has also been invoked for Paget's disease, a disease of high bone turnover. Delineation of pathogenetic mechanisms of viral-associated bone diseases has been impeded by the complexity of viral and host factors. In order to consider the relationship of HTLV-I infection to skeletal changes we have evaluated the role of a single viral gene in mice transgenic for HTLV-I tax under the control of the viral promoter. Tax mice exhibited severe skeletal abnormalities characterized by high bone turnover, increases in osteoblast and osteoclast numbers and activity, and myelofibrosis. These changes were apparent as early as two months of age. Tax mRNA and protein were highly expressed in bone but not in bone marrow nor in any other tissues except, as previously reported, salivary gland and neurofibromas when they did develop. Within bone, tax protein was detected in only two cell types, mature osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. These observations suggest that local expression of the tax gene, which encodes a viral regulatory protein known to influence host gene expression, can induce within the bone environment marked changes in bone cell activity, resulting in profound skeletal alterations.

  20. Artificial Gravity: Effects on Bone Turnover

    NASA Technical Reports Server (NTRS)

    Heer, M.; Zwart, S /R.; Baecker, N.; Smith, S. M.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

  1. Bone Growth and Turnover in Progesterone Receptor Knockout Mice

    PubMed Central

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jamie C.; Waters, Katrina M.; Lydon, John P.; O’Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-01-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence. PMID:18276762

  2. Bone growth and turnover in progesterone receptor knockout mice.

    SciTech Connect

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  3. Bone Matrix Turnover And Balance In Vitro

    PubMed Central

    Flanagan, Barry; Nichols, George

    1969-01-01

    Labeled proline from incubation media has been shown to be incorporated into living bone matrix collagen in vitro. Hydroxyproline is released from fresh bone slices in similar systems in a characteristic curve against time. This hydroxyproline is derived from three distinct sources, each of which may be separately quantitated. Part of the total represents passive solubilization of matrix collagen, part is derived from new synthesis of soluble collagen occurring in vitro, and the remainder is released by cell-mediated resorptive action. The latter two processes are linear with time up to 8 hr; the former decays to zero at about 2 hr. Consequently, rates of collagen synthesis and of new collagen deposition and resorption can be quantitated simultaneously in the same system. The ability to measure these parameters of bone collagen metabolism provides methods both for the accurate evaluation of organic matrix resorption in vitro and for the accurate measurement of rates of collagen synthesis and collagen deposition. The application of the method is illustrated using parathyroid hormone and thyrocalcitonin. Parathyroid hormone diminishes collagen synthesis and stimulates collagen resorption. It reduces slightly the deposition of newly formed collagen in stable matrix. The net effect of these changes is to produce a marked negative balance. It does not significantly affect the solubility of matrix collagen. Thyrocalcitonin does not affect collagen synthesis or its deposition. It causes a marked fall in resorption rate. It has no effect on matrix collagen solubility. The net effect is to produce a marked positive balance of matrix collagen. Images PMID:5774102

  4. Second-generation antipsychotics and bone turnover in schizophrenia.

    PubMed

    Okita, Kyoji; Kanahara, Nobuhisa; Nishimura, Motoi; Yoshida, Toshihiko; Yasui-Furukori, Norio; Niitsu, Tomihisa; Yoshida, Taisuke; Ishikawa, Masatomo; Kimura, Hiroshi; Nomura, Fumio; Iyo, Masaomi

    2014-08-01

    Accumulating evidence suggests that patients with schizophrenia are exposed to a high risk of osteoporosis/osteopenia caused by long-term antipsychotic treatment. The degree of bone mineral density (BMD) loss that a given antipsychotic may cause is not known. Examinations using a bone turnover marker may more accurately predict the ongoing bone states in psychiatric patients. We measured prolactin, estradiol, testosterone, and bone resorption marker (TRACP-5b) levels in 167 patients with schizophrenia and 60 normal controls. The patients showed significantly higher levels of prolactin and lower levels of TRACP-5b compared to the controls. Moreover, prolactin was negatively correlated with estradiol and testosterone in the group of all male subjects and the male patients. TRACP-5b was positively correlated with prolactin in the female patients and negatively correlated with estradiol in the group of all female subjects. The results show that the bone resorption rate was rather attenuated in the patients compared to the normal controls, suggesting a complicated etiology of BMD loss in schizophrenia patients. Several meaningful correlations between key factors in this study confirmed that hyperprolactinemia induced the suppression of sex hormones, and possibly led to the higher bone turnover. These results indicate that measurement of the resorption marker TRACP-5b might be useful to clarify the pathology of BMD loss. PMID:24888527

  5. Biochemical markers of bone turnover in osteonecrosis of the jaw in patients with osteoporosis and advanced cancer involving the bone.

    PubMed

    Cremers, Serge; Farooki, Azeez

    2011-02-01

    Osteonecrosis of the jaw (ONJ) has been hypothesized to result in part from a relative "oversuppression" of normal physiologic bone remodeling at the jaw brought about by bisphosphonate therapy. Biochemical markers of bone turnover give readily measurable information on integrated systemic bone remodeling activity, as measured by blood and urine assays. The intra- and interassay variability of most currently available assays is less than 10%, although many biological factors can influence levels of bone turnover markers. Bone turnover markers may show a dynamic response to changes in clinical status for a given disease state. Elevated bone turnover on and off treatment appears to predict adverse clinical consequences in both osteoporosis and cancer. Bisphosphonates effectively decrease the level of the bone turnover markers with a pattern depending on the marker, the bisphosphonate, the dose regimen, and the disease. However, long-term (10-year) treatment with bisphosphonates for osteoporosis does not appear to result in a progressive decline in bone turnover, as measured by markers and bone histology. The effects of long-term (greater than 2 years) treatment with monthly intravenous bisphosphonates on bone turnover markers in cancer are unknown. Discontinuation of bisphosphonate therapy appears to allow a recovery of bone turnover, which is related to the bisphosphonate, the duration of therapy, and the disease being treated. At this time, data are limited with regard to the utility of bone turnover markers in assessing risk for ONJ and whether bone marker-directed bisphosphonate holidays would be useful in prevention or treatment of ONJ.

  6. Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups

    PubMed Central

    Redmond, Jean; Fulford, Anthony J.; Jarjou, Landing; Zhou, Bo; Prentice, Ann

    2016-01-01

    Context: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role. Objective: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH. Participants: Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country). Interventions: Observational study with sample collection every 4 hours for 24 hours. Main Outcomes: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH. Results: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group. Conclusions: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss. PMID:27294326

  7. FSH Suppression Does Not Affect Bone Turnover in Eugonadal Men

    PubMed Central

    Finkelstein, Joel S.; Lee, Hang; Leder, Benjamin Z.

    2014-01-01

    Context: In vitro and animal studies have reported conflicting results regarding an independent role for FSH in the regulation of bone turnover. Objective: Our objective was to test the hypothesis that suppressing serum FSH while holding serum gonadal steroid levels stable in the eugonadal range will affect biochemical markers of bone metabolism in healthy men. Participants, Design, and Setting: Eugonadal men aged 20 to 50 years participated in this randomized controlled trial at a tertiary care academic teaching hospital. Interventions: Participants received monthly GnRH analog injections to suppress FSH secretion plus daily topical testosterone gel in prespecified doses (intervention group). Controls received matching placebos (control group). Subjects in the intervention group were individually matched with subjects in the control group to ensure that the mean testosterone and estradiol levels (measured every 4 weeks during the 16-week study period) in the 2 groups were similar. Main Outcome Measures: Biochemical markers of bone resorption (serum N-terminal telopeptide and C-terminal telopeptide), bone formation (serum osteocalcin), and FSH were measured at baseline and after 16 weeks of treatment. Results: Serum FSH declined by 2% in the control group and by 60% in the intervention group (P < .0001 for the between-group difference). Despite the substantial suppression of serum FSH in the intervention group, serum N-terminal telopeptide, C-terminal telopeptide, and osteocalcin did not change in the intervention group, nor were any between-group differences observed. Conclusion: When gonadal steroid levels are held constant, short-to midterm suppression of FSH does not affect bone turnover in men. FSH does not appear to be a significant regulator of bone metabolism in eugonadal men. PMID:24646101

  8. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    NASA Technical Reports Server (NTRS)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  9. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    PubMed Central

    Westerlind, Kim C.; Wronski, Thomas J.; Ritman, Erik L.; Luo, Zong-Ping; An, Kai-Nan; Bell, Norman H.; Turner, Russell T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain. PMID:9108129

  10. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    PubMed

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

  11. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    PubMed

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover. PMID:24126694

  12. RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

    PubMed

    Konca Degertekin, Ceyla; Turhan Iyidir, Ozlem; Aktas Yılmaz, Banu; Elbeg, Sehri; Pasaoglu, Ozge Tugce; Pasaoglu, Hatice; Cakır, Nuri; Arslan, Metin

    2016-10-01

    Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism. PMID:27328677

  13. RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

    PubMed

    Konca Degertekin, Ceyla; Turhan Iyidir, Ozlem; Aktas Yılmaz, Banu; Elbeg, Sehri; Pasaoglu, Ozge Tugce; Pasaoglu, Hatice; Cakır, Nuri; Arslan, Metin

    2016-10-01

    Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

  14. Sclerostin as a novel marker of bone turnover in athletes

    PubMed Central

    Jóźków, P; Mędraś, M; Majda, M; Słowińska-Lisowska, M

    2016-01-01

    Sclerostin is a protein secreted by osteocytes that acts as an inhibitor of bone formation. It has been shown that physical activity affects sclerostin concentration and thus bone remodelling. The aim of the study was to evaluate serum concentrations of sclerostin, selected bone turnover markers (PTH, P1NP), 25(OH)D3 and the intake of calcium and vitamin D in physically active versus sedentary men. A total of 59 healthy men aged 17-37 were enrolled in the study (43 athletes and 16 non-athletes). The mean sclerostin concentration in the group of athletes (A) was significantly higher than in non-athletes (NA) (35.3±8.9 vs 28.0±5.6 pmol·l-1, p= 0.004). A compared with NA had higher concentrations of P1NP (145.6±77.5 vs 61.2±22.3 ng·ml-1, p= <0.0001) and 25(OH)D3 (16.9±8.4 vs 10.3±4.3 ng·ml-1, p= 0.004) and lower concentrations of PTH (25.8±8.3 vs 38.2±11.5 pg·ml-1, p= <0.0001). Vitamin D deficiency was found in 77% of A and 100% of NA. A and NA had similar daily energy intake. They did not differ as to the intake of calcium and vitamin D. We observed a negative correlation between the serum concentrations of sclerostin and calcium in the studied subjects. Our results suggest that regular, long-lasting physical training may be associated with higher concentration of sclerostin. It seems that increased sclerostin is not related to other bone turnover markers (PTH, P1NP). PMID:26929475

  15. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats.

    PubMed

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei

    2012-06-01

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery.

  16. Bone GLA protein (BGP) levels and bone turnover in rheumatoid arthritis.

    PubMed

    Magaro, M; Altomonte, L; Mirone, L; Zoli, A; Corvino, G

    1989-06-01

    Bone GLA protein (BGP) and other biochemical indices of bone turnover were measured in 42 female patients with rheumatoid arthritis (RA) and in a group of normal subjects matched for sex and age. Mean serum BGP concentrations were significantly higher in patients with active arthritis than in patients with mild activity (p less than 0.01) and controls (p less than 0.01). No significant difference was found in serum BGP levels and in other parameters of bone turnover when the patients were stratified according to functional class or duration of disease. There was a correlation between BGP and alkaline phosphatase levels only in RA patients with high activity of disease. Our data suggest an accelerated bone turnover in patients with active RA. We infer that in such patients the impairment of bone metabolism is a determinant of RA-associated osteopenia. Disease activity rather than functional impairment or duration of arthritis should be regarded as a factor in the bone loss of RA.

  17. A 12-month prospective study of the relationship between stress fractures and bone turnover in athletes.

    PubMed

    Bennell, K L; Malcolm, S A; Brukner, P D; Green, R M; Hopper, J L; Wark, J D; Ebeling, P R

    1998-07-01

    Bone remodeling may be involved in the pathogenesis of stress fractures in athletes. We conducted a 12-month prospective study to evaluate bone turnover in 46 female and 49 male track and field athletes aged 17-26 years (mean age 20.3; SD 2.0) 20 of whom developed a stress fracture. Baseline levels of bone turnover were evaluated in all athletes and monthly bone turnover levels were evaluated in a subset consisting of the 20 athletes who sustained a stress fracture and a matched comparison group who did not sustain a stress fracture. Bone formation was assessed using serum osteocalcin (OC) measured by human immunoradiometric assay and bone resorption by urinary excretion of pyridinium cross-links (Pyr and D-Pyr); high performance liquid chromatography and N-telopeptides of type 1 collagen (NTx) using ELISA assay. Athletes who developed stress fractures had similar baseline levels of bone turnover compared with their nonstress fracture counterparts (P > 0.10). Results of serial measurements showed no differences in average levels of Pyr, D-Pyr, or OC in those who developed stress fractures (P = 0.10) compared with the control group. In the athletes with stress fractures, there was also no difference in bone turnover levels prior to or following the onset of bony pain. Our results show that single and multiple measurements of bone turnover are not clinically useful in predicting the likelihood of stress fractures in athletes. Furthermore, there were no consistent temporal changes in bone turnover associated with stress fracture development. However, our results do not negate the possible pathogenetic role of local changes in bone remodeling at stress fracture sites, given the high biological variability of bone turnover markers and the fact that levels of bone turnover reflect the integration of all bone remodeling throughout the skeleton. PMID:9632851

  18. Lack of seasonal variation in bone mass and biochemical estimates of bone turnover

    SciTech Connect

    Overgaard, K.; Nilas, L.; Johansen, J.S.; Christiansen, C.

    1988-01-01

    Three previous studies have indicated a seasonal variation in bone mineral content, with values during the summer being 1.7% to 7.5% higher than during the winter. We have examined the seasonal influence on both bone mass, biochemical estimates of bone turnover and vitamin D metabolites in 86 healthy women, aged 29-53 years. All participants were followed up for 2 years with examinations every 6 weeks or 3 months. Bone mineral content in the proximal and distal part of the forearm (single photon absorptiometry) did not reveal any significant seasonal variation, whereas bone mineral density of the lumbar spine (dual photon absorptiometry) indicated that the highest values occurred in winter. None of the biochemical parameters showed any statistically significant cyclical changes. Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D3 showed a highly significant seasonal variation, whereas the serum 1,25-dihydroxyvitamin D concentration was virtually unchanged. We conclude that seasonal variation in bone mineral content and bone turnover should not be taken into account when interpreting data from longitudinal studies of healthy pre- and postmenopausal women on a sufficient vitamin D nutriture.

  19. Assessment of age and risk factors on bone density and bone turnover in healthy premenopausal women.

    PubMed

    Hansen, M A

    1994-05-01

    The influence of age and risk factors on bone density and bone turnover was evaluated in 249 healthy premenopausal women. Risk factors were assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of caffeine, smoking habits and physical activity). Bone mineral density (BMD) measurements were obtained in the distal forearm, the lumbar spine and the proximal femur. Bone turnover were assessed by plasma bone Gla proteins (pBGP) and fasting urinary hydroxyproline corrected for creatinine (fUHPr/Cr). Peak bone density seems to be achieved before the age of 30 years, whereafter we found no appreciable bone loss at any skeletal site. Accordingly, the levels of pBGP and fUHPr/Cr were increased before the age of 30, whereafter the values stabilized at a lower level. A dairy calcium intake above 660 mg/day significantly increased BMD in the spine and proximal femur by 3%-5%. Physical activity alone had no influence on BMD, but in combination with calcium intake an additive effect was observed. Women who had an active lifestyle (corresponding to at least 1 h of daily walking) and a dairy calcium intake above 660 mg/day had a 3%-7% increase in BMD compared with more sedentary women with a calcium intake below this limit. Vitamin D supplements, caffeine, smoking and reproductive history did not consistently influence BMD or bone turnover. Only pBGP was selectively reduced by smoking and current use of oral contraceptives, respectively. We conclude that there is no appreciable change in BMD before the menopause once skeletal maturity has been reached.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Bone turnover in prolonged critical illness: effect of vitamin D.

    PubMed

    Van den Berghe, Greet; Van Roosbroeck, David; Vanhove, Philippe; Wouters, Pieter J; De Pourcq, Lutgart; Bouillon, Roger

    2003-10-01

    In prolonged critical illness, increased bone resorption and osteoblast dysfunction have been reported facing low 25 hydroxy vitamin D [25(OH)D] concentrations. The current study investigates the extent to which lack of nutritional vitamin D and time in intensive care contribute to bone loss in the critically ill. Prolonged critically ill patients (n = 22) were compared with matched controls and then randomized to daily vitamin D supplement of either +/- 200 IU (low dose) or +/- 500 IU (high dose). At intensive care admission, serum concentrations of 25(OH)D, 1,25 dihydroxyvitamin D(3), vitamin D-binding protein, ionized calcium, IL-1, and soluble IL-6-receptor were low, and PTH was normal. Circulating type-I collagen propeptides were high, alkaline phosphatase was normal, and osteocalcin was low. Bone resorption markers [(carboxy terminal cross-linked telopeptide of type I collagen (betaCTX), pyridinoline, deoxypyridinoline (DPD)] were 6-fold increased. Serum C-reactive protein (CRP) was 40-fold, IL-6 400-fold, TNFalpha levels 5-fold, and osteoprotegerin concentrations 3-fold higher than in controls. Soluble receptor activator of nuclear factor kappaB ligand was undetectable. High-dose vitamin D only slightly increased circulating 25 hydroxy vitamin D (P < 0.05), but 1,25 dihydroxyvitamin D(3) was unaltered. High-dose vitamin D slightly increased serum osteocalcin (P < 0.05) and decreased carboxy terminal propeptide type-I collagen (P < 0.05) but did not affect other bone turnover markers. Bone-specific alkaline phosphatase, urinary pyridinoline and DPD, and serum betaCTX markedly increased with time (P < 0.01). Circulating CRP and IL-6 decreased with time, whereas TNFalpha and IL-1 remained unaltered. The fall in CRP and IL-6 was more pronounced with the high- than low-dose vitamin D (P < 0.05). Except for a mirroring of betaCTX rise by a fall in osteoprotegerin, cytokines were unrelated to the progressively aggravating bone resorption. In conclusion, prolonged

  1. Bone turnover in passive smoking female rat: relationships to change in bone mineral density

    PubMed Central

    2011-01-01

    Background Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat. Methods Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats. Results BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats. Conclusion Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat. PMID:21663694

  2. Dental and bone abnormalities in patients with familial polyposis coli.

    PubMed

    Carl, W; Herrera, L

    1987-01-01

    Dental and bone abnormalities of the maxilla and mandible are present in approximately 80% of patients with familial polyposis coli. The dental abnormalities include impacted teeth (other than third molars), supernumerary teeth, congenitally missing teeth, fused roots of first and second molars, and unusually long and tapered roots of posterior teeth. The bone lesions consist mostly of osteomas, either isolated or in clusters, in the maxilla and mandible or of exostoses with lateral and/or lingual extensions. Since dental and bone abnormalities are already present early in life there is a strong suggestion that they may be used as diagnostic features in the recognition of familial polyposis coli.

  3. [Clinical usefulness of bone turnover markers in the management of osteoporosis].

    PubMed

    Yano, Shozo

    2013-09-01

    Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future. PMID:24369600

  4. Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

    PubMed

    Ok, Ercan; Asci, Gulay; Bayraktaroglu, Selen; Toz, Huseyin; Ozkahya, Mehmet; Yilmaz, Mumtaz; Kircelli, Fatih; Sevinc Ok, Ebru; Ceylan, Naim; Duman, Soner; Cirit, Mustafa; Monier-Faugere, Marie-Claude; Malluche, Hartmut H

    2016-08-01

    Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

  5. Biological and within-subject variability of calcium kinetics and biochemical markers of bone turnover

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone loss is a critical issue during space flight. Evaluating changes in bone and calcium metabolism in astronauts often requires multiple preflight data collection points. Bone turnover and calcium kinetics were measured in 4 healthy subjects, and the day-to-day and between-subject variations were ...

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

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  7. Determinants of bone turnover markers in healthy premenopausal women.

    PubMed

    Adami, Silvano; Bianchi, Gerolamo; Brandi, Maria Luisa; Giannini, Sandro; Ortolani, Sergio; DiMunno, Ombretta; Frediani, Bruno; Rossini, Maurizio

    2008-05-01

    Bone turnover markers (BTMs) are widely used for the management of osteoporosis, and the premenopausal reference range is the target value for the treatment of postmenopausal osteoporosis with antiresorbing agents. Three serum BTMs (serum C-telopeptide of type I collagen [CTX], osteocalcin [OC], and N-terminal propeptide of type I procollagen [P1NP]), serum calcium, creatinine, phosphate, magnesium, and follicle-stimulating hormone (FSH) were measured in 638 healthy premenopausal women aged 20-50 years. In 83 women on the contraceptive pill (CP), the levels of the three BTMs adjusted for all confounding factors were 14-26% lower (P < 0.005) than in non-CP users. In 18 women considered perimenopausal for serum FSH levels >30 IU/mL despite having regular menses, BTM levels were significantly higher than in age-matched women. This group of subjects and the women on the CP were excluded from further analysis. The three BTMs significantly decreased with advancing age and were negatively and independently correlated with body mass index (P < 0.001) and serum phosphate. In conclusion, we confirm that CP use is associated with significantly lower BTM values. An increase in BTM concentrations can be observed in perimenopausal women, i.e., women with normal menses but FSH levels >30 IU/mL. BTMs decrease substantially with advancing age, and this appears to be associated with changes in body weight and serum phosphate. New normative ranges for serum OC, CTX, and P1NP were identified; and our findings in general impose a redefinition of the criteria for establishing the normal ranges for BTMs.

  8. Gonadal steroid–dependent effects on bone turnover and bone mineral density in men

    PubMed Central

    Finkelstein, Joel S.; Lee, Hang; Leder, Benjamin Z.; Goldstein, David W.; Hahn, Christopher W.; Hirsch, Sarah C.; Linker, Alex; Perros, Nicholas; Servais, Andrew B.; Taylor, Alexander P.; Webb, Matthew L.; Youngner, Jonathan M.; Yu, Elaine W.

    2016-01-01

    BACKGROUND. Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS. One hundred ninety-eight healthy men, ages 20–50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. RESULTS. As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS. Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. TRIAL REGISTRATION. ClinicalTrials.gov, NCT00114114

  9. [Clinical usefulness of bone turnover markers with the treatment of osteoporosis].

    PubMed

    Miura, Masakazu

    2014-03-01

    Bone turnover markers (BTMs) are known the bone formation marker, the bone resorption marker and the bone matrix related marker participating in bone quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the reevaluation of MSC, and the influence of renal function on BTMs, respectively. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the measurement of ucOC and bone resorption markers when selecting drug treatment in osteoporosis, and the evaluation of therapeutic effects of bone antiresorption drugs using bone resorption markers were corrected newly in the guideline 2012 edition. It is thought that the BTMs have been continued more developing as essential biomarker with the treatment of osteoporosis in the future.

  10. Bone mass and bone turnover in power athletes, endurance athletes, and controls: a 12-month longitudinal study.

    PubMed

    Bennell, K L; Malcolm, S A; Khan, K M; Thomas, S A; Reid, S J; Brukner, P D; Ebeling, P R; Wark, J D

    1997-05-01

    Strain magnitude may be more important than the number of loading cycles in controlling bone adaptation to loading. To test this hypothesis, we performed a 12 month longitudinal cohort study comparing bone mass and bone turnover in elite and subelite track and field athletes and less active controls. The cohort comprised 50 power athletes (sprinters, jumpers, hurdlers, multievent athletes; 23 women, 27 men), 61 endurance athletes (middle-distance runners, distance runners; 30 women, 31 men), and 55 nonathlete controls (28 women, 27 men) aged 17-26 years. Total bone mineral content (BMC), regional bone mineral density (BMD), and soft tissue composition were measured by dual-energy X-ray absorptiometry. Bone turnover was assessed by serum osteocalcin (human immunoradiometric assay) indicative of bone formation, and urinary pyridinium crosslinks (high-performance liquid chromatography) indicative of bone resorption. Questionnaires quantified menstrual, dietary and physical activity characteristics. Baseline results showed that power athletes had higher regional BMD at lower limb, lumbar spine, and upper limb sites compared with controls (p < 0.05). Endurance athletes had higher BMD than controls in lower limb sites only (p < 0.05). Maximal differences in BMD between athletes and controls were noted at sites loaded by exercise. Male and female power athletes had greater bone density at the lumbar spine than endurance athletes. Over the 12 months, both athletes and controls showed modest but significant increases in total body BMC and femur BMD (p < 0.001). Changes in bone density were independent of exercise status except at the lumbar spine. At this site, power athletes gained significantly more bone density than the other groups. Levels of bone formation were not elevated in athletes and levels of bone turnover were not predictive of subsequent changes in bone mass. Our results provide further support for the concept that bone response to mechanical loading depends

  11. High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease

    PubMed Central

    Lau, Wei Ling; Linnes, Michael; Chu, Emily Y.; Foster, Brian L.; Bartley, Bryan A.; Somerman, Martha J.; Giachelli, Cecilia M.

    2013-01-01

    Background Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic syndrome characterized by imbalances in mineral homeostasis, renal osteodystrophy (ROD) and ectopic calcification. The mechanisms underlying this syndrome in individuals with chronic kidney disease (CKD) are not yet clear. Methods We examined the effect of normal phosphate (NP) or high phosphate (HP) feeding in the setting of CKD on bone pathology, serum biochemistry and vascular calcification in calcification-prone dilute brown non-agouti (DBA/2) mice. Results In both NP and HP-fed CKD mice, elevated serum parathyroid hormone and alkaline phosphatase (ALP) levels were observed, but serum phosphorus levels were equivalent compared with sham controls. CKD mice on NP diet showed trabecular alterations in the long bone consistent with high–turnover ROD, including increased trabecular number with abundant osteoblasts and osteoclasts. Despite trabecular bone and serum biochemical changes, CKD/NP mice did not develop vascular calcification. In contrast, CKD/HP mice developed arterial medial calcification (AMC), more severe trabecular bone alterations and cortical bone abnormalities that included decreased cortical thickness and density, and increased cortical porosity. Cortical bone porosity and trabecular number strongly correlated with the degree of aortic calcification. Conclusions HP feeding was required to induce the full spectrum of CKD-MBD symptoms in CKD mice. PMID:23045434

  12. miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis.

    PubMed

    Valencia, Karmele; Martín-Fernández, Marta; Zandueta, Carolina; Ormazábal, Cristina; Martínez-Canarias, Susana; Bandrés, Eva; de la Piedra, Concepción; Lecanda, Fernando

    2013-01-01

    Recent evidence suggests that miRNAs could be used as serum markers in a variety of normal and pathological conditions. In this study, we aimed to identify novel miRNAs associated with skeletal metastatic disease in a preclinical model of lung cancer bone metastasis. We assessed the validity of these miRNAs as reliable serum biochemical markers to monitor the extent of disease and response to treatment in comparison to imaging techniques and standard biochemical markers of bone turnover. Using a murine model of human lung cancer bone metastasis after zoledronic acid (ZA) treatment, PINP (procollagen I amino-terminal propeptide) was the only marker that exhibited a strong correlation with osteolytic lesions and tumor burden at early and late stages of bone colonization. In contrast, BGP (osteocalcin) and CTX (carboxyterminal telopeptide) demonstrated a strong correlation only at late stages. We performed qPCR based screening of a panel of 380 human miRNAs and quantified bone metastatic burden using micro-CT scans, X-rays and bioluminescence imaging. Interestingly, levels of miR-326 strongly associated with tumor burden and PINP in vehicle-treated animals, whereas no association was found in ZA-treated animals. Only miR-193 was associated with biochemical markers PINP, BGP and CTX in ZA-treated animals. Consistently, miR-326 and PINP demonstrated a strong correlation with tumor burden. Our findings, taken together, indicate that miR-326 could potentially serve as a novel biochemical marker for monitoring bone metastatic progression.

  13. Triple-phase bone image abnormalities in Lyme arthritis

    SciTech Connect

    Brown, S.J.; Dadparvar, S.; Slizofski, W.J.; Glab, L.B.; Burger, M. )

    1989-10-01

    Arthritis is a frequent manifestation of Lyme disease. Limited triple-phase Tc-99m MDP bone imaging of the wrists and hands with delayed whole-body images was performed in a patient with Lyme arthritis. This demonstrated abnormal joint uptake in the wrists and hands in all three phases, with increased activity seen in other affected joints on delayed whole-body images. These findings are nonspecific and have been previously described in a variety of rheumatologic conditions, but not in Lyme disease. Lyme disease should be considered in the differential diagnosis of articular and periarticular bone scan abnormalities.

  14. The osteocyte: key player in regulating bone turnover

    PubMed Central

    Goldring, Steven R

    2015-01-01

    Osteocytes are the most abundant cell type in bone and are distributed throughout the mineralised bone matrix forming an interconnected network that ideally positions them to sense and to respond to local biomechanical and systemic stimuli to regulate bone remodelling and adaptation. The adaptive process is dependent on the coordinated activity of osteoclasts and osteoblasts that form a so called bone multicellular unit that remodels cortical and trabecular bone through a process of osteoclast-mediated bone resorption, followed by a phase of bone formation mediated by osteoblasts. Osteocytes mediate their effects on bone remodelling via both cell–cell interactions with osteoclasts and osteoblasts, but also via signaling through the release of soluble mediators. The remodelling process provides a mechanism for adapting the skeleton to local biomechanical factors and systemic hormonal influences and for replacing bone that has undergone damage from repetitive mechanical loading. PMID:26557372

  15. Serum phosphorus adds to value of serum parathyroid hormone for assessment of bone turnover in renal osteodystrophy.

    PubMed

    Gentry, Jimmy; Webb, Jonathan; Davenport, Daniel; Malluche, Hartmut H

    2016-07-01

    It is well-established that parathyroid hormone (PTH) correlates with the level of bone turnover in patients with chronic kidney disease stage 5D (CKD-5D). Hyperphosphatemia is a well-established complication of end-stage renal disease and is usually attributed to dietary intake. This study evaluates the relationship between serum phosphorus levels and bone turnover in patients with CKD-5D. 93 patients with CKD-5D from the Kentucky Bone Registry who had sequentially undergone anterior iliac bone biopsies were reviewed. Undecalcified bone sections were qualitatively assessed for turnover and placed into a group with low turnover and a group with non-low (normal/high) turnover. Results of PTH and phosphorus concentrations in blood drawn at the time of biopsies were compared between the groups. PTH and phosphorus levels were significantly higher in the non-low turnover group compared to the low turnover group. Cutoff levels for PTH and phosphorus were tested for predictive power of bone turnover. Both PTH and phosphorus correlated with turnover. Adding serum phosphorus to serum PTH enhanced predictive power of PTH for low turnover. The vast majority of patients with serum phosphorus levels ≥ 6.0 mg/dL had non-low turnover, while the majority of those with low turnover had phosphorus values < 6.0 mg/dL. Classification and regression-tree analysis showed that elevated serum phosphorus (> 6.2 mg/dL) in patients with PTH < 440 pg/mL was helpful in diagnosing nonlow turnover in this range of PTH. In patients with PTH ranges of 440 - 814 pg/mL, serum phosphorus levels > 4.55 mg/dL ruled out low turnover bone disease. This suggests that not only dietary intake but also bone affects serum phosphorus levels. PMID:27191663

  16. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.

    PubMed

    Wensel, Terri M; Iranikhah, Maryam M; Wilborn, Teresa W

    2011-05-01

    Osteoporosis is a degenerative bone disease affecting approximately 10 million American adults. Several options are available to prevent development of the disease or slow and even stop its progression. Nonpharmacologic measures include adequate intake of calcium and vitamin D, exercise, fall prevention, and avoidance of tobacco and excessive alcohol intake. Current drug therapy includes bisphosphonates, calcitonin, estrogen or hormone therapy, selective estrogen receptor modulators, and teriparatide. Denosumab, a receptor activator of nuclear factor-K B ligand (RANKL) inhibitor, was recently approved by the United States Food and Drug Administration for treatment of postmenopausal osteoporosis. Patients treated with denosumab experienced significant gains in bone mineral density, rapid reductions in markers of bone turnover, and a reduced risk for new vertebral fracture. Compared with placebo, patients receiving denosumab 60 mg subcutaneously once every 6 months experienced gains in bone mineral density of 6.5-11% when treated for 24-48 months. One trial demonstrated the superiority of denosumab compared with alendronate, but the differences were small. The most common adverse reactions to denosumab include back pain, pain in extremities, musculoskeletal pain, and cystitis. Serious, but rare, adverse reactions include the development of serious infections, dermatologic changes, and hypocalcemia. The recommended dosing of denosumab is 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Although beneficial effects on bone mineral density and fracture rate have been established in clinical trials, the risks associated with denosumab must be evaluated before therapy initiation. Of concern is the risk of infection, and denosumab should likely be avoided in patients taking immunosuppressive therapy or at high risk for infection. Therefore, bisphosphonates will likely remain as first-line therapy. Denosumab should be considered in

  17. Arthritis Induces Early Bone High Turnover, Structural Degradation and Mechanical Weakness

    PubMed Central

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    Background We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Methods Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. Results AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. Conclusions We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness. PMID:25617902

  18. Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

    PubMed

    Peng, Jia; Hui, Kang; Hao, Chen; Peng, Zhao; Gao, Qian Xing; Jin, Qi; Lei, Guo; Min, Jiang; Qi, Zhou; Bo, Chen; Dong, Qian Nian; Bing, Zhou Han; Jia, Xu You; Fu, Deng Lian

    2016-07-01

    It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation. PMID:27028715

  19. Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats.

    PubMed

    Zhang, Yan; Lai, Wan-Ping; Leung, Ping-Chung; Wu, Chun-Fu; Yao, Xin-Sheng; Wong, Man-Sau

    2006-02-01

    The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p<0.05, vs. OVX) and urinary deoxypyridinoline (p<0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p<0.01, vs. OVX), suppressing urinary Ca excretion (p<0.05, vs. OVX) as well as increasing bone calcium content (p<0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis.

  20. Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats.

    PubMed

    Zhang, Yan; Lai, Wan-Ping; Leung, Ping-Chung; Wu, Chun-Fu; Yao, Xin-Sheng; Wong, Man-Sau

    2006-02-01

    The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p<0.05, vs. OVX) and urinary deoxypyridinoline (p<0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p<0.01, vs. OVX), suppressing urinary Ca excretion (p<0.05, vs. OVX) as well as increasing bone calcium content (p<0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis. PMID:16462034

  1. Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency.

    PubMed

    Ahmad, A M; Hopkins, M T; Fraser, W D; Ooi, C G; Durham, B H; Vora, J P

    2003-02-01

    Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0

  2. Biochemical Markers of Bone Turnover Part I: Biochemistry and Variability

    PubMed Central

    2005-01-01

    With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies has markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. Part I of this article provides an overview of the basic biochemistry of bone markers, and sources of non-specific variability. Part II (to be published in a subsequent issue of this journal) will review the current evidence regarding the clinical use of biochemical markers of bone remodelling in metabolic and metastatic bone disease. PMID:16648882

  3. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women.

    PubMed

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47-78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  4. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women

    PubMed Central

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47–78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  5. Abnormal Canine Bone Development Associated with Hypergravity Exposure

    NASA Technical Reports Server (NTRS)

    Morgan, J. P.; Fisher, G. L.; McNeill, K. L.; Oyama, J.

    1979-01-01

    Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 x g and 2.6 x g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.

  6. 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 κβ (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

  7. Sclerostin levels and bone turnover markers in adolescents with anorexia nervosa and healthy adolescent girls.

    PubMed

    Faje, Alexander T; Fazeli, Pouneh K; Katzman, Debra K; Miller, Karen K; Breggia, Anne; Rosen, Clifford J; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita

    2012-09-01

    Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study objectives were to (i) assess associations of sclerostin with surrogate bone turnover markers in girls with AN and controls and (ii) examine effects of transdermal estradiol on sclerostin in AN. 69 girls (44 with AN and 25 normal-weight controls) 13-18 years old were studied at baseline. 22 AN girls were randomized to transdermal estradiol (plus cyclic medroxyprogesterone) or placebo in a double-blind study for 12 months. Sclerostin correlated positively with P1NP and CTX in controls (r=0.67 and 0.53, p=0.0002 and 0.005, respectively) but not in AN despite comparable levels at baseline. Changes in sclerostin over twelve months did not differ in girls randomized to estradiol or placebo. The relationship between sclerostin and bone turnover markers is disrupted in adolescent girls with AN. Despite an increase in BMD with estradiol administration in AN, estrogen does not impact sclerostin levels in this group.

  8. Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

    PubMed

    Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

    2016-01-15

    Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts.

  9. Bone Mineral Density and Bone Turnover Markers Under Bisphosphonate Therapy Used in the First Year After Liver Transplantation.

    PubMed

    Nowacka-Cieciura, Ewa; Sadowska, Anna; Pacholczyk, Marek; Chmura, Andrzej; Tronina, Olga; Durlik, Magdalena

    2016-01-01

    BACKGROUND Rapid bone loss occurs early after liver transplantation (Tx), concomitantly with intensified bone turnover. In the present study we investigated the effect of bisphosphonates (bisph) added to vitamin D (vitD) and calcium on bone mineral density (BMD) and bone biomarkers in liver graft recipients in the first posttransplant year. MATERIAL AND METHODS In 28 patients BMD was determined at the third month after Tx. In case of osteopenia (Tscore ≤-1.0) and no contraindications, oral bisph was started for 1 year (group BP, n=14); other patients served as controls (CON, n=14). The changes in BMD and biomarkers of bone formation were osteocalcin (OC), bone alkaline phosphatase (BAP), and resorption. Study endpoints were active isoform 5b of the tartrate-resistant acid phosphatase (TRACP5b), serum pyridinoline crosslinks (PYD), and urine excretion of deoxypyridinoline (Dpd) crosslinks. RESULTS In 19 (68%) patients, reduced BMD (T-score ≤1.0) was observed at baseline. The changes in lumbar BMD in BP and CON groups were 5.2% and 1.5%, respectively, not reaching statistical significance. Baseline PYD, Dpd/creat, and OC were elevated in all patients, indicating high bone turnover. We observed decrease in PYD and Dpd/creat in both groups; however, OC decreased only under bisph therapy. Increase in BAP was observed in the control group but not in the BP group. The changes in BAP and OC were significantly different (p<0.01). CONCLUSIONS Combining bisph with vitD and calcium is an effective bone- sparing strategy in liver transplant recipients in the first posttransplant year. Bisph more efficiently decreased the rate of bone turnover than vitD and calcium alone. PMID:27112626

  10. CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts

    PubMed Central

    Greenblatt, Matthew B.; Park, Kwang Hwan; Oh, Hwanhee; Kim, Jung-Min; Shin, Dong Yeon; Lee, Jae Myun; Lee, Jin Woo; Singh, Anju; Lee, Ki-young; Hu, Dorothy; Xiao, Changchun; Charles, Julia F.; Penninger, Josef M.; Lotinun, Sutada; Baron, Roland; Ghosh, Sankar

    2015-01-01

    Physiological bone remodeling requires that bone formation by osteoblasts be tightly coupled to bone resorption by osteoclasts. However, relatively little is understood about how this coupling is regulated. Here, we demonstrate that modulation of NF-κB signaling in osteoclasts via a novel activity of charged multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased bone resorption by osteoclasts coupled with exuberant bone formation by osteoblasts, resembling an early onset, polyostotic form of human Paget’s disease of bone (PDB). These phenotypes are reversed by haploinsufficiency for Rank, as well as by antiresorptive treatments, including alendronate, zolendronate, and OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced NF-κB activation and osteoclast differentiation. Biochemical analysis demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin-containing protein (VCP/p97) to stabilize the inhibitor of NF-κBα (IκBα), down-regulating ubiquitination of IκBα via the deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-κB signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder. PMID:26195726

  11. Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women

    PubMed Central

    Bredella, Miriam A.; Gerweck, Anu V.; Barber, Lauren A.; Breggia, Anne; Rosen, Clifford J.; Torriani, Martin; Miller, Karen K.

    2014-01-01

    Purpose Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. Materials and Methods In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21–45y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. Results GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. Six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. Six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor

  12. Stanozolol Decreases Bone Turnover Markers, Increases Mineralization, and Alters Femoral Geometry in Male Rats.

    PubMed

    Nebot, E; Aparicio, V A; Camiletti-Moirón, D; Martinez, R; Erben, R G; Kapravelou, G; Sánchez-González, C; De Teresa, C; Porres, J M; López-Jurado, M; Aranda, P; Pietschmann, P

    2016-06-01

    Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10 mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality. PMID:26801156

  13. 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. PMID:27026330

  14. The regulation of bone turnover in ameloblastoma using an organotypic in vitro co-culture model

    PubMed Central

    Eriksson, Tuula M; Day, Richard M; Fedele, Stefano; Salih, Vehid M

    2016-01-01

    Ameloblastoma is a rare, odontogenic neoplasm with benign histopathology, but extensive, local infiltrative capacity through the bone tissue it originates in. While the mechanisms of ameloblastoma invasion through the bone and bone absorption are largely unknown, recent investigations have indicated a role of the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand regulatory mechanisms. Here, we present results obtained using a novel in vitro organotypic tumour model, which we have developed using tissue engineering techniques. Using this model, we analysed the expression of genes involved in bone turnover and detected a 700-fold increase in receptor activator of nuclear factor kappa-B ligand levels in the co-culture models with ameloblastoma cells cultured with bone cells. The model described here can be used for gene expression studies, as a basis for drug testing or for a more tailored platform for testing of the behaviour of different ameloblastoma tumours in vitro. PMID:27746893

  15. Common bone turnover markers in rheumatoid arthritis and ankylosing spondylitis: a literature review.

    PubMed

    Coiffier, Guillaume; Bouvard, Béatrice; Chopin, Florance; Biver, Emmanuel; Funck-Brentano, Thomas; Garnero, Patrick; Guggenbuhl, Pascal

    2013-05-01

    We studied the impact of inflammatory rheumatism and its treatment on the most common bone turnover markers, based on six previously defined questions in a systematic literature review in order to define their place in daily clinical practice. The role of bone is currently considered of particular importance concerning cartilage damage in inflammatory rheumatism (rheumatoid arthritis and ankylosing spondylitis) and the new concept of osteoimmunology has emerged. Some bone turnover markers are available in clinical practice. In spite of rich and extensive literature on bone turnover markers, their use in inflammatory rheumatism or even osteoporosis is not clear, and a systematic literature review became necessary. In spite of a large number of different markers used in literature, few of them that are useful in common practice have been studied in the field of inflammatory rheumatism such as rheumatoid arthritis and ankylosing spondylitis. Although their study enables understanding of the physiopathological mechanisms of osteoporosis in inflammatory rheumatism, their use in current common practice cannot be recommended. Interesting data on the forecast of the structural evolution of rheumatoid arthritis has been found within the framework of clinical research, without any real practical impact today.

  16. Low Bone Turnover and Low BMD in Down Syndrome: Effect of Intermittent PTH Treatment

    PubMed Central

    Akel, Nisreen S.; Vander Schilden, Jaclyn; Bacon, Anthony W.; Bracey, John W.; Sowder, Timothy; Skinner, Robert A.; Swain, Frances L.; Hogue, William R.; Leblanc, Donna B.; Gaddy, Dana; Wenger, Galen R.; Suva, Larry J.

    2012-01-01

    Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns of differences are now being recognized as patients’ age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD) has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population. PMID:22916188

  17. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications. PMID:27049105

  18. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

  19. Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.

    PubMed

    Morabito, Nunziata; Catalano, Antonino; Gaudio, Agostino; Morini, Elisabetta; Bruno, Lucia Maria; Basile, Giorgio; Tsiantouli, Eleni; Bellone, Federica; Agostino, Rita Maria; Piraino, Basilia; La Rosa, Maria Angela; Salpietro, Carmelo; Lasco, Antonino

    2016-09-01

    Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24 months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18 months in comparison to baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels. PMID:26204844

  20. Changes in Bone Turnover Markers and Bone Mass with Reducing Levels of Jumping Exercise Regimens in Female Rats

    PubMed Central

    Ooi, Foong Kiew; Singh, Rabindarjeet; Singh, Harbindar Jeet

    2012-01-01

    Purpose To date, little is known about the effects of a reduced level of jumping exercise regimens on bone turnover markers and mass. This study investigates the effects of different jumping exercise regimens with varying exercise loads on serum bone turnover markers and bone mass in female rats. Methods A total of 144 female rats aged 12 weeks, were divided into 12 groups as follows: no exercise for 8 (8S) or 32 weeks (32S), or 8 weeks of standard training program (8STP) consisting of 200 jumps per week (200J/w), given at 40 jumps per day (40J/d) for 5 days per week (5d/w) (8STP24E), followed by 24 weeks of exercise at loads of either 10J/d or 20J/d or 40J/d, for either 5d/w, or 3d/w, or 1d/w. Serum osteocalcin, alkaline phosphatase, C-terminal telopeptide of type 1 collagen (1CTP) concentrations, and tibial fat free dry weight were measured. Results Tibial mass was significantly higher in 8STP than 8S. No changes were evident in serum markers of bone turnover parameters after 8STP. Significant increases in tibial mass were observed in rats that continued to exercise at workloads of 30J/w and above after 8STP. Serum alkaline phosphatase concentrations increase whereas serum 1CTP concentrations decrease in rats given workloads of 40J/w and above. Conclusions It appears, an exercise load of 30J/w, i.e. 10J/d for 3d/w, was the minimum level of continuous exercise load that was required to maintain the 8STP-induced bone gains. In addition, significant increases in bone mass in young rats following 8STP might not always be reflected by changes in serum levels of osteocalcin, alkaline phosphatase and 1CTP. PMID:23342220

  1. Associations of total, dairy, and meat protein with markers for bone turnover in healthy, prepubertal boys.

    PubMed

    Budek, Alicja Z; Hoppe, Camilla; Michaelsen, Kim F; Bügel, Susanne; Mølgaard, Christian

    2007-04-01

    We previously reported that high intake of milk, but not meat, equal in protein content, increased serum insulin-like growth factor-I (sIGF-I) in prepubertal boys. sIGF-I plays a key role in bone metabolism. Therefore, the aim of this cross-sectional study was to investigate associations of total, dairy, and meat protein intake with markers for bone turnover and sIGF-I in prepubertal, healthy boys (n = 81). We measured bone turnover (enzyme-linked immunoassay) in serum osteocalcin (sOC), bone-specific alkaline phosphatase (sBAP), and C-terminal telopeptide of collagen type-I (sCTX); dietary intake was estimated from a 3-d weighed food record. sIGF-I and its binding protein-3 were assessed (immunoassay) in a subgroup of 56 boys. All statistical models included effects of age, BMI, and energy intake. Dairy protein was negatively associated with sOC (P = 0.05) but not significantly associated with sBAP and sCTX. Further analyses showed that dairy protein decreased (P = 0.05) sOC at a high meat protein intake (>0.8 g/kg), whereas meat protein increased (P = 0.03) sOC at a low dairy protein intake (<0.4 g/kg). Total and meat protein intake was positively associated with sBAP (P < or = 0.04) but not significantly associated with sOC and sCTX. Free sIGF-I was positively associated with total (P < 0.01) and dairy (P = 0.06) protein but not with meat protein. Our results indicate that dairy and meat protein may exhibit a distinct regulatory effect on different markers for bone turnover. Future studies should focus on differential effects of dairy and meat protein on bone health during growth.

  2. Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state

    PubMed Central

    Gossiel, Fatma; Finigan, Judith; Jacques, Richard; Reid, David; Felsenberg, D; Roux, Christian; Glueer, Claus; Eastell, Richard

    2014-01-01

    In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women. We studied women aged 30–39 years (n=258) and women aged 55–79 years (n=2419) from a five-European centre population-based study. We obtained a nonfasting serum and second morning void urine samples at a single baseline visit. BTMs were measured using automated immunoassay analysers. BTMs were higher in patients with vitamin D deficiency and chronic kidney disease. Three or more BTMs were higher in women who were osteoporotic and at least two BTMs were lower in women who were oestrogen replete, taking osteoporosis treatments or having diseases known to affect bone turnover. These were used as exclusion criteria for selecting the populations for the reference intervals. The reference intervals for BTMs were higher in postmenopausal than premenopausal women. Levels of BTMs were not dependent on geographical location and increased with age. PMID:25228986

  3. Ankle-brachial index and bone turnover in patients on dialysis.

    PubMed

    London, Gérard M; Marchais, Sylvain J; Guérin, Alain P; de Vernejoul, Marie-Christine

    2015-02-01

    An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.

  4. Ankle-Brachial Index and Bone Turnover in Patients on Dialysis

    PubMed Central

    Marchais, Sylvain J.; Guérin, Alain P.; de Vernejoul, Marie-Christine

    2015-01-01

    An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH. PMID:25231881

  5. Biochemical markers of bone' turnover in cosmonauts after long term space flight

    NASA Astrophysics Data System (ADS)

    Larina, I. M.; Morukov, B. V.; Tret'yakov, V. S.

    There were investigated biochemical markers of bone tissue' turnover by mean determination of osteocalcin (as parameter of bone construction de novo) and crosslinks (as parameters of bone' collagen destruction). The mineral-tropic hormones -- parathyroid hormone, calcitonine -- and ionized calcium have been determined as well in blood of cosmonauts who carried out long term space flights on Russian module of ISS in 2000-2003. Samples of blood were collected from 9 cosmonauts whose flight duration was between 4 and 6 months. The level of total calcium in blood was unchanged in landing day, comparing with pre-flight concentration, but the activity of ionized calcium was elevated during first recovery week (1,18± 0,02 vs 1,26± 0,03 mmol/L; p<0,05). In the same period of time the concentration on PTH was stable and higher then before launch (171± 52 & 172± 39, %% to pre-flight) and CT level continued to grow (from 190± 77 to 235± 83, %% to pre-flight). Additionally it was shown that post-flight concentration of both bone turnover markers in blood of participants of space missions has been higher than before flight. So after flight, relatively to preflight period, the elevation of both processes' activity was happened: the bone' destruction and bone construction de novo as well. Nevertheless post-flight dynamics of these processes was different - the marker of bone collagen destruction was decreased from the 1st to 14th days of recovery period (181,84% & 149,47%, relatively) and the marker of bone construction de novo was lightly increased (110,7% & 125,1%). We concede that during post-flight period calcium homeostasis was supported by tension of hormonal regulation. It can be noted that within the bone metabolism of calcium the process of osteosynthesis looks to be activated in this period but osteolisis is still remained. In this case the re-establishment of normal bone calcium turnover will occur later.

  6. Bone marrow mesenchymal stem cells are abnormal in multiple myeloma.

    PubMed

    Corre, J; Mahtouk, K; Attal, M; Gadelorge, M; Huynh, A; Fleury-Cappellesso, S; Danho, C; Laharrague, P; Klein, B; Rème, T; Bourin, P

    2007-05-01

    Recent literature suggested that cells of the microenvironment of tumors could be abnormal as well. To address this hypothesis in multiple myeloma (MM), we studied bone marrow mesenchymal stem cells (BMMSCs), the only long-lived cells of the bone marrow microenvironment, by gene expression profiling and phenotypic and functional studies in three groups of individuals: patients with MM, patients with monoclonal gamopathy of undefined significance (MGUS) and healthy age-matched subjects. Gene expression profile independently classified the BMMSCs of these individuals in a normal and in an MM group. MGUS BMMSCs were interspersed between these two groups. Among the 145 distinct genes differentially expressed in MM and normal BMMSCs, 46% may account for a tumor-microenvironment cross-talk. Known soluble factors implicated in MM pathophysiologic features (i.e. IL (interleukin)-6, DKK1) were revealed and new ones were found which are involved in angiogenesis, osteogenic differentiation or tumor growth. In particular, GDF15 was found to induce dose-dependent growth of MOLP-6, a stromal cell-dependent myeloma cell line. Functionally, MM BMMSCs induced an overgrowth of MOLP-6, and their capacity to differentiate into an osteoblastic lineage was impaired. Thus, MM BMMSCs are abnormal and could create a very efficient niche to support the survival and proliferation of the myeloma cells.

  7. Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

    PubMed

    Oesterreich, Steffi; Henry, N Lynn; Kidwell, Kelley M; Van Poznak, Catherine H; Skaar, Todd C; Dantzer, Jessica; Li, Lang; Hangartner, Thomas N; Peacock, Munro; Nguyen, Anne T; Rae, James M; Desta, Zeruesenay; Philips, Santosh; Storniolo, Anna M; Stearns, Vered; Hayes, Daniel F; Flockhart, David A

    2015-11-01

    Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway. PMID:26536870

  8. Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population.

    PubMed

    Dai, Zhaoli; Wang, Renwei; Ang, Li-Wei; Yuan, Jian-Min; Koh, Woon-Puay

    2016-02-01

    While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case-control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45-74years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), N-terminal and C-terminal crosslinking telopeptide of type I collagen (NTX-I and CTX-I) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, PINP, CTX-I and NTX-I than controls (p<0.05). There was a dose-dependent positive relationship between OC, PINP, CTX-I and NTX-I and risk of hip fracture (all Ps for trend≤0.006), where the risk was significantly increased by 4.32-8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% CI)] at the highest quartile (Q4) was 6.63 (2.02-21.18) for PINP and 4.92 (1.67-14.51) for CTX-I. The joint effect of PINP and CTX-I showed a 7-fold increase in risk (OR: 7.36; 95% CI: 2.53-21.41) comparing participants with higher levels of PINP (Q4) and CTX-I (Q3-Q4) to those with low levels of PINP (Q1-Q3) and CTX-I (Q1-Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population.

  9. The pitfall of treating low bone turnover: Effects on cortical porosity.

    PubMed

    Araujo, Maria Julia C L N; Karohl, Cristina; Elias, Rosilene M; Barreto, Fellype C; Barreto, Daniela Veit; Canziani, Maria Eugenia F; Carvalho, Aluizio B; Jorgetti, Vanda; Moyses, Rosa M A

    2016-10-01

    Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2)=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.

  10. Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis.

    PubMed

    Wisłowska, Margaret; Jakubicz, Danuta; Stepień, Krystyna; Cicha, Małgorzata

    2009-10-01

    Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-alpha, IL-1, IL-6) osteoclasts' activation, osteoprotegerin and its ligand's (RANKL) function disorders, patients' immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation--serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler-Rose's test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers' concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers' concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers' concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale's than at

  11. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    PubMed

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  12. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    PubMed

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis. PMID:18037367

  13. Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

    NASA Technical Reports Server (NTRS)

    Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

    2016-01-01

    The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

  14. 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.

  15. Physical activity and bone turnover markers: a cross-sectional and a longitudinal study.

    PubMed

    Adami, Silvano; Gatti, Davide; Viapiana, Ombretta; Fiore, Carmelo Erio; Nuti, Ranuccio; Luisetto, Giovanni; Ponte, Marco; Rossini, Maurizio

    2008-12-01

    Strenuous physical activity in young individuals has an important effect on both bone mass and bone turnover but the effect of moderate physical activity in adults remains uncertain. In a large cohort (N = 530) of healthy premenopausal women, bone formation markers (osteocalcin and N-terminal propeptide of type 1 procollagen [P1NP]), but not serum C-telopeptide of type 1 collagen (sCTX), were found to be significantly associated with the level of physical activity, and this association remained significant after adjusting the data (ANCOVA) by age and body mass index. Mean spine and hip bone mineral density (BMD) values were positively associated with physical activity but this was statistically significant (P = 0.050) only for adjusted values of spine BMD. Twenty-four healthy sedentary premenopausal women, subscribing to participate in a community exercise program lasting a month, and 18 age-matched controls were included in the longitudinal study. Serum osteocalcin and P1NP, but not sCTX, rose significantly, by ca. 25%, only in the active group after a month of exercise. The changes in the two bone formation markers remained statistically significant for values adjusted for body weight, which fell significantly in the exercise group. In conclusion, both the cross-sectional and the longitudinal parts of our study demonstrate that even minor changes in physical activity are associated with a clear effect on bone formation markers.

  16. Effects of endocrine and inflammatory changes on markers of bone turnover following Roux-en-Y gastric bypass surgery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bariatric surgery is associated with increased bone turnover. The mechanisms involved are unclear but may involve nutrition, mechanical unloading, altered secretion of gastrointestinal and adipose hormones and changes in inflammatory status leading to weight loss induced bone loss. We assessed marke...

  17. Changes of mesenchymal stromal cells mobilization and bone turnover in an experimental bone fracture model in ovariectomized mice

    PubMed Central

    Pang, Jian; Guo, Hai-Ling; Ding, Dao-Fang; Wu, Yu-Yun; Zhao, Yong-Fang; Gu, Xin-Feng; Zheng, Yu-Xin

    2015-01-01

    Objective: The aim of this study was to characterize the mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) mobilization, and bone turnover in osteoporotic fracture healing in ovariectomized mice. Methods: In total, 112 female C57/BL mice were divided into two groups. The first group was sham-operated (SO), and the other group was ovariectomized (OVX). After three weeks, the right femora of the mice were fractured under anesthesia and internally fixed with steel pin. Peripheral blood and bone marrow were was collected for flow cytometry analysis, at 0 hours (h), 12 h, 24 h, 72 h and 168 h after fracture. MSCs and EPCs levels were assessed using cell surface antigens in different combinations (CD44+ CD34-CD45-, and CD34+ KDR+CD45-) by flow cytometry. At 0, 14, 28 and 42 days after fracture, sera were assayed for circulating levels of procollagen type I-N-terminal propeptide (P1NP) and C-terminal telopeptide of type I-collagen (CTX) by ELISA. Femurs were harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT) and histology. Results: Our results showed that bone marrow and peripheral blood MSCs numbers of the OVX mice were significantly lower than the SO mice, at 12 h, 24 h and 72 h after fracture. In addition, circulating P1NP and CTX levels of the OVX mice were significantly higher than the SO mice, at 2 and 4 weeks. Conclusion: Results of the present study revealed disorders of bone marrow MSCs mobilization and bone turnover may partially account for the delay of osteoporotic fracture healing. PMID:26617731

  18. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis

    PubMed Central

    Salerni, H.; González, D.; Bagur, A.; Oliveri, B.; Farías, V.; Maffei, L.; Mansur, J. L.; Larroudé, M. S.; Pavlove, M. M.; Karlsbrum, S.

    2016-01-01

    The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed. PMID:27579211

  19. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis.

    PubMed

    Sánchez, A; Brun, L R; Salerni, H; Costanzo, P R; González, D; Bagur, A; Oliveri, B; Zanchetta, M B; Farías, V; Maffei, L; Premrou, V; Mansur, J L; Larroudé, M S; Sarli, M A; Rey, P; Ulla, M R; Pavlove, M M; Karlsbrum, S; Brance, M L

    2016-01-01

    The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed. PMID:27579211

  20. Effect of Calcitriol on Bone Turnover and Osteocalcin in Recent-Onset Type 1 Diabetes

    PubMed Central

    Napoli, Nicola; Strollo, Rocky; Pitocco, Dario; Bizzarri, Carla; Maddaloni, Ernesto; Maggi, Daria; Manfrini, Silvia; Schwartz, Ann; Pozzilli, Paolo

    2013-01-01

    Background Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of β-cell function and metabolic control was examined. Methodology/Principal Findings We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve β-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 µg calcitriol per day or placebo (1∶1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01) while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and β-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels. Conclusions Supplementation with 0.25 µg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to β-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction. PMID:23437144

  1. Biochemical Markers of Bone Turnover in Percutaneous Vertebroplasty for Osteoporotic Compression Fracture

    SciTech Connect

    Komemushi, Atsushi Tanigawa, Noboru; Kariya, Shuji; Kojima, Hiroyuki; Shomura, Yuzo; Tokuda, Takanori; Nomura, Motoo; Terada, Jiro; Kamata, Minoru; Sawada, Satoshi

    2008-03-15

    Purpose. To evaluate relationships between biochemical markers of bone turnover, bone mineral density, and new compression fractures following vertebroplasty. Methods. Initially, we enrolled 30 consecutive patients with vertebral compression fractures caused by osteoporosis. Twenty-three of the 30 patients visited our hospital for follow-up examinations for more than 4 weeks after vertebroplasty. The patients were divided into two groups: patients with new fractures (group F) and patients with no new fractures (group N). We analyzed differences in the following parameters between these two groups: serum bone alkaline phosphatase, urinary crosslinked N-telopeptide of type I collagen, urinary deoxypyridinoline, and bone mineral density. Next, the patients were divided into another two groups: patients with higher risk (group H: urinary crosslinked N-telopeptide of type I collagen >54.3 nmol BCE/mmol Cr or urinary deoxypyridinoline >7.6 nmol/mmol Cr, and serum bone alkaline phosphatase <29.0 U/l) and patients with lower risk (group L). We analyzed the difference in the rate of new fractures between these two groups. Results. We identified 9 new fractures in 7 patients. There were no significant differences between groups F and N. We identified 5 new fractures in 3 of the 4 patients in group H, and 4 new fractures in 4 of the 19 patients in group L. There was a significant difference in the rate of new fractures between groups H and L. Conclusions. A combination of high levels of bone resorption markers and normal levels of bone formation markers may be associated with increased risk of new recurrent fractures after percutaneous vertebroplasty.

  2. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    SciTech Connect

    Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

  3. Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

    NASA Technical Reports Server (NTRS)

    Kidder, L. S.; Schmidt, I. U.; Evans, G. L.; Turner, R. T.

    1997-01-01

    Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone

  4. Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature.

    PubMed

    Sousa, Cristina P; Dias, Isabel R; Lopez-Peña, Mónica; Camassa, José A; Lourenço, Paulo J; Judas, Fernando M; Gomes, Manuela E; Reis, Rui L

    2015-01-01

    Imaging techniques are the standard method for assessment of fracture healing processes. However, these methods are perhaps not entirely reliable for early detection of complications, the most frequent of these being delayed union and non-union. A prompt diagnosis of such disorders could prevent prolonged patient distress and disability. Efforts should be directed towards the development of new technologies for improving accuracy in diagnosing complications following bone fractures. The variation in the levels of bone turnover markers (BTMs) have been assessed with regard to there ability to predict impaired fracture healing at an early stage, nevertheless the conclusions of some studies are not consensual. In this article the authors have revised the potential of BTMs as early predictors of prognosis in adult patients presenting traumatic bone fractures but who did not suffer from osteopenia or postmenopausal osteoporosis. The available information from the different studies performed in this field was systematized in order to highlight the most promising BTMs for the assessment of fracture healing outcome. PMID:25993365

  5. Effects of Glycemic Control on Bone Turnover in Older Mexican Americans with Type 2 Diabetes: Data from the Cameron County Hispanic Cohort in Texas

    NASA Technical Reports Server (NTRS)

    Rianon, N.; Smith, S. M.; Lee, M.; Musgrave, P.; Nader, S.; Khosla, S.; Ambrose, C.; McCormick, J.; Fisher-Hoch, S.

    2016-01-01

    for younger group ( less than 65 years) was minus 25.54 (minus 38.02 to minus 13.05). There were no significant associations between HbA1c and OC in women. Altered metabolic state due to poor glycemic control may be responsible for the low turnover indicating underlying structural changes leading to fracture risk. A more active younger bone with higher turnover may be magnifying the deleterious effects on OC compared to the older less active bones with longer effects of metabolic changes. Understanding impact of disease duration on bone metabolism resulting from abnormal glycemic control over time is recommended to demystify effects of HbA1c on diabetic bones.

  6. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover.

    PubMed

    van Lierop, Antoon H; Hamdy, Neveen At; Hamersma, Herman; van Bezooijen, Rutger L; Power, Jon; Loveridge, Nigel; Papapoulos, Socrates E

    2011-12-01

    Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss-of-function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked C-telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age- and gender-matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in

  7. Bone turnover markers in patients with prostate carcinoma: influence of sex steroids levels.

    PubMed

    Varsavsky, Mariela; Reyes-García, Rebeca; García-Martín, Antonia; Rozas-Moreno, Pedro; González-Ramírez, Rocío; Rocío, González-Ramírez; Muñoz-Torres, Manuel

    2014-01-01

    There are limited data about bone turnover markers (BTM) in androgen deprivation therapy (ADT)-treated prostate cancer (PCa) patients, and the relationship between sex steroids, bone mass, and BTM has not been explored. Our objective was to analyze the influence of sex steroids levels on BTM in patients with PCa treated with or without ADT. We performed a cross-sectional study including 83 subjects with PCa (54% with ADT). BTM, bone mineral density (BMD), and sex steroids were determined. BTM were inversely related to serum level of estrogens. Tartrate-specific acid phosphatase (TRAP-5b) showed a negative correlation with free estradiol (Free E) (r = -0.274, p = 0.014) and Bio E (r = -0.256, p = 0.022) that remained after adjustment for age: Free E (β = -0.241, p = 0.03) and Bio E (β = -0.213, p = 0.063). Bone-specific alkaline phosphatase (BSAP) concentrations were inversely related to Free E (r = -0.281, p = 0.011, age-adjusted β = -0.256, p = 0.024). There was a negative correlation between osteocalcin (OC) levels and Free E (r = -0.195, p = 0.082; age-adjusted β = -0.203, p = 0.076) and Bio E (r = -0.215, p = 0.054; age-adjusted β = -0.240, p = 0.039). BTM and androgens were inversely related to TRAP-5b: total testosterone (total T) (r = -0.238, p = 0.033), Free T (r = -0.309, p = 0.05), and Bio T (r = -0.310, p = 0.05), but these correlations disappeared after age-adjustment. We did not find any relationship between BMD at different locations and sex steroids. In conclusion, in patients with PCa, estrogen levels influence bone resorption and bone formation whereas androgens may exert actions only in bone resorption. These results suggest that estradiol is the main sex steroid that regulates bone metabolism in males with prostate carcinoma.

  8. Weight-bearing exercise and markers of bone turnover in female athletes.

    PubMed

    Creighton, D L; Morgan, A L; Boardley, D; Brolinson, P G

    2001-02-01

    Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes (n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n = 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 +/- 0.03 and 1.05 +/- 0.03) than in the Non (1.05 +/- 0.04 and 0.86 +/- 0.04) and Con (1.03 +/- 0.05 and 0.85 +/- 0.05) groups and greater at the TR in the Med group (1.01 +/- 0.03) than in the Non (0.86 +/- 0.04) and Con (0.85 +/- 0.05) groups. Total body BMD was higher in the High group (4.9 +/- 0.12) than in the Med (4.5 +/- 0.12), Non (4.2 +/- 0.14), and Con (4.1 +/- 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 +/- 2.6) than in the High (30.6 +/- 3.0) and Med (32.9 +/- 1.9, P < or = 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers. PMID:11160054

  9. Weight-bearing exercise and markers of bone turnover in female athletes.

    PubMed

    Creighton, D L; Morgan, A L; Boardley, D; Brolinson, P G

    2001-02-01

    Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes (n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n = 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 +/- 0.03 and 1.05 +/- 0.03) than in the Non (1.05 +/- 0.04 and 0.86 +/- 0.04) and Con (1.03 +/- 0.05 and 0.85 +/- 0.05) groups and greater at the TR in the Med group (1.01 +/- 0.03) than in the Non (0.86 +/- 0.04) and Con (0.85 +/- 0.05) groups. Total body BMD was higher in the High group (4.9 +/- 0.12) than in the Med (4.5 +/- 0.12), Non (4.2 +/- 0.14), and Con (4.1 +/- 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 +/- 2.6) than in the High (30.6 +/- 3.0) and Med (32.9 +/- 1.9, P < or = 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers.

  10. Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies with genetically modified mice and dietary antioxidants have suggested an important role for superoxide derived from NADPH oxidase (NOX) enzymes and other reactive oxygen species (ROS) such as hydrogen peroxide in regulation of normal bone turnover during development and also in the r...

  11. Flaxseed enhances the beneficial effect of low-dose estrogen therapy at reducing bone turnover and preserving bone microarchitecture in ovariectomized rats.

    PubMed

    Sacco, Sandra M; Chen, Jianmin; Ganss, Bernhard; Thompson, Lilian U; Ward, Wendy E

    2014-07-01

    Our previous research showed greatest protection to vertebral bone mineral density and strength in ovariectomized (OVX) rats when lignan- and α-linolenic acid-rich flaxseed (FS) is combined with low-dose estrogen therapy (LD) compared with either treatment alone. This study determined the effects of combined FS+LD on serum and tissue markers of bone turnover and microarchitecture to explain our previous findings. Three-month-old OVX rats were randomized to negative control (NEG), FS, LD or FS+LD for 2 or 12 weeks, meaningful time points for determining effects on markers of bone metabolism and bone structure, respectively. Ground FS was added to the AIN-93M diet (100 g/kg diet) and LD (0.42 μg 17β-estradiol/(kg body weight·day)) was delivered by subcutaneous implant. Sham rats were included as positive control. Bone formation (e.g., osteocalcin), bone resorption (e.g., tartrate-resistant acid phosphatase-5β (TRAP-5β)), as well as osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANKL) were analyzed from the 2-week study by commercial assays (serum) and (or) histology (vertebra). Vertebral bone microarchitecture was measured from the 12-week study using microcomputed tomography. In serum, FS+LD and LD induced lower TRAP-5β and osteocalcin, and higher OPG and OPG/RANKL ratio versus NEG and FS (p < 0.05). In vertebrae, FS+LD induced higher OPG and lower osteocalcin versus NEG (p < 0.01) and did not differ from LD and FS. FS+LD improved bone microarchitecture versus NEG, FS, and LD (p < 0.05). In conclusion, FS+LD protects bone tissue because of a reduction in bone turnover. However, elucidating the distinctive action of FS+LD on bone turnover compared with LD requires further investigation.

  12. Spaceflight and bone turnover - Correlation with a new rat model of weightlessness

    NASA Technical Reports Server (NTRS)

    Morey, E. R.

    1979-01-01

    Earlier manned spaceflight studies have revealed that the near-weightless environment of orbital flight produce certain biological effects in humans, including abnormalities in mineral metabolism. The data collected were compatible with bone mineral loss. Cosmos 782 and 936 experiments have shown a decrease in rat bone formation rate. In this paper, a rat model of weightlessness is described, which is unique in that the animal is free to move about a 360-deg arc. The model meets the requirements for an acceptable system. Data from the model and spaceflight are presented. Many of the responses noted in suspended animals indicate that the model closely mimics results from rats and man exposed to near-weightlessness during orbital spaceflight.

  13. Increased Intake of Selected Vegetables, Herbs and Fruit may Reduce Bone Turnover in Post-Menopausal Women

    PubMed Central

    Gunn, Caroline Ann; Weber, Janet Louise; McGill, Anne-Thea; Kruger, Marlena Cathorina

    2015-01-01

    Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (−3.2 μg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (−0.065 μg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation. PMID:25856221

  14. Periodontal and alveolar bone abnormalities associated with pachydermoperiostosis.

    PubMed

    Akdeniz, B G; Seçkin, T

    2001-01-01

    Pachydermoperiostosis (PDP) is an unusual syndrome manifested clinically by finger clubbing, extremity enlargement, hypertrophic skin changes, and periosteal bone formation. A rare case of pachydermoperiostosis (primary hypertrophic osteoarthropathy) with oral manifestations in a 47-year-old man is presented. The possible correlation between physiological mechanisms of this disease and their influence on oral periodontal tissues and alveolar bone is discussed.

  15. Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

    PubMed

    Hoy, Jennifer; Grund, Birgit; Roediger, Mollie; Ensrud, Kristine E; Brar, Indira; Colebunders, Robert; Castro, Nathalie De; Johnson, Margaret; Sharma, Anjali; Carr, Andrew

    2013-06-01

    Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p ≤ 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.

  16. Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover

    PubMed Central

    Wilson, Caroline; Gossiel, Fatma; Leonard, Robert; Anderson, Richard A; Adamson, Douglas J A; Thomas, Geraldine; Coleman, Robert E

    2016-01-01

    Background The Ovarian Protection Trial In Premenopausal Breast Cancer Patients “OPTION” trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6–8 cycles of (neo)adjuvant chemotherapy (CT) +/− goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CT+/-G on markers of bone turnover. Methods Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (≤40 vs >40 years) and with exploratory analysis according to POI rates at 12 months. Results In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CT+G (40.81 vs 57.82 p=0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CT+G, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CT+G 5.845 vs CT 8.5 p=0.0006). These changes were predominantly seen in women >40 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses. Conclusion Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI. PMID:26998426

  17. Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition.

    PubMed

    Crandall, Carolyn J; Tseng, Chi-Hong; Crawford, Sybil L; Thurston, Rebecca C; Gold, Ellen B; Johnston, Janet M; Greendale, Gail A

    2011-04-01

    The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We analyzed data from 2283 participants of the Study of Women's Health Across the Nation, a longitudinal community-based cohort study of women aged 42 to 52 years at baseline. At baseline and annually through follow-up visit 8, participants provided questionnaire data, urine samples, serum samples, and anthropometric measurements. Using multivariable repeated-measures mixed models, we examined associations between annually assessed VMS frequency and annual NTX measurements. Our results show that mean adjusted NTX was 1.94 nM of bone collagen equivalents (BCE)/mM of creatinine higher among early perimenopausal women with any VMS than among early perimenopausal women with no VMS (p < .0001). Mean adjusted NTX was 2.44 nM BCE/mM of creatinine higher among late perimenopausal women with any VMS than among late perimenopausal women with no VMS (p = .03). Among premenopausal women, VMS frequency was not significantly associated with NTX level. When NTX values among women with frequent VMS (≥6 days in past 2 weeks) were expressed as percentages of NTX values among women without frequent VMS, the differences were 3% for premenopausal women, 9% for early perimenopausal women, 7% for late perimenopausal women, and 4% for postmenopausal women. Adjustment for serum follicle-stimulating hormone (FSH) level greatly reduced the magnitudes of associations between VMS and NTX level. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health.

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

    PubMed Central

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

    2015-01-01

    Osteoporosis-related fractures are one of the complications of Graves’ disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves’ disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves’ disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves’ disease. PMID:26650844

  19. The influence of folic acid supplementation on maternal and fetal bone turnover.

    PubMed

    Hossein-nezhad, Arash; Mirzaei, Khadijeh; Maghbooli, Zhila; Najmafshar, Azam; Larijani, Bagher

    2011-03-01

    The aim of our study was to investigate the relationship between maternal and fetal bone turnover markers and folic acid supplementation during pregnancy. In an observational study performed in Tehran University of Medical Sciences related hospitals, 113 healthy pregnant women with gestational age between 8 and 12 weeks and aged between 15 and 42 years were recruited and followed until delivery time. The participants were divided into two groups; women who took 1 mg of folic acid daily supplement from the beginning of the pregnancy until the end of the second trimester entered into group I and women who choose to continue their daily intake of folic acid until the delivery time entered into group II. The two groups were matched based on the maternal anthropometric data, energy, calcium and vitamin D intake. Following the delivery, venous blood samples were collected from mothers and umbilical cords of the neonates. Maternal and fetal serum concentrations of 25-hydroxy vitamin D3, PTH, osteocalcin (OC), crosslaps and maternal serum level of homocysteine, folate, soluble receptor activator of NF-kappaB ligand (sRANKL), osteoprotegerin (OPG), calcium, and phosphate were measured. Measured birth outcome parameters included weight, length, head circumference, appearance, and respiration. With regard to maternal assessment, the serum levels of OC and OPG and folate were significantly higher in group II compared to group I, while the serum levels of RANKL and homocysteine were significantly higher in group I. We did not find significant differences in serum levels of 25-OH vitamin D, PTH, crosslaps, calcium, or phosphate between the two groups. The neonates from mothers recruited in group II had higher (but not significantly) serum level of OC. We observed that the neonates born from mothers in group II had overall better birth outcome parameters and apgar scores compare to the neonates born from mothers in group I. Our results show that daily supplementation of folic

  20. Interrelationship between bone turnover markers and dietary calcium intake in pregnant women: a longitudinal study.

    PubMed

    Zeni, Susana N; Ortela Soler, Carlos R; Lazzari, Araceli; López, Laura; Suarez, Marisa; Di Gregorio, Silvana; Somoza, Julia I; de Portela, Maria L

    2003-10-01

    This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P < 0.02). A negative correlation between the absolute change in betaCTX, NTX, and b-ALP between the third and second trimester and calcium intake at the end of pregnancy was observed in pregnant women who did not cover adequately calcium intake requirements (r = -0.47, P < 0.03; r = -0.41, P < 0.05; and r = -0.43, P < 0.05, respectively). These results suggest that skeletal response to pregnancy may not be entirely independent of maternal calcium intake, especially in women with usually low calcium intake. In summary, not only hormonal changes in calcium metabolism that occur during pregnancy but also other considerations, such as low dietary calcium intake, may lead to an increment in the biological activity of the skeleton. Additional studies must be

  1. Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

    PubMed

    Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

    2015-10-01

    Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets. PMID:26218891

  2. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance

    PubMed Central

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    Background It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). Material/Methods We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. Results During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. Conclusions Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  3. Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We

  4. Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS).

    PubMed

    Tavella, Sara; Ruggiu, Alessandra; Giuliani, Alessandra; Brun, Francesco; Canciani, Barbara; Manescu, Adrian; Marozzi, Katia; Cilli, Michele; Costa, Delfina; Liu, Yi; Piccardi, Federica; Tasso, Roberta; Tromba, Giuliana; Rustichelli, Franco; Cancedda, Ranieri

    2012-01-01

    Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.

  5. Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children.

    PubMed

    Thiering, E; Brüske, I; Kratzsch, J; Hofbauer, L C; Berdel, D; von Berg, A; Lehmann, I; Hoffmann, B; Bauer, C P; Koletzko, S; Heinrich, J

    2015-01-01

    Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC), and β-Crosslaps (β-CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC, and β-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in β-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate, and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the β-CTx-to-OC ratio was inversely associated with 25(OH)D (-1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and β-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker β-CTx was observed. PMID:26667774

  6. Peripheral Blood and Bone Marrow Abnormalities in the Acquired Immunodeficiency Syndrome

    PubMed Central

    Frontiera, Michael; Myers, Adam M.

    1987-01-01

    In reviewing the peripheral hematologic manifestations, bone marrow changes and clinical course in 41 consecutive patients with acquired immunodeficiency syndrome (AIDS), frequent findings included anemia (95%), leukopenia (76%), bone marrow hypercellularity (73%) and pancytopenia (41%). These hematologic abnormalities were not clearly associated with specific clinical manifestations of AIDS, but support the conclusion that the hematopoietic system is a target organ in AIDS. The mechanisms of these abnormalities still need to be evaluated. Clinicians should be aware of these commonly encountered changes. Images PMID:3660772

  7. Relating micromechanical properties and mineral densities in severely suppressed bone turnover patients, osteoporotic patients, and normal subjects.

    PubMed

    Tjhia, Crystal K; Stover, Susan M; Rao, D Sudhaker; Odvina, Clarita V; Fyhrie, David P

    2012-07-01

    Mineralization of bone, from the tissue level to whole bones, is associated with mechanical properties. The relationship between bone tissue mineralization and micromechanical properties may be affected by age, disease, and drug treatment. Patients with severely suppressed bone turnover (SSBT) suffered atypical fractures while on bisphosphonate treatment. The role of tissue level mineralization in predicting material level properties of SSBT bone may be different from that of other osteoporotic patients and of normal subjects. The aim of this study was to compare the relationships between mineralization and micromechanical properties of bone biopsies from patients with SSBT, bisphosphonate-naive osteoporotic patients with typical vertebral fracture, and normal young and age-matched subjects. We used nanoindentation and quantitative backscattered electron microscopy to characterize the elastic modulus, contact hardness, plastic deformation resistance, and tissue mineralization of the biopsies at site-matched locations within each biopsy. The linear mineralization-mechanical property relationships were different among the groups with respect to the intercepts for only cortical bone tissue but not the slopes for cortical and trabecular bone tissues. For a given mineral density, there was a trend of greater plastic deformation resistance in SSBT cortical bone compared to young normal bone. Similarly, there was a trend of greater plastic deformation resistance in osteoporotic trabecular bone compared to young normal bone for a given mineral density. The age-matched normal group had higher elastic modulus and a trend of higher contact hardness compared to the young normal group for a given mineral density. However, the mechanical property-mineralization relationships within an individual were weak, and only 21 of 53 biopsies that were analyzed had at least one significant association between mineralization and a mechanical property measurement for either cortical or

  8. Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice.

    PubMed

    Alund, Alexander W; Mercer, Kelly E; Suva, Larry J; Pulliam, Casey F; Chen, Jin-Ran; Badger, Thomas M; Van Remmen, Holly; Ronis, Martin J J

    2016-07-01

    Chronic ethyl alcohol (EtOH) consumption results in reactive oxygen species (ROS) generation in bone and osteopenia due to increased bone resorption and reduced bone formation. In this study, transgenic C57Bl/6J mice overexpressing human catalase (TgCAT) were used to test whether limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. Micro-computed tomography analysis of the skeletons of 6-week-old female chow-fed TgCAT mice revealed a high bone mass phenotype with increased cortical bone area and thickness as well as significantly increased trabecular bone volume (P < 0.05). Six-week-old wild-type (WT) and TgCAT female mice were chow fed or pair fed (PF) liquid diets with or without EtOH, approximately 30% of calories, for 8 weeks. Pair feeding of WT had no demonstrable effect on the skeleton; however, EtOH feeding of WT mice significantly reduced cortical and trabecular bone parameters along with bone strength compared with PF controls (P < 0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared with PF controls. At 14 weeks of age, there was significantly less trabecular bone and cortical cross-sectional area in TgCAT mice than WT mice (P < 0.05), suggesting impaired normal bone accrual with age. TgCAT mice expressed less collagen1α and higher sclerostin mRNA (P < 0.05), suggesting decreased bone formation in TgCAT mice. In conclusion, catalase overexpression resulted in greater bone mass than in WT mice at 6 weeks and lower bone mass at 14 weeks. EtOH feeding induced significant reductions in bone architecture and strength in WT mice, but TgCAT mice were partially protected. These data implicate ROS signaling in the regulation of bone turnover in an age-dependent manner, and indicate that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia. PMID:27189961

  9. Blood biochemical markers of bone turnover: pre-analytical and technical aspects of sample collection and handling.

    PubMed

    Lombardi, Giovanni; Lanteri, Patrizia; Colombini, Alessandra; Banfi, Giuseppe

    2012-02-03

    Casual or systematic errors occurring in pre-analytical, analytical or post-analytical phases influence laboratory test results. The areas where pre-analytical phase errors most often arise are: timing of specimen collection; selection of specimen type; and time and temperature of storage/transport. Bone turnover markers are clinically useful in evaluating bone metabolism. Although unquestionably valuable tools, little is known about the pre-analytical precautions for their correct use and there is no consensus on kind of sample, or storage time and temperature before analysis. Moreover, biological variability, because of uncontrollable and controllable factors, will affect pre-analytical variability. Serum should be preferred to simplify blood drawing; therefore, only one tube should be used for the analysis of all bone markers. Short-term storage at 4°C may be advisable to preserve stability, immediate storage at -70°C is recommended for longer periods, while avoiding repeated freeze-thawing cycles. Sampling should be performed in the morning in fasting subjects who have abstained from physical exercise for 24 h. This review aimed to give a knowledge update on pre-analytical phase precautions in performing bone turnover marker measurement.

  10. Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice.

    PubMed

    Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

    2016-10-01

    The third generation aromatase inhibitors are currently the drugs of choice for the treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In this study, we compared the effects of a nonsteroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa B ligand (RANKL), sclerostin, and dickkopf-1 (DKK-1) in vinylcyclohexene diepoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1 mg/kg) administration for 1 month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice. Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone. PMID:27279630

  11. Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice.

    PubMed

    Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

    2016-10-01

    The third generation aromatase inhibitors are currently the drugs of choice for the treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In this study, we compared the effects of a nonsteroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa B ligand (RANKL), sclerostin, and dickkopf-1 (DKK-1) in vinylcyclohexene diepoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1 mg/kg) administration for 1 month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice. Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone.

  12. Mechanical property and tissue mineral density differences among severely suppressed bone turnover (SSBT) patients, osteoporotic patients, and normal subjects.

    PubMed

    Tjhia, Crystal K; Odvina, Clarita V; Rao, D Sudhaker; Stover, Susan M; Wang, Xiang; Fyhrie, David P

    2011-12-01

    Pathogenesis of atypical fractures in patients on long term bisphosphonate therapy is poorly understood, and the type, the manner in which they occur and the fracture sites are quite different from the usual osteoporotic fractures. We hypothesized that the tissue-level mechanical properties and mean degree of mineralization of the iliac bone would differ among 1) patients with atypical fractures and severely suppressed bone turnover (SSBT) associated with long-term bisphosphonate therapy, 2) age-matched, treatment-naïve osteoporotic patients with vertebral fracture, 3) age-matched normals and 4) young normals. Large differences in tissue-level mechanical properties and/or mineralization among these groups could help explain the underlying mechanism(s) for the occurrence of typical osteoporotic and the atypical femoral shaft fractures. Elastic modulus, contact hardness, plastic deformation resistance, and tissue mineral densities of cortical and trabecular bone regions of 55 iliac bone biopsies--12 SSBT patients (SSBT; aged 49-77), 11 age-matched untreated osteoporotic patients with vertebral fracture (Osteoporotic), 12 age-matched subjects without bone fracture (Age-Matched Normal), and 20 younger subjects without bone fracture (Young Normal)--were measured using nanoindentation and quantitative backscattered electron microscopy. For cortical bone nanoindentation properties, only plastic deformation resistance was different among the groups (p<0.05), with greater resistance to plastic deformation in the SSBT group compared to all other groups. For trabecular bone, all nanoindentation properties and mineral density of the trabecular bone were different among the groups (p<0.05). The SSBT group had greater plastic deformation resistance and harder trabecular bone compared to the other three groups, stiffer bone compared to the Osteoporotic and Young Normal groups, and a trend of higher mineral density compared to the Age-Matched Normal and Osteoporotic groups. Lower

  13. Daily Parathyroid Hormone 1-34 Replacement Therapy for Hypoparathyroidism Induces Marked Changes in Bone Turnover and Structure

    PubMed Central

    Gafni, Rachel I.; Brahim, Jaime S.; Andreopoulou, Panagiota; Bhattacharyya, Nisan; Kelly, Marilyn H.; Brillante, Beth A.; Reynolds, James C.; Zhou, Hua; Dempster, David W.; Collins, Michael T.

    2012-01-01

    Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic leading to osteoporosis, yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated five hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected 2-3 times daily for 18 months, with doses individualized to maintain serum calcium at 1.9-2.25 mmol/L. Biochemical markers and bone density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged, however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased, however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in

  14. The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women

    PubMed Central

    Shin, Chaeho; Lee, Seung Hun; Koh, Jung-Min

    2016-01-01

    Background Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women. Methods A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria. Results Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73). Conclusion This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women. PMID:27469066

  15. Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy prote...

  16. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass.

    PubMed

    Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O C; Chun, Jerold; Salles, Jean Pierre

    2011-09-01

    Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1-LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1 may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1((-/-)) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1((-/-)) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1((-/-)) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology.

  17. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass☆,☆☆

    PubMed Central

    Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O. C.; Chun, Jerold; Salles, Jean Pierre

    2013-01-01

    Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1–LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1(−/−) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1(−/−) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1(−/−) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology. PMID:21569876

  18. Disruption of c-Kit Signaling in Kit(W-sh/W-sh) Growing Mice Increases Bone Turnover.

    PubMed

    Lotinun, Sutada; Krishnamra, Nateetip

    2016-01-01

    c-Kit tyrosine kinase receptor has been identified as a regulator of bone homeostasis. The c-Kit loss-of-function mutations in WBB6F1/J-Kit(W/W-v) mice result in low bone mass. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to a sex hormone deficiency. In contrast, C57BL/6J-Kit(W-sh)/(W-sh) (W(sh)/W(sh)) mice, which carry an inversion mutation affecting the transcriptional regulatory elements of the c-Kit gene, are fertile. Here, we showed that W(sh)/W(sh) mice exhibited osteopenia with elevated bone resorption and bone formation at 6- and 9-week-old. The c-Kit W(sh) mutation increased osteoclast differentiation, the number of committed osteoprogenitors, alkaline phosphatase activity and mineralization. c-Kit was expressed in both osteoclasts and osteoblasts, and c-Kit expression was decreased in W(sh)/W(sh)osteoclasts, but not osteoblasts, suggesting an indirect effect of c-Kit on bone formation. Furthermore, the osteoclast-derived coupling factor Wnt10b mRNA was increased in W(sh)/W(sh) osteoclasts. Conditioned medium from W(sh)/W(sh) osteoclasts had elevated Wnt10b protein levels and induced increased alkaline phosphatase activity and mineralization in osteoblast cultures. Antagonizing Wnt10b signaling with DKK1 or Wnt10b antibody inhibited these effects. Our data suggest that c-Kit negatively regulates bone turnover, and disrupted c-Kit signaling couples increased bone resorption with bone formation through osteoclast-derived Wnt 10 b. PMID:27527615

  19. Disruption of c-Kit Signaling in KitW-sh/W-sh Growing Mice Increases Bone Turnover

    PubMed Central

    Lotinun, Sutada; Krishnamra, Nateetip

    2016-01-01

    c-Kit tyrosine kinase receptor has been identified as a regulator of bone homeostasis. The c-Kit loss-of-function mutations in WBB6F1/J-KitW/W-v mice result in low bone mass. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to a sex hormone deficiency. In contrast, C57BL/6J-KitW-sh/W-sh (Wsh/Wsh) mice, which carry an inversion mutation affecting the transcriptional regulatory elements of the c-Kit gene, are fertile. Here, we showed that Wsh/Wsh mice exhibited osteopenia with elevated bone resorption and bone formation at 6- and 9-week-old. The c-Kit Wsh mutation increased osteoclast differentiation, the number of committed osteoprogenitors, alkaline phosphatase activity and mineralization. c-Kit was expressed in both osteoclasts and osteoblasts, and c-Kit expression was decreased in Wsh/Wshosteoclasts, but not osteoblasts, suggesting an indirect effect of c-Kit on bone formation. Furthermore, the osteoclast-derived coupling factor Wnt10b mRNA was increased in Wsh/Wsh osteoclasts. Conditioned medium from Wsh/Wsh osteoclasts had elevated Wnt10b protein levels and induced increased alkaline phosphatase activity and mineralization in osteoblast cultures. Antagonizing Wnt10b signaling with DKK1 or Wnt10b antibody inhibited these effects. Our data suggest that c-Kit negatively regulates bone turnover, and disrupted c-Kit signaling couples increased bone resorption with bone formation through osteoclast-derived Wnt 10 b. PMID:27527615

  20. Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

    PubMed Central

    Ruan, Jianwei; Gong, Xiaokang; Kong, Jinsong; Wang, Haibao; Zheng, Xin; Chen, Tao

    2015-01-01

    Background B vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies. Material/Methods Relevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation. Results Based on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover. Conclusions B vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future. PMID:25805360

  1. Effects of Sigma Anti-bonding Molecule Calcium Carbonate on bone turnover and calcium balance in ovariectomized rats.

    PubMed

    Choi, So-Young; Park, Dongsun; Yang, Goeun; Lee, Sun Hee; Bae, Dae Kwon; Hwang, Seock-Yeon; Lee, Paul K; Kim, Yun-Bae; Kim, Ill-Hwa; Kang, Hyun-Gu

    2011-12-01

    This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

  2. Is Gastrectomy-Induced High Turnover of Bone with Hyperosteoidosis and Increase of Mineralization a Typical Osteomalacia?

    PubMed Central

    Ueyama, Takashi; Yamamoto, Yuta; Ueda, Kazuki; Yajima, Aiji; Maeda, Yoshimasa; Yamashita, Yasunobu; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

    2013-01-01

    Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B) were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone. PMID:23776526

  3. Contralateral subtraction technique for detection of asymmetric abnormalities on whole-body bone scintigrams

    NASA Astrophysics Data System (ADS)

    Shiraishi, Junji; Li, Qiang; Appelbaum, Daniel; Pu, Yonglin; Doi, Kunio

    2007-03-01

    We developed a computer-aided diagnostic (CAD) scheme for assisting radiologists in the detection of asymmetric abnormalities on a single whole-body bone scintigram by applying a contralateral subtraction (CS) technique. Twenty whole-body bone scans including 107 abnormal lesions in anterior and/or posterior images (the number of lesions per case ranged from 1 to 16, mean 5.4) were used in this study. In our scheme, the original bone scan image was flipped horizontally to provide a mirror image. The mirror image was first rotated and shifted globally to match the original image approximately, and then was nonlinearly warped by use of an elastic matching technique in order to match the original image accurately. We applied a nonlinear lookup table to convert the difference in pixel values between the original and the warped images to new pixel values for a CS image, in order to enhance dark shadows at the locations of abnormal lesions where uptake of radioisotope was asymmetrically high, and to suppress light shadows of the lesions on the contralateral side. In addition, we applied a CAD scheme for the detection of asymmetric abnormalities by use of rule-based tests and sequential application of artificial neural networks with 25 image features extracted from the original and CS images. The performance of the CAD scheme, which was evaluated by a leave-one-case-out method, indicated an average sensitivity of 80.4 % with 3.8 false positives per case. This CAD scheme with the contralateral subtraction technique has the potential to improve radiologists' diagnostic accuracy and could be used for computerized identification of asymmetric abnormalities on whole-body bone scans.

  4. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Ruml, L. A.; Gottschalk, F.; Pak, C. Y.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal

  5. 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.

  6. Biochemical and morphological changes associated with long bone abnormalities in silicon deficiency.

    PubMed

    Carlisle, E M

    1980-05-01

    The purpose of this paper was to investigate long bone changes in silicon deficiency more extensively and under a new set of conditions. Long bone abnormalities have been produced in silicon-deficient chicks fed a casein-based rather than amino acid-based diet and under an entirely new set of conditions. As demonstrated previously feeding amino acid diets, the long bones of cockerels fed a silicon-supplemented basal diet and sacrificed at 4 weeks had a significantly greater amount of articular cartilage and water content as compared with the silicon-deficient group. Biochemical analyses of tibia for bone mineral, non-collagenous protein, hexosamine and collagen demonstrated that tibia from supplemented chicks had a significantly greater percentage and total amount of hexosamine and greater percentage of collagen than deficient chicks, the difference being greater for hexosamines than collagen. Tibia from silicon-deficient chicks also showed marked lesions, profound changes being demonstrated in epiphyseal cartilage, especially striking in the proliferative zone. The disturbed epiphyseal cartilage sequences resulted in defective endochondral bone growth indicating that silicon is involved in the metabolic chain of events required for the normal growth of bone.

  7. Effects of Pegylated Interferon/Ribavirin on Bone Turnover Markers in HIV/Hepatitis C Virus-Coinfected Patients

    PubMed Central

    Kang, Minhee; Tebas, Pablo; Overton, Edgar T.; Hollabaugh, Kimberly; McComsey, Grace; Bhattacharya, Debika; Evans, Christopher; Brown, Todd T.; Taiwo, Babafemi

    2016-01-01

    Abstract HIV/hepatitis C virus (HCV) patients have a 3-fold increased fracture incidence compared to uninfected patients. The impact of HCV therapy on bone health is unclear. We evaluated bone turnover markers (BTM) in well-controlled (HIV RNA <50 copies/ml) HIV/HCV-coinfected patients who received pegylated interferon-α and ribavirin (PEG-IFN/RBV) in ACTG trial A5178. Early virologic responders (EVR: ≥2 log HCV RNA drop at week 12) continued PEG-IFN/RBV and non-EVRs were randomized to continuation of PEG-IFN alone or observation. We assessed changes in C-terminal telopeptide of type 1 collagen (CTX; bone resorption marker) and procollagen type I intact N-terminal propeptide (P1NP; bone formation marker), and whether BTM changes were associated with EVR, complete early virologic response (cEVR: HCV RNA <600 IU/ml at week 12), or PEG-IFN treatment. A total of 192 subjects were included. After 12 weeks of PEG-IFN/RBV, CTX and P1NP decreased: −120 pg/ml and −8.48 μg/liter, respectively (both p < 0.0001). CTX declines were greater in cEVR (N = 91; vs. non-cEVR (N = 101; p = 0.003). From week 12 to 24, CTX declines were sustained among EVR patients who continued PEG-IFN/RBV (p = 0.027 vs. non-EVR) and among non-EVR patients who continued PEG-IFN alone (p = 0.022 vs. Observation). Median decreases of P1NP in EVR vs. non-EVR were similar at weeks 12 and 24. PEG-IFN-based therapy for chronic HCV markedly reduces bone turnover. It is unclear whether this is a direct IFN effect or a result of HCV viral clearance, or whether they will result in improved bone mineral density. Further studies with IFN-free regimens should explore these questions. PMID:26499270

  8. Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover.

    PubMed

    Kruger, Marlena C; Kruger, Iolanthé M; Wentzel-Viljoen, Edelweiss; Kruger, Annamarie

    2011-10-01

    Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women.

  9. Associations between ambient air pollution and bone turnover markers in 10-year old children: results from the GINIplus and LISAplus studies.

    PubMed

    Liu, Chuang; Fuertes, Elaine; Flexeder, Claudia; Hofbauer, Lorenz C; Berdel, Dietrich; Hoffmann, Barbara; Kratzsch, Jürgen; von Berg, Andrea; Heinrich, Joachim

    2015-01-01

    Negative associations between bone turnover markers and bone mineral density have been reported. In order to study the association between ambient air pollution and bone turnover markers, as indicators of bone loss, we investigated associations between land-use regression modeled air pollution (NO2, PM2.5 mass, PM2.5 - 10 [coarse particles], PM10 mass and PM2.5 absorbance) and bone turnover markers in 2264 children aged 10 years. Serum osteocalcin and C-terminal telopeptide of type I collagen (CTx), measured by Modular-System (Roche), were the two bone turnover markers considered in this analysis. In total population, NO2, PM2.5 - 10 and PM10 mass exposure were positively and significantly associated with both osteocalcin and CTx. A 2.5 (95% CI: 0.6, 4.4) ng/ml increase in osteocalcin and a 24.0 (95% CI: 6.7, 41.3) ng/L increase in CTx were observed per IQR (6.7μg/m(3)) increase in NO2, independent of socioeconomic status, sex, age, pubertal status, fasting status and total physical activity. The estimated coefficients were 3.0 (95% CI: 0.1, 5.8) for osteocalcin and 32.3 (95% CI: 6.1, 58.5) for CTx with PM2.5 - 10; 3.2 (95% CI: 0.0, 6.4) for osteocalcin and 30.7 (95% CI: 1.7, 59.7) for CTx with PM10. Children living close to a major road (≤ 350m) had higher levels of both osteocalcin (1.4 [-1.2, 4.0] ng/ml) and CTx (16.2 [-7.4, 39.8] ng/L). The adverse impact of ambient air pollution on bone turnover rates observed in one of the study areas showed stimulation of more such studies.

  10. Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

    PubMed

    Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

    2013-11-01

    Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

  11. Pregnancy-associated changes in bone density and bone turnover in the physiological state: prospective data on sixteen women.

    PubMed

    Fiore, C E; Pennisi, P; DiStefano, A; Riccobene, S; Caschetto, S

    2003-05-01

    Areal bone mineral density (BMD, g/cm 2) was measured for the total body, lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) before pregnancy and after delivery in sixteen women aged 21 - 35 years. Additional measurements included quantitative ultrasound indices (broadband ultrasound attenuation, BUA, at the calcaneus at baseline and at 16, 26, and 36 weeks of pregnancy, and postpartum) as well as biochemical markers of bone formation and resorption (measured before pregnancy and during pregnancy at 16, 22, 26, 30, 34, and 36 weeks of pregnancy and postpartum). The results of measurements were as follows: 1. Postpartum BMD showed a significant reduction in the total body (- 13.4 %), in the spine (- 9.2 %) and in the hip (-7.8 % at the femoral neck and - 9.2 % at the Ward's triangle) compared to pre-pregnancy values. 2. Biochemical markers of bone resorption increased by 26 weeks. 3. Bone ultrasound measurements that provide information on bone density before delivery did not change throughout pregnancy. A significant reduction of BUA (- 14.5 % compared to baseline) was observed postpartum only. These data would suggest that pregnancy-induced bone loss develops rapidly after the 36 week of pregnancy, possibly via enhanced bone resorption. PMID:12916002

  12. [Musculoskeletal rehabilitation and bone. Abnormal bone metabolism in female elite athletes].

    PubMed

    Enatsu, Akiko

    2010-04-01

    Recently, female athletes are particularly well, the other hand, many athletes suffer from amenorrhea due to excessive training. Especially, in sports with weight restrictions, they suffer from "Female athlete triad" , eating disorders, amenorrhea and osteoporosis. Amenorrhea is nothing else than a lack of estrogen, action on bone resorption and promote bone formation, by neglect this, it lead to osteoporosis and a stress fracture, and they would often give up their career as elite athletes. So we should consider it as serious sports injury. The problems of amenorrhea is should be recognized as a deficiency of estrogen. A Case of amenorrhea in female athletes, it is necessary to consider the hormone replacement therapy based on the appropriate diagnosis. However, it is important to start the management of body fat and body weight and strength of exercises since adolescent for the prevention the amenorrhea. PMID:20354328

  13. Focal spinal abnormalities on bone scans in ankylosing spondylitis: a clue to the presence of fracture or pseudarthrosis.

    PubMed

    Resnick, D; Williamson, S; Alazraki, N

    1981-05-01

    Four cases of ankylosing spondylitis are presented in which radionuclide bone studies indicated focal abnormalities of the spine. In three patients, the area of abnormal nuclide uptake corresponded to a site of pseudarthrosis, and in the fourth an acute fracture was present. As such focal lesions on bone scans are unusual in cases of chronic ankylosing spondylitis in which a complication is not apparent, their presence can be a useful finding. PMID:6262000

  14. Focal spinal abnormalities on bone scans in ankylosing spondylitis: a clue to the presence of fracture or pseudarthrosis

    SciTech Connect

    Resnick, D.; Williamson, S.; Alazraki, N.

    1981-05-01

    Four cases of ankylosing spondylitis are presented in which radionuclide bone studies indicated focal abnormalities of the spine. In three patients, the area of abnormal nuclide uptake corresponded to a site of pseudarthrosis, and in the fourth an acute fracture was present. As such focal lesions on bone scans are unusual in cases of chronic ankylosing spondylitis in which a complication is not apparent, their presence can be a useful finding.

  15. Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group.

    PubMed

    Chapuy, M C; Schott, A M; Garnero, P; Hans, D; Delmas, P D; Meunier, P J

    1996-03-01

    It was recently demonstrated that calcium and vitamin D supplements were capable of decreasing the incidence of hip fractures in institutionalized elderly subjects through a reduction of senile secondary hyperparathyroidism. As there are no appropriate data to recommend such a supplement to the elderly living at home, the aim of this study was to determine the incidence of senile secondary hyperparathyroidism in old French women from the general community, its relation to vitamin D status, and its contribution to bone turnover. Four hundred and forty women, aged 75-90 yr, were randomly selected from the general community by mailing from electoral listing in 5 French cities whose latitude varies from 49 degrees 9N to 43 degrees 6N. At the end of the winter, with previous hip fractures or those who were institutionalized were excluded. The results obtained in these women were compared to those obtained in 59 institutionalized old women and 54 younger healthy women. In the five cities for the women living at home, we found a mean PTH value greater than that obtained in young women (63 +/- 28 vs. 43 +/- 15 pg/ml; P = 0.001), but lower that that found in institutionalized women (76 +/- 49 pg/mL; P = 0.05). The mean 25-hydroxyvitamin D (25OHD) level was not different in subjects from the 5 cities, but in all of them it was significantly greater than that found in 59 institutionalized women (42.5 +/- 25.0 vs. 15.5 +/- 6.5 nmol/L; P = 0.0001) but lower than that in young adults (P < 0.001). The main determinants of PTH were in equal ratio, i.e. age (r = 0.19; P < 0.001), 25OHD, and, to a lesser degree, creatinine clearance (r = 0.10; P = 0.03). For 25OHD, the main determinant was the personal outdoor score and, to a lesser extent, the amount of daily sunlight in the city. The mean values of biochemical markers of bone turnover, bone alkaline phosphatase, osteocalcin, and Crosslaps, were significantly increased compared with the results obtained in young women, and

  16. Conditional expression of human bone Gla protein in osteoblasts causes skeletal abnormality in mice.

    PubMed

    Ikeda, Kazuhiro; Tsukui, Tohru; Tanaka, Daisuke; Maruyama, Yojiro; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-07-20

    Bone Gla protein (BGP), also known as osteocalcin, is one of the most abundant γ-carboxylated noncollagenous protein in bone matrix and plays important roles in mineralization and calcium ion homeostasis. BGP is synthesized specifically in osteoblasts; however, its precise function in bone metabolism has not been fully elucidated. To investigate the in vivo function of human BGP (hBGP), we generated CAG-GFP(floxed)-hBGP transgenic mice carrying a transgene cassette composed of the promoter and a floxed GFP linked to hBGP cDNA. The mice were crossed with ColI-Cre mice, which express the Cre recombinase driven by the mouse collagen type 1a1 gene promoter, to obtain hBGP(ColI) conditional transgenic mice that expressed human BGP in osteoblasts. The hBGP(ColI) mice did not survive more than 2days after birth. The analysis of the 18.5-day post coitum fetuses of the hBGP(ColI) mice revealed that they displayed abnormal skeletal growth such as deformity of the rib and short femur and cranium lengths. Moreover, increased BGP levels were detected in the serum of the neonates. These findings indicate that hBGP expression in osteoblasts resulted in the abnormal skeletal growth in the mice. Our study provides a valuable model for understanding the fundamental role of BGP in vivo.

  17. Biochemical Markers of Bone Turnover Part II: Clinical Applications in the Management of Osteoporosis

    PubMed Central

    Seibel, Markus J

    2006-01-01

    With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This second part of the two part series reviews the current evidence regarding the clinical use of biochemical markers of bone remodelling in the management of osteoporosis. PMID:17268581

  18. Bone calcium turnover during pregnancy and lactation in women with low calcium diets is associated with calcium intake and circulating insulin-like growth factor 1 concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Few data exist on longitudinal changes in bone calcium turnover rates across pregnancy and lactation. OBJECTIVE: Our aim was to characterize calcium kinetic variables and predictors of these changes across pregnancy and early lactation in women with low calcium intakes. DESIGN: Stable ca...

  19. Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover.

    PubMed

    Fung, Ellen B; Vichinsky, Elliott P; Kwiatkowski, Janet L; Huang, James; Bachrach, Laura K; Sawyer, Aenor J; Zemel, Babette S

    2011-06-01

    Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n = 25, 11 male, 10 to 30 years) and local controls (n=34, 15 male, 7 to 30 years). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p < 0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (> 18 years, n = 11) had lower tibial trabecular vBMD (p = 0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p < 0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p = 0.02) were significantly lower in young Thal (≤ 18 years, n = 14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p < 0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of

  20. Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial

    PubMed Central

    Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J; Gilhooly, Cheryl H; Shea, M Kyla; Fielding, Roger A; Ceglia, Lisa

    2016-01-01

    The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group (p =0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group (p =0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed. PMID:25990255

  1. Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial.

    PubMed

    Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J; Gilhooly, Cheryl H; Shea, M Kyla; Fielding, Roger A; Ceglia, Lisa

    2015-11-01

    The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3 ) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group (p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group (p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed.

  2. Effect of chronic activity-based therapy on bone mineral density and bone turnover in persons with spinal cord injury

    PubMed Central

    Harness, Eric T.; Witzke, Kara A.

    2014-01-01

    Purpose Osteoporosis is a severe complication of spinal cord injury (SCI). Many exercise modalities are used to slow bone loss, yet their efficacy is equivocal. This study examined the effect of activity-based therapy (ABT) targeting the lower extremities on bone health in individuals with SCI. Methods Thirteen men and women with SCI (age and injury duration = 29.7 ± 7.8 and 1.9 ± 2.7 years) underwent 6 months of ABT. At baseline and after 3 and 6 months of training, blood samples were obtained to assess bone formation (serum procollagen type 1 N propeptide (PINP) and bone resorption (serum C-terminal telopeptide of type I collagen (CTX), and participants underwent dual-energy X-ray absorptiometry scans to obtain total body and regional estimates of bone mineral density (BMD). Results Results demonstrated significant increases (p < 0.05) in spine BMD (+4.8 %; 1.27 ± 0.22–1.33 ± 0.24 g/cm2) and decreases (p < 0.01) in total hip BMD (−6.1 %; 0.98 ± 0.18–0.91 ± 0.16 g/cm2) from 0 to 6 months of training. BMD at the bilateral distal femur (−7.5 to −11.0 %) and proximal tibia (− 8.0 to −11.2 %) declined but was not different (p > 0.05) versus baseline. Neither PINP nor CTX was altered (p> 0.05) with training. Conclusions Chronic activity-based therapy did not reverse bone loss typically observed soon after injury, yet reductions in BMD were less than the expected magnitude of decline in lower extremity BMD in persons with recent SCI. PMID:24097172

  3. Role of B₁₂ and homocysteine status in determining BMD and bone turnover in young Indians.

    PubMed

    Haroon, Nisha Nigil; Marwaha, Raman K; Godbole, Madan M; Gupta, Sushil K

    2012-01-01

    Vitamin B(12) (B(12)) deficiency and hyperhomocysteinemia (HHcy) are independent risk factors for low bone mineral density (BMD) and fracture risk. We studied the role of HHcy and B(12) deficiency in determining the peak bone mass in Indians. Randomly selected 151 healthy young adult subjects (females 100, mean age: 26 yr) underwent evaluation of dietary intake of calcium and B(12); sun exposure; estimation of BMD by dual-energy X-ray absorptiometry at total hip, forearm, and lumbar spine; serum 25(OH)D(3); intact parathyroid hormone; B(12); homocysteine (Hcy); and bone turnover markers (BTMs) serum crosslaps, N-mid osteocalcin, and bone-specific alkaline phosphatase. Hypovitaminosis D (serum 25OHD(3)<20 ng/mL) and serum ALP level >150 IU/L were seen in 83% and 27%, respectively. Median serum B(12) and Hcy levels were 140 pg/mL (interquartile range [IQR]: 72-230 pg/mL) and 18 μmol/L (IQR 14-32 μmol/L); B(12) deficiency (serum B(12)<200 pg/mL) and HHcy (serum Hcy>30 μmol/L) were present in 71% and 68%, respectively. Low BMD (Z-score <-2.0) was present in 17% of subjects. There was no significant correlation between serum Hcy, folate, B(12), BTM, and BMD. BMD was predicted by height, weight, and body mass index. Young Indian healthy adults have high prevalence of hypovitaminosis D, B(12) deficiency, and HHcy. There is no correlation of serum B(12), folate, and Hcy status with BTMs and BMD in young, healthy, vegetarian Indian adults. Anthropometric variables predict BMD in young Indians.

  4. 1-alpha-Hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women.

    PubMed

    Chen, J T; Shiraki, M; Hasumi, K; Tanaka, N; Katase, K; Kato, T; Hirai, Y; Nakamura, T; Ogata, E

    1997-06-01

    50 Japanese women within 10 years after menopause (mean age 52.5 years) were studied to determine the effects of 0.75 microgram of 1-alpha-hydroxyvitamin D3 [1-alpha-(OH)D3] with calcium (150 mg/day) (treated group: N = 25) and calcium only (control group: N = 25) for 12 months on bone mass and metabolism. Their L2-4 BMD measurements were 1.5 SD below the mean value of Japanese young, normal women. L2-4 BMDs increased significantly in the treated group (+2.1%; p < 0.01), but decreased significantly in controls (-2.1%; p < 0.01). Although serum calcium and creatinine remained unchanged in both groups, phosphorus levels increased significantly in the treated group (p < 0.01). Urinary calcium/creatinine (Cr) increased in both groups. Urinary pyridinoline/Cr and deoxypyridinoline/Cr decreased significantly in the treated group (p < 0.05), but not in the control group. Serum osteocalcin levels remained unchanged in both groups. Intact parathyroid hormone levels decreased significantly (p < 0.05) and calcitonin levels significantly increased in the treated group (p < 0.05), but these changes were not observed in the control group. These data clearly demonstrate that 0.75 microgram of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by modulation of calcium-regulating hormones. Temporarily increased urinary calcium excretion was observed in control group, but did not appear to be effective in modulating bone turnover. PMID:9177871

  5. Three-dimensional assessment of bone turnover using computed microtomography and laser-scanning confocal microscopy

    NASA Astrophysics Data System (ADS)

    Prevrhal, Sven; Jiang, Yebin; Zhao, Jenny; Genant, Harry K.

    2000-06-01

    Objective: Metabolic activity in trabecular bone is an important indicator in the therapy of bone diseases like osteoporosis. It is reflected by the amount of osteoid (young, not yet mineralized bone) and young calcified tissue (YCT). Our aim was to replace standard 2D histomorphometry with a 3D approach for osteoid and YCT measurement. Measurement Methods: Excised lumbar vertebrae of 5 ovariectomized (OVX) and 5 control rats were 3D-scanned with computed micro-tomography ((mu) CT, isotropic spatial resolution 20 micrometer3) and laser scanning confocal microscopy (LSCM, 20X magnification, 1X1X2 micrometer3 spatial resolution). (mu) CT shows trabecular bone structure; LSCM shows osteoid and YCT by fluorescent light. Image Processing Methods: The fraction of bone to tissue volume (BV/TV) and the number of trabeculae (Tb.N) were calculated from globally thresholded (mu) CT images. LSCM images were enhanced using top-hat transform, globally thresholded and morphologically closed. Separate regions were labeled by volume growing. We measured feature volume to background volume ratio and number of features per unit volume. Results and Conclusions: In the specimens obtained from the OVX rats, a significant increase in the volume fractions of osteoid and YCT could be seen. The (mu) CT-LSCM approach presents a significant improvement over time-consuming, standard histomorphometry. The image processing for both modalities could be achieved automatically.

  6. Abnormal WT1 expression in the CD34-negative compartment in myelodysplastic bone marrow.

    PubMed

    Van Dijk, Jeroen P; Knops, Gertrudis H J N; Van De Locht, Louis T F; Menke, Aswin L; Jansen, Joop H; Mensink, Ewald J B M; Raymakers, Reinier A P; De Witte, Theo

    2002-09-01

    In normal bone marrow, WT1 expression is restricted to CD34+ cells. We assessed WT1 mRNA expression levels with quantitative, real-time reverse transcription polymerase chain reaction in normal, myelodysplastic (MDS) and secondary acute myeloid leukaemia (sAML) bone marrow subfractions, based on differentiation status. The highest WT1 expression was observed in the primitive CD34+ rhodamine-123 (rho) dull cells, both in healthy donors and MDS or sAML patients. In contrast to normal CD34-negative bone marrow cells, WT1 was present in CD34-negative bone marrow cells in 12 out of 13 MDS patients and two sAML samples. Further analysis of this aberrant WT1 expression was performed in the CD34-negative subfractions of three MDS patients. In one of these, WT1 expression was found exclusively in the erythroid cells. This patient was completely transfusion dependent and showed morphological dyserythropoiesis. In another MDS patient, WT1 expression was found in a non-erythroid compartment. We conclude that abnormal WT1 expression may contribute to the disturbed differentiation of haematopoietic cells in MDS patients.

  7. The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women.

    PubMed

    Hwang, You-Cheol; Jeong, In-Kyung; Ahn, Kyu Jeung; Chung, Ho Yeon

    2009-01-01

    The purpose of this prospective randomized study was to investigate the effects of the extract of Acanthopanax senticosus (AS extract), a widely used oriental herb, on bone remodeling and bone mineral density in Korean postmenopausal women. A total of 81 postmenopausal women with osteopenia or osteoporosis, an age of less than 65 years, were enrolled in the study. Subjects were randomly assigned to two groups: (1) the control group (n = 40), calcium intake (500 mg per day), and (2) the treatment group (n = 41), calcium (500 mg per day) plus AS extract (3 g per day). After treatment with AS extract for 6 months, the AS extract group showed a significant increase in serum osteocalcin levels compared with the control group (P = 0.041). However, no significant changes in bone mineral density were observed by dual-energy X-ray absorptiometry (DXA). AS extract was generally well tolerated, and no differences were observed between the two groups in terms of adverse events. This study suggests that AS extract supplementation may have beneficial effects on bone remodeling in Korean postmenopausal women and that it has no significant adverse events.

  8. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives.

    PubMed

    He, Feng J; Marciniak, Maciej; Carney, Christine; Markandu, Nirmala D; Anand, Vidya; Fraser, William D; Dalton, R Neil; Kaski, Juan C; MacGregor, Graham A

    2010-03-01

    To determine the effects of potassium supplementation on endothelial function, cardiovascular risk factors, and bone turnover and to compare potassium chloride with potassium bicarbonate, we carried out a 12-week randomized, double-blind, placebo-controlled crossover trial in 42 individuals with untreated mildly raised blood pressure. Urinary potassium was 77+/-16, 122+/-25, and 125+/-27 mmol/24 hours after 4 weeks on placebo, potassium chloride, and potassium bicarbonate, respectively. There were no significant differences in office blood pressure among the 3 treatment periods, and only 24-hour and daytime systolic blood pressures were slightly lower with potassium chloride. Compared with placebo, both potassium chloride and potassium bicarbonate significantly improved endothelial function as measured by brachial artery flow-mediated dilatation, increased arterial compliance as assessed by carotid-femoral pulse wave velocity, decreased left ventricular mass, and improved left ventricular diastolic function. There was no significant difference between the 2 potassium salts in these measurements. The study also showed that potassium chloride reduced 24-hour urinary albumin and albumin:creatinine ratio, and potassium bicarbonate decreased 24-hour urinary calcium, calcium:creatinine ratio, and plasma C-terminal cross-linking telopeptide of type 1 collagen significantly. These results demonstrated that an increase in potassium intake had beneficial effects on the cardiovascular system, and potassium bicarbonate may improve bone health. Importantly, these effects were found in individuals who already had a relatively low-salt and high-potassium intake.

  9. Adequate dietary vitamin D and calcium are both required to reduce bone turnover and increased bone mineral volume.

    PubMed

    Lee, Alice M C; Sawyer, Rebecca K; Moore, Alison J; Morris, Howard A; O'Loughlin, Peter D; Anderson, Paul H

    2014-10-01

    Clinical studies indicate that the combination of vitamin D and dietary calcium supplementation is more effective for reducing fracture risk than either supplement alone. Our previous dietary studies demonstrated that an adequate serum 25-hydroxyvitamin D3 (25D) of 80nmol/L or more reduces bone RANKL expression, osteoclastogenesis and maintains the optimal levels of trabecular bone volume (BV/TV%) in young rats. The important clinical question of the interaction between vitamin D status, dietary calcium intake and age remains unclear. Hence, 9 month-old female Sprague-Dawley rats (n=5-6/group) were pair-fed a semi-synthetic diet containing varying levels of vitamin D (0, 2, 12 or 20IU/day) and dietary calcium (0.1% or 1%) for 6 months. At 15 months of age, animals were killed, for biochemical and skeletal analyses. While changes to serum 25D were determined by both dietary vitamin D and calcium levels, changes to serum 1,25-dihydroxyvitamin D3 (1,25D) were consistently raised in animals fed 0.1% Ca regardless of dietary vitamin D or vitamin D status. Importantly, serum cross-laps levels were significantly increased in animals fed 0.1% Ca only when combined with 0 or 2 IUD/day of vitamin D, suggesting a contribution of both dietary calcium and vitamin D in determining bone resorption activity. Serum 25(OH)D3 levels were positively correlated with both femoral mid-diaphyseal cortical bone volume (R(2)=0.24, P<0.01) and metaphyseal BV/TV% (R(2)=0.23, P<0.01, data not shown). In multiple linear regressions, serum 1,25(OH)2D3 levels were a negative determinant of CBV (R(2)=0.24, P<0.01) and were not a determinant of metaphyseal BV/TV% levels. These data support clinical data that reduced bone resorption and increased bone volume can only be achieved with adequate 25D levels in combination with high dietary calcium and low serum 1,25D levels. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24309068

  10. ROS/redox signaling regulates bone turnover in an age-specific manner in female mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In bone, oxidant signaling through NADPH oxidase (NOX)-derived reactive oxygen species (ROS) superoxide and/or hydrogen peroxide appears to be an important stimulus for osteoclast differentiation and activity. ROS signaling has been suggested to increase RANKL mRNA and protein expression, thus enha...

  11. Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

    1994-01-01

    The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX+0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-micron-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX; there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, inereased bone formation more than did the cancellous bone in the PTM.

  12. Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

    1994-01-01

    The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate, (the distal tibial metaphysis (DTM), to ovariectomy (OVX) and OVX plus a prostaglandin E(2) treatment, and compare the site's response to previous findings reported for another site, the proximal tibial metaphysis (PTM). Thirty five 3-month old female Sprague-Dawley rats were divided into five groups; basal, sham OVX, and OVX+0, +1, or +6 mg PGE(2)/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20 micrometer thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months POST OVX there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE(2)/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE(2)/kd/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation, without altering bone resportion. Futhermore, After PGE(2) admimnistration, the DTM, a cancellous bone site with a closed growth plate, increased bone formation more than did the cancellous bone in the PTM.

  13. Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

    PubMed

    Bristow, Sarah M; Gamble, Greg D; Stewart, Angela; Horne, Lauren; House, Meaghan E; Aati, Opetaia; Mihov, Borislav; Horne, Anne M; Reid, Ian R

    2014-11-28

    Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

  14. Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities.

    PubMed

    Hirukawa, Takashi; Kakuta, Takatoshi; Nakamura, Michio; Fukagawa, Masafumi

    2015-08-01

    Given the advances in medical technologies related to kidney transplantation, the post-transplant graft survival rate and quality of life have improved dramatically. Nevertheless, post-transplant mortality rate still remains high as compared to the general population due to the development of cardiovascular events. It has recently been widely recognized that chronic kidney disease-mineral and bone disorders (CKD-MBD) significantly contribute to such poor prognosis at least in part. In the majority of kidney recipients, abnormal serum parameters for mineral and bone disorder (MBD), such as phosphorus, calcium, 1,25-dihydroxyvitamin D, parathyroid hormone and fibroblast growth factor 23, gradually return toward acceptable levels following the re-establishment of kidney function after transplantation; however, some irreversible abnormalities, developed as the result of long-term dialysis, persist, require treatment, or even progress after kidney transplantation. Thus, better management of CKD-MBD during pre-dialysis and dialysis period as well as after kidney transplantation is highly appreciated. PMID:25931403

  15. Clinical usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase activity in evaluating bone turnover.

    PubMed

    Nakanishi, M; Yoh, K; Uchida, K; Maruo, S; Rai, S K; Matsuoka, A

    1999-01-01

    This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04+/-1.98, n = 49, P < .05; female: 1.49+/-2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93+/-1.49, P < .05; female: 1.66+/-2.42, P < .05) compared with normal subjects: but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37+/-2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30-75 years (n = 95) were inversely and significantly correlated with stiffness (r = -.465, P < .01 ), SOS (r = -.484, P < .01), and BUA (r = -.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = -.521, P < .05) and SOS (r = -.527, P < .05) only in the age group of 46-55 years. BUA (r = -.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.

  16. Circulating levels of osteoclast activating cytokines, interleukin-11 and transforming growth factor-beta2, as valuable biomarkers for the assessment of bone turnover in postmenopausal osteoporosis.

    PubMed

    Shaarawy, Mohamed; Zaki, Sameh; Sheiba, Mamdouh; El-Minawi, Ahmad M

    2003-01-01

    The objective of this study was to evaluate the role of osteoclast activating cytokines, interleukin-11 (IL-11) and transforming growth factor-beta2 (TGF-beta2) in the assessment of bone turnover in postmenopausal osteoporosis (PO). Eighty postmenopausal osteoporotic women with lumbar spine bone mineral densities (BMD) as measured by DEXA that were more than 2.5 SD below the normal mean of healthy women (controls), participated in this study. Various therapeutic modalities (hormone replacement therapy, HRT, alendronate, calcitonin and 1alpha-hydroxyvitamin D (alfacalcidol) were administered for 12 months to 4 groups of postmenopausal osteoporotic patients. Fasting blood samples and two hour urine samples were collected from control subjects and from patients before and after treatment. Serum samples were assayed for IL-11, TGF-beta2, osteocalcin (OC) and bone alkaline phosphatase (B-ALP), whereas urine samples were assayed for N-telopeptide for type I collagen (NTX) and deoxypyridinoline (DPyr). The results demonstrated a significant increase of both IL-11 and TGF-beta2 in postmenopausal osteoporosis. Positive correlations exist between TGF-beta2 or IL-11 and markers of bone resorption (NTX and DPyr). Moreover, there was a significant positive correlation between TGF-beta2 and IL-11. Therapeutic modalities enhancing bone formation and/or with antiresorptive effect revealed a significant decrease in markers of bone resorption, formation and osteoclast activating cytokines, indicating a decrease in bone turnover. The decrease of IL-11 and TGF-beta2 may be attributed to a drug inhibitory effect of these cytokines on enhancing osteoblast mediated osteoid degradation. In conclusion, both serum IL-11 and TGF-beta2 determinations may be considered as biomarkers for the assessment of bone turnover and for monitoring antiresorptive therapy in postmenopausal osteoporosis.

  17. Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice

    PubMed Central

    Li, Ming; Guo, Kequan; Adachi, Yasushi; Ikehara, Susumu

    2016-01-01

    Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice. PMID:26840301

  18. Serum Sclerostin Levels in Patients with Human Immunodeficiency Virus Infection and Their Association with Bone Turnover Markers and Bone Mineral Densitometry

    PubMed Central

    Abdulfatah, Mohammed E.; Baaqil, Omar H.; Bakheet, Alaa A.; Turki, Sarah A.; Kotb, Mamdouh M.; Althubaiti, Alaa; Almaghrabi, Majed M.; Althubaiti, Abdulrahman M.; Madani, Badr M.; Jawad, Ali S. M.

    2016-01-01

    Background The aim of the study was to compare serum sclerostin levels in human im-munodeficiency virus (HIV)-infected patients and healthy controls, and to evaluate their relationship with bone turnover markers (BTM) and bone mineral density (BMD). Methods We prospectively studied 33 HIV treatment-naive patients and 63 healthy individuals; matched for age and sex. Serum sclerostin levels, BTM, BMD were measured. Viral load and cluster of differentiation 4 (CD4) levels were also assessed in HIV-infected patients. Results The mean±standard deviation (SD) age of sample was 37.6±10.3 years (range, 19 to 59 years). Of the 96 subjects, 58 (60.4%) were male and 38 (39.6%) were female. Infection with HIV is associated with significant reduction in serum sclerostin levels (HIV-infected: 39.4±28.3 vs. non HIV: 76.6±15.7 pmol/L; P<0.001) and a decrease in BMD at femoral neck and lumbar spine compared to healthy controls. Sclerostin however was not correlated with BMD and was not related to age, generally a strong correlation. There were no significant correlations between sclerostin and BTM (P>0.05). Conclusions These findings suggest that untreated HIV and the resulting immune deficiency and/or systemic inflammation could be an important regulator of serum sclerostin in this population. PMID:26981516

  19. Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

    PubMed Central

    2012-01-01

    Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

  20. Abnormal humoral immune responses in peripheral blood lymphocyte cultures of bone marrow transplant recipients.

    PubMed Central

    Pahwa, S G; Pahwa, R N; Friedrich, W; O'Reilly, R J; Good, R A

    1982-01-01

    The present study was aimed at investigating recovery of humoral immunity in vitro after bone marrow transplantation in patients with acute leukemia and severe aplastic anemia. Hemolytic plaque assays were utilized to quantitate pokeweed mitogen-stimulated polyclonal immunoglobulin production and sheep erythrocyte antigen-specific antibody responses in cultures of peripheral blood mononuclear cells of 39 patients beginning at 1 month, for variable periods up to a maximum of 4 years after marrow transplantation. Three phases were identified: an early period of primary B cell dysfunction with concomitant immunoregulatory T cell abnormalities--i.e., decreased helper and increased suppressor activities; an intermediate phase in which B cell dysfunction could be attributed in large measure to immunoregulatory T cell abnormalities; and a late phase of normal B and T lymphocyte functions. Patients with graft-versus-host disease differed from those without it in that they often did not manifest increased T cell suppressor activity in the early period, and they were noted to have prolonged and profound B and T cell abnormalities in the chronic phase of their disease. In selected patients, simultaneous assessment of ratios of Leu-2 to Leu-3 antigens on T cells by monoclonal antibodies and of immunoregulatory T cell functions revealed a correlation between the two only late in the post-transplant period. These studies provide an insight into the ontogeny of B cell function in the post-transplant period and indicate that in certain situations phenotypic alterations in T cell subsets cannot reliably be used to predict abnormalities in their function in recipients of marrow transplantation. Images PMID:6211673

  1. Turnover Begets Turnover

    ERIC Educational Resources Information Center

    Castle, Nicholas G.

    2005-01-01

    Purpose: This study examined the association between turnover of caregivers and turnover of nursing home top management. The top managers examined were administrators and directors of nursing, and the caregivers examined were registered nurses, licensed practical nurses, and nurse aides. Design and Methods: The data came from a survey of 419…

  2. Serum Sema4D levels are associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis

    PubMed Central

    Zhang, Yiyuan; Feng, Eryou; Xu, Yang; Wang, Wulian; Zhang, Tao; Xiao, Lili; Chen, Rong; Lin, Yu; Chen, Dongdong; Lin, Liqiong; Chen, Kangyao; Lin, Yanbin

    2015-01-01

    To investigate the association of serum semaphorin 4D (Sema4D) levels with lumbar spine bone mineral density (BMD) and bone turnover markers in patients with postmenopausal osteoporosis (PO). Lumbar spine BMD was measured by dual-energy X-ray absorptiometry in 257 PO patients (aged from 50 to 75) and 90 healthy controls (aged from 51 to 83). Serum Sema4D, BAP, BGP and TRACP-5b levels were measured by enzyme linked immunosorbent assay. Serum cross linked N-telopeptides of type I (NTX), 25-hydroxyvitamin D (25(OH)D) and N-mid fragment of osteocalcin (N-MID-OT) levels were measured using automated electrochemiluminescence system. Sema4D level was significantly higher in PO women compared to healthy controls (1.40±0.33 vs. 0.58±0.18 μg/L, P=0.006). Sema4D level was positively correlated with serumTRACP-5b and NTX levels and negatively correlated with lumbar spine BMD and serum BAP and BGP levels. There were no correlations between Sema4D level and age, body mass index, and serum 25(OH)D and N-MID-OT levels. Lumbar spine BMD (β=-0.354, P<0.001) and serum BAP level (β=0.127, P=0.019) were independent predictors of serum Sema4D level in PO patients. Sema4D may be involved in the pathogenesis of PO and play a critical role in bone formation and resorption. Sema4D may represent a novel therapeutic target for treatment of PO and function as a predictive indicator of PO. PMID:26629156

  3. Thyroid-Stimulating Hormone Within Normal Range Does Not Affect Bone Turnover in Euthyroid Postmenopausal Women with Osteoporotic Fracture - A Preliminary Report

    PubMed Central

    Nowacki, Wieslaw; Sypniewska, Grazyna

    2011-01-01

    Background Pathogenic role of TSH suppression in the damaged bone tissue, in contrast to increased concentrations of thyroid hormones is still unknown. The aim of study was to evaluate the relationship between serum TSH and biochemical bone turnover markers in postmenopausal women with normal thyroid function and to answer whether the differences in TSH concentration within reference range may affect bone metabolism. Material and Methods 34 women (60-93 years old) admitted to the hospital after osteoporotic fracture participated in the study. Serum propeptide of type 1 procollagen (P1NP) as a bone formation marker and crosslinked C-terminal telopeptides (CTX-I), as a bone resorption marker and TSH were assayed. Results Median P1NP (p=0,05) was significantly higher in the 1st tertile of TSH values (0,35-1,88 mlU/mL). In the 3rd tertile of TSH concentrations (3,42-4,94 mlU/mL), the highest CTX-I value was found that exceed the reference range for age. No differences were found in bone markers between a group of euthyroid and a group of subjects with TSH<0,35 mlU/mL. No relationship was observed between TSH and bone formation and resorption markers in the whole group of euthyroid postmenopausal women, however bone formation was found to be in the lower reference range for age in the euthyroid subjects as well as in these with decreased TSH. Weight and BMI correlated negatively with CTX (r=-0,68 p<0,03) in fractured women in the 1st tertile of TSH. Conclusion We found no consistent evidence that TSH concentrations within reference range was associated with changes in bone turnover markers.

  4. Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys.

    PubMed

    Kostenuik, Paul J; Smith, Susan Y; Samadfam, Rana; Jolette, Jacquelin; Zhou, Lei; Ominsky, Michael S

    2015-04-01

    Postmenopausal osteoporosis is a chronic disease wherein increased bone remodeling reduces bone mass and bone strength. Antiresorptive agents including bisphosphonates are commonly used to mitigate bone loss and fracture risk. Osteoclast inhibition via denosumab (DMAb), a RANKL inhibitor, is a newer approach for reducing fracture risk in patients at increased risk for fracture. The safety of transitioning from bisphosphonate therapy (alendronate; ALN) to DMAb was examined in mature ovariectomized (OVX) cynomolgus monkeys (cynos). One day after OVX, cynos (7-10/group) were treated with vehicle (VEH, s.c.), ALN (50 μg/kg, i.v., twice monthly) or DMAb (25 mg/kg/month, s.c.) for 12 months. Other animals received VEH or ALN for 6 months and then transitioned to 6 months of DMAb. DMAb caused significantly greater reductions in serum CTx than ALN, and transition from ALN to DMAb caused further reductions relative to continued ALN. DMAb and ALN decreased serum calcium (Ca), and transition from ALN to DMAb resulted in a lesser decline in Ca relative to DMAb or to VEH-DMAb transition. Bone histomorphometry indicated significantly reduced trabecular and cortical remodeling with DMAb or ALN. Compared with ALN, DMAb caused greater reductions in osteoclast surface, eroded surface, cortical porosity and fluorochrome labeling, and transition from ALN to DMAb reduced these parameters relative to continued ALN. Bone mineral density increased in all active treatment groups relative to VEH controls. Destructive biomechanical testing revealed significantly greater vertebral strength in all three groups receiving DMAb, including those receiving DMAb after ALN, relative to VEH controls. Bone mass and strength remained highly correlated in all groups at all tested skeletal sites, consistent with normal bone quality. These data indicate that cynos transitioned from ALN to DMAb exhibited reduced bone resorption and cortical porosity, and increased BMD and bone strength, without

  5. Abnormal Bone Mechanical and Structural Properties in Adolescent Idiopathic Scoliosis: A Study with Finite Element Analysis and Structural Model Index.

    PubMed

    Cheuk, K Y; Zhu, T Y; Yu, F W P; Hung, V W Y; Lee, K M; Qin, L; Cheng, J C Y; Lam, T P

    2015-10-01

    Previous studies found adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD) and abnormal bone quality, whilst the association between AIS and their bone strength is unknown. From high-resolution peripheral quantitative computed tomography-generated images, bone mechanical properties can be evaluated with finite element analysis (FEA), and trabecular rod-plate configuration related to trabecular bone strength can be quantified by structure model index (SMI). This study aimed to compare trabecular configuration and bone mechanical properties between AIS and the controls. 95 AIS girls aged 12-14 years and 97 age- and gender-matched normal controls were recruited. Bilateral femoral necks and non-dominant distal radius were scanned by dual-energy X-ray absorptiometry for areal BMD and HR-pQCT for SMI and FEA, respectively. Subjects were further classified into osteopenic and non-osteopenic group based on their areal BMD. Bone mechanical properties (stiffness, failure load and apparent modulus) were calculated using FEA. Linear regression model was used for controlling age, physical activity and calcium intake. AIS was associated with lower failure load and apparent modulus after adjusting for age, whereas AIS was associated with lower apparent modulus after adjusting for all confounders. Osteopenic AIS was associated with more rod-like trabeculae when compared with non-osteopenic AIS, whereas no difference was detected between osteopenic and non-osteopenic controls. This might be the result of abnormal regulation and modulation of bone metabolism and bone modelling and remodelling in AIS which will warrant future studies with a longitudinal design to determine the significance of micro-architectural abnormalities in AIS.

  6. Pathophysiology of chronic kidney disease-mineral and bone disorder.

    PubMed

    Mac Way, Fabrice; Lessard, Myriam; Lafage-Proust, Marie-Hélène

    2012-12-01

    Chronic kidney disease (CKD) alters the metabolism of several minerals, thereby inducing bone lesions and vessel-wall calcifications that can cause functional impairments and excess mortality. The histological bone abnormalities seen in CKD, known as renal osteodystrophy, consist of alterations in the bone turnover rate, which may be increased (osteitis fibrosa [OF]) or severely decreased (adynamic bone disease [AD]); abnormal mineralization (osteomalacia [OM]), and bone loss. Secondary hyperparathyroidism is related to early phosphate accumulation (responsible for FGF23 overproduction by bone tissue), decreased calcitriol production by the kidneys, and hypocalcemia. Secondary hyperparathyroidism is associated with OF. Other factors that affect bone include acidosis, chronic inflammation, nutritional deficiencies, and iatrogenic complications.

  7. [The effect of sodium fluoride on selected biochemical markers of bone turnover in ovariectomized rats].

    PubMed

    Bohatyrewicz, A

    1998-10-01

    The aim of the study was to investigate the effect of fluoride on selected biochemical markers of bone remodelling in young growing rats and after ovariectomy performed on 12-weeks-old female Wistar rats. Seventy 6-weeks-old female Wistar rats were randomized into seven groups. The first baseline control group was sacrificed before the beginning of the experiment. Two groups served as controls receiving distilled water and the other groups received fluoridated water at different doses (two received 8 and two received 60 mgF-/l). 30 rats (ten from each group) were sacrificed after 6 weeks. Serum was then collected for measurement of fluoride concentration, serum total alkaline phosphatase activity (ALP) and concentration of telopeptide of rat type I collagen (ICTP). Last three groups (ten rats each) were ovariectomized and received than only distilled water to drink. After following six weeks all rats were sacrificed. After six weeks of experiment the group receiving 8 mg F-/l showed the lowest ICTP values and the smallest decrease of serum ALP activity compared to the baseline control group. The rats with higher plasma fluoride concentrations after ovariectomy demonstrated lower ICTP concentrations and higher ALP activity than animals with lower fluoride concentrations. PMID:10101440

  8. Relationship among dietary estimates of net endogenous acid production, bone mineral density and biochemical markers of bone turnover in an Iranian general population.

    PubMed

    Rahbar, Alireza; Larijani, Bagher; Nabipour, Iraj; Mohamadi, Mohamad Mehdi; Mirzaee, Kamran; Amiri, Zahra

    2009-11-01

    Chronic, low-grade metabolic acidosis due to Western diets may be a risk factor for osteoporosis. The severity can be determined in part by net endogenous acid production (NEAP). In a population-based study, a total of 1028 healthy men and women aged 20-72 years were evaluated for dietary intakes and NEAP estimates with a validated food frequency questionnaire. Dual-energy X-ray absorptiometry (DXA) was used to determine BMD of the lumbar spine (L2-L4), distal third of radius, and proximal femur. Serum CrossLaps, degradation products of the C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific ELISA methods. Lower estimates of energy-adjusted rates of NEAP were associated with greater femoral neck BMD (p=0.01) in premenopausal women and with greater BMDs at the distal radius (p=0.001) and lumbar spine (p=0.04) in postmenopausal women. Compared with women in the highest quartile of the estimates of the energy-adjusted rates of NEAP, pre- and postmenopausal women in the lowest quartile had significantly greater means of osteocalcin [9.12 (SD+/-1.62) vs. 5.24 (SD+/-1.41) ng/ml, p=0.02 and 11.74 (SD+/-1.69) vs. 7.79 (SD+/-2.63) ng/ml, p=0.002, respectively]. Analysis by quartiles of the estimates of energy-adjusted rates of NEAP did not reveal a relationship between BMD and bone turnover markers in men. In conclusion, we found that a high energy-adjusted rate of NEAP was associated with a significantly lower BMD in women but not in men and the energy-adjusted rate of NEAP had a negative relationship with bone formation.

  9. Bone Turnover in Wild Type and Pleiotrophin-Transgenic Mice Housed for Three Months in the International Space Station (ISS)

    PubMed Central

    Brun, Francesco; Canciani, Barbara; Manescu, Adrian; Marozzi, Katia; Cilli, Michele; Costa, Delfina; Liu, Yi; Piccardi, Federica; Tasso, Roberta; Tromba, Giuliana; Rustichelli, Franco; Cancedda, Ranieri

    2012-01-01

    Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity’s negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice. PMID:22438896

  10. Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure

    PubMed Central

    Damment, Stephen; Secker, Roger; Shen, Victor; Lorenzo, Victor; Rodriguez, Mariano

    2011-01-01

    Background. Lanthanum carbonate (FOSRENOL®, Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD–mineral and bone disorder (CKD–MBD). Methods. Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion. Results. Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis. Conclusions. Long-term treatment with lanthanum carbonate reduced the biochemical and bone abnormalities of CKD–MBD in a rat model of CRF. PMID:21098011

  11. Bone loss in chronic kidney disease: Quantity or quality?

    PubMed

    Zheng, Cai-Mei; Zheng, Jin-Quan; Wu, Chia-Chao; Lu, Chien-Lin; Shyu, Jia-Fwu; Yung-Ho, Hsu; Wu, Mei-Yi; Chiu, I-Jen; Wang, Yuan-Hung; Lin, Yuh-Feng; Lu, Kuo-Cheng

    2016-06-01

    Chronic kidney disease (CKD) patients experience bone loss and fracture because of a specific CKD-related systemic disorder known as CKD-mineral bone disorder (CKD-MBD). The bone turnover, mineralization, and volume (TMV) system describes the morphological bone lesions in renal osteodystrophy related to CKD-MBD. Bone turnover and bone volume are defined as high, normal, or low, and bone mineralization is classified as normal or abnormal. All types of bone histology related to TMV are responsible for both bone quantity and bone quality losses in CKD patients. This review focuses on current bone quantity and bone quality losses in CKD patients and finally discusses potential therapeutic measures. PMID:27049042

  12. Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging.

    PubMed

    Bhutani, Manisha; Turkbey, Baris; Tan, Esther; Korde, Neha; Kwok, Mary; Manasanch, Elisabet E; Tageja, Nishant; Mailankody, Sham; Roschewski, Mark; Mulquin, Marcia; Carpenter, Ashley; Lamping, Elizabeth; Minter, Alex R; Weiss, Brendan M; Mena, Esther; Lindenberg, Liza; Calvo, Katherine R; Maric, Irina; Usmani, Saad Z; Choyke, Peter L; Kurdziel, Karen; Landgren, Ola

    2016-05-01

    The incidence and importance of bone marrow involvement and/or early bone lesions in multiple myeloma (MM) precursor diseases is largely unknown. This study prospectively compared the sensitivity of several imaging modalities in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Thirty patients (10 each with MGUS, SMM and MM) were evaluated with skeletal survey, [18F]FDG-PET/CT, [18F]NaF-PET/CT and morphologic dynamic contrast enhanced (DCE)-MRI. An additional 16 SMM patients had skeletal surveys and FDG-PET/CT. Among MGUS patients, DCE-MRI found only one focal marrow abnormality; other evaluations were negative. Among 26 SMM patients, five (19%) were re-classified as MM based on lytic bone lesions on CT and six had unifocal or diffuse marrow abnormality. Among MM, marrow abnormalities were observed on FDG-PET/CT in 8/10 patients and on DCE-MRI in nine evaluable patients. Abnormal NaF uptake was observed only in MM patients with lytic lesions on CT, providing no additional clinical information. PMID:26690712

  13. Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

    PubMed

    Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

    2013-11-01

    The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

  14. Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

    PubMed Central

    Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

    2013-01-01

    The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

  15. Imaging microfractures and other abnormalities of bone using a supercontinuum laser source with wavelengths in the four NIR optical windows

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Leproux, Philippe; Alfano, R. R.

    2015-02-01

    Many areas of the body such as the tibia have minimal tissue thickness overlying bone. Near-infrared (NIR) optical windows may be used to image more deeply to reveal abnormalities hidden beneath tissue. We report on the potential application of a compact Leukos supercontinuum laser source (model STM-2000-IR) with wavelengths in the four NIR optical windows (from 650 nm to 950 nm, 1,100 nm to 1,350 nm, 1,600 to 1,870, and 2,100 nm to 2,300 nm, respectively) and between 200 - 500 microwatt/nm power, with InGaAs (Goodrich Sensors Inc. SU320- 1.7RT) and InSb detectors (Teledyne Technologies) to image microfractures and abnormalities of bone hidden beneath tissue.

  16. The relation of the XbaI and PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene to peak bone mass and bone turnover rate among young healthy men.

    PubMed

    Välimäki, Ville-Valtteri; Piippo, Kirsi; Välimäki, Stiina; Löyttyniemi, Eliisa; Kontula, Kimmo; Välimäki, Matti J

    2005-12-01

    The genes coding for estrogen receptor-alpha (ER-alpha) and androgen receptors (AR) are potential candidates for the regulation of bone mass and turnover, which may contribute to both the achievement of peak bone mass and bone loss after completion of growth. The present study was aimed at elucidating the role of two restriction fragment lengths (XbaI and PvuII) polymorphisms of the ER gene and the CAG repeat polymorphism of the AR gene as determinants of peak bone mass in men; special attention was paid to the interaction between serum free estradiol (E2) levels and the XbaI and PvuII genotypes. A cross-sectional study, with data on lifestyle factors collected retrospectively, was performed in 234 young men, aged 18.3 to 20.6 years. Of the men, 184 were recruits of the Finnish Army and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content (BMC), density (BMD) and scan area were measured in the lumbar spine and upper femur by dual-energy X-ray absorptiometry (DXA). The bone turnover rate was assessed by measuring serum type I procollagen aminoterminal propeptide (PINP) and tartrate-resistant acid phosphatase 5b (TRACP5b) as well as urinary excretion of type I collagen aminoterminal telopeptide (NTX). After adjusting for age, height, weight, exercise, smoking, calcium and alcohol intake, BMC, scan area and BMD at all measurement sites were similar for the different XbaI and PvuII genotypes of the ER and independent of the number of the CAG repeats of the AR gene. No association was found between free E2 levels and bone parameters among any genotype group of the XbaI and PvuII polymorphisms. Except for urinary NTX, which showed a tendency to higher values for the xx (P=0.08) and pp (P=0.10) genotypes of the ER, bone turnover markers were not related to the genotypes studied. Our study does not support the view that the XbaI and PvuII polymorphisms of the ER gene and the CAG polymorphism of the AR

  17. Abnormal bone formation induced by implantation of osteosarcoma-derived bone-inducing substance in the X-linked hypophosphatemic mouse

    SciTech Connect

    Yoshikawa, H.; Masuhara, K.; Takaoka, K.; Ono, K.; Tanaka, H.; Seino, Y.

    1985-01-01

    The X-linked hypophosphatemic mouse (Hyp) has been proposed as a model for the human familial hypophosphatemia (the most common form of vitamin D-resistant rickets). An osteosarcoma-derived bone-inducing substance was subcutaneously implanted into the Hyp mouse. The implant was consistently replaced by cartilage tissue at 2 weeks after implantation. The cartilage matrix seemed to be normal, according to the histological examination, and 35sulphur (TVS) uptake was also normal. Up to 4 weeks after implantation the cartilage matrix was completely replaced by unmineralized bone matrix and hematopoietic bone marrow. Osteoid tissue arising from the implantation of bone inducing substance in the Hyp mouse showed no radiologic or histologic sign of calcification. These findings suggest that the abnormalities of endochondral ossification in the Hyp mouse might be characterized by the failure of mineralization in cartilage and bone matrix. Analysis of the effects of bone-inducing substance on the Hyp mouse may help to give greater insight into the mechanism and treatment of human familial hypophosphatemia.

  18. Effect of the Medicinal Mushroom, Grifola gargal (Agaricomycetes), on Bone Turnover Markers and Serum Lipids in Middle-Aged and Elderly Japanese Women.

    PubMed

    Harada, Etsuko; Morizono, Toshihiro; Sumiya, Toshimitsu; Kawagishi, Hirokazu

    2016-01-01

    A clinical study was performed to examine the effect of the edible mushroom, Grifola gargal, on bone turnover markers and serum lipids in middle-aged and elderly Japanese women. Postmenopausal women aged 51-73 years (mean age, 61 years) received daily oral administration of 5 g G. gargal fruiting bodies (hot air-dried and powdered; G. gargal powder [GGP]). Serum levels of bone alkaline phosphatase (BAP) and lipids and urinary deoxypyridinoline (DPD) levels were measured before and 2 weeks after the start of GGP treatment. As a result, urinary DPD bone resorption marker levels in women treated with GGP decreased significantly. Serum levels of the BAP bone formation marker also tended to increase, but the difference was not significant. By contrast, the atherogenic index decreased and the high-density lipoprotein (HDL) ratio increased significantly. However, there were no statistically significant differences in serum lipids of total cholesterol, HDL cholesterol, and low-density lipoprotein cholesterol. In addition, this study demonstrated for the first time that G. gargal is safe for human consumption. PMID:27279439

  19. Bone and the immune system.

    PubMed

    Gruber, H E

    1991-07-01

    There are several lines of evidence which provide support for an important relationship between immune cells and bone. Clinical studies of immunodeficiency syndromes have shown that abnormalities in bone shape are evident on x-rays, and peculiarities in the structure of the growth plate have been identified by histopathology. Studies of bone histology, and quantitation of cellular abnormalities, are scarce. Abnormalities in bone turnover, have, however, been identified in the nude mouse model. Many lines of evidence derived from in vitro bone studies have shown that lymphokines and monokines can influence bone formation and bone resorption. Some clinical studies of postmenopausal osteoporosis have indicated the possible presence of immune cell changes in this condition. Although several hypotheses have been formed regarding the exact mechanisms of the effect of immune cytokine on bone, this is clearly a very large area of study and there is a need for additional carefully controlled experiments with special emphasis on bone cells and bone matrix, especially in the human. As knowledge progresses regarding immunology and hematology, a clearer understanding of the lineages of the osteoblast and osteoclast will emerge and we will better understand how specialized bone cells interact with and react to their immune cell neighbors in the bone marrow and to immune system signals. These findings will have especially important implications for the local bone loss seen in rheumatoid arthritis, periodontal disease, and chronic osteomyelitis. PMID:2068116

  20. Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicor...

  1. Effect of non-steroidal anti-inflammatory drugs on bone turnover: an evidence-based review.

    PubMed

    Konstantinidis, Ioannis; Papageorgiou, Spyridon N; Kyrgidis, Athanassios; Tzellos, Thrasivoulos-George; Kouvelas, Dimitrios

    2013-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review. PMID:23016823

  2. Comparison of the effects of cholecalciferol and calcitriol on calcium metabolism and bone turnover in Chinese postmenopausal women with vitamin D insufficiency

    PubMed Central

    Zhang, Hao; Huang, Qi-ren; Gu, Jie-mei; Hu, Wei-wei; Liu, Yu-juan; Hu, Yun-qiu; Zhang, Zhen-lin

    2012-01-01

    Aim: To compare the effects of cholecalciferol (800 IU/d) and calcitriol (0.25 μg/d) on calcium metabolism and bone turnover in Chinese postmenopausal women with vitamin D insufficiency. Methods: One hundred Chinese postmenopausal women aged 63.8±7.0 years and with serum 25-hydroxyvitamin D [25(OH)D] concentration <30 ng/mL were recruited. The subjects were divided into 2 groups based on the age and serum 25(OH)D concentration: 50 subjects (group A) received cholecalciferol (800 IU/d), and 50 subjects (group B) received calcitriol (0.25 μg/d) for 3 months. In addition, all the subjects received Caltrate D (calcium plus 125 IU cholecalciferol) daily in the form of one pill. The markers of calcium metabolism and bone turnover, including the serum levels of calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, 25(OH)D and β-CrossLaps of type I collagen containing cross-linked C-telopeptide (β-CTX), were measured before and after the intervention. Results: After the 3-month intervention, the serum 25(OH)D concentration in group A was significantly increased from 16.01±5.0 to 20.02±4.5 ng/mL, while that in group B had no significant change. The serum calcium levels in both the groups were significantly increased (group A: from 2.36±0.1 to 2.45±0.1 mmol/L; group B: from 2.36±0.1 to 2.44±0.1 mmol/L). The levels of serum intact parathyroid hormone in both the groups were significantly decreased (group A: from 48.56±12.8 to 39.59±12.6 pg/mL; group B: from 53.67±20.0 to 40.32±15.4 pg/mL). The serum levels of β-CTX in both the groups were also significantly decreased (group A: from 373.93±135.3 to 325.04±149.0 ng/L; group B: from 431.00±137.1 to 371.74±185.0 ng/L). Conclusion: We concluded that both cholecalciferol (800 IU/d) and calcitriol (0.25 μg/d) plus Caltrate D modifies the serum calcium and bone turnover markers in Chinese postmenopausal women with vitamin D insufficiency. In addition, cholecalciferol (800 IU/d) significantly

  3. Novel, near-infrared spectroscopic, label-free, techniques to assess bone abnormalities such as Paget's disease, osteoporosis and bone fractures

    NASA Astrophysics Data System (ADS)

    Sordillo, Diana C.; Sordillo, Laura A.; Shi, Lingyan; Budansky, Yury; Sordillo, Peter P.; Alfano, Robert R.

    2015-02-01

    Near- infrared (NIR) light with wavelengths from 650 nm to 950 nm (known as the first NIR window) has conventionally been used as a non-invasive technique that can reach deeper penetration depths through media than light at shorter wavelengths. Recently, several novel, NIR, label-free, techniques have been developed to assess Paget's disease of bone, osteoporosis and bone microfractures. We designed a Bone Optical Analyzer (BOA) which utilizes the first window to measure changes of Hb and HbO2. Paget's disease is marked by an increase in vascularization in bones, and this device can enable easy diagnosis and more frequent monitoring of the patient's condition, without exposing him to a high cumulative dose of radiation. We have also used inverse imaging algorithms to reconstruct 2D and 3D maps of the bone's structure. This device could be used to assess diseases such as osteoporosis. Using 800 nm femtosecond excitation with two-photon (2P) microscopy, we acquired 2PM images of the periosteum and spatial frequency spectra (based on emission of collagen) from the periosteal regions. This technique can provide information on the structure of the periosteum and can detect abnormalities which may be an indication of disease. Most recently, we showed that longer NIR wavelengths in the second and third NIR windows (1100 nm-1350 nm, 1600 nm-1870 nm), could be used to image bone microfractures. Use of NIR light could allow for repeated studies in patients with diseases such as Paget's and osteoporosis quickly and non-invasively, and could impact the current management for these diseases.

  4. Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

    PubMed

    Kristensen, Mette; Jensen, Marlene; Kudsk, Jane; Henriksen, Marianne; Mølgaard, Christian

    2005-12-01

    In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.

  5. The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors.

    PubMed

    Simonavice, Emily; Liu, Pei-Yang; Ilich, Jasminka Z; Kim, Jeong-Su; Arjmandi, Bahram; Panton, Lynn B

    2014-06-01

    The purpose of this study was to examine the effects of resistance training (RT) and dried plum (DP) consumption on strength, body composition, blood markers of bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n = 12; RT+DP, n = 11), aged 64 ± 7 years, were evaluated at baseline and after 6 months of intervention on the following: muscular strength (chest press and leg extension) via 1-repetition maximums (1RMs); body composition, specifically bone mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT prescription was 2 days/week of 10 exercises, including 2 sets of 8-12 repetitions at ∼60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were no baseline differences between groups or any group-by-time interactions for any of the variables. BCS increased upper (p < 0.05) (RT: 64 ± 14 to 80 ± 17 kg; RT+DP: 72 ± 23 to 91 ± 20 kg) and lower (p < 0.05) (RT: 69 ± 20 to 87 ± 28 kg; RT+DP: 78 ± 19 to 100 ± 21 kg) body strength. Body composition and BMD improvements were not observed. TRAP-5b decreased in the RT group (p < 0.05) (4.55 ± 1.57 to 4.04 ± 1.63 U/L) and the RT+DP group (p = 0.07) (5.10 ± 2.75 to 4.27 ± 2.03 U/L). Changes in BAP and CRP were not observed. RT was effective for improving biochemical markers of bone turnover and muscular strength in BCS. A longer and higher intensity intervention may be needed to reveal the true effects of RT and DP on body composition and biochemical markers of inflammation.

  6. Chronic kidney disease and bone metabolism.

    PubMed

    Kazama, Junichiro James; Matsuo, Koji; Iwasaki, Yoshiko; Fukagawa, Masafumi

    2015-05-01

    Chronic kidney disease-related mineral and bone disease (CKD-MBD) is a syndrome defined as a systemic mineral metabolic disorder associated with CKD, and the term renal osteodystrophy indicates a pathomorphological concept of bone lesions associated with CKD-MBD. Cortical bone thinning, abnormalities in bone turnover and primary/secondary mineralization, elevated levels of circulating sclerostin, increased apoptosis in osteoblasts and osteocytes, disturbance of the coupling phenomenon, iatrogenic factors, accumulated micro-crackles, crystal/collagen disorientation, and chemical modification of collagen crosslinks are all possible candidates found in CKD that could promote osteopenia and/or bone fragility. Some of above factors are the consequences of abnormal systemic mineral metabolism but for others it seem unlikely. We have used the term uremic osteoporosis to describe the uremia-induced bone fragility which is not derived from abnormal systemic mineral metabolism. Interestingly, the disease aspect of uremic osteoporosis appears to be similar to that of senile osteoporosis. PMID:25653092

  7. Osteoblast-Specific Deletion of Pkd2 Leads to Low-Turnover Osteopenia and Reduced Bone Marrow Adiposity

    PubMed Central

    Xiao, Zhousheng; Cao, Li; Liang, Yingjuan; Huang, Jinsong; Stern, Amber Rath; Dallas, Mark; Johnson, Mark; Quarles, Leigh Darryl

    2014-01-01

    Polycystin-1 (Pkd1) interacts with polycystin-2 (Pkd2) to form an interdependent signaling complex. Selective deletion of Pkd1 in the osteoblast lineage reciprocally regulates osteoblastogenesis and adipogenesis. The role of Pkd2 in skeletal development has not been defined. To this end, we conditionally inactivated Pkd2 in mature osteoblasts by crossing Osteocalcin (Oc)-Cre;Pkd2+/null mice with floxed Pkd2 (Pkd2flox/flox) mice. Oc-Cre;Pkd2flox/null (Pkd2Oc-cKO) mice exhibited decreased bone mineral density, trabecular bone volume, cortical thickness, mineral apposition rate and impaired biomechanical properties of bone. Pkd2 deficiency resulted in diminished Runt-related transcription factor 2 (Runx2) expressions in bone and impaired osteoblastic differentiation ex vivo. Expression of osteoblast-related genes, including, Osteocalcin, Osteopontin, Bone sialoprotein (Bsp), Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex), Dentin matrix protein 1 (Dmp1), Sclerostin (Sost), and Fibroblast growth factor 23 (FGF23) were reduced proportionate to the reduction of Pkd2 gene dose in bone of Oc-Cre;Pkd2flox/+ and Oc-Cre;Pkd2flox/null mice. Loss of Pkd2 also resulted in diminished peroxisome proliferator-activated receptor γ (PPARγ) expression and reduced bone marrow fat in vivo and reduced adipogenesis in osteoblast culture ex vivo. Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP), reciprocally acting as co-activators and co-repressors of Runx2 and PPARγ, were decreased in bone of Oc-Cre;Pkd2flox/null mice. Thus, Pkd1 and Pkd2 have coordinate effects on osteoblast differentiation and opposite effects on adipogenesis, suggesting that Pkd1 and Pkd2 signaling pathways can have independent effects on mesenchymal lineage commitment in bone. PMID:25464512

  8. An Abnormal Bone Lesion of the Scapula in a Collegiate Basketball Player: A Case Report

    PubMed Central

    O'Brien, Matthew S.; Donnell, Allison; Miller, Jason; Iven, Val Gene; Pascale, Mark

    2013-01-01

    Objective: To present the case of a bone lesion of the scapula in a collegiate basketball player. Background: A 19-year-old National Collegiate Athletic Association Division I male basketball player presented with pain in the posterior region of the right shoulder. During practice, he was performing a layup when his arm was forced into hyperflexion by a defender. Evaluation revealed a bone lesion involving the scapular spine and base of the acromion. Differential Diagnosis: Acromioclavicular joint sprain, subacromial bursitis, subscapular bursitis, humeral head contusion, acromial fracture. Treatment: The patient was treated for 2 months with therapeutic modalities and rehabilitation exercises. Because of persistent pain and the risk of a pathologic fracture, open surgical biopsy and bone grafting were then undertaken. Uniqueness: Most simple bone cysts affect the proximal humerus and femur, whereas our patient's lesion was in the acromial complex. Conclusions: Athletic trainers should be alert to the unusual possibility of bone cysts, which are usually identified incidentally when radiographs are obtained for other reasons. Most simple bone cysts are asymptomatic, but a pathologic fracture can occur with trauma. PMID:23725460

  9. Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

    PubMed Central

    de la Piedra, C; Alcaraz, A; Bellmunt, J; Meseguer, C; Gómez-Caamano, A; Ribal, M J; Vázquez, F; Anido, U; Samper, P; Esteban, E; Álvarez-Ossorio, J L; Lara, P C; San José, L A; Contreras, J A; del Alba, A G; González-Gragera, B; Tabernero, A J; González-Enguita, C; Fernández, J M; García-Escudero, A; Gómez-Veiga, F; Méndez, M J; Segarra, J; Virizuela, J A; Carles, J; Lassa, A; Calderero, V; Constela, M; Delgado, D; Mañas, A; Murias, A; Reynes, G; Rodriguez, B; Rubio, G; Sánchez, E; Unda, M; Solsona, E; Martínez-Javaloyas, J M; Comet-Batlle, J; Quicios, C; Martín-Fernández, M; Mahillo-Fernández, I; Morote, J

    2013-01-01

    Background: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important. PMID:23722472

  10. Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures.

    PubMed

    Shigdel, Rajesh; Osima, Marit; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Zebaze, Roger; Bjørnerem, Åshild

    2015-12-01

    Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both p<0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to

  11. Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures.

    PubMed

    Shigdel, Rajesh; Osima, Marit; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Zebaze, Roger; Bjørnerem, Åshild

    2015-12-01

    Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both p<0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to

  12. Osteochondrosis and epiphyseal bone abnormalities associated with copper deficiency in bison calves.

    PubMed Central

    Woodbury, M R; Feist, M S; Clark, E G; Haigh, J C

    1999-01-01

    Two bison calves were submitted to the Western College of Veterinary Medicine to confirm suspected copper deficiency. In addition to clinical signs, there were pathologic changes in the cartilage and subchondral bone of several joints. Water analysis indicated high levels of sulfate in the drinking water, contributing to a secondary copper deficiency. Images Figure 1. Figure 2. PMID:10646064

  13. Vitamin D receptor gene BsmI-polymorphism in Finnish premenopausal and postmenopausal women: its association with bone mineral density, markers of bone turnover, and intestinal calcium absorption, with adjustment for lifestyle factors.

    PubMed

    Laaksonen, Marika; Kärkkäinen, Merja; Outila, Terhi; Vanninen, Tarja; Ray, Carola; Lamberg-Allardt, Christel

    2002-01-01

    Bone mineral density (BMD) is regulated by genetic and environmental factors. Sixty percent to 80% of bone mass is suggested to be under polygenetic control, but the role of individual genes seems to be modest. Several studies have indicated that the vitamin D receptor ( VDR) gene has a role in the regulation of BMD and bone metabolism, but the results are very controversial. We studied the associations between BsmI-polymorphism of the VDR gene and BMD and bone metabolism in 24 premenopausal (aged 22-45 years) and 69 postmenopausal (aged 48-65 years) Finnish women. The BMD of the lumbar spine and femoral neck and bone turnover markers were measured, and the intestinal calcium absorption was investigated, using a method based on the absorption of non-radioactive strontium. The genotype distribution was 16%, BB; 34.5%, Bb; and 49.5%, bb, which differs from the genotype distribution found in other Caucasian populations, but is similar to earlier Finnish reports. The winter value of 25-hydroxyvitamin-D (25-OH-D) was highest for the BB genotype in both age groups (analysis of covariance [ANCOVA]; premenopausal women P = 0.5, postmenopausal women P = 0.03, and for the groups combined P = 0.02). Lumbar spine BMD and intestinal strontium absorption were highest for the BB genotype in both age groups, but these results were nonsignificant. The markers of bone metabolism did not differ significantly between the VDR genotypes. The BB genotype had the best vitamin D status, which could explain the differences in calcium absorption between the genotypes. However, the conclusions of our study are limited because of the small number of subjects. PMID:12434167

  14. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits.

    PubMed

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  15. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits

    PubMed Central

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  16. Prevalence of Bone Mineral Density Abnormalities and Factors Affecting Bone Density in Patients with Chronic Obstructive Pulmonary Disease in a Tertiary Care Hospital in Southern India

    PubMed Central

    Mani, Sathish Kumar; Gopal, Gopinath Kango; Rangasami, Srinivasan

    2016-01-01

    Introduction Chronic Obstructive Pulmonary Disease (COPD) is a disease of wasting with airflow limitation, associated with a variety of systemic manifestations such as reduced Bone Mineral Density (BMD). There is a paucity of Indian studies on the effects of COPD on BMD. Aim This study was conducted to estimate the prevalence of osteopenia and osteoporosis in COPD patients and the correlation between bone density and severity of COPD classified according to GOLD Global initiative for chronic Obstructive Lung Disease guidelines (GOLD). Materials and Methods A prospective study of 60 patients diagnosed to have COPD, was conducted in the outpatient department of Respiratory Medicine, at a tertiary care hospital in Southern India, between September 2012 and September 2013. BMD was measured using ultrasound bone densitometer (ACHILLES GE HEALTH CARE). Patients with a T-score between -1 and -2.5 were considered to be osteopenic while patients with a T score less than -2.5 were considered to be osteoporotic (WHO criteria). Results Overall, 40 (67%) patients had an abnormal bone mineral density. A total of 21 (35%) patients were osteoporotic while 19 (33%) were osteopenic. BMD levels correlated with severity of obstruction (p<0.001), smoking status (p=0.02), age (p=0.05) and number of pack years (p=0.001). Conclusion Patients with COPD are at an increased risk for lower BMD and osteoporotic fractures and the risk appears to increase with disease severity. Further studies are required to assess whether routine BMD measurements in COPD patients is beneficial to diagnose osteoporosis and reduce morbidity. PMID:27790490

  17. Potassium bicarbonate supplementation lowers bone turnover and calcium excretion in older men and women a randomized dose-finding trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bic...

  18. Eosinophilic fasciitis associated with hypereosinophilia, abnormal bone-marrow karyotype and inversion of chromosome 5.

    PubMed

    Ferguson, J S; Bosworth, J; Min, T; Mercieca, J; Holden, C A

    2014-03-01

    We report the case of a male patient presenting with eosinophilia, pulmonary oedema and eosinophilic fasciitis (EF). He had the classic clinical appearance and magnetic resonance imaging of EF. Cytogenetic analysis of the bone marrow revealed a previously undescribed pericentric inversion of chromosome 5. Overall, the presentation was consistent with a diagnosis of chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS). Dermatologists should consult a haematologist in cases of EF, in order to rule out possible haematological malignancies.

  19. Do abnormal hemipelvic bone stresses contribute to loosening and migration of screw-threaded cups?

    PubMed

    Learmonth, I D; Spirakis, A

    1994-03-01

    Excellent long-term results have been reported with the Charnley low-friction arthroplasty. Failure of the cemented acetabular component has been identified as a problem in the longer term, while cemented hip replacements in active young patients have exhibited a disconcerting incidence of early clinical or radiological failure. This resulted in the development of the cementless arthroplasty. Bone responds favourably to an optimal stress window and reacts dynamically to metal implants that have a greatly differing modulus of elasticity. This study represents a comparative qualitative analysis of the peri-acetabular hemipelvic stresses after loading two cementless (press-fit and screw-threaded) acetabular components inserted into identical bone models. A simplified model of the artificial hip joint was constructed and the very sensitive stress analysis technique of holographic interferometry was used for the investigation. Peri-acetabular stress concentrations were noted with the screw-threaded cup. This may predispose to bone resorption and it is suggested that these could be implicated in the migration of these cups described in published reports.

  20. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients.

    PubMed

    Bieghs, Liesbeth; Brohus, Malene; Kristensen, Ida B; Abildgaard, Niels; Bøgsted, Martin; Johnsen, Hans E; Conover, Cheryl A; De Bruyne, Elke; Vanderkerken, Karin; Overgaard, Michael T; Nyegaard, Mette

    2016-01-01

    Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and 125I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5-3.8 fold) and decrease in intact IGFBP-3 (0.6-0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration. PMID:27111220

  1. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients

    PubMed Central

    Bieghs, Liesbeth; Brohus, Malene; Kristensen, Ida B.; Abildgaard, Niels; Bøgsted, Martin; Johnsen, Hans E.; Conover, Cheryl A.; De Bruyne, Elke; Vanderkerken, Karin

    2016-01-01

    Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and 125I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5–3.8 fold) and decrease in intact IGFBP-3 (0.6–0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration. PMID:27111220

  2. Potential Usefulness of BMD and Bone Turnover Monitoring of Zoledronic Acid Therapy Among Women With Osteoporosis: Secondary Analysis of Randomized Controlled Trial Data.

    PubMed

    Bell, Katy Jl; Hayen, Andrew; Glasziou, Paul; Irwig, Les; Eastell, Richard; Harrison, Stephanie L; Black, Dennis M; Bauer, Douglas C

    2016-09-01

    We aimed to compare the clinical validity and the detectability of response of short-term changes in bone mineral density (BMD; hip and spine) and bone turnover markers (serum PINP and CTX) through secondary analysis of trial data. We analyzed data on 7765 women with osteoporosis randomized to 5-mg once-yearly infusions of zoledronic acid or placebo in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT; trial ran from 2002 to 2006) and the first extension trial (trial ran from 2006 to 2009). We assessed the clinical validity and detectability of response for 1-year measurements of the following monitoring tests: total hip and lumbar spine BMD, serum N-terminal propeptide of type I collagen (sPINP), and serum C-telopeptide of type I collagen (sCTX; 6-month measurement used). Clinical validity was assessed by examining prediction of clinical fracture in Cox models; detectability of response to treatment was assessed by the ratio of signal to noise, estimated from the distributions of change in zoledronic acid and placebo groups. Baseline measurements were available for 7683 women with hip BMD, 558 with spine BMD, 1246 with sPINP, and 517 women with sCTX. Hip BMD and sPINP ranked highly for prediction of clinical fracture, whereas sPINP and sCTX ranked highly for detectability of response to treatment. Serum PINP had the highest overall ranking. In conclusion, serum PINP is potentially useful in monitoring response to zoledronic acid. Further research is needed to evaluate the effects of monitoring PINP on treatment decisions and other clinically relevant outcomes. © 2016 American Society for Bone and Mineral Research. PMID:27027655

  3. Interrelationships between tooth properties and biochemical bone turnover markers investigated on six-month-old pig model.

    PubMed

    Tymczyna, Barbara; Tatara, Marcin R; Krupski, Witold; Tymczyna-Sobotka, Monika; Bachanek, Teresa

    2013-01-01

    The aim of the study was to determine interrelationships between bone tissue metabolism indices and morphological, biomechanical and densitometric properties of hard dental tissues. First primary maxillary incisor from 6-month-old pigs (N=27) was evaluated in terms of weight and length. Mean volumetric tooth mineral density, total tooth volume, enamel total volume, enamel volumetric mineral density, dentine total volume and dentine volumetric mineral density were estimated with the use of quantitative computed tomography and micro computed tomography techniques. Tooth mineral density and tooth mineral content were evaluated with the use of dual-energy X-ray absorptiometry. Microhardness of enamel was measured using Vicker's test. Evaluations of total calcium, ionized calcium, magnesium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type-I collagen (CTX), insulin-like growth factor-1, growth hormone and parathyroid hormone were performed in plasma and serum samples. Pearson's correlation coefficients were determined between all the investigated variables, and P<0.05 was considered as statistically significant. The obtained results have shown mainly mutual dependences between biochemical indicators of bone metabolism. Evaluation of CTX concentration in serum of pigs has shown the highest predictive value in relation to morphological, densitometric and biomechanical properties of teeth. PMID:23076035

  4. Bone Markers

    MedlinePlus

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

  5. Altered material properties are responsible for bone fragility in rats with chronic kidney injury.

    PubMed

    Iwasaki, Yoshiko; Kazama, Junichiro J; Yamato, Hideyuki; Matsugaki, Aira; Nakano, Takayoshi; Fukagawa, Masafumi

    2015-12-01

    Chronic kidney disease (CKD) is associated with an increased risk of fragility fractures, but the underlying pathophysiological mechanism remains obscure. We performed an in vivo experimental study to examine the roles of uremia and abnormal mineral/parathyroid metabolism in the development of bone metabolic abnormalities in uremic rats. Male Sprague-Dawley rats were divided into four groups, comprising sham operation (high turnover bone control=HTB-Cont), 5/6-nephrectomy (high turnover bone nephrectomized=HTB-Nx), thyroparathyroidectomy (low turnover bone control=LTB-Cont), and thyroparathyroidectomy plus 5/6 nephrectomy (low turnover bone nephrectomized=LTB-Nx), and maintained for 16 weeks. Uremia was successfully created in the LTB-Nx and HTB-Nx groups, while hyperparathyroidism was only found in the HTB-Nx group. Cancellous bone histomorphometry revealed significantly higher bone turnover in the HTB-Nx group than in the LTB-Nx group. Storage modulus at 1 Hz and tan delta in cortical bone of the femur, which represent the viscoelastic mechanical properties, were significantly lower in both Nx groups than in the Cont groups regardless of bone metabolism. Pentosidine-to-matrix ratio was increased and crystallinity was decreased in both Nx groups regardless of bone turnover. Mineral-to-matrix ratio was significantly decreased in the HTB-Nx group, but increased in the LTB-Nx group. Enzymatic collagen crosslinks were decreased in the HTB-Nx group. The degree of orientation of the c-axis in carbonated hydroxyapatite (biological apatite=BAp) crystallites was decreased in both Nx groups regardless of bone metabolism. Stepwise multivariate regression revealed that pentosodine-to-matrix ratio and BAp preferential c-axis orientation were significantly associated with storage modulus and tan delta. In conclusion, bone elastic mechanical properties deteriorated regardless of bone metabolism or bone mass in rats with chronic kidney injury. Various changes in bone mineral

  6. Bone biopsy in the diagnosis of renal osteodystrophy.

    PubMed

    Spasovski, Goce B

    2004-01-01

    When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse manifestations in bone cells and structure as well as the rate of bone turnover. In ESRF when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology named renal osteodystrophy (ROD). On the other hand, survival rates of patients on dialysis have increased with improved dialytic therapy and the resultant increased duration of dialysis has led to a rise in renal osteodystrophy. Because this metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH levels are commonly used to assess bone turnover in dialyzed patients. However, it is found that serum PTH levels between 65 and 450 pg/ml seen in the majority of dialysis patients are not predictive of the underlying bone disease. To date, bone biopsy is the most powerful and informative diagnostic tool to provide important information on precisely the type of renal osteodystrophy affecting patients, the degree of severity of the lesions, and the presence and amount of aluminum and strontium deposition in bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered as an invasive procedure, bone biopsy has been proven as safe and free from major complications besides pain, haematoma or wound infections, but the operator's experience and skill is important in minimizing morbidity. Alternatives to bone biopsy continue to be pursued, but the non-invasive bone markers have not been proven to hold sufficient diagnostic performance related to the bone turnover, mineralization process and bone cell abnormality. At present however, the transiliac bone biopsy remains the golden standard in the diagnosis of renal osteodystrophy. PMID:15735537

  7. Changes in the vitamin D endocrine system and bone turnover after oral vitamin D3 supplementation in healthy adults: results of a randomised trial

    PubMed Central

    2012-01-01

    Background There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks’ daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. Methods Healthy adults aged 19–48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). Results S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters. Conclusions Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. Trial Registration Clinical

  8. Cold-batter mincing of hot-boned and crust-freezing air-chilled turkey breast improved meat turnover time and product quality.

    PubMed

    Medellin-Lopez, M; Sansawat, T; Strasburg, G; Marks, B P; Kang, I

    2014-03-01

    The purpose of this research was to evaluate the combined effects of turkey hot-boning and cold-batter mincing technology on acceleration of meat turnover and meat quality improvement. For each of 3 replications, 15 turkeys were slaughtered and eviscerated. Three of the eviscerated carcasses were randomly assigned to water-immersion chilling for chill-boning (CB) and the remaining were immediately hot-boned (HB), half of which were used without chilling whereas the remaining were subjected to crust-freezing air chilling (CFAC) in an air-freezing room (1.0 m/s, -12°C) with/without 1/4; sectioning (HB-1/4;CFAC, HB-CFAC). As a result, CB and HB breasts were minced using 1 of 5 treatments: (1) CB and traditional mincing (CB-T), (2) HB and mincing with no chilling (HB-NC), (3) HB and mincing with CO2 (HB-CO2), (4) HB and mincing after CFAC (HB-CFAC), and (5) HB and mincing after quarter sectioning and CFAC (HB-1/4;CFAC). Traditional water-immersion chilling took an average of 5.5 h to reduce the breast temperature to 4°C, whereas HB-CFAC and HB-1/4;CFAC took 1.5 and 1 h, respectively. The breast of HB-CFAC and HB-1/4;CFAC showed significantly higher pH (6.0-6.1), higher fragmentation index (196-198), and lower R-value (1.0-1.1; P < 0.05) than those of the CB controls. No significant differences (P > 0.05) in sarcomere length were seen between CB-T and HB-CFAC filets regardless of quarter sectioning. When muscle was minced, the batter pH (5.9) of CB-T was significantly lower (P < 0.05) than those (6.1-6.3) of HB-NC, HB-CO2, and HB-1/4;CFAC, with the intermediate pH (6.0) seen for the HB-CFAC. When meat batters were cooked, higher cooking yield (90 - 91%; P < 0.05) was found in HB-CFAC, HB-1/4;CFAC, and HB-CO2, followed by HB-NC (90%) and finally CB-T (86%). Stress values (47-51 kPa) of HB-CFAC gels were significantly higher (P < 0.05) than those of CB-T (30 kPa) and HB-NC (36 kPa). A similar trend was found in strain values.

  9. Long-Term Administration of High-Fat Diet Corrects Abnormal Bone Remodeling in the Tibiae of Interleukin-6-Deficient Mice.

    PubMed

    Feng, Wei; Liu, Bo; Liu, Di; Hasegawa, Tomoka; Wang, Wei; Han, Xiuchun; Cui, Jian; Yimin; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

    2016-01-01

    In this study, we aimed to evaluate the influence of diet-induced obesity on IL-6 deficiency-induced bone remodeling abnormality. Seven-week-old IL-6(-/-) mice and their wild type (WT) littermates were fed a standard diet (SD) or high-fat diet (HFD) for 25 weeks. Lipid formation and bone metabolism in mice tibiae were investigated by histochemical analysis. Both IL-6(-/-) and WT mice fed the HFD showed notable body weight gain, thickened cortical bones, and adipose accumulation in the bone marrow. Notably, the HFD normalized the bone phenotype of IL-6(-/-) mice to that of their WT counterpart, as characterized by a decrease in bone mass and the presence of an obliquely arranged, plate-like morphology in the trabecular bone. Alkaline phosphatase and osteocalcin expressions were attenuated in both genotypes after HFD feeding, especially for the IL-6(-/-) mice. Meanwhile, tartrate-resistant acid phosphatase staining was inhibited, osteoclast apoptosis rate down-regulated (revealed by TUNEL assay), and the proportion of cathepsin K (CK)-positive osteoclasts significantly increased in IL-6(-/-) mice on a HFD as compared with IL-6(-/-) mice on standard chow. Our results demonstrate that HFD-induced obesity reverses IL-6 deficiency-associated bone metabolic disorders by suppressing osteoblast activity, upregulating osteoclastic activity, and inhibiting osteoclast apoptosis. PMID:26416243

  10. Turnover Time

    EPA Science Inventory

    Ecosystems contain energy and materials such as carbon, nitrogen, phosphorus, and water, and are open to their flow-through. Turnover time refers to the amount of time required for replacement by flow-through of the energy or substance of interest contained in the system, and is ...

  11. Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.

    PubMed Central

    Peled-Kamar, M; Lotem, J; Okon, E; Sachs, L; Groner, Y

    1995-01-01

    The copper-zinc superoxide dismutase (CuZnSOD) gene resides on chromosome 21 and is overexpressed in Down syndrome (DS) patients. Transgenic CuZnSOD mice with elevated levels of CuZnSOD were used to determine whether, as in DS, overexpression of CuZnSOD was also associated with thymus and bone marrow abnormalities. Three independently derived transgenic CuZnSOD strains had abnormal thymi showing diminution of the cortex and loss of corticomedullary demarcation, resembling thymic defects in children with DS. Transgenic CuZnSOD mice were also more sensitive than control mice to in vivo injection of lipopolysaccharide (LPS), reflected by an earlier onset and enhanced apoptotic cell death in the thymus. This higher susceptibility to LPS-induced apoptosis was associated with an increased production of hydrogen peroxide and a higher degree of lipid peroxidation. When cultured under suboptimal concentrations of interleukin 3 or in the presence of tumour necrosis factor, bone marrow cells from transgenic CuZnSOD mice produced 2- to 3-fold less granulocyte and macrophage colonies than control. The results indicate that transgenic CuZnSOD mice have certain thymus and bone marrow abnormalities which are similar to those found in DS patients, and that the defects are presumably due to an increased oxidative damage resulting in enhanced cell death by apoptosis. Images PMID:7588627

  12. Application of the FICTION technique for the simultaneous detection of immunophenotype and chromosomal abnormalities in routinely fixed, paraffin wax embedded bone marrow trephines.

    PubMed

    Korac, P; Jones, M; Dominis, M; Kusec, R; Mason, D Y; Banham, A H; Ventura, R A

    2005-12-01

    The use of interphase fluorescence in situ hybridisation (FISH) to study cytogenetic abnormalities in routinely fixed paraffin wax embedded tissue has become commonplace over the past decade. However, very few studies have applied FISH to routinely fixed bone marrow trephines (BMTs). This may be because of the acid based decalcification methods that are commonly used during the processing of BMTs, which may adversely affect the suitability of the sample for FISH analysis. For the first time, this report describes the simultaneous application of FISH and immunofluorescent staining (the FICTION technique) to formalin fixed, EDTA decalcified and paraffin wax embedded BMTs. This technique allows the direct correlation of genetic abnormalities to immunophenotype, and therefore will be particularly useful for the identification of genetic abnormalities in specific tumour cells present in BMTs. The application of this to routine clinical practice will assist diagnosis and the detection of minimal residual disease.

  13. A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study.

    PubMed

    Horwitz, Mara J; Augustine, Marilyn; Khan, Leila; Kahn, Leila; Martin, Emily; Oakley, Christine C; Carneiro, Raquel M; Tedesco, Mary Beth; Laslavic, Angela; Sereika, Susan M; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Gundberg, Caren M; Cauley, Jane A; Stewart, Andrew F

    2013-11-01

    Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 µg/day; PTHrP(1-36) 600 µg/day; and PTH(1-34) 20 µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p < 0.05) at the TH and for PTHrP(1-36) 400 (p < 0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2 D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia

  14. Evaluating bone quality in patients with chronic kidney disease

    PubMed Central

    Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

    2013-01-01

    Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

  15. Exome sequencing identifies a nonsense mutation in Fam46a associated with bone abnormalities in a new mouse model for skeletal dysplasia.

    PubMed

    Diener, Susanne; Bayer, Sieglinde; Sabrautzki, Sibylle; Wieland, Thomas; Mentrup, Birgit; Przemeck, Gerhard K H; Rathkolb, Birgit; Graf, Elisabeth; Hans, Wolfgang; Fuchs, Helmut; Horsch, Marion; Schwarzmayr, Thomas; Wolf, Eckhard; Klopocki, Eva; Jakob, Franz; Strom, Tim M; Hrabě de Angelis, Martin; Lorenz-Depiereux, Bettina

    2016-04-01

    We performed exome sequencing for mutation discovery of an ENU (N-ethyl-N-nitrosourea)-derived mouse model characterized by significant elevated plasma alkaline phosphatase (ALP) activities in female and male mutant mice, originally named BAP014 (bone screen alkaline phosphatase #14). We identified a novel loss-of-function mutation within the Fam46a (family with sequence similarity 46, member A) gene (NM_001160378.1:c.469G>T, NP_001153850.1:p.Glu157*). Heterozygous mice of this mouse line (renamed Fam46a (E157*Mhda)) had significantly high ALP activities and apparently no other differences in morphology compared to wild-type mice. In contrast, homozygous Fam46a (E157*Mhda) mice showed severe morphological and skeletal abnormalities including short stature along with limb, rib, pelvis, and skull deformities with minimal trabecular bone and reduced cortical bone thickness in long bones. ALP activities of homozygous mutants were almost two-fold higher than in heterozygous mice. Fam46a is weakly expressed in most adult and embryonic tissues with a strong expression in mineralized tissues as calvaria and femur. The FAM46A protein is computationally predicted as a new member of the superfamily of nucleotidyltransferase fold proteins, but little is known about its function. Fam46a (E157*Mhda) mice are the first mouse model for a mutation within the Fam46a gene. PMID:26803617

  16. Abnormal bone composition in female juvenile American alligators from a pesticide-polluted lake (Lake Apopka, Florida).

    PubMed Central

    Lind, P Monica; Milnes, Matthew R; Lundberg, Rebecca; Bermudez, Dieldrich; Orberg, Jan A; Guillette, Louis J

    2004-01-01

    Reproductive disorders have been found in pesticide-exposed alligators living in Lake Apopka, Florida (USA). These disorders have been hypothesized to be caused by exposure to endocrine- disruptive estrogen-like contaminants. The aim of this study was to expand our analysis beyond previous studies by investigating whether bone tissue, known to be affected by sex steroid hormones, is a potential target of endocrine disruptors. Long bones from 16 juvenile female alligators from Lake Apopka (pesticide-contaminated lake) and Lake Woodruff (control lake) were evaluated by peripheral quantitative computed tomography. We observed significant differences in bone composition, with female alligators from the contaminated lake having greater trabecular bone mineral density (BMD), total BMD, and trabecular mineral content compared with females from the control lake (p < 0.05). Increased trabecular and total BMD measurements suggest that juvenile female alligators from Lake Apopka were exposed to contaminants that created an internal environment more estrogenic than that normally observed. This estrogenic environment could be caused by both natural and anthropogenic compounds. Effects on BMD indicate interference with bone homeostasis. We hypothesize that contaminants present in the lake inhibit the natural and continuous resorption of bone tissue, resulting in increased bone mass. Although this is the only study performed to date examining effects of environmental estrogenic compounds on alligator bones, it supports previous laboratory-based studies in rodents. Further, this study is important in demonstrating that the alterations in morphology and physiology induced in free-ranging individuals living in environments contaminated with endocrine-active compounds are not limited to a few systems or tissues; rather, effects can be observed in many tissues affected by these hormones. PMID:14998753

  17. Bone Disease after Kidney Transplantation.

    PubMed

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

    2016-07-01

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

  18. Bone biopsy as a diagnostic tool in the assessment of renal osteodystrophy.

    PubMed

    Spasovski, G B

    2004-11-01

    When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse modifications in bone cells, bone structure and the rate of bone turnover. In end stage renal failure (ESRF) when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology known as renal osteodystrophy (ROD). Moreover, survival rates of patients on dialysis have increased because of therapeutic improvement and the resultant increase in duration of dialysis has led to a further rise in renal osteodystrophy. Because metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH and various bone markers are commonly used to assess bone changes in ESRF patients, but the diagnosis of underlying bone disease is still rather uncertain. To date, bone biopsy is the most powerful and informative diagnostic tool to provide precise information on the type and severity of renal osteodystrophy, and on the presence and amount of aluminum and strontium deposited in the bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered an invasive procedure, bone biopsy has been proven to be safe and free from major complications, but the operator's experience and skill is important in further minimizing morbidity. Alternatives to bone biopsy continue to be sought, but the non-invasive bone markers have not been proven to be sufficient in diagnostic performance related to bone turnover, mineralization process and bone cell abnormality. Hence, transiliac bone biopsy remains the gold standard for the diagnosis of renal osteodystrophy. PMID:15636048

  19. NF1 frameshift mutation (c.6520_6523delGAGA) association with nervous system tumors and bone abnormalities in a Chinese patient with neurofibromatosis type 1.

    PubMed

    Su, S Y; Zhou, X; Pang, X M; Chen, C Y; Li, S H; Liu, J L

    2016-01-01

    Neurofibromatosis type 1, also known as NF1 or von Recklinghausen's disease, is a common neurocutaneous syndrome that presents with multiple café-au-lait patches, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. The mutations of the gene NF1, encoding the protein neurofibromin, have been identified as the cause of this disease. Here, we report a clinical and molecular study of a Chinese patient with multiple café-au-lait skin freckles, dermatofibroma, central and peripheral nervous system tumors, and bone abnormalities attributed to NF1. The patient showed >6 café-au-lait spots on the body and multiple dermatofibromas. A brain glioma and multiple nerve sheath tumors inside and outside the vertebral canal were identified by magnetic resonance imaging, which also showed multiple intercostal nerve schwannomas and hydrocephalies above the cerebellar tentorium. Talipes equinus was also apparent. A mutation analysis of the NF1 gene revealed a novel frameshift mutation in exon 43, consisting of a heterozygous deletion of four nucleotides (GAGA) between positions 6520 and 6523. No NF1 mutations were detected in the patient's parents or younger brother. These results extend the list of known mutations in this gene. The absence of the NF1 mutation in the healthy family members suggests that it is responsible for the NF1 phenotype. To our knowledge, this frameshift mutation represents a novel NF1 case, and may be associated with nervous system tumors and bone abnormalities. PMID:27173220

  20. Abnormal Skeletal Strength and Microarchitecture in Women With Celiac Disease

    PubMed Central

    Rogers, Halley; Leib, Alexa; McMahon, Donald J.; Young, Polly; Nishiyama, Kyle; Guo, X. Edward; Lewis, Suzanne; Green, Peter H.; Shane, Elizabeth

    2015-01-01

    Context: Osteoporosis is often a presenting sign of celiac disease (CD). Whether skeletal fragility in CD is associated with microarchitectural abnormalities is not known. Objective: The objective of the study was to evaluate microarchitecture and biomechanical properties of bone in CD. Design: This was a case-control study. Setting: The study was conducted at a university hospital outpatient facility. Patients: Patients included premenopausal women with newly diagnosed CD (n = 33) and healthy controls (n = 33). Main Outcome Measures: Areal bone mineral density by dual-energy x-ray absorptiometry was measured as was trabecular and cortical volumetric bone mineral density (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia. Whole-bone stiffness estimated by finite element analysis. PTH, 25-hydroxyvitamin D, and bone turnover markers were also measured. Results: Groups had similar age, race, and body mass index. Both groups had sufficient 25-hydroxyvitamin D and normal calcium and PTH. Areal bone mineral density was lower in CD. By high-resolution peripheral computed tomography, CD had lower trabecular vBMD, fewer, more widely, and irregularly spaced trabeculae at both the radius and tibia (8%–33%). At the tibia, they also had lower total density (8%) and thinner cortices (10%). Whole-bone stiffness and failure load were lower (11%–21%) in CD at both sites. Biomechanical deficits were associated with trabecular abnormalities. Conclusions: Women with CD had abnormal vBMD and microarchitecture at both the radius and tibia. Trabecular bone was preferentially affected. These deficits were associated with lower estimates of skeletal strength. These findings suggest a potential structural mechanism for skeletal fragility in CD and support further research into the pathogenesis of fracture in this population. PMID:25867815

  1. Cyclin D1 and E2F-1 immunoreactivity in bone marrow biopsy specimens of multiple myeloma: relationship to proliferative activity, cytogenetic abnormalities and DNA ploidy.

    PubMed

    Wilson, C S; Butch, A W; Lai, R; Medeiros, L J; Sawyer, J R; Barlogie, B; McCourty, A; Kelly, K; Brynes, R K

    2001-03-01

    Cyclin D1, encoded by the CCND1 gene, is immunohistochemically detectable in up to one-third of cases of multiple myeloma (MM). To examine the mechanism of cyclin D1 overexpression, we compared cyclin D1 immunoreactivity with the results of conventional cytogenetics to determine if the t(11;14)(q13;q32) or other abnormalities of 11q11-14 explained cyclin D1 overexpression. Karyotypic abnormalities were found in 45 out of 67 (67%) MM cases; the t(11;14) was present in seven cases (10%). Additional 11q11-14 abnormalities were not identified. The t(11;14) correlated with cyclin D1 upregulation in low to intermediately proliferative MM, but was not present in highly proliferative tumours (assessed using bromodeoxyuridine labelling index). Cyclin D1 indirectly activates the transcription factor E2F-1. In the bone marrow biopsy specimens of MM cases, E2F-1 was concurrently expressed with cyclin D1 (P = 0.001), indicating that cyclin D1 is functional. However, as neither E2F-1 nor cyclin D1 expression correlated with proliferative activity, the speculation that t(11;14) upregulates the CCND1 gene to induce higher proliferation and possibly more aggressive disease is not supported. We conclude that in low to intermediately proliferative MM cases, cyclin D1 is probably upregulated by t(11;14), but an alternative mechanism is more probable in highly proliferative MM.

  2. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  3. [Bone quality and strength relating with bone remodeling].

    PubMed

    Mori, Satoshi

    2016-01-01

    The bone has the functions of mineral reservoir and mechanical support as skeleton. Bone remodeling is the adult mode of bone metabolism, replacing old bone tissue to new one. Bone strength is determined by bone volume, structure and quality such as micro damage, degree of mineralization and collagen cross linkage, which are all controlled by bone remodeling. Bone strength decreases under high turn-over condition by decreasing bone volume and deterioration of bone structure, which also decreases under low turn-over condition by increased micro damage, increasing mineralization and AGE collagen cross linkage.

  4. Cytogenetic abnormalities in multiple myeloma: poor prognosis linked to concomitant detection in random and focal lesion bone marrow samples and associated with high-risk gene expression profile.

    PubMed

    Zhou, Yiming; Nair, Bijay; Shaughnessy, John D; Cartron, Marie-Astrid; Haessler, Jeff; Anaissie, Elias; van Rhee, Frits; Crowley, John; Barlogie, Bart

    2009-06-01

    The clinical significance of cytogenetic abnormalities (CA) present in randomly sampled (RS) or focal lesion (FL) bone marrow sites was examined in 419 untreated myeloma patients. Among 290 patients with gene expression profiling (GEP) data generated from RS sites, GEP-defined high-risk was present in 52% of the RS+/FL+ group but in only 9% of the remainder (P < 0.001). The RS+/FL+ constellation (18%) was an independent predictor of poor survival, also after adjusting for GEP-derived risk and TP53 status (Hazard ratio = 2.42, P = 0.004). The prevalence of high-risk myeloma in the RS+/FL+ group may reflect a dissemination-prone condition not shared by the other three groups. PMID:19344415

  5. Bone lesion biopsy

    MedlinePlus

    Benign (noncancerous) bone tumors include: Bone cyst Fibroma Osteoblastoma Osteoid osteoma Cancerous tumors include: Ewing sarcoma Multiple myeloma Osteosarcoma Other types of cancer that may have spread to the bone Abnormal ...

  6. Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis

    PubMed Central

    Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

    2015-01-01

    Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression. PMID:25945040

  7. Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis.

    PubMed

    Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

    2015-01-01

    Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression. PMID:25945040

  8. Low turnover osteodystrophy and vascular calcification are amenable to skeletal anabolism in an animal model of chronic kidney disease and the metabolic syndrome.

    PubMed

    Davies, Matthew R; Lund, Richard J; Mathew, Suresh; Hruska, Keith A

    2005-04-01

    LDL receptor (LDLR)-null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome, have vascular calcification (VC) worsened by chronic kidney disease (CKD) and ameliorated by bone morphogenetic protein-7 (BMP-7), an efficacious agent in treating animal models of renal osteodystrophy. Here, LDLR-/- high-fat-fed mice without CKD were shown to have significant reductions in bone formation rates, associated with increased VC and hyperphosphatemia. Superimposing CKD resulted in a low turnover osteodystrophy, whereas VC worsened and hyperphosphatemia persisted. BMP-7 treatment corrected the hyperphosphatemia, corrected the osteodystrophy, and prevented VC, compatible with skeletal phosphate deposition leading to reduced plasma phosphate and removal of a major stimulus to VC. A pathologic link between abnormal bone mineralization and VC through the serum phosphorus was supported by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in this model of the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to low bone turnover rates, producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through deposition of phosphate and increased bone formation. PMID:15743994

  9. When, how, and why a bone biopsy should be performed in patients with chronic kidney disease.

    PubMed

    Torres, Pablo Ureña; Bover, Jordi; Mazzaferro, Sandro; de Vernejoul, Marie Christine; Cohen-Solal, Martine

    2014-11-01

    In chronic kidney disease the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed down excessively by a multitude of factors including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts, calcimimetics, steroids, and so forth, leading to low bone turnover or adynamic bone disease. Both high and low bone turnover diseases actually are observed equally in chronic kidney disease patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes. Unfortunately, the diagnosis of these bone abnormalities cannot be obtained correctly by current clinical, biochemical, and imaging methods. Therefore, bone biopsy has been, and still remains, the gold standard analysis for assessing the exact type of renal osteodystrophy. It is also the unique way to assess the mechanisms of action, safety, and efficacy of new bone-targeting therapies. PMID:25498380

  10. Noninvasive assessment of bone health in Indian patients with chronic kidney disease.

    PubMed

    Jabbar, Z; Aggarwal, P K; Chandel, N; Khandelwal, N; Kohli, H S; Sakhuja, V; Jha, V

    2013-05-01

    Abnormalities in mineral and bone disease are common in chronic kidney disease (CKD). Evaluation of bone health requires measurement of parameters of bone turnover, mineralization, and volume. There are no data on bone health in CKD patients from India. In this cross-sectional study, we evaluated serum biomarkers of bone turnover: Bone-specific alkaline phosphatase (BAP) and total deoxypyridinoline (tDPD) along with parathyroid hormone, 25(OH) vitamin D, and bone mineral density (BMD) using dual absorption X-ray absorptiometry in a cohort of 74 treatment-naive patients with newly diagnosed stage 4 and 5 CKD (age 42 ± 14.5 years, 54 men) and 52 non-CKD volunteers (age 40.2 ± 9.3 years, 40 men). Compared to the controls, CKD subjects showed elevated intact PTH (iPTH), BAP, and tDPD and lower BMD. There was a strong correlation between iPTH and BAP (r = 0.88, P < 0.0001), iPTH and tDPD (r = 0.51, P < 0.0001), and BAP and tDPD (r = 0.46, P = 0.0004). The iPTH elevation was greater than twice the upper range of normal in 73% cases, and BAP was >40 U/L in 66% cases. The combination of these markers suggests high turnover bone disease in over 60% cases. The prevalence of osteopenia and osteoporosis was 37% and 12%, respectively. Osteoporotic subjects had higher iPTH, BAP, and tDPD, suggesting a role of high turnover in genesis of osteoporosis. Vitamin D deficiency was seen in 80%, and another 13% had insufficient levels. Vitamin D correlated inversely with BAP (r = -0.3, P = 0.009), and levels were lower in those with iPTH >300 pg/ml (P = 0.0.04). In conclusion, over 60% of newly diagnosed Indian stage 4-5 CKD patients show biochemical parameters consistent with high turnover bone disease. High turnover could contribute to the development of osteoporosis in CKD subjects. Deficiency of 25 (OH) vitamin D is widespread and seems to have a role in the genesis of renal bone disease. Studies on the effect of supplementation of native vitamin D are needed. PMID:23814412

  11. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

    PubMed Central

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  12. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

    PubMed

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  13. Bone changes of mucolipidosis II at different ages. Postmortem study of three cases.

    PubMed

    Pazzaglia, U E; Beluffi, G; Castello, A; Coci, A; Zatti, G

    1992-03-01

    Bone changes are a constant feature of mucolipidosis II, with striking differences between newborns and older children. Intracellular, membrane-bound vacuoles were found in the chondrocytes, osteoblasts, osteocytes, and stromal fibroblasts of three affected children. Osteoclasts and marrow cells were unaffected. Ricketslike lesions were present at birth in the two younger cases, whereas signs of high bone turnover and defective calcification were no longer present in the older child. Severe abnormalities of the metaphyseal plate with the loss of normal cartilage architecture and the absence of endochondral ossification were the major changes in this age group.

  14. Predicting Turnover Intentions and Turnover Behavior: A Multivariate Analysis.

    ERIC Educational Resources Information Center

    Parasuraman, Saroj

    1982-01-01

    Assessed the relative influence of personal, attitudinal, and behavioral variables on behavioral intentions and voluntary turnover among nonsupervisory plant workers. Results show that personal variables have little direct effect on turnover; rather, their influence on turnover is channeled through their effects on behavioral intentions. (Author)

  15. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  16. Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

    PubMed

    Khor, Ee-Cheng; Fanshawe, Bruce; Qi, Yue; Zolotukhin, Sergei; Kulkarni, Rishikesh N; Enriquez, Ronaldo F; Purtell, Louise; Lee, Nicola J; Wee, Natalie K; Croucher, Peter I; Campbell, Lesley; Herzog, Herbert; Baldock, Paul A

    2016-01-01

    Prader-Willi Syndrome (PWS), a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR), including a set of small non-translated nucleolar RNA's (snoRNA). Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health and disease

  17. Vascular calcification and renal bone disorders.

    PubMed

    Lu, Kuo-Cheng; Wu, Chia-Chao; Yen, Jen-Fen; Liu, Wen-Chih

    2014-01-01

    At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC. PMID:25136676

  18. A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

    PubMed

    Tong, H-X; Li, M; Zhang, Y; Zhu, J; Lu, W-Q

    2012-08-29

    Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

  19. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  20. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  1. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  2. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  3. Current options for the treatment of Paget’s disease of the bone

    PubMed Central

    Merlotti, Daniela; Gennari, Luigi; Martini, Giuseppe; Nuti, Ranuccio

    2009-01-01

    Paget’s disease of bone (PDB) is a chronic bone remodelling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP) activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.

  4. Bone disease in hypoparathyroidism.

    PubMed

    Clarke, Bart L

    2014-07-01

    Hypoparathyroidism is a rare disorder that may be acquired or inherited. Postsurgical hypoparathyroidism is responsible for the majority of acquired hypoparathyroidism. Bone disease occurs in hypoparathyroidism due to markedly reduced bone remodeling due to the absence or low levels of parathyroid hormone. Chronically reduced bone turnover in patients with hypoparathyroidism typically leads to higher bone mass than in age- and sex-matched controls. Whether this increased bone density reduces fracture risk is less certain, because while increased bone mineralization may be associated with increased brittleness of bone, this does not appear to be the case in hypoparathyroidism. Treatment of hypoparathyroidism with recombinant parathyroid hormone may reduce bone mineral density but simultaneously strengthen the mechanical properties of bone.

  5. Basic bone radiology

    SciTech Connect

    Griffiths, H.J.

    1987-01-01

    This clinical book surveys the skeletal system as seen through radiological imaging. It emphasizing abnormalities, disease, and trauma, and includes vital information on bones, bone growth, and the cells involved in bone pathology. It covers many bone diseases and injuries which are rarely covered in medical texts, as well as descriptions of radiologic procedures that specifically relate to the skeleton. This edition includes many illustrations, information on MR imaging and CT scanning, and discussions of osteoporosis, dysplasias, and metabolic bone disease.

  6. Infant formula increases bone turnover favoring bone formation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the first year of life, the major infant food choices have traditionally been breast milk (BM), cow's milk formula (MF), or soy formula (SF). Studies examining the effects of infant formula on early life skeletal development are extremely limited. We have enrolled 120 healthy 6-month-old infants ...

  7. Triazolopyrimidine (trapidil), a platelet-derived growth factor antagonist, inhibits parathyroid bone disease in an animal model for chronic hyperparathyroidism

    NASA Technical Reports Server (NTRS)

    Lotinun, Sutada; Sibonga, Jean D.; Turner, Russell T.

    2003-01-01

    Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.

  8. Flow cytometric differentiation of abnormal and normal plasma cells in the bone marrow in patients with multiple myeloma and its precursor diseases.

    PubMed

    Tembhare, Prashant R; Yuan, Constance M; Venzon, David; Braylan, Raul; Korde, Neha; Manasanch, Elisabet; Zuchlinsky, Diamond; Calvo, Katherine; Kurlander, Roger; Bhutani, Manisha; Tageja, Nishant; Maric, Irina; Mulquin, Marcia; Roschewski, Mark; Kwok, Mary; Liewehr, David; Landgren, Ola; Stetler-Stevenson, Maryalice

    2014-03-01

    Flow cytometric (FC) enumeration of abnormal plasma cells (APCs) for diagnosis and prognostication of plasma cell dyscrasias (PCD) is challenging. We studied antigen expression in normal plasma cells (NPC) (N = 34) and APC in a series of unselected PCD (N = 59). NPC subpopulations often demonstrated CD19(-), CD20(+), CD45(-) or dim and CD56(+), an immunophenotype observed in PCD. However abnormal CD81 was only observed in APCs (APC detection sensitivity 95%; specificity 100%). We evaluated differences in antigen expression patterns among MGUS (N = 14), SMM (N = 35) and MM (N = 10), finding the combination of CD45 and CD56 helpful in differentiating MGUS from SMM and MM (p = 0.0002). PMID:24462038

  9. Rapid Skeletal Turnover In A Radiographic Mimic Of Osteopetrosis

    PubMed Central

    Whyte, Michael P.; Madson, Katherine L.; Mumm, Steven; McAlister, William H.; Novack, Deborah V.; Blair, Jo C.; Helliwell, Timothy R.; Stolina, Marina; Abernethy, Laurence J.; Shaw, Nicholas J.

    2015-01-01

    Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis, and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was > 5,000 IU/L (normal < 850). After partial resection, the granuloma re-grew but then regressed and stabilized during three years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, BMD z-scores reached + 9.1 and + 5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of LRP4, LRP5, or TGFβ1 and for defective SOST, OPG, RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his non-consanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown. PMID:24919763

  10. THE IMMUNE SYSTEM AND BONE

    PubMed Central

    Pacifici, Roberto

    2010-01-01

    T cells and B cells produce large amounts of cytokines which regulate bone resorption and bone formation. These factors play a critical role in the regulation of bone turnover in health and disease. In addition, immune cells of the bone marrow regulate bone homeostasis by cross-talking with bone marrow stromal cells and osteoblastic cells via cell surface molecules. These regulatory mechanisms are particularly relevant for postmenopausal osteoporosis and hyperparathyroidism, two common forms of bone loss caused primarily by an expansion of the osteoclastic pool only partially compensated by a stimulation of bone formation. This article describes the cytokines and immune factors that regulate bone cells, the immune cells relevant to bone, examines the connection between T cells and bone in health and disease, and reviews the evidence in favor of a link between T cells and the mechanism of action of estrogen and PTH in bone. PMID:20599675

  11. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

    PubMed Central

    van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

    2000-01-01

    Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. PMID:10869429

  12. Integrating Turnover Reasons and Shocks with Turnover Decision Processes

    ERIC Educational Resources Information Center

    Maertz, Carl P., Jr.; Kmitta, Kayla R.

    2012-01-01

    We interviewed and classified 186 quitters from many jobs and organizations via a theoretically-based protocol into five decision process types. We then tested exploratory hypotheses comparing users of these types on their propensity to report certain turnover reasons and turnover shocks. "Impulsive-type quitters," with neither a job offer in hand…

  13. Commitment Profiles and Employee Turnover

    ERIC Educational Resources Information Center

    Stanley, Laura; Vandenberghe, Christian; Vandenberg, Robert; Bentein, Kathleen

    2013-01-01

    We examined how affective (AC), normative (NC), perceived sacrifice (PS), and few alternatives (FA) commitments combine to form profiles and determine turnover intention and turnover. We theorized that three mechanisms account for how profiles operate, i.e., the degree to which membership is internally regulated, the perceived desirability and…

  14. Breaking the turnover cycle.

    PubMed

    Nakhnikian, Elise

    2005-01-01

    The Paraprofessional Healthcare Institute, Bronx, NY, identifies seven elements which are essential for employers in their creation of a stable, well-qualified direct-care workforce. These "common sense" elements--ranging from paying family-sustaining wages to strengthening the caregiving relationship between the workers and those whom they serve--can make the difference between chronic turnover, on one hand, and employing a dedicated staff large enough to keep pace with the growing need for long-term care and services, on the other. However, implementing the seven elements requires the commitment, coordination, and the cooperation of the entire long-term care system, especially the state and federal reimbursement systems that pay for most care and services. By joining forces with other long-term care stakeholders, through organizations such as the Direct Care Alliance, providers can help stabilize the workforce and, ultimately, help to increase the allocation of public resources. PMID:16350897

  15. Cardiovascular risk and mineral bone disorder in patients with chronic kidney disease.

    PubMed

    Staude, Hagen; Jeske, Susann; Schmitz, Karin; Warncke, Gert; Fischer, Dagmar-Christiane

    2013-01-01

    The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e. i) biochemical alterations in the homeostasis of calcium, phosphate and their key player parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), klotho and vitamin-D, ii) the occurrence of vascular and/or soft tissue calcification, and iii) an abnormal bone structure and/or turnover. Apart from the combined and synergistic action of "traditional" and uremia-related risk factors, promoters and inhibitors of calcification have to be considered as well. This review will focus on the disturbed mineral metabolism as the triggering force behind distortion of vascular integrity and cardiovascular malfunction in CKD patients.

  16. Radionuclide bone imaging

    SciTech Connect

    Bassett, L.W.; Gold, R.H.; Webber, M.M.

    1981-12-01

    Radionuclide bone imaging of the skeleton, now well established as the most important diagnostic procedure in detecting bone metastases, is also a reliable method for the evaluation of the progression or regression of metastatic bone disease. The article concentrates on the technetium-99m agents and the value of these agents in the widespread application of low-dose radioisotope scanning in such bone diseases as metastasis, osteomyelitis, trauma, osteonecrosis, and other abnormal skeletal conditions.

  17. Stem cells and bone diseases: new tools, new perspective.

    PubMed

    Riminucci, Mara; Remoli, Cristina; Robey, Pamela G; Bianco, Paolo

    2015-01-01

    Postnatal skeletal stem cells are a unique class of progenitors with biological properties that extend well beyond the limits of stemness as commonly defined. Skeletal stem cells sustain skeletal tissue homeostasis, organize and maintain the complex architectural structure of the bone marrow microenvironment and provide a niche for hematopoietic progenitor cells. The identification of stem cells in the human post-natal skeleton has profoundly changed our approach to the physiology and pathology of this system. Skeletal diseases have been long interpreted essentially in terms of defective function of differentiated cells and/or abnormal turnover of the matrix that they produce. The notion of a skeletal stem cell has brought forth multiple, novel concepts in skeletal biology that provide potential alternative concepts. At the same time, the recognition of the complex functions played by skeletal progenitors, such as the structural and functional organization of the bone marrow, has provided an innovative, unifying perspective for understanding bone and bone marrow changes simultaneously occurring in many disorders. Finally, the possibility to isolate and highly enrich for skeletal progenitors, enables us to reproduce perfectly normal or pathological organ miniatures. These, in turn, provide suitable models to investigate and manipulate the pathogenetic mechanisms of many genetic and non-genetic skeletal diseases. This article is part of a Special Issue entitled Stem cells and Bone.

  18. Bone scintiscanning updated.

    PubMed

    Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I

    1976-03-01

    Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

  19. Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

    PubMed

    Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

    2014-01-01

    Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck

  20. Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy†

    PubMed Central

    Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

    2014-01-01

    Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystropy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-βs role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. μCT confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum PTH levels indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore

  1. [Many issues about bone quality].

    PubMed

    Saito, Mitsuru

    2012-06-01

    According to the present definition of osteoporosis, bone mineral density, architecture, and tissue material properties are important factors in determining bone strength. Bone matrix consists of a two-phase composite material in which the mineral phase provides stiffness and collagen provide tensile strength and ductility. The proposed determinants of bone strength at the material level are the degree of mineralization of basic structure units, microdamage accumulation, and collagen cross-link formation. These are regulated by cellular activities, tissue turnover rate, and the levels of oxidative stress and glycation. In this review, I describe the concerns regarding bone qualities. PMID:22653026

  2. A Rare Stapes Abnormality

    PubMed Central

    Kanona, Hala; Virk, Jagdeep Singh; Kumar, Gaurav; Chawda, Sanjiv; Khalil, Sherif

    2015-01-01

    The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively. PMID:25628909

  3. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    PubMed

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  4. Biomarkers of bone health and osteoporosis risk.

    PubMed

    Eastell, Richard; Hannon, Rosemary A

    2008-05-01

    The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-mid fragment) and the procollagen type I N-terminal propeptide assay. Among the various markers of bone resorption, measurements of the urinary excretion of N- and C-terminal cross-linked telopeptides) and of serum C-terminal cross-linked telopeptides are the most sensitive and specific. Markers of bone turnover can be used to predict the rate of bone loss in post-menopausal women and can also be used to assess the risk of fractures. In osteoporosis-treatment studies (with alendronate, risedronate, raloxifene) markers of bone turnover appear even more strongly associated with fracture risk reduction than bone mineral density (BMD). These observations support the use of markers of bone turnover as surrogates for fracture risk reduction, perhaps even more so than BMD. Bone markers can also be used to monitor the efficacy of antiresorptive therapy such as hormone-replacement therapy, raloxifene and bisphosphonates in individual patients. Furthermore, they have also proved to be helpful in monitoring the response to nutritional interventions and have the advantage over BMD in that they provide information about mechanism of effect and changes are often observed much more rapidly.

  5. Bone markers after total body irradiation in childhood.

    PubMed

    Couto-Silva, A-C; Trivin, C; Espérou, H; Michon, J; Baruchel, A; Souberbielle, J-C; Brauner, R

    2010-03-01

    Total body irradiation (TBI) can cause short stature because of decreased growth hormone (GH) and skeletal abnormalities. To evaluate the plasma concentrations of markers of bone formation (osteocalcin and procollagen type 1 amino-terminal propeptide, P1NP) and resorption (carboxy-terminal telopeptide, CTX), in patients (n=65) who had been given TBI at 6.6+/-0.4 years were evaluated at 9.8+/-0.4 years. Patients given single 10 Gy or fractionated 12 Gy TBI had similar characteristics, except that plasma insulin-like growth factor (IGF-1) was lower in those given a single 10 Gy. Seven had lower osteocalcin and two had higher CTX than controls. Bone markers (as zs) were positively correlated (osteocalcin with P1NP, rho=0.42, P=0.0007; osteocalcin with CTX, rho=0.3, P<0.02), but not P1NP with CTX. Plasma osteocalcin and CTX were also positively correlated with plasma IGF-1, but not with growth rate during the first year on GH (n=28). Adult height was -2.5+/-0.2 s.d.s. (n=49). Those irradiated when young (P=0.0002) or given single TBI lost more height between TBI and adult height. Most TBI patients had normal bone formation and resorption markers. Thus, impaired bone turnover is probably not the cause of their short stature and poor response to GH.

  6. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    PubMed Central

    Yardley, Denise A

    2016-01-01

    There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. PMID:27217795

  7. Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection.

    PubMed

    Beil, Frank Timo; Oheim, Ralf; Barvencik, Florian; Hissnauer, Tim N; Pestka, Jan M; Ignatius, Anita; Rueger, Johannes M; Schinke, Thorsten; Clarke, Iain J; Amling, Michael; Pogoda, Pia

    2012-08-01

    The hypothalamus is of critical importance in regulating bone remodeling. This is underscored by the fact that intracerebroventricular-application of leptin in ewe leads to osteopenia. As a large animal model of osteoporosis, this approach has some limitations, such as high technical expenditure and running costs. Therefore we asked if a surgical ablation of the leptin signaling axis would have the same effects and would thereby be a more useful model. We analyzed the bone phenotype of ewe after surgical hypothalamo-pituitary disconnection (HPD + OVX) as compared to control ewe (OVX) after 3 and 12 months. Analyses included histomorphometric characterization, micro-CT and measurement of bone turnover parameters. Already 3 months after HPD we found osteopenic ewe with a significantly decreased bone formation (69%) and osteoclast activity (49%). After a period of 12 months the HPD group additionally developed an (preclinical) osteoporosis with significant reduction (33%) of femoral cortical thickness, as compared to controls (OVX). Taken together, HPD leads after 12 month to osteoporosis with a reduction in both trabecular and cortical bone caused by a low bone turnover situation, with reduced osteoblast and osteoclast activity, as compared to controls (OVX). The HPD-sheep is a suitable large animal model of osteoporosis. Furthermore our results indicate that an intact hypothalamo-pituitary axis is required for activation of bone turnover.

  8. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.

    PubMed Central

    Hamdy, N. A.; Kanis, J. A.; Beneton, M. N.; Brown, C. B.; Juttmann, J. R.; Jordans, J. G.; Josse, S.; Meyrier, A.; Lins, R. L.; Fairey, I. T.

    1995-01-01

    OBJECTIVE--To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN--Double blind, prospective, randomised, placebo controlled study. SETTING--17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS--176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS--Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES--Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS--132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION--Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure. PMID:7677827

  9. PTH(1-84) Administration in Hypoparathyroidism Transiently Reduces Bone Matrix Mineralization.

    PubMed

    Misof, Barbara M; Roschger, Paul; Dempster, David W; Zhou, Hua; Bilezikian, John P; Klaushofer, Klaus; Rubin, Mishaela R

    2016-01-01

    Patients with hypoparathyroidism have low circulating parathyroid (PTH) levels and higher cancellous bone volume and trabecular thickness. Treatment with PTH(1-84) was shown to increase abnormally low bone remodeling dynamics. In this work, we studied the effect of 1-year or 2-year PTH(1-84) treatment on cancellous and cortical bone mineralization density distribution (Cn.BMDD and Ct.BMDD) based on quantitative backscattered electron imaging (qBEI) in paired transiliac bone biopsy samples. The study cohort comprised 30 adult hypoparathyroid patients (14 treated for 1 year; 16 treated for 2 years). At baseline, Cn.BMDD was shifted to higher mineralization densities in both treatment groups (average degree of mineralization Cn.CaMean +3.9% and +2.7%, p < 0.001) compared to reference BMDD. After 1-year PTH(1-84), Cn.CaMean was significantly lower than that at baseline (-6.3%, p < 0.001), whereas in the 2-year PTH(1-84) group Cn.CaMean did not differ from baseline. Significant changes of Ct.BMDD were observed in the 1-year treatment group only. The change in histomorphometric bone formation (mineralizing surface) was predictive for Cn.BMDD outcomes in the 1-year PTH(1-84) group, but not in the 2-year PTH(1-84) group. Our findings suggest higher baseline bone matrix mineralization consistent with the decreased bone turnover in hypoparathyroidism. PTH(1-84) treatment caused differential effects dependent on treatment duration that were consistent with the histomorphometric bone formation outcomes. The greater increase in bone formation during the first year of treatment was associated with a decrease in bone matrix mineralization, suggesting that PTH(1-84) exposure to the hypoparathyroid skeleton has the greatest effects on BMDD early in treatment.

  10. Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study.

    PubMed

    Dempster, David W; Zhou, Hua; Recker, Robert R; Brown, Jacques P; Recknor, Christopher P; Lewiecki, E Michael; Miller, Paul D; Rao, Sudhaker D; Kendler, David L; Lindsay, Robert; Krege, John H; Alam, Jahangir; Taylor, Kathleen A; Janos, Boris; Ruff, Valerie A

    2016-04-01

    We compared effects of teriparatide and denosumab on PTH, bone turnover markers, and bone histomorphometry in osteoporotic postmenopausal women. The findings were inconsistent with an early indirect anabolic effect of denosumab.

  11. Estimating Teacher Turnover Costs: A Case Study

    ERIC Educational Resources Information Center

    Levy, Abigail Jurist; Joy, Lois; Ellis, Pamela; Jablonski, Erica; Karelitz, Tzur M.

    2012-01-01

    High teacher turnover in large U.S. cities is a critical issue for schools and districts, and the students they serve; but surprisingly little work has been done to develop methodologies and standards that districts and schools can use to make reliable estimates of turnover costs. Even less is known about how to detect variations in turnover costs…

  12. Measuring Staff Turnover in Nursing Homes

    ERIC Educational Resources Information Center

    Castle, Nicholas G.

    2006-01-01

    Purpose: In this study the levels of staff turnover reported in the nursing home literature (1990-2003) are reviewed, as well as the definitions of turnover used in these prior studies. With the use of primary data collected from 354 facilities, the study addresses the various degrees of bias that result, depending on how staff turnover is defined…

  13. Using Turnover as a Recruitment Strategy

    ERIC Educational Resources Information Center

    Duncan, Sandra

    2009-01-01

    Teacher turnover is notoriously high in the field of early childhood education with an estimated 33% of staff exiting the workplace each year. Turnover is costly. Not only do high levels of turnover negatively impact children's growth and development, it also erodes the program's economic stability and wherewithal to provide effective operations…

  14. How Teacher Turnover Harms Student Achievement

    ERIC Educational Resources Information Center

    Ronfeldt, Matthew; Loeb, Susanna; Wyckoff, James

    2013-01-01

    Researchers and policymakers often assume that teacher turnover harms student achievement, though recent studies suggest this may not be the case. Using a unique identification strategy that employs school-by-grade level turnover and two classes of fixed-effects models, this study estimates the effects of teacher turnover on over 850,000 New York…

  15. Fat and Bone: An Odd Couple

    PubMed Central

    Kremer, Richard; Gilsanz, Vicente

    2016-01-01

    In this review, we will first discuss the concept of bone strength and introduce how fat at different locations, including the bone marrow, directly or indirectly regulates bone turnover. We will then review the current literature supporting the mechanistic relationship between marrow fat and bone and our understanding of the relationship between body fat, body weight, and bone with emphasis on its hormonal regulation. Finally, we will briefly discuss the importance and challenges of accurately measuring the fat compartments using non-invasive methods. This review highlights the complex relationship between fat and bone and how these new concepts will impact our diagnostic and therapeutic approaches in the very near future. PMID:27014187

  16. Bone Health in Childhood: Usefulness of Biochemical Biomarkers

    PubMed Central

    Eapen, E.; Grey, V.; Don-Wauchope, A.; Atkinson, S. A.

    2008-01-01

    Development of the human skeleton begins in early embryonic life and continues through childhood into early adulthood. The acquisition of peak bone mass during these vulnerable periods may impact on skeletal fragility in later adult years. Once the skeleton has reached maturity, bone remodelling continues with periodic replacement of old bone with new at the same location. Bone biomarkers are specifically derived biomarkers that reflect both formation by osteoblasts and resorption by osteoclasts. Children have significantly higher concentrations of bone biomarkers than adults due to both skeletal growth and rapid bone turnover during childhood and adolescence. Biochemical assessment of markers of bone turnover may be important in the diagnosis, prognosis and management of metabolic bone disease. This review will discuss the various serum bone markers used for assessing bone health and the factors that influence their utility.

  17. Synthesis, modification and turnover of proteins during aging.

    PubMed

    Rattan, Suresh I S

    2010-01-01

    Iterations in the rate and extent of protein synthesis, accuracy, post-translational modifications and turnover are among the main molecular characteristics of aging. A decline in the cellular capacity through proteasomal and lysosomal pathways to recognize and preferentially degrade damaged proteins leads to the accumulation of abnormal proteins during aging. The consequent increase in molecular heterogeneity and impaired functioning of proteins is the basis of several age-related pathologies, such as cataracts, sarcopenia and neurodegerative diseases. Understanding the proteomic spectrum and its functional implications during aging can facilitate developing effective means of intervention, prevention and therapy of aging and age-related diseases.

  18. New trends in bone research.

    PubMed

    Hewison, M

    1995-01-01

    Recent advances in bone research have employed novel cell and molecular biology techniques to determine some of the fundamental mechanisms regulating bone function. Endocrine control of bone cell development and matrix turnover have been defined at a molecular level by studying the interaction of steroid/thyroid hormones with gene promoters. New steroid/thyroid hormone receptors have been cloned, suggesting that our current view of hormonal regulation of bone metabolism is far from complete. The function of one particular steroid hormone receptor, the vitamin D receptor, has come under close scrutiny following the observation that polymorphic variations in this receptor are linked to differences in bone mineral density. Detailed studies of bone cell differentiation have shown that cytokines may be particularly important targets for hormonal control in bone. The role of cell adhesion molecules in regulating bone resorption has also been explored; modulation of their activity may be of benefit in the treatment of diseases such as osteoporosis. Pharmacological intervention via the newly cloned calcium-sensing receptor offers another site for regulation of bone turnover. PMID:8847678

  19. Reproductive hormones and bone.

    PubMed

    Nicks, Kristy M; Fowler, Tristan W; Gaddy, Dana

    2010-06-01

    Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates secretion of pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which directly regulate ovarian function. Pituitary FSH can modulate osteoclast development, and thereby influence bone turnover. Pituitary oxytocin and prolactin effects on the skeleton are not merely limited to pregnancy and lactation; oxytocin stimulates osteoblastogenesis and bone formation, whereas prolactin exerts skeletal effects in an age-dependent manner. Cyclic levels of inhibins and estrogen suppress FSH and LH, respectively, and also suppress bone turnover via their suppressive effects on osteoblast and osteoclast differentiation. However, continuous exposure to inhibins or estrogen/androgens is anabolic for the skeleton in intact animals and protects against gonadectomy-induced bone loss. Alterations of one hormone in the hypothalamic-pituitary-gonadal (HPG) axis influence other bone-active hormones in the entire feedback loop in the axis. Thus, we propose that the action of the HPG axis should be extended to include its combined effects on the skeleton, thus creating the HPG skeletal (HPGS) axis.

  20. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    PubMed

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-01

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres.

  1. In Vivo Assessment of Bone Quality in Postmenopausal Women with Type 2 Diabetes

    PubMed Central

    Farr, Joshua N.; Drake, Matthew T.; Amin, Shreyasee; Melton, L. Joseph; McCready, Louise K.; Khosla, Sundeep

    2013-01-01

    While patients with type 2 diabetes (T2D) are at significant risk for well recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to non-diabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone “quality”). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50–80 yrs) including 30 patients diagnosed with T2D for >10 yrs and 30 age-matched, non-diabetic controls. Regional BMD was measured by DXA; cortical and trabecular bone microarchitecture was assessed from HRpQCT images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (−11.7%; p<0.001); following adjustment for BMI (−10.5%; p<0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (−9.2%; p=0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p<0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 yrs was negatively correlated with BMS (r = −0.41; p=0.026). In conclusion, these findings represent the first demonstration of compromised bone material strength in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone

  2. Protein turnover, ureagenesis and gluconeogenesis.

    PubMed

    Schutz, Yves

    2011-03-01

    The major processes discussed below are protein turnover (degradation and synthesis), degradation into urea, or conversion into glucose (gluconeogenesis, Figure 1). Daily protein turnover is a dynamic process characterized by a double flux of amino acids: the amino acids released by endogenous (body) protein breakdown can be reutilized and reconverted to protein synthesis, with very little loss. Daily rates of protein turnover in humans (300 to 400 g per day) are largely in excess of the level of protein intake (50 to 80 g per day). A fast growing rate, as in premature babies or in children recovering from malnutrition, leads to a high protein turnover rate and a high protein and energy requirement. Protein metabolism (synthesis and breakdown) is an energy-requiring process, dependent upon endogenous ATP supply. The contribution made by whole-body protein turnover to the resting metabolic rate is important: it represents about 20 % in adults and more in growing children. Metabolism of proteins cannot be disconnected from that of energy since energy balance influences net protein utilization, and since protein intake has an important effect on postprandial thermogenesis - more important than that of fats or carbohydrates. The metabolic need for amino acids is essentially to maintain stores of endogenous tissue proteins within an appropriate range, allowing protein homeostasis to be maintained. Thanks to a dynamic, free amino acid pool, this demand for amino acids can be continuously supplied. The size of the free amino acid pool remains limited and is regulated within narrow limits. The supply of amino acids to cover physiological needs can be derived from 3 sources: 1. Exogenous proteins that release amino acids after digestion and absorption 2. Tissue protein breakdown during protein turnover 3. De novo synthesis, including amino acids (as well as ammonia) derived from the process of urea salvage, following hydrolysis and microflora metabolism in the hind gut

  3. Bone Cancer: Questions and Answers

    MedlinePlus

    ... determine the level of an enzyme called alkaline phosphatase. A large amount of this enzyme is present ... abnormal bone tissue. Because high levels of alkaline phosphatase are normal in growing children and adolescents, this ...

  4. Osteocalcin and bone-specific alkaline phosphatase in Asian elephants (Elephas maximus) at different ages.

    PubMed

    Arya, Nlin; Moonarmart, Walasinee; Cheewamongkolnimit, Nareerat; Keratikul, Nutcha; Poon-Iam, Sawinee; Routh, Andrew; Bumpenpol, Pitikarn; Angkawanish, Taweepoke

    2015-11-01

    Bone turnover markers could offer a potential alternative means for the early diagnosis of metabolic bone disease in young growing elephants although the baseline of bone turnover markers in elephant is not well established. The aim of this study was to determine any relationship between the age of captive Asian elephants (Elephas maximus) and markers of bone formation. Serum samples from 24 female Asian elephants were collected to evaluate levels of two bone formation markers, namely, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Both intact and N-terminal midfragment OC and BAP were negatively correlated with age. The findings demonstrate that younger elephants have a higher rate of bone turnover than older elephants. Use of these and additional bone markers could lead to the establishment of validated protocols for the monitoring of bone disease in elephants. PMID:26361748

  5. Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-i...

  6. Guide to good practices for operations turnover

    SciTech Connect

    1998-12-01

    This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Turnover, Chapter XII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing operations turnover programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Turnover is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for a formal operations turnover program to promote safe and efficient operations.

  7. Alcohol, signaling, and ECM turnover.

    PubMed

    Seth, Devanshi; D'Souza El-Guindy, Nympha B; Apte, Minoti; Mari, Montserrat; Dooley, Steven; Neuman, Manuela; Haber, Paul S; Kundu, Gopal C; Darwanto, Agus; de Villiers, Willem J; Vonlaufen, A; Xu, Z; Phillips, P; Yang, S; Goldstein, D; Pirola, R M; Wilson, J S; Moles, Anna; Fernández, Anna; Colell, Anna; García-Ruiz, Carmen; Fernández-Checa, José C; Meyer, Christoph; Meindl-Beinker, Nadja M

    2010-01-01

    Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways that are important for the initiation and progression of alcohol-induced tissue injury are not completely understood. The current understanding of alcohol toxicity to organs suggests that alcohol initiates injury by generation of oxidative and nonoxidative ethanol metabolites and via translocation of gut-derived endotoxin. These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. With continuing alcohol abuse, the injury progresses through impairment of tissue regeneration and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, the predominant being stellate cells, macrophages, and parenchymal cells. In response to alcohol, growth factors and cytokines activate many signaling cascades that regulate fibrogenesis. This mini-review brings together research focusing on the underlying mechanisms of alcohol-mediated injury in a number of organs. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, susceptibility to infection, ECM turnover and fibrogenesis in the liver, pancreas, and lung triggered by alcohol abuse.

  8. Validation of estimating food intake in gray wolves by 22Na turnover

    USGS Publications Warehouse

    DelGiudice, G.D.; Duquette, L.S.; Seal, U.S.; Mech, L.D.

    1991-01-01

    We studied 22sodium (22Na) turnover as a means of estimating food intake in 6 captive, adult gray wolves (Canis lupus) (2 F, 4 M) over a 31-day feeding period. Wolves were fed white-tailed deer (Odocoileus virginianus) meat only. Mean mass-specific exchangeable Na pool was 44.8 .+-. 0.7 mEq/kg; there was no differeence between males and females. Total exchangeable Na was related (r2 = 0.85, P < 0.009) to body mass. Overall, 22Na turnover overestimated Na intake by 9.8 .+-. 2.4% after 32 days. Actual Na intake was similar in males and females; however, Na turnover (P < 0.05) and the discrepancy (P < 0.01) between turnover and actual Na intake were greater in females than males. From Day 8 to the end of the study, the absolute difference (mEq) between Na intake and Na turnover remained stable. Sodium turnover (mEq/kg/day) was a reliable (r2 = 0.91, P < 0.001) estimator of food consumption (g/kg/day) in wolves over a 32-day period. Sampling blood and weighing wolves every 1-4 days permitted identification of several potential sources of error, including changes in size of exchangeable Na pools, exchange of 22Na with gastrointestinal and bone Na, and rapid loss of the isotope by urinary excretion.

  9. Bone histology in chronic kidney disease-related mineral and bone disorder.

    PubMed

    Kazama, Junichiro James

    2011-06-01

    A quantitative histological analysis of biopsied bone samples is currently regarded as the gold standard for a diagnosing procedure for bone diseases associated with chronic kidney disease-related mineral and bone disorder. Conventionally, "bone cell activities" and "bone mineralization" are applied as two independent assessment axes, and the histology results are classified into five categories according to these axes. Recently, a new bone histology classification system called the Turnover-Mineralization-Volume system, which applied "cancellous bone volume" as another major assessing axis, was advocated; however, both classification systems have many unsolved problems. Clinicians must realize the limitations in evaluating bone metabolism by bone histology. We will need to establish a new classification method for renal bone diseases independent of histological findings.

  10. [Clinical nuclear medicine in bone metastases].

    PubMed

    Kawabe, Joji; Higashiyama, Shigeaki; Shiomi, Susumu

    2013-03-01

    (99m)Tc-hydroxymethylene diphosphonate is not directly to Calcium of the bone matrix, but is binding to hydroxyapatite within the bone matrix. Strontium-89 is a member of family II A of the periodic table, same as Calcium, and is incorporated into bone matrix directly. It is very important that the the regions of the pain from bone metastases are present in the site of the abnormal uptake by bone metastases. PMID:23445892

  11. Dynamic Aspects of Voluntary Turnover: An Integrated Approach to Curvilinearity in the Performance-Turnover Relationship

    ERIC Educational Resources Information Center

    Becker, William J.; Cropanzano, Russell

    2011-01-01

    Previous research pertaining to job performance and voluntary turnover has been guided by 2 distinct theoretical perspectives. First, the push-pull model proposes that there is a quadratic or curvilinear relationship existing between these 2 variables. Second, the unfolding model of turnover posits that turnover is a dynamic process and that a…

  12. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, ... fractures or cancers. Once your body accepts the bone graft, it provides a framework for growth of new, ...

  13. Bone Diseases

    MedlinePlus

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

  14. Diphosphonates in the evaluation of metabolic bone disease.

    PubMed

    Fogelman, I; Smith, M L

    1982-03-01

    The bone scan may be of value in the assessment of patients with metabolic bone disease. However the superiority of the bone scan when compared to radiology in conditions such as renal osteodystrophy, osteomalacia, primary hyperparathyroidism, and osteoporosis requires substantiation with the newer radiopharmaceuticals which have a higher affinity for bone. Two methods of quantitating skeletal uptake of tracer have been assessed to try to remove the subjective aspect of bone scan evaluation. Measurements of bone to soft tissue ratios have proved clinically disappointing, but 24 hour whole body retention of diphosphonate appears to provide a sensitive index of increased bone turnover.

  15. Function of osteocytes in bone.

    PubMed

    Aarden, E M; Burger, E H; Nijweide, P J

    1994-07-01

    Although the structural design of cellular bone (i.e., bone containing osteocytes that are regularly spaced throughout the bone matrix) dates back to the first occurrence of bone as a tissue in evolution, and although osteocytes represent the most abundant cell type of bone, we know as yet little about the role of the osteocyte in bone metabolism. Osteocytes descend from osteoblasts. They are formed by the incorporation of osteoblasts into the bone matrix. Osteocytes remain in contact with each other and with cells on the bone surface via gap junction-coupled cell processes passing through the matrix via small channels, the canaliculi, that connect the cell body-containing lacunae with each other and with the outside world. During differentiation from osteoblasts to mature osteocyte the cells lose a large part of their cell organelles. Their cell processes are packed with microfilaments. In this review we discuss the various theories on osteocyte function that have taken in consideration these special features of osteocytes. These are 1) osteocytes are actively involved in bone turnover; 2) the osteocyte network is through its large cell-matrix contact surface involved in ion exchange; and 3) osteocytes are the mechanosensory cells of bone and play a pivotal role in functional adaptation of bone. In our opinion, especially the last theory offers an exciting concept for which some biomechanical, biochemical, and cell biological evidence is already available and which fully warrants further investigations.

  16. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover.

    PubMed

    Jugdaohsingh, Ravin; Watson, Abigail I E; Pedro, Liliana D; Powell, Jonathan J

    2015-06-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than

  17. Metabolic bone disease associated with total parenteral nutrition.

    PubMed

    Klein, G L; Coburn, J W

    1984-01-01

    Patients receiving long-term treatment with total parenteral nutrition often develop bony abnormalities characterized by patchy osteomalacia and low bone turnover. The patients present evidence of physiologic hypoparathyroidism, although low levels of iPTH cannot entirely explain the osteomalacia. Abnormally low serum levels of 1,25(OH)2-vitamin D have been demonstrated, but the significance of these reduced levels in the pathogenesis of the bone lesions is not defined. Aluminum has been detected in large quantities in the plasma, urine, and bone of some patients treated with TPN, and there is mounting evidence that aluminum may be associated with skeletal pathology, particularly osteomalacia. There is, however, no clear documentation that aluminum accumulation produces the skeletal lesions observed, although it could be a contributing factor. There has been the unusual empiric observation that the removal of vitamin D2 from the infusate is associated with a decrease in the quantity of unmineralized osteoid in TPN patients. A possible role of vitamin D2 in producing osteomalacia is not easy to understand since normal serum levels of 25(OH)-D2, the circulating form of vitamin D2, have been reported. The long-term consequences of intravenous nutritional support for many aspects of metabolism remain unknown. Administration into the systemic circulation of predetermined quantities of calcium and phosphorus via a route that bypasses their passage across the intestinal mucosa, the portal system and the liver may have adverse consequences. It is possible that bypassing homeostatic mechanisms may affect bone formation and metabolism or lead to alterations in vitamin D sterols. Alternatively, a deficiency of an essential trace metal or the accumulation of a toxic trace substance could be responsible for the bony abnormalities. Much remains to be clarified concerning calcium homeostasis and bone disease during total parenteral nutrition. Among various possible factors, it

  18. Bone's mechanostat: a 2003 update.

    PubMed

    Frost, Harold M

    2003-12-01

    The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well. PMID:14613308

  19. Contextual Factors Related to Elementary Principal Turnover

    ERIC Educational Resources Information Center

    Partlow, Michelle C.

    2007-01-01

    The issue of school leadership instability and how it affects schools and student achievement has been studied. The question of how to predict turnover of the principal remains an unknown. The purpose of this research was to search for possible relationships between certain contextual variables and principal turnover and to test the independent…

  20. Employee Turnover: Evidence from a Case Study.

    ERIC Educational Resources Information Center

    Borland, Jeff

    1997-01-01

    Patterns of employee turnover from a medium-sized law firm in Australia were examined in regard to theories of worker mobility (matching, sectoral shift, and incentive). Results support a role for matching effects, but personnel practices affect the timing of turnover. Matching and incentive-based theories do not explain the high rates of turnover…

  1. Principal Turnover. Information Capsule. Volume 0914

    ERIC Educational Resources Information Center

    Blazer, Christie

    2010-01-01

    Recent studies indicate that school districts are facing increasing rates of principal turnover. Frequent principal changes deprive schools of the leadership stability they need to succeed, disrupt long-term school reform efforts, and may even be linked to increased teacher turnover and lower levels of student achievement. This Information Capsule…

  2. Social Disadvantage and Network Turnover

    PubMed Central

    2015-01-01

    Objectives. Research shows that socially disadvantaged groups—especially African Americans and people of low socioeconomic status (SES)—experience more unstable social environments. I argue that this causes higher rates of turnover within their personal social networks. This is a particularly important issue among disadvantaged older adults, who may benefit from stable networks. This article, therefore, examines whether social disadvantage is related to various aspects of personal network change. Method. Social network change was assessed using longitudinal egocentric network data from the National Social Life, Health, and Aging Project, a study of older adults conducted between 2005 and 2011. Data collection in Wave 2 included a technique for comparing respondents’ confidant network rosters between waves. Rates of network losses, deaths, and additions were modeled using multivariate Poisson regression. Results. African Americans and low-SES individuals lost more confidants—especially due to death—than did whites and college-educated respondents. African Americans also added more confidants than whites. However, neither African Americans nor low-SES individuals were able to match confidant losses with new additions to the extent that others did, resulting in higher levels of confidant network shrinkage. These trends are partly, but not entirely, explained by disadvantaged individuals’ poorer health and their greater risk of widowhood or marital dissolution. Discussion. Additional work is needed to shed light on the role played by race- and class-based segregation on group differences in social network turnover. Social gerontologists should examine the role these differences play in explaining the link between social disadvantage and important outcomes in later life, such as health decline. PMID:24997286

  3. Chemical makeup of microdamaged bone differs from undamaged bone.

    PubMed

    Ruppel, Meghan E; Burr, David B; Miller, Lisa M

    2006-08-01

    Microdamage naturally occurs in bone tissue as a result of cyclic loading placed on the body from normal daily activities. While it is usually repaired through the bone turnover process, accumulation of microdamage may result in reduced bone quality and increased fracture risk. It is unclear whether certain areas of bone are more susceptible to microdamage than others due to compositional differences. This study examines whether areas of microdamaged bone are chemically different than undamaged areas of bone. Bone samples (L3 vertebrae) were harvested from 15 dogs. Samples were stained with basic fuchsin, embedded in poly-methylmethacrylate, and cut into 5-microm-thick sections. Fuchsin staining was used to identify regions of microdamage, and synchrotron infrared microspectroscopic imaging was used to determine the local bone composition. Results showed that microdamaged areas of bone were chemically different than the surrounding undamaged areas. Specifically, the mineral stoichiometry was altered in microdamaged bone, where the carbonate/protein ratio and carbonate/phosphate ratio were significantly lower in areas of microdamage, and the acid phosphate content was higher. No differences were observed in tissue mineralization (phosphate/protein ratio) or crystallinity between the microdamaged and undamaged bone, indicating that the microdamaged regions of bone were not over-mineralized. The collagen cross-linking structure was also significantly different in microdamaged areas of bone, consistent with ruptured cross-links and reduced fracture resistance. All differences in composition had well-defined boundaries in the microcrack region, strongly suggesting that they occurred after microcrack formation. Even so, because microdamage results in an altered bone composition, an accumulation of microdamage might result in a long-term reduction in bone quality.

  4. Chemical Makeup of Microdamaged Bone Differs from Undamaged Bone

    SciTech Connect

    Ruppel,M.; Burr, D.; Miller, L.

    2006-01-01

    Microdamage naturally occurs in bone tissue as a result of cyclic loading placed on the body from normal daily activities. While it is usually repaired through the bone turnover process, accumulation of microdamage may result in reduced bone quality and increased fracture risk. It is unclear whether certain areas of bone are more susceptible to microdamage than others due to compositional differences. This study examines whether areas of microdamaged bone are chemically different than undamaged areas of bone. Bone samples (L3 vertebrae) were harvested from 15 dogs. Samples were stained with basic fuchsin, embedded in poly-methylmethacrylate, and cut into 5-{micro}m-thick sections. Fuchsin staining was used to identify regions of microdamage, and synchrotron infrared microspectroscopic imaging was used to determine the local bone composition. Results showed that microdamaged areas of bone were chemically different than the surrounding undamaged areas. Specifically, the mineral stoichiometry was altered in microdamaged bone, where the carbonate/protein ratio and carbonate/phosphate ratio were significantly lower in areas of microdamage, and the acid phosphate content was higher. No differences were observed in tissue mineralization (phosphate/protein ratio) or crystallinity between the microdamaged and undamaged bone, indicating that the microdamaged regions of bone were not over-mineralized. The collagen cross-linking structure was also significantly different in microdamaged areas of bone, consistent with ruptured cross-links and reduced fracture resistance. All differences in composition had well-defined boundaries in the microcrack region, strongly suggesting that they occurred after microcrack formation. Even so, because microdamage results in an altered bone composition, an accumulation of microdamage might result in a long-term reduction in bone quality.

  5. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

    PubMed

    Yuan, Quan; Sato, Tadatoshi; Densmore, Michael; Saito, Hiroaki; Schüler, Christiane; Erben, Reinhold G; Lanske, Beate

    2012-01-01

    Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH), Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/-) and Klotho(-/-) (Kl(-/-)) mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/-) mice ameliorated the phenotype in Fgf23(-/-)/PTH(-/-) mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/-) mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/-) (Kl(-/-)/PTH(-/-) or DKO) mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-)/PTH(-/-) mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn) in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-)/PTH(-/-) mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-)/PTH(-/-) mice. Moreover, continuous PTH infusion of Kl(-/-) mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-), but not of Fgf23(-/-) mice, possibly by regulating Opn expression. These are significant new perceptions

  6. The role of bone biopsy for the diagnosis of renal osteodystrophy: a short overview and future perspectives.

    PubMed

    Carvalho, Catarina; Alves, Catarina Moniz; Frazão, João Miguel

    2016-10-01

    Chronic kidney disease (CKD) patients present specific bone and mineral metabolism disturbances, which account for important morbidity and mortality. The term renal osteodystrophy, classically used for the nomination of CKD-associated bone disorder, has been limited to the histologic description of bone lesions, requiring the use of bone biopsy. Biochemical markers and imaging tools do not adequately predict the complex bone changes that are observed in renal osteodystrophy. Parathyroid hormone, which is a universally used biomarker of bone turnover in clinical practice, lacks specificity and sensitivity. Therefore, tetracycline double-labelled transiliac bone biopsy, with bone histology and histomorphometric evaluation, remains the best clinical tool to discriminate bone turnover and to evaluate the other dimensions of renal osteodystrophy. This review will focus on the value of classic bone histomorphometric analysis of trabecular bone in CKD patients and unfold new perspectives of this diagnostic tool, including cortical bone evaluation and bone tissue immunohistochemistry. PMID:27473148

  7. B Vitamins, Homocysteine and Bone Health

    PubMed Central

    Fratoni, Valentina; Brandi, Maria Luisa

    2015-01-01

    Nutrition is one of the most important modifiable factors involved in the development and maintenance of good bone health. Calcium and Vitamin D have confirmed and established roles in the maintenance of proper bone health. However, other nutritional factors could also be implicated. This review will explore the emerging evidence of the supporting role of certain B Vitamins as modifiable factors associated with bone health. Individuals with high levels of homocysteine (hcy) exhibit reduced bone mineral density (BMD), alteration in microarchitecture and increased bone fragility. The pathophysiology caused by high serum homocysteine is not completely clear regarding fractures, but it may involve factors, such as bone mineral density, bone turnover, bone blood flow and collagen cross-linking. It is uncertain whether supplementation with B Vitamins, such as folate, Vitamin B1, and Vitamin B6, could decrease hip fracture incidence, but the results of further clinical trials should be awaited before a conclusion is drawn. PMID:25830943

  8. B vitamins, homocysteine and bone health.

    PubMed

    Fratoni, Valentina; Brandi, Maria Luisa

    2015-03-30

    Nutrition is one of the most important modifiable factors involved in the development and maintenance of good bone health. Calcium and Vitamin D have confirmed and established roles in the maintenance of proper bone health. However, other nutritional factors could also be implicated. This review will explore the emerging evidence of the supporting role of certain B Vitamins as modifiable factors associated with bone health. Individuals with high levels of homocysteine (hcy) exhibit reduced bone mineral density (BMD), alteration in microarchitecture and increased bone fragility. The pathophysiology caused by high serum homocysteine is not completely clear regarding fractures, but it may involve factors, such as bone mineral density, bone turnover, bone blood flow and collagen cross-linking. It is uncertain whether supplementation with B Vitamins, such as folate, Vitamin B1, and Vitamin B6, could decrease hip fracture incidence, but the results of further clinical trials should be awaited before a conclusion is drawn.

  9. TGF-β in cancer and bone: implications for treatment of bone metastases.

    PubMed

    Juárez, Patricia; Guise, Theresa A

    2011-01-01

    Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.

  10. Changing bone patterns with progression of chronic kidney disease.

    PubMed

    Drüeke, Tilman B; Massy, Ziad A

    2016-02-01

    It is commonly held that osteitis fibrosa and mixed uremic osteodystrophy are the predominant forms of renal osteodystrophy in patients with chronic kidney disease. Osteitis fibrosa is a high-turnover bone disease resulting mainly from secondary hyperparathyroidism, and mixed uremic osteodystrophy is in addition characterized by a mineralization defect most often attributed to vitamin D deficiency. However, there is ancient and more recent evidence that in early chronic kidney disease stages adynamic bone disease characterized by low bone turnover occurs first, at least in a significant proportion of patients. This could be due to the initial predominance of bone turnover-inhibitory conditions such as resistance to the action of parathyroid hormone (PTH), reduced calcitriol levels, sex hormone deficiency, diabetes, and, last but not least, uremic toxins leading to repression of osteocyte Wnt/β-catenin signaling and increased expression of Wnt antagonists such as sclerostin, Dickkopf-1, and sFRP4. The development of high-turnover bone disease would occur only later on, when serum PTH levels are able to overcome peripheral PTH resistance and the other inhibitory factors of bone formation. Whether FGF23 and Klotho play a direct role in the transition from low- to high-turnover bone disease or participate only indirectly via regulating PTH secretion remains to be seen. PMID:26806832

  11. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  12. Exercise and pharmacological countermeasures for bone loss during long-duration space flight

    NASA Technical Reports Server (NTRS)

    Cavanagh, Peter R.; Licata, Angelo A.; Rice, Andrea J.

    2005-01-01

    Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

  13. Exercise and pharmacological countermeasures for bone loss during long-duration space flight.

    PubMed

    Cavanagh, Peter R; Licata, Angelo A; Rice, Andrea J

    2005-06-01

    Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

  14. Exercise and pharmacological countermeasures for bone loss during long-duration space flight.

    PubMed

    Cavanagh, Peter R; Licata, Angelo A; Rice, Andrea J

    2005-06-01

    Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space. PMID:16038092

  15. Significance of abnormalities of chromosomes 5 and 8 in chondroblastoma.

    PubMed

    Swarts, S J; Neff, J R; Johansson, S L; Nelson, M; Bridge, J A

    1998-04-01

    Tumor specific chromosomal abnormalities have been identified in several histologic subtypes of benign and malignant bone tumors. These anomalies have proven to be useful diagnostically. Characterization of recurrent chromosomal abnormalities also has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of chondroblastoma, a rare benign bone tumor, are few. Cytogenetic analysis of a benign and a malignant chondroblastoma in this study revealed the following abnormal chromosomal complements: 47,XY,+5,t(5;5)(p10;q10) and 45, XY,del(2)(p23),del(3)(q23q27),dup(8)(q12q21.), del(11) (q14q23), -13, add (17) (q25) x 2, respectively. Although a specific chromosomal abnormality has not yet emerged for chondroblastoma, abnormalities of chromosomes 5 and 8 have been reported previously in this neoplasm, suggesting preferential involvement of these two chromosomes. PMID:9584382

  16. [Bone Cell Biology Assessed by Microscopic Approach. Assessment of bone quality using Raman and infrared spectroscopy].

    PubMed

    Suda, Hiromi Kimura

    2015-10-01

    Bone quality, which was defined as "the sum total of characteristics of the bone that influence the bone's resistance to fracture" at the National Institute of Health (NIH) conference in 2001, contributes to bone strength in combination with bone mass. Bone mass is often measured as bone mineral density (BMD) and, consequently, can be quantified easily. On the other hand, bone quality is composed of several factors such as bone structure, bone matrix, calcification degree, microdamage, and bone turnover, and it is not easy to obtain data for the various factors. Therefore, it is difficult to quantify bone quality. We are eager to develop new measurement methods for bone quality that make it possible to determine several factors associated with bone quality at the same time. Analytic methods based on Raman and FTIR spectroscopy have attracted a good deal of attention as they can provide a good deal of chemical information about hydroxyapatite and collagen, which are the main components of bone. A lot of studies on bone quality using Raman and FTIR imaging have been reported following the development of the two imaging systems. Thus, both Raman and FTIR imaging appear to be promising new bone morphometric techniques.

  17. Radionuclide bone scanning of osteosarcoma: falsely extended uptake patterns

    SciTech Connect

    Chew, F.S.; Hudson, T.M.

    1982-07-01

    The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative /sup 99m/Tc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

  18. The island-mainland species turnover relationship.

    PubMed

    Stuart, Yoel E; Losos, Jonathan B; Algar, Adam C

    2012-10-01

    Many oceanic islands are notable for their high endemism, suggesting that islands may promote unique assembly processes. However, mainland assemblages sometimes harbour comparable levels of endemism, suggesting that island biotas may not be as unique as is often assumed. Here, we test the uniqueness of island biotic assembly by comparing the rate of species turnover among islands and the mainland, after accounting for distance decay and environmental gradients. We modelled species turnover as a function of geographical and environmental distance for mainland (M-M) communities of Anolis lizards and Terrarana frogs, two clades that have diversified extensively on Caribbean islands and the mainland Neotropics. We compared mainland-island (M-I) and island-island (I-I) species turnover with predictions of the M-M model. If island assembly is not unique, then the M-M model should successfully predict M-I and I-I turnover, given geographical and environmental distance. We found that M-I turnover and, to a lesser extent, I-I turnover were significantly higher than predicted for both clades. Thus, in the first quantitative comparison of mainland-island species turnover, we confirm the long-held but untested assumption that island assemblages accumulate biodiversity differently than their mainland counterparts.

  19. Prenatal imaging of distal limb abnormalities using OCT in mice

    NASA Astrophysics Data System (ADS)

    Larina, Irina V.; Syed, Saba H.; Dickinson, Mary E.; Overbeek, Paul; Larin, Kirill V.

    2012-01-01

    Congenital abnormalities of the limbs are common birth defects. These include missing or extra fingers or toes, abnormal limb length, and abnormalities in patterning of bones, cartilage or muscles. Optical Coherence Tomography (OCT) is a 3-D imaging modality, which can produce high-resolution (~8 μm) images of developing embryos with an imaging depth of a few millimeters. Here we demonstrate the capability of OCT to perform 3D imaging of limb development in normal embryos and a mouse model with congenital abnormalities. Our results suggest that OCT is a promising tool to analyze embryonic limb development in mammalian models of congenital defects.

  20. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  1. Morphological abnormalities among lampreys

    USGS Publications Warehouse

    Manion, Patrick J.

    1967-01-01

    The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.

  2. Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.

    PubMed

    Javaheri, B; Carriero, A; Staines, K A; Chang, Y-M; Houston, D A; Oldknow, K J; Millan, J L; Kazeruni, Bassir N; Salmon, P; Shefelbine, S; Farquharson, C; Pitsillides, A A

    2015-12-01

    PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay

  3. Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

    PubMed Central

    Bassett, J. H. Duncan

    2016-01-01

    The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

  4. Role of Thyroid Hormones in Skeletal Development and Bone Maintenance.

    PubMed

    Bassett, J H Duncan; Williams, Graham R

    2016-04-01

    The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art.

  5. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    PubMed

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria.

  6. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    PubMed

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

  7. Biomimetic catalysis: Taking on the turnover challenge

    NASA Astrophysics Data System (ADS)

    Hooley, Richard J.

    2016-03-01

    Emulating the efficiency with which enzymes catalyse reactions has often been used as inspiration to develop self-assembled cages. Now two studies present approaches to achieving catalyst turnover -- one of the biggest challenges in achieving truly biomimetic catalysis.

  8. [Paget's disease of bone: diagnosis and treatment].

    PubMed

    Winter, E M; Hamdy, N A T; de Jongh, R T; Eekhoff, E M W; Zillikens, M C; Appelman-Dijkstra, N M

    2016-01-01

    Paget's disease of bone is a focal disorder of bone remodelling that leads to changes in the shape and size of affected bones, and is associated with articular and vascular complications. The disorder is characterised by a localised increase in osteoclast number and activity in one or more affected sites while the rest of the skeleton remains unaffected. The excessive bone resorption leads to recruitment of osteoblasts to the remodelling sites, resulting in increased bone formation. This accelerated bone turnover causes deposition of bone with disorganised architecture and structural weakness. The precise aetiology is unknown. It is thought that the disease is caused by interactions between environmental and genetic factors; the nature of this interaction still has to be determined. The disease is progressive, but can be treated with a single infusion of zoledronic acid. In this manuscript three cases are described, along with a review of the current diagnostic tools and treatment. PMID:27650015

  9. The costs of nurse turnover, part 2: application of the Nursing Turnover Cost Calculation Methodology.

    PubMed

    Jones, Cheryl Bland

    2005-01-01

    This is the second article in a 2-part series focusing on nurse turnover and its costs. Part 1 (December 2004) described nurse turnover costs within the context of human capital theory, and using human resource accounting methods, presented the updated Nursing Turnover Cost Calculation Methodology. Part 2 presents an application of this method in an acute care setting and the estimated costs of nurse turnover that were derived. Administrators and researchers can use these methods and cost information to build a business case for nurse retention. PMID:15647669

  10. Spatial turnover in the global avifauna.

    PubMed

    Gaston, Kevin J; Davies, Richard G; Orme, C David L; Olson, Valerie A; Thomas, Gavin H; Ding, Tzung-Su; Rasmussen, Pamela C; Lennon, Jack J; Bennett, Peter M; Owens, Ian P F; Blackburn, Tim M

    2007-07-01

    Despite its wide implications for many ecological issues, the global pattern of spatial turnover in the occurrence of species has been little studied, unlike the global pattern of species richness. Here, using a database on the breeding distributions of birds, we present the first global maps of variation in spatial turnover for an entire taxonomic class, a pattern that has to date remained largely a matter of conjecture, based on theoretical expectations and extrapolation of inconsistent patterns from different biogeographic realms. We use these maps to test four predictions from niche theory as to the form that this variation should take, namely that turnover should increase with species richness, towards lower latitudes, and with the steepness of environmental gradients and that variation in turnover is determined principally by rare (restricted) species. Contrary to prediction, we show that turnover is high both in areas of extremely low and high species richness, does not increase strongly towards the tropics, and is related both to average environmental conditions and spatial variation in those conditions. These results are closely associated with a further important and novel finding, namely that global patterns of spatial turnover are driven principally by widespread species rather than the restricted ones. This complements recent demonstrations that spatial patterns of species richness are also driven principally by widespread species, and thus provides an important contribution towards a unified model of how terrestrial biodiversity varies both within and between the Earth's major land masses.

  11. Automated trabecular bone histomorphometry

    NASA Technical Reports Server (NTRS)

    Polig, E.; Jee, W. S. S.

    1985-01-01

    The toxicity of alpha-emitting bone-seeking radionuclides and the relationship between bone tumor incidence and the local dosimetry of radionuclides in bone are investigated. The microdistributions of alpha-emitting radionuclides in the trabecular bone from the proximal humerus, distal humerus, proximal ulna, proximal femur, and distal femur of six young adult beagles injected with Am-241 (three with 2.8 micro-Ci/kg and three with 0.9 micro-Ci/kg) are estimated using a computer-controlled microscope photometer system; the components of the University of Utah Optical Track Scanner are described. The morphometric parameters for the beagles are calculated and analyzed. It is observed that the beagles injected with 0.9 micro-Ci of Am-241/kg showed an increase in the percentage of bone and trabecular bone thickness, and a reduction in the width of the bone marrow space and surface/volume ratio. The data reveal that radiation damage causes abnormal bone structure.

  12. Abnormal uterine bleeding.

    PubMed

    Jennings, J C

    1995-11-01

    Physicians who care for female patients cannot avoid the frequent complaint of abnormal uterine bleeding. Knowledge of the disorders that cause this problem can prevent serious consequences in many patients and improve the quality of life for many others. The availability of noninvasive and minimally invasive diagnostic studies and minimally invasive surgical treatment has revolutionized management of abnormal uterine bleeding. Similar to any other disorder, the extent to which a physician manages abnormal uterine bleeding depends on his or her own level of comfort. When limitations of either diagnostic or therapeutic capability are encountered, consultation and referral should be used to the best interest of patients.

  13. 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. PMID:27617358

  14. The costs of nurse turnover: part 1: an economic perspective.

    PubMed

    Jones, Cheryl Bland

    2004-12-01

    Nurse turnover is costly for healthcare organizations. Administrators and nurse executives need a reliable estimate of nurse turnover costs and the origins of those costs if they are to develop effective measures of reducing nurse turnover and its costs. However, determining how to best capture and quantify nurse turnover costs can be challenging. Part 1 of this series conceptualizes nurse turnover via human capital theory and presents an update of a previously developed method for determining the costs of nurse turnover, the Nursing Turnover Cost Calculation Method. Part 2 (January 2005) presents a recent application of the methodology in an acute care hospital. PMID:15632752

  15. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  16. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  17. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  18. Inulin, oligofructose and bone health: experimental approaches and mechanisms.

    PubMed

    Weaver, Connie M

    2005-04-01

    Inulin-type fructans have been proposed to benefit mineral retention, thereby enhancing bone health. Many, but not all, experimental animal studies have shown increased mineral absorption by feeding non-digestible oligosaccharides. Possible reasons for inconsistencies are explored. A few studies have reported an enhanced bone mineral density or content. Bone health can be evaluated in chronic feeding studies with bone densitometry, bone breaking strength, bone mineral concentration and bone structure. Isotopic Ca tracers can be used to determine the point of metabolism affected by feeding a functional food ingredient. These methods and the effects of feeding inulin-type fructose are reviewed. Inulin-type fructans enhance Mg retention. Chicory long-chain inulin and oligofructose enhance femoral Ca content, bone mineral density and Ca retention through enhanced Ca absorption and suppressed bone turnover rates, but it is not bone-promoting under all conditions.

  19. Phytonutrients for bone health during ageing.

    PubMed

    Sacco, Sandra Maria; Horcajada, Marie-Noëlle; Offord, Elizabeth

    2013-03-01

    Osteoporosis is a skeletal disease characterized by a decrease in bone mass and bone quality that predispose an individual to an increased risk of fragility fractures. Evidence demonstrating a positive link between certain dietary patterns (e.g. Mediterranean diet or high consumption of fruits and vegetables) and bone health highlights an opportunity to investigate their potential to protect against the deterioration of bone tissue during ageing. While the list of these phytonutrients is extensive, this review summarizes evidence on some which are commonly consumed and have gained increasing attention over recent years, including lycopene and various polyphenols (e.g. polyphenols from tea, grape seed, citrus fruit, olive and dried plum). Evidence to define a clear link between these phytonutrients and bone health is currently insufficient to generate precise dietary recommendations, owing to mixed findings or a scarcity in clinical data. Moreover, their consumption typically occurs within the context of a diet consisting of a mix of phytonutrients and other nutrients rather than in isolation. Future clinical trials that can apply a robust set of outcome measurements, including the determinants of bone strength, such as bone quantity (i.e. bone mineral density) and bone quality (i.e. bone turnover and bone microarchitecture), will help to provide a more comprehensive outlook on how bone responds to these various phytonutrients. Moreover, future trials that combine these phytonutrients with established bone nutrients (i.e. calcium and vitamin D) are needed to determine whether combined strategies can produce more robust effects on skeletal health.

  20. Phytonutrients for bone health during ageing.

    PubMed

    Sacco, Sandra Maria; Horcajada, Marie-Noëlle; Offord, Elizabeth

    2013-03-01

    Osteoporosis is a skeletal disease characterized by a decrease in bone mass and bone quality that predispose an individual to an increased risk of fragility fractures. Evidence demonstrating a positive link between certain dietary patterns (e.g. Mediterranean diet or high consumption of fruits and vegetables) and bone health highlights an opportunity to investigate their potential to protect against the deterioration of bone tissue during ageing. While the list of these phytonutrients is extensive, this review summarizes evidence on some which are commonly consumed and have gained increasing attention over recent years, including lycopene and various polyphenols (e.g. polyphenols from tea, grape seed, citrus fruit, olive and dried plum). Evidence to define a clear link between these phytonutrients and bone health is currently insufficient to generate precise dietary recommendations, owing to mixed findings or a scarcity in clinical data. Moreover, their consumption typically occurs within the context of a diet consisting of a mix of phytonutrients and other nutrients rather than in isolation. Future clinical trials that can apply a robust set of outcome measurements, including the determinants of bone strength, such as bone quantity (i.e. bone mineral density) and bone quality (i.e. bone turnover and bone microarchitecture), will help to provide a more comprehensive outlook on how bone responds to these various phytonutrients. Moreover, future trials that combine these phytonutrients with established bone nutrients (i.e. calcium and vitamin D) are needed to determine whether combined strategies can produce more robust effects on skeletal health. PMID:23384080

  1. Phytonutrients for bone health during ageing

    PubMed Central

    Sacco, Sandra Maria; Horcajada, Marie‐Noëlle; Offord, Elizabeth

    2013-01-01

    Osteoporosis is a skeletal disease characterized by a decrease in bone mass and bone quality that predispose an individual to an increased risk of fragility fractures. Evidence demonstrating a positive link between certain dietary patterns (e.g. Mediterranean diet or high consumption of fruits and vegetables) and bone health highlights an opportunity to investigate their potential to protect against the deterioration of bone tissue during ageing. While the list of these phytonutrients is extensive, this review summarizes evidence on some which are commonly consumed and have gained increasing attention over recent years, including lycopene and various polyphenols (e.g. polyphenols from tea, grape seed, citrus fruit, olive and dried plum). Evidence to define a clear link between these phytonutrients and bone health is currently insufficient to generate precise dietary recommendations, owing to mixed findings or a scarcity in clinical data. Moreover, their consumption typically occurs within the context of a diet consisting of a mix of phytonutrients and other nutrients rather than in isolation. Future clinical trials that can apply a robust set of outcome measurements, including the determinants of bone strength, such as bone quantity (i.e. bone mineral density) and bone quality (i.e. bone turnover and bone microarchitecture), will help to provide a more comprehensive outlook on how bone responds to these various phytonutrients. Moreover, future trials that combine these phytonutrients with established bone nutrients (i.e. calcium and vitamin D) are needed to determine whether combined strategies can produce more robust effects on skeletal health. PMID:23384080

  2. Bioactive silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and enhance bone mineral density in vivo.

    PubMed

    Beck, George R; Ha, Shin-Woo; Camalier, Corinne E; Yamaguchi, Masayoshi; Li, Yan; Lee, Jin-Kyu; Weitzmann, M Neale

    2012-08-01

    Bone is a dynamic tissue that undergoes renewal throughout life in a process whereby osteoclasts resorb worn bone and osteoblasts synthesize new bone. Imbalances in bone turnover lead to bone loss and development of osteoporosis and ultimately fracture, a debilitating condition with high morbidity and mortality. Silica is a ubiquitous biocontaminant that is considered to have high biocompatibility. The authors report that silica nanoparticles (NPs) mediate potent inhibitory effects on osteoclasts and stimulatory effects on osteoblasts in vitro. The mechanism of bioactivity is a consequence of an intrinsic capacity to antagonize activation of NF-κB, a signal transduction pathway required for osteoclastic bone resorption but inhibitory to osteoblastic bone formation. We further demonstrate that silica NPs promote a significant enhancement of bone mineral density (BMD) in mice in vivo, providing a proof of principle for the potential application of silica NPs as a pharmacological agent to enhance BMD and protect against bone fracture.

  3. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change Over Time Matters.

    PubMed

    Garner, Bryan R; Hunter, Brooke D

    2014-01-01

    This study examined the extent to which changes over time in clinicians' responses to measures of work attitude (eg, job satisfaction) and psychological climate (eg, supervisor support) could predict actual turnover and turnover intentions above and beyond absolute levels of these respective measures. Longitudinal data for this study were collected from a sample of clinicians (N = 96) being trained to implement an evidence-based treatment for adolescent substance use disorders. Supporting findings from a recent staff turnover study, we found job satisfaction change was able to predict actual turnover above and beyond average levels of job satisfaction. Representing new contributions to the staff turnover literature, we also found that change over time in several other key measures (eg, job satisfaction, role manageability, role clarity) explained a significant amount of variance in turnover intentions above and beyond the absolute level of each respective measure. A key implication of the current study is that organizations seeking to improve their ability to assess risk for staff turnover may want to consider assessing staff at multiple points in time in order to identify systematic changes in key employee attitudes like turnover intentions and job satisfaction. PMID:25336960

  4. Space Radiation and Bone Loss.

    PubMed

    Willey, Jeffrey S; Lloyd, Shane A J; Nelson, Gregory A; Bateman, Ted A

    2011-01-01

    Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within the irradiated volume. The resulting suppression of bone formation and a general state of low bone-turnover is thought to be the primary contributor to bone loss and eventual fracture. Recent investigations using mouse models have identified a rapid, but transient, increase in osteoclast activity immediately after irradiation with both spaceflight and clinically-relevant radiation qualities and doses. Together with a chronic suppression of bone formation after radiation exposure, this acute skeletal damage may contribute to long-term deterioration of bone quality, potentially increasing fracture risk. Direct evidence for the damaging effects of radiation on human bone are primarily demonstrated by the increased incidence of fractures at sites that absorb high doses of radiation during cancer therapy: exposures are considerably higher than what could be expected during spaceflight. However, both the rapidity of bone damage and the chronic nature of the changes appear similar between exposure scenarios. This review will outline our current knowledge of space and clinical exploration exposure to ionizing radiation on skeletal health. PMID:22826632

  5. The suture provides a niche for mesenchymal stem cells of craniofacial bones

    PubMed Central

    Zhao, Hu; Feng, Jifan; Ho, Thach-Vu; Grimes, Weston; Urata, Mark; Chai, Yang

    2015-01-01

    Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the major MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating these cells are an indispensible stem cell population. Twist1+/− mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair. PMID:25799059

  6. Remodeling and vascular spaces in bone.

    PubMed

    Eriksen, Erik Fink; Eghbali-Fatourechi, Guiti Z; Khosla, Sundeep

    2007-01-01

    In recent years, we have come to appreciate that the close association between bone and vasculature plays a pivotal role in the regulation of bone remodeling and fracture repair. In 2001, Hauge et al. characterized a specialized vascular structure, the bone remodeling compartment (BRC), and showed that the outer lining of this compartment was made up of flattened cells, displaying all the characteristics of lining cells in bone. A decrease in bone turnover leads to a decrease in surfaces covered with remodeling compartments, whereas increased turnover causes an increase. Immunoreactivity for all major osteotropic growth factors and cytokines including osteoprotegerin (OPG) and RANKL has been shown in the cells lining the BRC, which makes the BRC the structure of choice for coupling between resorption and formation. The secretion of these factors inside a confined space separated from the bone marrow would facilitate local regulation of the remodeling process without interference from growth factors secreted by blood cells in the marrow space. The BRC creates an environment where cells inside the structure are exposed to denuded bone, which may enable direct cellular interactions with integrins and other matrix factors known to regulate osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC also constitutes an ideal environment for the seeding of bone metastases, known to have high affinity for bone matrix. Reduction in BRC space brought about by antiresorptive therapies such as bisphosphonates reduce the number of skeletal events in advanced cancer, whereas an increase in BRC space induced by remodeling activators like PTH may increase the bone metastatic burden. The BRC has only been characterized in detail in trabecular bone; there is, however, evidence that a similar structure may exist in cortical bone, but further characterization is needed.

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

    PubMed Central

    Rehman, Moghis Ur; Narchi, Hassib

    2015-01-01

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

  8. [Italian guidelines for the diagnosis and treatment of Paget's disease of bone].

    PubMed

    Adami, S; Bartolozzi, P; Brandi, M L; Falchetti, A; Filipponi, P; Gonnelli, S; Bianchi, G; Isaia, G C; Nuti, R

    2007-01-01

    Paget's disease of bone is a chronic focal abnormality of bone turnover that remains totally asymptomatic over a very long period of time but that eventually ensue in bone pain and skeletal deformities. Although, in the last decade new insights have been obtained on its etiology, this remains largely obscure. Effective medical treatment (based on the use of bisphosphonates) has become available and the diagnostic procedures are now well defined. However, there remains considerable controversy regarding the hierarchy of diagnostic procedures and the medical treatment threshold. In the last few years different institution have published national guidelines, reflecting local national health systems and the available medical treatment. In this review, a working group derived from members of the SIOMMMS has examined the information available regarding the diagnosis and treatment of Paget's disease in order to develop guidelines to assist in the management of this condition. The first draft was then extensively reviewed by experts derived from the most representative scientific societies of rheumatology, internal medicine, and orthopaedic surgery. The document provides the most updated recommendations based primarily on the "evidence-based- medicine" but also on the Italian regulation for the diagnostic procedures and on the available medical treatments.

  9. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    PubMed Central

    Kim, Tae-Ho; Park, Eui Kyun; Huh, Man-Il; Kim, Hong Kyun; Kim, Shin-Yoon; Lee, Sang-Han

    2016-01-01

    Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr) cocoons spun by Rhus javanica (Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss. PMID:27313644

  10. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss.

    PubMed

    Kim, Tae-Ho; Park, Eui Kyun; Huh, Man-Il; Kim, Hong Kyun; Kim, Shin-Yoon; Lee, Sang-Han

    2016-01-01

    Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr) cocoons spun by Rhus javanica (Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss. PMID:27313644

  11. Factors that characterize bone health with aging in healthy postmenopausal women.

    PubMed

    Ikegami, Shota; Uchiyama, Shigeharu; Nakamura, Yukio; Mukaiyama, Keijiro; Hirabayashi, Hiroki; Kamimura, Mikio; Nonaka, Kiichi; Kato, Hiroyuki

    2015-07-01

    The exponential increase in the incidence of fragility fractures in older people is attributed to attenuation of both bone strength and neuromuscular function. Decrease in bone mineral density (BMD) does not entirely explain this increase. The objective of this study is to investigate the effect of age on various parameters related to bone health with aging, and to identify combinations of factors that collectively express the bone metabolic state in healthy postmenopausal women. Height, weight, and grip strength were measured in 135 healthy postmenopausal volunteer women. Hip BMD, biomechanical indices derived from quantitative computed tomography (QCT), cross-sectional areas of muscle and fat of the proximal thigh, and various biochemical markers of bone metabolism were measured. A smaller group of factors explanatory for bone health was identified using factor analysis and each was newly named. As a result, the factors bone mass, bone turnover, bone structure, and muscle strength had the greatest explanatory power for assessing the bone health of healthy postmenopausal women. Whereas dual X-ray absorptiometry parameters only loaded on the factor bone mass, QCT parameters loaded on both the factors bone mass and bone structure. Most bone turnover markers loaded on the factor bone turnover, but deoxypyridinoline loaded on both bone turnover and muscle strength. Age was negatively correlated with bone mass (r = -0.49, p < 0.001) and muscle strength (r = -0.67, p < 0.001). We conclude that aging is associated as much with muscle weakening as with low BMD. More attention should be paid to the effects of muscle weakening during aging in assessments of bone health. PMID:25113438

  12. Living Bones, Strong Bones

    NASA Video Gallery

    In this classroom activity, engineering, nutrition, and physical activity collide when students design and build a healthy bone model of a space explorer which is strong enough to withstand increas...

  13. A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy

    SciTech Connect

    Otsuka, N.; Morita, R.; Yamamoto, T.; Muranaka, A.; Tomomitsu, T.; Yanagimoto, S.; Sone, T.; Fukunaga, M.

    1985-04-01

    In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue.

  14. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  15. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  16. [Hair shaft abnormalities].

    PubMed

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  17. Bone disease in primary hypercalciuria

    PubMed Central

    Sella, Stefania; Cattelan, Catia; Realdi, Giuseppe; Giannini, Sandro

    2008-01-01

    Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α are high in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH

  18. Thyroid hormones and bone development.

    PubMed

    Combs, C E; Nicholls, J J; Duncan Bassett, J H; Williams, G R

    2011-03-01

    Thyroid hormones are critical determinants of postnatal skeletal development. Thyroid hormone deficiency or excess in children results in severe abnormalities of linear growth and bone maturation. These clinical observations have been recapitulated in mutant mice and these models have facilitated studies of the mechanisms of thyroid hormone action in the developing skeleton. In this review, we consider in detail the direct and indirect effects of thyroid hormone on bone and the molecular mechanisms involved.

  19. Quantification of isotopic turnover in agricultural systems

    NASA Astrophysics Data System (ADS)

    Braun, A.; Auerswald, K.; Schnyder, H.

    2012-04-01

    The isotopic turnover, which is a proxy for the metabolic rate, is gaining scientific importance. It is quantified for an increasing range of organisms, from microorganisms over plants to animals including agricultural livestock. Additionally, the isotopic turnover is analyzed on different scales, from organs to organisms to ecosystems and even to the biosphere. In particular, the quantification of the isotopic turnover of specific tissues within the same organism, e.g. organs like liver and muscle and products like milk and faeces, has brought new insights to improve understanding of nutrient cycles and fluxes, respectively. Thus, the knowledge of isotopic turnover is important in many areas, including physiology, e.g. milk synthesis, ecology, e.g. soil retention time of water, and medical science, e.g. cancer diagnosis. So far, the isotopic turnover is quantified by applying time, cost and expertise intensive tracer experiments. Usually, this comprises two isotopic equilibration periods. A first equilibration period with a constant isotopic input signal is followed by a second equilibration period with a distinct constant isotopic input signal. This yields a smooth signal change from the first to the second signal in the object under consideration. This approach reveals at least three major problems. (i) The input signals must be controlled isotopically, which is almost impossible in many realistic cases like free ranging animals. (ii) Both equilibration periods may be very long, especially when the turnover rate of the object under consideration is very slow, which aggravates the first problem. (iii) The detection of small or slow pools is improved by large isotopic signal changes, but large isotopic changes also involve a considerable change in the input material; e.g. animal studies are usually carried out as diet-switch experiments, where the diet is switched between C3 and C4 plants, since C3 and C4 plants differ strongly in their isotopic signal. The

  20. Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.

    PubMed Central

    Jacobs, A

    1985-01-01

    The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities. PMID:2999194

  1. Employee Development and Turnover Intention: Theory Validation

    ERIC Educational Resources Information Center

    Rahman, Wali; Nas, Zekeriya

    2013-01-01

    Purpose: This study aims to examine the pattern of behavior of turnover intentions in developing countries "vis-a-vis" the one in advanced countries through the empirical data from public universities in Khyber Pakhtunkhwa, Pakistan. The study provides empirical evidence from academia in Pakistan, thereby enriching the understanding of…

  2. Antecedents of Norwegian Beginning Teachers' Turnover Intentions

    ERIC Educational Resources Information Center

    Tiplic, Dijana; Brandmo, Christian; Elstad, Eyvind

    2015-01-01

    This study aims at exploring several individual, organizational, and contextual factors that may affect beginning teachers' turnover intentions during their first years of practice. The sample consists of 227 beginning teachers (69% female and 31% male) from 133 schools in Norway. The results show four important antecedents of beginning teachers'…

  3. Teacher Turnover in Charter Schools. Research Brief

    ERIC Educational Resources Information Center

    Stuit, David; Smith, Thomas M.

    2010-01-01

    The current study aimed to contribute to a deeper understanding of the organizational conditions of charter schools by examining teacher turnover. Using data from the National Center for Education Statistics (NCES) 2003-04 Schools and Staffing Survey (SASS) and the Teacher Follow-Up Survey (TFS), researchers from the National Center on School…

  4. Turnover of Public School Superintendents in Arizona

    ERIC Educational Resources Information Center

    Meyer, Joyce Ntsoaki

    2013-01-01

    This study used a descriptive qualitative design utilizing a phenomenological approach to determine and examine the reasons behind the voluntary or involuntary turnover of Arizona school superintendents. Open-ended questions were used to interview five superintendents who had left their districts between 2008 and 2013 about their perceptions on…

  5. Home Visitor Job Satisfaction and Turnover.

    ERIC Educational Resources Information Center

    Buchbinder, Sharon B.; Duggan, Anne K.; Young, Elizabeth; Fuddy, Loretta; Sia, Cal

    This paper summarizes findings of a 3-year study of the job satisfaction and turnover of home visitors, both professional and paraprofessional, in programs which link families-at-risk for impaired functioning to medical home care and other resources. Specifically, the study examined: (1) home visitor personal characteristics that influence…

  6. Identifying Determinants of Commitment and Turnover Behavior.

    ERIC Educational Resources Information Center

    Grady, Thomas L.

    A study tested the precursors to vocational teachers' commitment to teaching as suggested by the commitment model proposed by Pierce and Dunham. Important consequences of commitment were examined by identifying relationships between commitment, behavioral intentions, and resulting turnover. The study examined the entire population of teachers…

  7. Job Turnover Intentions Among Pharmacy Faculty

    PubMed Central

    Conklin, Mark H.

    2007-01-01

    Objectives To determine the primary reasons why pharmacy faculty intend to remain or leave their current institution and why they left their most recent academic institution, and the relative contribution of various organizational and individual characteristics toward explaining variance in turnover intentions. Methods A survey instrument was e-mailed to pharmacy faculty members asking respondents to indicate up to 5 reasons for their intentions and up to 5 reasons why they left a previous institution. The survey also elicited perceptions on quality of work life in addition to demographic and institutional data, upon which turnover intentions were regressed using a forward-conditional procedure. Organizational commitment as a moderator of turnover intentions was regressed over the remaining variables not acting directly on employer intentions. Results Just over 1 in 5 respondents indicated intentions to leave their current academic institution. Excessive workload, seeking a new challenge, poor salary, and poor relationships with college or school administrators were frequently cited as reasons for leaving. Turnover intentions are influenced directly by department chair support and organizational commitment, which moderates various support and satisfaction variables. Conclusions Pharmacy faculty members’ decision to remain or leave an institution is dependent upon developing a sense of commitment toward the institution. Commitment is facilitated by support from the institution and department chair, in addition to a sense of satisfaction with the teaching environment. PMID:17786250

  8. Director Turnover: An Australian Academic Development Study

    ERIC Educational Resources Information Center

    Fraser, Kym; Ryan, Yoni

    2012-01-01

    Although it can be argued that directors of central academic development units (ADUs) are critical to the implementation of university teaching and learning strategies, it would appear there is a high director turnover rate. While research in the USA, the UK, and Australia illustrates that ADUs are frequently closed or restructured, that research…

  9. Isochromosome 20p associated with multiple congenital abnormalities.

    PubMed

    Fryer, Alan E; Ashworth, Michael; Hawe, Jed; Pilling, David; Pauling, Margaret; Maye, Una

    2005-01-01

    A second case of tetrasomy 20p due to an additional isochromosome 20p is reported. This resulted in a spontaneous intrauterine death with multiple congenital abnormalities. In keeping with the previous report, the foetus had poor ossification resulting in multiple long bone fractures.

  10. Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo.

    PubMed

    Holen, I; Walker, M; Nutter, F; Fowles, A; Evans, C A; Eaton, C L; Ottewell, P D

    2016-03-01

    Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, post-menopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER+ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth. ER+ve (MCF7, T47D) or ER-ve (MDA-MB-231) cells were administered by inter-mammary or inter-cardiac injection into female nude mice ± estradiol. Mice were administered saline or 100 μg/kg ZOL weekly. Tumour growth, dissemination of tumour cells in blood, bone and bone turnover were monitored by luciferase imaging, histology, flow cytometry, two-photon microscopy, micro-CT and TRAP/P1NP ELISA. Estradiol induced metastasis of ER+ve cells to bone in 80-100 % of animals whereas bone metastases from ER-ve cells were unaffected. Administration of ZOL had no effect on tumour growth in the fat pad but significantly inhibited dissemination of ER+ve tumour cells to bone and frequency of bone metastasis. Estradiol and ZOL increased bone volume via different mechanisms: Estradiol increased activity of bone forming osteoblasts whereas administration of ZOL to estradiol supplemented mice decreased osteoclast activity and returned osteoblast activity to levels comparable to that of saline treated mice. ER-ve cells require increased osteoclast activity to grow in bone whereas ER+ve cells do not. Zol does not affect ER+ve tumour growth in soft tissue, however, inhibition of bone turnover by ZOL reduced dissemination and growth of ER+ve breast cancer cells in bone.

  11. 38 CFR 4.44 - The bones.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false The bones. 4.44 Section 4... DISABILITIES Disability Ratings The Musculoskeletal System § 4.44 The bones. The osseous abnormalities incident... malalignment of joint surfaces, should be depicted from study and observation of all available data,...

  12. Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo

    PubMed Central

    Nagaoka, Akira; Takehara, Hiroaki; Hayashi-Takagi, Akiko; Noguchi, Jun; Ishii, Kazuhiko; Shirai, Fukutoshi; Yagishita, Sho; Akagi, Takanori; Ichiki, Takanori; Kasai, Haruo

    2016-01-01

    Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca2+ signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD. PMID:27221801

  13. 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

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

    PubMed Central

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

    2006-01-01

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

  15. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed.

  16. Investing in Leadership: The District's Role in Managing Principal Turnover

    ERIC Educational Resources Information Center

    Mascall, Blair; Leithwood, Kenneth

    2010-01-01

    This article presents the results of research into the impact of principal turnover on schools, and the ability of schools to mitigate the negative effects of frequent turnover by distributing leadership in the schools. The findings from this qualitative and quantitative analysis show that rapid principal turnover does indeed have a negative…

  17. Salary and Ranking and Teacher Turnover: A Statewide Study

    ERIC Educational Resources Information Center

    Garcia, Cynthia Martinez; Slate, John R.; Delgado, Carmen Tejeda

    2009-01-01

    This study examined three years of data obtained from the Academic Excellence Indicator System of the State of Texas regarding teacher turnover rate and teacher salary. Across all public school districts, teacher salary was consistently negatively related to teacher turnover; that is, where salary was lower, turnover rate was higher When data were…

  18. High School Band Students' Perspectives of Teacher Turnover

    ERIC Educational Resources Information Center

    Kloss, Thomas E.

    2013-01-01

    Teacher turnover remains an important issue in education. The least researched perspectives, though, are those of the students who experience teacher turnover. The purpose of this study was to examine how high school band students experience teacher turnover. A total of twelve students were interviewed, representing three schools that experienced…

  19. Superintendent Turnover in Kentucky. Issues & Answers. REL 2011-No. 113

    ERIC Educational Resources Information Center

    Johnson, Jerry; Huffman, Tyler; Madden, Karen; Shope, Shane

    2011-01-01

    This study examines superintendent turnover in Kentucky public school districts for 1998/99-2007/08, looking at how turnover varies by rural status, Appalachian and non-Appalachian region, and 2007/08 school district characteristics. Key findings include: (1) Kentucky school districts averaged one superintendent turnover during 1998/99-2007/08;…

  20. A Ministudy of employee turnover in US hospitals.

    PubMed

    Collins, Sandra K; McKinnies, Richard C; Matthews, Eric P; Collins, Kevin S

    2015-01-01

    A ministudy was conducted to collect self-reported employee turnover rates in US hospitals. The results indicate many hospitals are struggling with high employee turnover rates. Widespread variances in ratings were observed across hospitals, which may be due to lack of consistency in how they each calculate their employee turnover. This makes benchmarking for the purposes of performance improvement challenging. PMID:25627851

  1. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  2. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  3. Bone scanning.

    PubMed

    Greenfield, L D; Bennett, L R

    1975-03-01

    Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton. PMID:1054210

  4. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  5. Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease.

    PubMed

    de Oliveira, Rodrigo A; Barreto, Fellype C; Mendes, Monique; dos Reis, Luciene M; Castro, João Henrique; Britto, Zita Maria L; Marques, Igor D B; Carvalho, Aluizio B; Moysés, Rosa M; Jorgetti, Vanda

    2015-05-01

    Chronic kidney disease--mineral bone disorder (CKD-MBD) is a complex syndrome influenced by various factors, such as age, CKD etiology, uremic toxins, and dialysis modality. Although extensively studied in hemodialysis (HD) patients, only a few studies exist for peritoneal dialysis (PD) patients. Since most of these older studies contain no bone biopsy data, we studied the pattern of renal osteodystrophy in 41 prevalent PD patients. The most common presentation was adynamic bone disease (49%). There was a significant inverse association between serum sclerostin (a Wnt/β-catenin pathway inhibitor that decreases osteoblast action and bone formation) and the bone formation rate. Bone alkaline phosphatase had the best sensitivity and specificity to detect both high- and low-turnover diseases. The comparison between nondiabetic PD and HD patients, matched by age, gender, parathyroid hormone level, and length of dialysis, revealed low 25-hydroxyvitamin D levels, worse bone mineralization, and low bone turnover in the nondiabetic PD group. Thus, adynamic bone disease was the most frequent type of renal osteodystrophy in PD patients. Sclerostin seems to participate in the pathophysiology of adynamic bone disease and bone alkaline phosphatase was the best serum marker of bone turnover in these patients. PMID:25493951

  6. Bone-protective effects of nonviral gene therapy with folate-chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis.

    PubMed

    Fernandes, Julio C; Wang, Huijie; Jreyssaty, Christian; Benderdour, Mohamed; Lavigne, Patrick; Qiu, Xingpin; Winnik, Francoise M; Zhang, Xiaoling; Dai, Kerong; Shi, Qin

    2008-07-01

    Interleukin-1 receptor antagonist (IL-1Ra), is a natural blocker of the inflammatory cytokine interleukin-1. Using a rat adjuvant-induced arthritis (AIA) model of rheumatoid arthritis (RA), we examined the protective effects of IL-1Ra in bone metabolism in vivo after folate-mediated nonviral gene delivery. We detected secreted human IL-1Ra protein in serum and cultured primary osteoblasts of rats that were treated with chitosan-IL-1Ra and folate-IL-1Ra-chitosan nanoparticles, respectively. In vivo, IL-1Ra gene delivery significantly reverted alterations in bone turnover observed in arthritic animals by modulating the level of osteocalcin (OC) as well as the activities of alkaline phosphatase and tartrate-resistant acid phosphatase. The protective effects of these nanoparticles were evident from the decrease in the expression levels of interleukine-1beta and prostaglandin E(2) as well as osteoclast number and other histopathological findings. Compared to naked DNA and chitosan-DNA, folate-chitosan-DNA nanoparticles were less cytotoxic and enhanced IL-1Ra protein synthesis in vitro and offered a better protection against inflammation and abnormal bone metabolism in vivo. Nonviral gene therapy with folate-chitosan-DNA nanoparticles containing the IL-1 Ra gene seemed to protect against bone damage and inflammation in rat adjuvant-induced arthritis model.

  7. Effect of cadmium on bone resorption in cultured fetal bone

    SciTech Connect

    Miyahara, T.; Miyakoshi, M.; Kozuka, H.

    1980-08-01

    Itai-itai disease which occurred in Toyama Prefecture, Japan, was thought to be due, at least partly, to chronic cadmium poisoning. Patients suffered severe pain in the waist, back and joints as well as kyphosis spinal column. In addition, x-ray film of these patients revealed abnormalities in the humerus and ribs. These bone lesions have been considered to be caused secondarily by dysfunction of other tissues, especially that of the kidneys, but there are some reports that the bone lesions appear before the occurrence of pathological changes in the kidneys of Cd-administered rat. It is currently unclear whether bone lesions by Cd are due to the direct action on the bone or indirect action which is caused by dysfunction of the kidney or intestine. To clarify the direct action of Cd on the bone, we studied the effect of Cd on the ossification of chick-embryo cultured bones biochemically and histologically. The results showed that Cd inhibited the bone matrix formation and brought about a malfunction in the ossification process. In the present work the effect of Cd on demineralization was studied using /sup 45/Ca-prelabeled bone in tissue culture and low levels of Cd were found to stimulate /sup 45/Ca from the bone.

  8. Bone Scintigraphic Findings in MRSA Osteomyelitis.

    PubMed

    Cornejo, Patricia; Mandell, Gerald A

    2016-02-01

    Methicillin-resistant Staphylococcus aureus osteomyelitis is a severe form of infection characterized by multifocal or multiple segmental osseous involvement and subperiosteal abscess formation with increased frequency of extraosseous complications including pyomyositis, septic thrombus, and septic arthritis. Bone scan showed long segment and/or multifocal involvement in 4 of 5 patients with areas of abnormal increased and decreased uptake. The clinical presentations included limp and/or pain. Joint involvement was seen in 4 cases. Bone scan abnormalities correlated well with MRI findings of severe and extensive bone disease, abscess formation, muscle, as well as joint and soft tissue involvement.

  9. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  10. Optimizing Bone Health in Duchenne Muscular Dystrophy

    PubMed Central

    Buckner, Jason L.; Bowden, Sasigarn A.; Mahan, John D.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA. PMID:26124831

  11. Bone Metastasis from Renal Cell Carcinoma.

    PubMed

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The "vicious cycle" hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  12. Bone Metastasis from Renal Cell Carcinoma

    PubMed Central

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  13. Bone marrow metastases from alveolar rhabdomyosarcoma with impressive FDG PET/CT finding but less-revealing bone scintigraphy.

    PubMed

    Yang, Jigang; Zhen, Lishi; Zhuang, Hongming

    2013-12-01

    An 18F-FDG PET/CT scan was performed in a 26-year-old man with a known alveolar rhabdomyosarcoma for staging. The PET/CT scan showed abnormally increased FDG activity involving almost all bones in the imaged regions. In contrast, 99mTc-MDP whole-body bone scan demonstrated only very limited bone metastases.

  14. Organisation turnover among registered nurses: an exploratory model.

    PubMed

    Bloom, J R; Alexander, J A; Flatt, S

    1988-11-01

    In light of current concerns over nursing shortages and productivity, turnover among hospital nurses has assumed renewed importance as a managerial issue. This study examines the thesis that organisation of hospital work is a determinant of voluntary turnover among registered nurses. This perspective differs from previous work in this area in that both turnover and its determinants are conceptualised at the organisational rather than individual level, thus opening the way for administrative intervention to reduce turnover. The conceptual model is tested using multiple regression techniques on a sample of 310 community hospitals. Results suggest the importance of administrative work structures and the professionalisation of the workforce as contributors to higher turnover.

  15. Replicator dynamics with turnover of players

    NASA Astrophysics Data System (ADS)

    Juul, Jeppe; Kianercy, Ardeshir; Bernhardsson, Sebastian; Pigolotti, Simone

    2013-08-01

    We study adaptive dynamics in games where players abandon the population at a given rate and are replaced by naive players characterized by a prior distribution over the admitted strategies. We demonstrate how such a process leads macroscopically to a variant of the replicator equation, with an additional term accounting for player turnover. We study how Nash equilibria and the dynamics of the system are modified by this additional term for prototypical examples such as the rock-paper-scissors game and different classes of two-action games played between two distinct populations. We conclude by showing how player turnover can account for nontrivial departures from Nash equilibria observed in data from lowest unique bid auctions.

  16. Occupational turnover intentions among substance abuse counselors.

    PubMed

    Rothrauff, Tanja C; Abraham, Amanda J; Bride, Brian E; Roman, Paul M

    2011-01-01

    This study examined predictor, moderator, and mediator variables of occupational turnover intention (OcTI) among substance abuse counselors. Data were obtained via questionnaires from 929 counselors working in 225 private substance abuse treatment (SAT) programs across the United States. Hierarchical multiple regression models were conducted to assess predictor, moderator, and mediator variables of OcTI. OcTI scores were relatively low on a 7-point scale, indicating that very few counselors definitely intended to leave the SAT field. Age, certification, positive perceptions of procedural and distributive justice, and hospital-based status negatively predicted OcTI. Counselors' substance use disorder-impacted history moderated the association between organizational commitment and OcTI. Organizational turnover intention partially mediated the link between organizational commitment and OcTI. Workforce stability might be achieved by promoting perceptions of advantages to working in a particular treatment program, having organizational commitment, showing appreciation for counselors' work, and valuing employees from diverse backgrounds.

  17. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  18. Exercises to Improve Gait Abnormalities

    MedlinePlus

    ... Home About iChip Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  19. Low Bone Density

    MedlinePlus

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  20. High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats.

    PubMed

    Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

    2015-01-01

    Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

  1. Facts about Women's Absenteeism and Labor Turnover.

    ERIC Educational Resources Information Center

    Women's Bureau (DOL), Washington, DC.

    The average worktime lost in 1967 because of illness or injury for persons 17 years of age or older was 5.6 days for women and 5.3 days for men. Women lost more time because of acute illness, but men were more likely to be absent because of chronic conditions such as heart trouble. Labor turnover rates show that absentee rates of women have been…

  2. Turnover of soil monosaccharides: Recycling versus Stabilization

    NASA Astrophysics Data System (ADS)

    Basler, Anna; Dyckmans, Jens

    2014-05-01

    Soil organic matter (SOM) represents a mixture of differently degradable compounds. Each of these compounds are characterised by different dynamics due to different chemical recalcitrance, transformation or stabilisation processes in soil. Carbohydrates represent one of these compounds and contribute up to 25 % to the soil organic matter. Vascular plants are the main source of pentose sugars (Arabinose and Xylose), whereas hexoses (Galactose and Mannose) are primarily produced by microorganisms. Several studies suggest that the mean turnover times of the carbon in soil sugars are similar to the turnover dynamics of the bulk carbon in soil. The aim of the study is to characterise the influence of stabilisation and turnover of soil carbohydrates. Soil samples are collected from (i) a continuous maize cropping experiment ('Höhere Landbauschule' Rotthalmünster, Bavaria) established 1979 on a Stagnic Luvisol and (ii) from a continuous wheat cropping, established 1969, as reference site. The effect of stabilisation is estimated by the comparison of turnover times of microbial and plant derived soil carbohydrates. As the dynamics of plant derived carbohydrate are solely influenced by stabilisation processes, whereas the dynamics of microbial derived carbohydrates are affected by recycling of organic carbon compounds derived by C3 plant substrate as well as stabilisation processes. The compound specific isotopic analysis (CSIA) of soil carbohydrates was performed using a HPLC/o/IRMS system. The chromatographic and mass spectrometric subunits were coupled with a LC-Isolink interface. Soil sugars were extracted after mild hydrolysis using 4 M trifluoroacetic acid (TFA). Chromatographic separation of the sugars was achieved using a low strength 0.25 mM NaOH solution as mobile phase at a ?ow rate of 250 μL min-1 at 10 ° C.

  3. Affective Disorders, Bone Metabolism, and Osteoporosis.

    PubMed

    Mezuk, Briana

    2008-12-01

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

  4. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

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

  5. Abnormal ionization in sonoluminescence

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%-70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  6. Generational differences in registered nurse turnover.

    PubMed

    LeVasseur, Sandra A; Wang, Chen-Yen; Mathews, Barbara; Boland, Mary

    2009-08-01

    The chronic nature of the nursing workforce shortage in the United States is a continuing concern. As the nationwide gap between supply and demand grows, it remains unknown what impact turnover will have on nursing, access to care, and efforts to improve quality and safety of health care. It also remains unclear whether the recent turnover trends among new graduate registered nurses differ from past generational cohorts of new nurses. The aims of this study were to identify the reasons why registered nurses turnover by generational cohort (Veterans, Baby Boomers, and GenXMs) and to compare the length of time nurses were employed in their first five nursing positions by generational cohort. The findings suggest the three generational cohorts displayed similar reasons for leaving nursing positions with relocation, career advancement, and personal/family reasons reported most frequently. Except for the first nursing position, significant generational effects were found in the length of time Veterans, Baby Boomer, and GenXMs stayed employed in their nursing positions. It remains unknown why the GenXMs displayed a significantly shorter length of employment time in their second, third, fourth, and fifth nursing positions. The decline in length of employment time displayed in both the Baby Boomers and GenXMs may be an issue of concern requiring future research. PMID:20026454

  7. Quantitative analysis of protein turnover in plants.

    PubMed

    Nelson, Clark J; Li, Lei; Millar, A Harvey

    2014-03-01

    Proteins are constantly being synthesised and degraded as plant cells age and as plants grow, develop and adapt the proteome. Given that plants develop through a series of events from germination to fruiting and even undertake whole organ senescence, an understanding of protein turnover as a fundamental part of this process in plants is essential. Both synthesis and degradation processes are spatially separated in a cell across its compartmented structure. The majority of protein synthesis occurs in the cytosol, while synthesis of specific components occurs inside plastids and mitochondria. Degradation of proteins occurs in both the cytosol, through the action of the plant proteasome, and in organelles and lytic structures through different protease classes. Tracking the specific synthesis and degradation rate of individual proteins can be undertaken using stable isotope feeding and the ability of peptide MS to track labelled peptide fractions over time. Mathematical modelling can be used to follow the isotope signature of newly synthesised protein as it accumulates and natural abundance proteins as they are lost through degradation. Different technical and biological constraints govern the potential for the use of (13)C, (15)N, (2)H and (18)O for these experiments in complete labelling and partial labelling strategies. Future development of quantitative protein turnover analysis will involve analysis of protein populations in complexes and subcellular compartments, assessing the effect of PTMs and integrating turnover studies into wider system biology study of plants.

  8. Forest turnover rates follow global and regional patterns of productivity

    USGS Publications Warehouse

    Stephenson, N.L.; van Mantgem, P.J.

    2005-01-01

    Using a global database, we found that forest turnover rates (the average of tree mortality and recruitment rates) parallel broad-scale patterns of net primary productivity. First, forest turnover was higher in tropical than in temperate forests. Second, as recently demonstrated by others, Amazonian forest turnover was higher on fertile than infertile soils. Third, within temperate latitudes, turnover was highest in angiosperm forests, intermediate in mixed forests, and lowest in gymnosperm forests. Finally, within a single forest physiognomic type, turnover declined sharply with elevation (hence with temperature). These patterns of turnover in populations of trees are broadly similar to the patterns of turnover in populations of plant organs (leaves and roots) found in other studies. Our findings suggest a link between forest mass balance and the population dynamics of trees, and have implications for understanding and predicting the effects of environmental changes on forest structure and terrestrial carbon dynamics. ??2005 Blackwell Publishing Ltd/CNRS.

  9. Abnormal hematological indices in cirrhosis

    PubMed Central

    Qamar, Amir A; Grace, Norman D

    2009-01-01

    Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis. PMID:19543577

  10. Bone and TNF in rheumatoid arthritis: clinical implications

    PubMed Central

    Manara, Maria; Sinigaglia, Luigi

    2015-01-01

    Experimental data have demonstrated that tumour necrosis factor (TNF) plays a significant role in systemic and local bone loss related to rheumatoid arthritis (RA). In clinical studies on patients with RA, treatment with TNF inhibitors was able to arrest systemic bone loss assessed by bone mineral density and bone turnover markers, but there is scarce evidence of a clinically meaningful effect of TNF inhibition in preventing fractures. TNF inhibitors showed a higher efficacy in reducing radiographic progression related to the disease compared to methotrexate in randomised clinical trials. Data from observational studies seem to confirm the effectiveness of anti-TNF therapy in reducing joint damage evolution. PMID:26557382

  11. Decreased bone mineral density and periodontal management.

    PubMed

    Reddy, Michael S; Morgan, Sarah L

    2013-02-01

    The definition of osteoporosis has evolved beyond low bone mineral density to include impaired bone morphology and matrix properties. As such, the subsequent bone density insufficiencies extend beyond the skeletal risks of fracture and have implications for oral health management patients. As our population ages there is a worldwide increase in the risk of decreased bone mineral density and its subsequent morbidity. This makes age an independent risk factor for fracture and decreased bone mineral density. Multiple examinations and diagnostic tests are currently used in combination to develop an algorithm to assess osteoporotic risk. Oral health care professionals should follow these principles and caution should be used in applying a single independent assessment to determine a patient's osteoporotic or bone metabolism risk. Therapeutic approaches for osteoporosis are often divided into nonpharmacological interventions and pharmacological therapies. The periodontist and other oral health care professionals should have a full understanding of the therapeutic options, benefits and implementation of preventive therapies. Bone turnover is a coupled event of bone formation and bone resorption and it is the imbalance of this homeostasis that results in osteoporosis. Based on this uncoupling of bone resorption and formation, osteoporosis or decreased bone mineral density and osteopenia, may be a risk factor for alveolar bone loss in periodontitis. The role of prevention and maintenance with a history of periodontitis and oesteopenia extends beyond biofilm control and should include management of bone mineral density. The chronic periodontal infection in a patient with osteopenia may place the patient at greatly increased risk for alveolar bone loss, gingival recession and root caries. A key component in the management is the oral health professional's knowledge of the interrelationship between skeletal health and periodontal health.

  12. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. )

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  13. Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis.

    PubMed

    Ismail, F; Epstein, S; Pacifici, R; Droke, D; Thomas, S B; Avioli, L V

    1986-10-01

    Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E2), estrone (E1), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm3). Serum BGP correlated positively with CT scan (r + 0.647, P less than 0.001). CT and age were negatively correlated (r - 0.661, P less than 0.001) while CT and E2 showed a positive correlation (r + 0.554, P less than 0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r - 0.421, P less than 0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis.

  14. Is Having Clonal Cytogenetic Abnormalities the Same as Having Leukaemia.

    PubMed

    Farina, Mirko; Rossi, Giuseppe; Bellotti, Daniella; Marchina, Eleonora; Gale, Robert Peter

    2016-01-01

    A finding of cytogenetic abnormalities, even when these are clonal and even when the abnormalities are typically associated with leukaemia, is not the same as a person having leukaemia. We describe a person who had acute myeloid leukaemia (AML) and achieved a complete haematological remission and who then had persistent and transient clonal cytogenetic abnormalities for 22 years but no recurrence of leukaemia. These data suggest that clones of myeloid cells with mutations and capable of expanding to levels detectable by routine cytogenetic analyses do not all eventuate in leukaemia, even after a prolonged observation interval. The possibility of incorrectly diagnosing a person as having leukaemia becomes even greater when employing more sensitive techniques to detect mutations such as by polymerase chain reaction and whole-exome or whole-genome sequencing. Caution is needed when interpreting clonal abnormalities in AML patients with normal blood and bone marrow parameters.

  15. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome.

    PubMed

    Ullrich, N J; Silvera, V M; Campbell, S E; Gordon, L B

    2012-09-01

    HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the scope of structural bone and soft-tissue craniofacial abnormalities in HGPS through CT or MR imaging. Using The Progeria Research Foundation Medical and Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age, were comprehensively reviewed. Eight newly identified abnormalities involving the calvaria, skull base, and soft tissues of the face and orbits were present with prevalences between 43% and 100%. These included J-shaped sellas, a mottled appearance and increased vascular markings of the calvaria, abnormally configured mandibular condyles, hypoplastic articular eminences, small zygomatic arches, prominent parotid glands, and optic nerve kinking. This expanded craniofacial characterization helps link disease features and improves our ability to evaluate how underlying genetic and cellular abnormalities culminate in a disease phenotype.

  16. Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.

    PubMed

    Mishina, Yuji; Starbuck, Michael W; Gentile, Michael A; Fukuda, Tomokazu; Kasparcova, Viera; Seedor, J Gregory; Hanks, Mark C; Amling, Michael; Pinero, Gerald J; Harada, Shun-ichi; Behringer, Richard R

    2004-06-25

    Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling. PMID:15090551

  17. Bone balance within a cortical BMU: local controls of bone resorption and formation.

    PubMed

    Smith, David W; Gardiner, Bruce S; Dunstan, Colin

    2012-01-01

    Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the 'integration of information' occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors.

  18. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation

    PubMed Central

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-01-01

    ABSTRACT Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

  19. Bone tumor

    MedlinePlus

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... may also be ordered to monitor the disease: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  20. Bone Infections

    MedlinePlus

    ... of the body, bones can get infected. The infections are usually bacterial, but can also be fungal. ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent ...

  1. A histomorphometric analysis of subchondral bone in juvenile arthropathy of the dog knee.

    PubMed

    Holm, I E; Bünger, C; Melsen, F

    1985-11-01

    Subchondral bone changes in arthropathy were investigated in an animal model using mongrel dog knees. Unilateral arthritis of the knee was induced by repeated intra-articular instillations of Carrageenin solution in 14 mongrel puppies. Histomorphometric analysis of cartilage and bone was performed blindly in both knees of each dog. Arthritis resulted in a significant increase in the joint cartilage thickness and a significant decrease in subchondral epiphyseal trabecular bone volume (VTB%) and trabecular thickness (TRTH), suggesting negative bone balance. No significant changes in osteoid surfaces (OS%) and resorptive surfaces (RS%) were found. The dynamic parameters suggest an increased bone turnover in the arthritic subchondral bone. PMID:4090984

  2. Serum biomarkers of bone metabolism in castration resistant prostate cancer patients with skeletal metastases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value ...

  3. Bone metabolic activity measured with positron emission tomography and [[sup 18]F] fluoride ion in renal osteodystrophy: Correlation with bone histomorphometry

    SciTech Connect

    Messa, C.; Goodman, W.G.; Hoh, C.K.; Choi, Y.; Nissenson, A.R.; Salusky, I.B.; Phelps, M.E.; Hawkins, R.A. )

    1993-10-01

    The authors evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [[sup 18]F] fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [[sup 18]F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [[sup 18]F] fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystropy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.

  4. Palladacycle-Catalyzed Carbonylative Suzuki-Miyaura Coupling with High Turnover Number and Turnover Frequency.

    PubMed

    Gautam, Prashant; Bhanage, Bhalchandra M

    2015-08-01

    This work reports the carbonylative Suzuki-Miyaura coupling of aryl iodides catalyzed by palladacycles. More importantly, the palladacycles have been used to generate high turnover numbers (TON's) and turnover frequencies (TOF's). A range of aryl iodides can be coupled with arylboronic acids, generating TON's in the range of 10(6) to 10(7) and TOF's in the range of 10(5) to 10(6) h(-1). Comparison of the palladacycles with a conventional palladium source shows their superiority in generating high TON's and TOF's. PMID:26166246

  5. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    PubMed

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician.

  6. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    PubMed Central

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician. PMID:27471408

  7. Microgravity and bone cell mechanosensitivity.

    PubMed

    Klein-Nulend, J; Bacabac, R G; Veldhuijzen, J P; Van Loon, J J W A

    2003-01-01

    mechanosensitivity of bone cells is altered under near weightlessness conditions, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts. In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

  8. Microgravity and bone cell mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R. G.; Veldhuijzen, J. P.; Van Loon, J. J. W. A.

    2003-10-01

    mechanosensitivity of bone cells is altered under near weightlessness conditions, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts. In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

  9. [Hormones and osteoporosis update. Insulin/IGF-I and bone].

    PubMed

    Kawaguchi, Hiroshi

    2009-07-01

    Insulin and insulin-like growth factor-I (IGF-I) are potent bone anabolic factors through the balance of distinct signals of the two adaptor molecules, insulin receptor substrate (IRS) -1 and IRS-2 : IRS-1 for maintenance of bone turnover by up-regulating anabolic and catabolic functions of osteoblasts, while IRS-2 for retaining the predominance of the anabolic function over the catabolic function. PMID:19568000

  10. Sweet Bones: The Pathogenesis of Bone Alteration in Diabetes

    PubMed Central

    2016-01-01

    Diabetic patients have increased fracture risk. The pathogenesis underlying the status of bone alterations in diabetes mellitus is not completely understood but is multifactorial. The major deficits appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts due to abnormal insulin signaling pathway. Other prominent features of diabetes mellitus are an increased urinary excretion of calcium and magnesium, accumulation of advanced glycation end products, and oxidative stress leading to sweet bones (altered bone's strength, metabolism, and structure). Every diabetic patient should be assessed for risk factors for fractures and osteoporosis. The pathogenesis of the bone alterations in diabetes mellitus as well as their molecular mechanisms needs further study. PMID:27777961

  11. Ganglioside/glycosphingolipid turnover: new concepts.

    PubMed

    Tettamanti, G

    2004-01-01

    In this review focus is given to the metabolic turnover of gangliosides/glycosphingolipids. The metabolism and accompanying intracellular trafficking of gangliosides/glycosphingolipids is illustrated with particular attention to the following events: (a) the de novo biosynthesis in the endoplasmic reticulum and Golgi apparatus, followed by vesicular sorting to the plasma membrane; (b) the enzyme-assisted chemical modifications occurring at the plasma membrane level; (c) the internalization via endocytosis and recycling to the plasma membrane; (d) the direct glycosylations taking place after sorting from endosomes to the Golgi apparatus; (e) the degradation at the late endosomal/lysosomal level with formation of fragments of sugar (glucose, galactose, hexosamine, sialic acid) and lipid (ceramide, sphingosine, fatty acid) nature; (f) the metabolic recycling of these fragments for biosynthetic purposes (salvage pathways); and (g) further degradation of fragments to waste products. Noteworthy, the correct course of ganglioside/glycosphingolipid metabolism requires the presence of the vimentin intracellular filament net work, likely to assist intracellular transport of sphingoid molecules. ut of the above events those that can be quantitatively evaluated with acceptable reliability are the processes of de novo biosynthesis, metabolic salvage and direct glycosylation. Depending on the cultured cells employed, the percentage of distribution of de novo biosynthesis, salvage pathways, and direct glycosylation, over total metabolism were reported to be: 35% (range: 10-90%) for de novo biosynthesis, 7% (range: 5-10%) for direct glycosylation, and 58% (range: 10-90%) for salvage pathways. The attempts made to calculate the half-life of overall ganglioside turnover provided data of unsure reliability, especially because in many studies salvage pathways were not taken into consideration. The values of half-life range from 2 to 6.5 h to 3 days depending on the cells used

  12. Radionuclide evaluation of nonmalignant bone disorders

    SciTech Connect

    Winzelberg, G.G.

    1983-02-01

    Recent advances in nuclear imaging have improved the noninvasive evaluation of patients with nonmalignant bone disorders. When bone scanning agents are combined with bone marrow scanning agents and gallium-67 scintigraphy, a more accurate diagnosis can be obtained. By selecting the appropriate imaging sequence, it is often possible to distinguish cellulitis from underlying osteomyelitis. In patients with total hip replacements, it may be possible to separate postsurgical changes from prosthetic loosening or infection. Stress fractures in joggers may be detected by radionuclide bone scintigraphy before radiographs become abnormal. These nuclear imaging procedures can be done in most hospitals.

  13. Bone cells, sclerostin, and FGF23: what's bred in the bone will come out in the flesh.

    PubMed

    Ott, Susan M

    2015-03-01

    Bone metabolism is linked to systemic diseases, and new research shows that the bone cells have endocrine functions that affect multiple organs. They secrete sclerostin, FGF23, prostaglandins, and osteocalcin. Pereira et al. examined gene expression of cells grown from bone biopsies of adolescents with renal osteodystrophy, as a first step to understanding how the bone-cell abnormalities contribute to cardiovascular and metabolic problems in these patients. PMID:25723633

  14. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. 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.

  16. Long-term food restriction prevents aging-associated sphingolipid turnover dysregulation in the brain.

    PubMed

    Babenko, Nataliya A; Shakhova, Elena G

    2014-01-01

    Abnormalities of sphingolipid turnover in the brain during normal aging and age-related neurological disorders were associated with the neurons loss and cognitive malfunction. Calorie restriction (CR) prevented age-related deficits in hippocampal long-term potentiation and improved cognitive function at old age. In the paper we investigated the ceramide and sphingomyelin (SM) levels in the brain regions, which are critical for learning and memory of 3- and 24-month-old rats, as well as the correction of sphingolipid turnover in the brain of old rats, by means of the CR diet and modulators of SM turnover. Using the [methyl-(14)C-choline]SM, the neutral, but not the acid SMase activity has been observed to increase in both the hippocampus and brain cortex of 24-month-old rats with respect to 3-month-old animals. Age-dependent changes of neutral SMase activities were associated with ceramide accumulation and SM level drop in the brain structures studied. Treatment of the rats with the CR diet or N-acetylcysteine (NAC) or α-tocopherol acetate, but not an inhibitor of acid SMase imipramine, reduced the ceramide content and neutral SMase activity in the hippocampus of 24-month-old animals with respect to control rats of the same age. These results suggest that redox-sensitive neutral SMase plays important role in SM turnover dysregulation in both the hippocampus and neocortex at old age and that the CR diet can prevent the age-dependent accumulation of ceramide mainly via neutral SMase targeting.

  17. Bone targeted therapies in metastatic castration-resistant prostate cancer.

    PubMed

    Rajpar, Shanna; Fizazi, Karim

    2013-01-01

    Prostate cancer is the most common male cancer. About 90% of metastatic patients will develop bone metastases. Bone disease is responsible of pain, deterioration of quality of life and serious bone complications. Proliferation of prostate cancer cells in the bone marrow induces osteoclast activation and osteolysis. Targeting the bone microenvironment reduces morbidity. Relevant preclinical and clinical studies of bone-targeted therapies in castration-resistant prostate cancer were identified in PubMed and clinical trial databases. Different drugs are available or in development that target bone resorption (bisphosphonates, RANK ligand inhibitors), bone formation (endothelin 1 inhibitors), cancer cell migration (SRC-family kinase inhibitors, vascular endothelial growth factor-MET inhibitors), and survival (radiopharmaceuticals). In phase III trials, zoledronic acid, denosumab, and radium-223 were shown to significantly delay skeletal-related events. Radium-223 was also shown to improve overall survival. Biomarkers of bone resorption (urinary N-telopeptide) and bone making (alkaline phosphatase) have an independent prognostic impact. Targeting the bone microenvironment is an important component of castration-resistant prostate cancer management to reduce bone complications and improve overall survival. Biomarkers of bone turnover have an independent prognostic impact.

  18. Microgravity and Bone Cell Mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R.; Veldhuijzen, J.; van Loon, J.

    , and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts.In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

  19. Ictal Cardiac Ryhthym Abnormalities

    PubMed Central

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic–clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  20. Ictal Cardiac Ryhthym Abnormalities.

    PubMed

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  1. Communication and abnormal behaviour.

    PubMed

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

  2. Communication and abnormal behaviour.

    PubMed

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential). PMID:261653

  3. Abnormal uterine bleeding.

    PubMed

    Whitaker, Lucy; Critchley, Hilary O D

    2016-07-01

    Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID:26803558

  4. Abortion for fetal abnormality.

    PubMed

    Maclean, N E

    1979-07-25

    I wish to thank Dr. Pauline Bennett for her reply (NZ Med J, 13 June). She has demonstrated well that in dealing with sensitive difficult issues such as abortion for fetal abnormality, the one thing the doctor is not recommended to do is to speak the truth] I am prompted to write this letter for 2 reasons. Firstly, the excellent letter written by Dr. A. M. Rutherford (NZ Med J, 13 June) on the subject of abortion stated, "The most disturbing feature about the whole controversy is the 'blunting of our conscience'." When the doctors are not encouraged to be honest with patients then indeed our conscience has been blunted. Secondly, I watched Holocaust last night, and cannot refrain from stating that I see frightening parallels between our liberal abortion policy and the activities of the Nazis. As I watched the "mental patients" being herded into the shed for gassing by the polite, tidy, white coated medical staff, and then heard the compassionate, sensitive, letter of the hospital authorities to the relatives of the deceased, the parallel became obvious. The mental patients were weak, defenseless, burdensome, and uneconomic; the unborn are weak, defenseless, burdensome, and uneconomic. The hospital authority's letter was acceptable in many ways, acceptable except that its words bore no relation to the truth. It is said that the "first casualty of war is the truth". Whether that war involves the Jews, or the insane, or the unborn, the statement would seem correct.

  5. Occupational turnover intentions among substance abuse counselors.

    PubMed

    Rothrauff, Tanja C; Abraham, Amanda J; Bride, Brian E; Roman, Paul M

    2011-01-01

    This study examined predictor, moderator, and mediator variables of occupational turnover intention (OcTI) among substance abuse counselors. Data were obtained via questionnaires from 929 counselors working in 225 private substance abuse treatment (SAT) programs across the United States. Hierarchical multiple regression models were conducted to assess predictor, moderator, and mediator variables of OcTI. OcTI scores were relatively low on a 7-point scale, indicating that very few counselors definitely intended to leave the SAT field. Age, certification, positive perceptions of procedural and distributive justice, and hospital-based status negatively predicted OcTI. Counselors' substance use disorder-impacted history moderated the association between organizational commitment and OcTI. Organizational turnover intention partially mediated the link between organizational commitment and OcTI. Workforce stability might be achieved by promoting perceptions of advantages to working in a particular treatment program, having organizational commitment, showing appreciation for counselors' work, and valuing employees from diverse backgrounds. PMID:20947285

  6. Dynamics of Adipocyte Turnover in Humans

    SciTech Connect

    Spalding, K; Arner, E; Westermark, P; Bernard, S; Buchholz, B; Bergmann, O; Blomqvist, L; Hoffstedt, J; Naslund, E; Britton, T; Concha, H; Hassan, M; Ryden, M; Frisen, J; Arner, P

    2007-07-16

    Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells is thought to be most important. We show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese and even under extreme conditions, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analyzing the integration of {sup 14}C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in obesity, suggesting a tight regulation of fat cell number that is independent of metabolic profile in adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.

  7. Inhibition of bone resorption and growth of breast cancer in the bone microenvironment.

    PubMed

    Buijs, Jeroen T; Que, Ivo; Löwik, Clemens W G M; Papapoulos, Socrates E; van der Pluijm, Gabri

    2009-02-01

    Breast cancer frequently metastasizes to bone, where tumor cells induce osteoclasts to locally destroy bone. During bone resorption, growth factors are locally released that may support bone metastatic growth. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates and osteoprotegerin (OPG), are available for bone. We examined the hypothesis that inhibition of bone resorption by two different mechanisms may also affect the growth of cancer cells in bone. For this, we tested the effects of high doses of OPG and zoledronic acid (ZOL) on progression of MDA-231-B/Luc+ breast cancer cells in the bone microenvironment using whole body bioluminescent reporter imaging (BLI). Both treatments significantly inhibited the development of radiographically detectable osteolytic lesions. Histologic examination corroborated the radiographic findings, showing that both treatments preserved the integrity of bone trabeculae and prevented bone destruction (significantly higher trabecular bone volumes vs. vehicle). However, whereas practically no TRAcP-positive osteoclasts were observed in tibiae preparations of animals treated with Fc-OPG, TRAcP-positive osteoclasts were still present in the animals treated with ZOL. Intra-bone tumor burden was reduced with ZOL and Fc-OPG treatment. Although there appeared to be a trend for less overall total tumor burden upon treatment with both compounds, this was not significant as assessed by BLI and histomorphometric analysis due to the extramedullary growth of cancer cells which was not affected by these treatments. Collectively, anti-resorptive agents with different mechanisms of action - ZOL and OPG - significantly reduced cancer-induced osteolysis and intra-osseous tumor burden, but failed to restrain local tumor growth. However, interference with the bone micro-environmental growth support could still be of therapeutic relevance when given to patients early in the course of bone metastatic disease.

  8. Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats.

    PubMed

    Gasser, Jürg A; Hulter, Henry N; Imboden, Peter; Krapf, Reto

    2014-03-01

    Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and μCT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean Δ[HCO3(-)]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal +2.1 ± 0.9% vs. intact acidosis -3.6 ± 1.2%, P < 0.001), an effect attributable to a decrease in cortical thickness and, thus, cortical bone mass (no significant effect on cancellous vBMD, week 10) attributed to an increase in endosteal bone resorption (nominally increased endosteal circumference). Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6 and 10 wk, associated with a decrease in trabecular number. CMA significantly decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In conclusion, chronic metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number. PMID:24352505

  9. Microgravity and bone cell mechanosensitivity.

    PubMed

    Burger, E H; Klein-Nulend, J

    1998-05-01

    Bone cells, in particular osteocytes, are extremely sensitive to mechanical stress, a quality that is probably linked to the process of mechanical adaptation (Wolff's law). The in vivo operating cell stress derived from bone loading is likely a flow of an interstitial fluid along the surface of the osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin synthesis and expression of inducible prostaglandin G/H synthase (PGHS-2 or inducible cyclooxygenase, COX-2), an enzyme that mediates the induction of bone formation by mechanical loading in vivo. Disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity has catabolic effects on the skeleton of astronauts, as well as on mineral metabolism in bone organ cultures. This might be explained simply as resulting from an exceptional form of disuse under weightlessness conditions. However, under microgravity conditions, the assembly of cytoskeletal elements may be altered, as gravity has been shown to determine the pattern of microtubular orientation assembled in vitro. Therefore, it is possible that the mechanosensitivity of bone cells is altered under microgravity conditions, and that this abnormal mechanosensation contributes to the disturbed bone metabolism observed in astronauts. In vitro experiments on the International Space Station should test this hypothesis experimentally.

  10. Olives and Bone: A Green Osteoporosis Prevention Option

    PubMed Central

    Chin, Kok-Yong; Ima-Nirwana, Soelaiman

    2016-01-01

    Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly. PMID:27472350

  11. Olives and Bone: A Green Osteoporosis Prevention Option.

    PubMed

    Chin, Kok-Yong; Ima-Nirwana, Soelaiman

    2016-01-01

    Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly. PMID:27472350

  12. [Bone diseases].

    PubMed

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

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

  13. Bone and Gallium scintigraphy in primary malignant and benign bone tumors of the extremities

    SciTech Connect

    Sepahdari, S.; Martin, W.B.; Ryan, J.; Simon, M.; Kirchner, P.

    1985-05-01

    A six yer prospective evaluation of 129 patients suspected of having a primary bone tumor included Tc-99m MDP bone scintigraphy followed by Ga-67 imaging at 48-72 hours. Blood pool images were part of bone scintigraphy in nearly half of the patients. Extent and intensity of tracer uptake in tumor and adjacent bone and joints were recorded for each tracer by two observers blind to the diagnosis. Tissue samples obtained in every patient by biopsy or tumor excision after scintigraphy, revealed 72 malignant and 57 benign bone tumors. The bone scan was positive in 95% (69/72) of malignancies. The scintigraphic intensity of benign and malignant lesions was comparable with both Tc-99m MDP and Ga-67. On the other hand, bone scintigraphy showed 72% (52/72) of bone malignancies to have abnormal proximal and distal bone/joint uptake whereas the Ga-67 images revealed this in only 6% (4/65) of malignancies. Benign lesions manifested this enhanced contiguous bone/joint uptake on only 8% (5/55) of bone and 0% of Ga-67 scans. This study concludes positive bone, blood pool, or Ga-67 images have less specificity for malignancy than the presence of increased Tc-99m MDP deposition in a contiguous bone/joint, but negative scintigraphic results strongly favor a benign lesion. Ga-67 was more accurate than Tc-99m MDP in portraying intraosseous extent of malignant tumors; however, this is now preferably done with C.T.

  14. Haem degradation in abnormal haemoglobins.

    PubMed Central

    Brown, S B; Docherty, J C

    1978-01-01

    The coupled oxidation of certain abnormal haemoglobins leads to different bile-pigment isomer distributions from that of normal haemoglobin. The isomer pattern may be correlated with the structure of the abnormal haemoglobin in the neighbourhood of the haem pocket. This is support for haem degradation by an intramolecular reaction. PMID:708385

  15. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  16. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  17. Electrocardiograph abnormalities revealed during laparoscopy.

    PubMed

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    This brief case presents a well patient in whom an electrocardiograph abnormality consistent with an accessory pathway was found during a routine procedure. We present the electrocardiographs, explain the underlying condition, and consider why the abnormality was revealed in this manner.

  18. [Vertebral trabecular bone in various age groups and in osteoporosis-- morphometry and bone matrix biochemistry].

    PubMed

    Diebold, J; Bätge, B; Stein, H; Müller, P K; Löhrs, U

    1990-01-01

    Vertebral trabecular bone was analysed by morphometry and bone matrix biochemistry. Trabecular bone volume (TBV) and mean trabecular plate thickness (MTPT) decreased with age. TBV was significantly correlated with MTPT and mean trabecular plate density (MTPD). The individual structure of trabecular bone could be described by both MTPT and MTPD together, but changes of these parameters, that were pathognomonic for osteopenia, were not found. By measuring TBV 3 cases of severe osteopenia were identified (TBV less than 2s of controls); 2 of them showed matrix abnormalities so far not described. In one case (a 67 year old woman without risk factors for osteoporosis) an abnormal high content of type III collagen was found, in the other case (a 44 year old woman with acromegaly) bone matrix analysis atypically revealed a significant fraction of type II collagen. Further studies will be needed to assess the pathogenetic or diagnostic importance of these new findings.

  19. Adynamic bone disease: from bone to vessels in chronic kidney disease.

    PubMed

    Bover, Jordi; Ureña, Pablo; Brandenburg, Vincent; Goldsmith, David; Ruiz, César; DaSilva, Iara; Bosch, Ricardo J

    2014-11-01

    Adynamic bone disease (ABD) is a well-recognized clinical entity in the complex chronic kidney disease (CKD)-mineral and bone disorder. Although the combination of low intact parathyroid hormone (PTH) and low bone alkaline phosphatase levels may be suggestive of ABD, the gold standard for precise diagnosis is histomorphometric analysis of tetracycline double-labeled bone biopsies. ABD essentially is characterized by low bone turnover, low bone volume, normal mineralization, and markedly decreased cellularity with minimal or no fibrosis. ABD is increasing in prevalence relative to other forms of renal osteodystrophy, and is becoming the most frequent type of bone lesion in some series. ABD develops in situations with reduced osteoanabolic stimulation caused by oversuppression of PTH, multifactorial skeletal resistance to PTH actions in uremia, and/or dysregulation of Wnt signaling. All may contribute not only to bone disease but also to the early vascular calcification processes observed in CKD. Various risk factors have been linked to ABD, including calcium loading, ageing, diabetes, hypogonadism, parathyroidectomy, peritoneal dialysis, and antiresorptive therapies, among others. The relationship between low PTH level, ABD, increased risk fracture, and vascular calcifications may at least partially explain the association of ABD with increased mortality rates. To achieve optimal bone and cardiovascular health, attention should be focused not only on classic control of secondary hyperparathyroidism but also on prevention of ABD, especially in the steadily growing proportions of diabetic, white, and elderly patients. Overcoming the insufficient osteoanabolic stimulation in ABD is the ultimate treatment goal. PMID:25498381

  20. Bone biosensors: knowing the present and predicting the future

    NASA Astrophysics Data System (ADS)

    Khashayar, Patricia; Amoabediny, Ghassem; Larijani, Bagher; Vanfleteren, Jan

    2016-02-01

    Bone is an active organ with the capacity of continuous remodeling throughout adult life. In view of the fact that the current gold standard to assess bone remodeling, bone mineral density, suffers from certain limitations, newer techniques are being developed. Currently enzyme-linked immunosorbent assay is commonly used to assess bone turnover markers; the technique, however, is expensive, time consuming and needs trained personnel. Thus, there is a growing demand to fabricate different types of biosensors to provide low cost miniaturized platforms to assess the bone remodeling process more accurately. This review focuses on the latest advancements in the field of bone biosensing technologies. Its results might help provide possible solutions for translation of this technology for point-of-care diagnostic applications.

  1. Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.

    PubMed

    Javaheri, B; Carriero, A; Staines, K A; Chang, Y-M; Houston, D A; Oldknow, K J; Millan, J L; Kazeruni, Bassir N; Salmon, P; Shefelbine, S; Farquharson, C; Pitsillides, A A

    2015-12-01

    PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay

  2. Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing

    PubMed Central

    Javaheri, B.; Carriero, A.; Staines, K.A.; Chang, Y.-M.; Houston, D.A.; Oldknow, K.J.; Millan, J.L.; Kazeruni, Bassir N.; Salmon, P.; Shefelbine, S.; Farquharson, C.; Pitsillides, A.A.

    2015-01-01

    PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial