Science.gov

Sample records for accelerated bone turnover

  1. 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

  2. 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.

  3. Normal Bone Turnover in Transient Hyperphosphatasemia

    PubMed Central

    Kutilek, Stepan; Cervickova, Barbora; Bebova, Pavla; Kmonickova, Marie; Nemec, Vladimir

    2012-01-01

    Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by a temporary isolated elevation of serum alkaline phosphatase activity (ALP), predominantly its bone or liver isoform, in either sick or healthy children under 5 years of age. Return to normal ALP levels usually occurs within four months. Spontaneous rise of ALP might concern the physician, especially when treating seriously ill children. However, THI is considered a benign biochemical disorder with no clinical consequences. Some existing reports support the hypothesis that THI is a result of increased bone turnover. We present evidence of normal bone turnover in two children with THI. In a one-year-old girl and a boy of the same age, high ALP levels (31 and 109 μkat/L, respectively) were accidentally detected. The children had no signs of metabolic bone disease or of liver disease. The high ALP levels returned to normal in two months, thus fulfilling the diagnosis of THI. In both patients, serum parathyroid hormone and bone turnover markers, serum CrossLaps, and serum osteocalcin were neither elevated, nor did these markers follow the ALP dynamics, thus reflecting normal bone turnover in THI. Children with THI should be spared from extensive investigations and unnecessary vitamin D treatment. Conflict of interest:None declared. PMID:22664360

  4. Strategies to manage low-bone turnover.

    PubMed

    Spasovski, G

    2009-01-01

    A change in paradigm occurred lately whereby not hypocalcemia but hypercalcemia and positive calcium balance were considered negative factors. Namely, the use of calcium- based binders in combination with vitamin D analogues, has been shown to lead to an over-suppression of parathyroid hormone (PTH) and development of low-bone turnover adynamic bone disease (ABD). The changing prevalence of various types of bone diseases from a high to low-bone turnover goes in line with the presence of increased risk for vascular calcification (VC), morbidity and mortality in the dialysis population. The attenuation of the previous great expectations in calcium-based phosphate binders and vitamin D-analogues entailed a new treatment strategy to preserve bone and vascular health. Hence, a new evidence for treatment of ABD with various types of non calcium based binders and low calcium dialysate is presented. Sevelamer treatment has reduced calcium concentration and increased PTH levels, resulting in the improvement of markers of bone turnover, increased bone formation and improved trabecular architecture, providing a slower progression of VC. Data on lanthanum beneficial effect on ABD histology have been demonstrated in long-term clinical studies. Although there is a slow release of lanthanum from its bone deposits after discontinuation of the treatment and no association with aluminium- like bone toxicity, there is still an ongoing scientific debate about its long-term toxic potential. Finally, reducing the number of calcium based binders and low calcium dialysate (1.25 mmol/l) has been reported to have an impact on the evolution towards markers reflecting higher bone turnover. Then, adoption of the non calcium-based binders should be reserved to high risk patients with ABD and progression of vascular calcifications associated with increased morbidity and mortality. PMID:19668299

  5. Uncoupling of bone turnover following hip replacement.

    PubMed

    Whitson, H; DeMarco, D; Reilly, D; Murphy, S; Yett, H S; Mattingly, D; Greenspan, S L

    2002-07-01

    Studies using total hip replacement surgery as a model for acute hip injury have shown that bone mineral density of the proximal femur decreases 6-18% in the 6 months following surgery. To examine the acute biochemical mechanism associated with bone loss, we measured two indicators of bone formation [serum osteocalcin (OC), serum bone-specific alkaline phosphatase (BSAP)], as well as two markers for bone resorption [urine and serum N-telopeptide cross-linked collagen type 1 (NTx)], in 20 patients (10 men, 10 women, mean age 59.4 years) prior to hip replacement and 1-2 days postsurgery. The average OC value (ng/ml) decreased by 57.3% following surgery (7.5 +/- 4.3 to 3.2 +/- 1.1, P <0.001), and the average BSAP level (U/L) decreased by 27.6% (19.9 +/- 5.6 to 14.4 +/- 3.7, P <0.001). In contrast, levels of urine NTx (nmol BCE/mmol Cr) did not change significantly after the surgery (73.9 +/- 47.2 to 70.1 +/- 29.7). In addition, there was no change in serum NTx (nmol BCE) after surgery (11.8 +/- 2.3 to 11.8 +/- 3.0). Six months after surgery, bone mass had not changed significantly from baseline. These findings suggest that there is an uncoupling of bone turnover following hip replacement surgery which is characterized by significant reductions in bone formation without compensatory decreases in bone resorption, potentially leading to bone loss. Longer periods of follow-up are needed to assess long-term bone mass changes. PMID:12200656

  6. [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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism.

    PubMed

    Kumeda, Y; Inaba, M; Tahara, H; Kurioka, Y; Ishikawa, T; Morii, H; Nishizawa, Y

    2000-11-01

    Hyperthyroid patients exhibit accelerated bone loss by increased bone turnover, and normalization of thyroid function is associated with a significant attenuation of increased bone turnover, followed by an increase in bone mineral density. However, of patients with Graves' disease (GD) maintained on antithyroid drug (ATD) treatment, some exhibit persistent suppression of TSH long after normalization of their serum free T3 (FT3) and free T4 (FT4) levels. The aim of this study was to examine whether bone metabolism is still enhanced in TSH-suppressed premenopausal GD patients with normal FT3 and FT4 levels after ATD therapy (n = 19) compared with that in TSH-normal premenopausal GD patients (n = 30), and to evaluate the relationship between serum TSH receptor antibody (TRAb), an indicator of disease activity of GD, and various biochemical markers of bone metabolism. No difference was found between the two groups in serum Ca, phosphorus, or intact PTH, or in urinary Ca excretion. Serum bone alkaline phosphatase (B-ALP), bone formation markers, and urinary excretions of pyridinoline (U-PYD) and deoxypyridinoline (U-DPD), which are bone resorption markers, were significantly higher in the TSH-suppression group than in the TSH-normal group (B-ALP, P < 0.05; U-PYD, P < 0.001; U-DPD, P < 0.001). For the group of all GD patients enrolled in this study, TSH, but neither FT3 nor FT4, exhibited a significant negative correlation with B-ALP (r = -0.300; P < 0.05), U-PYD (r = -0.389; P < 0.05), and U-DPD (r = -0.446; P < 0.05), whereas TRAb exhibited a highly positive and significant correlation with B-ALP (r = 0.566; P < 0.0001), U-PYD (r = 0.491; P < 0.001), and U-DPD (r = 0.549; P < 0.0001). Even in GD patients with normal TSH, serum TRAb was positively correlated with B-ALP (r = 0.638; P < 0.001), U-PYD (r = 0.638; P < 0.001), and U-DPD (r = 0.641; P < 0.001). In conclusion, it is important to achieve normal TSH levels during ATD therapy to normalize bone turnover. TRAb was

  18. 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

  19. Teriparatide and bone turnover and formation in a hemodialysis patient with low-turnover bone disease: a case report.

    PubMed

    Palcu, Patricia; Dion, Natalie; Ste-Marie, Louis-Georges; Goltzman, David; Radziunas, Ina; Miller, Paul D; Jamal, Sophie A

    2015-06-01

    Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in women and men with osteoporosis. However, it is not well studied in people with chronic kidney disease (CKD). We report on a patient with stage 5 CKD treated with dialysis who presented to our clinic with multiple fractures, including bilateral nondisplaced pelvic fractures resulting in chronic pain and interfering with the patient's ability to work. Bone histomorphometry demonstrated low-turnover bone disease, and he was treated with 20μg of teriparatide (subcutaneous injection) every morning for 24 months. Within 6 months of initiating therapy, the patient's pain resolved and he was able to resume work. Serum calcium and phosphate levels remained within reference ranges throughout his treatment, and he sustained no further fractures. During 24 months of treatment, bone mineral density was maintained at the lumbar spine, and there was an increase of 4% at the femoral neck and total hip. A second transiliac bone biopsy demonstrated improvements in static and dynamic parameters of bone formation. In our patient, 24-month treatment with teriparatide was safe and effective; however, larger studies are needed to determine the efficacy of teriparatide in the dialysis-dependent CKD population. PMID:25843705

  20. 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

  1. 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.

  2. [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

  3. 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 ...

  4. Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover

    PubMed Central

    Farkas, Zoltán; Horvath, Peter; Bódi, Zoltán; Daraba, Andreea; Szamecz, Béla; Gut, Ivo; Bayes, Mónica; Santos, Manuel A. S.; Pál, Csaba

    2015-01-01

    Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. To investigate how organisms mitigate the deleterious effects of protein synthesis errors during evolution, a mutant yeast strain was engineered to translate a codon ambiguously (mistranslation). It thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. This strain was used to study the capacity of the yeast genome to compensate the deleterious effects of protein mistranslation. Laboratory evolutionary experiments revealed that fitness loss due to mistranslation can rapidly be mitigated. Genomic analysis demonstrated that adaptation was primarily mediated by large-scale chromosomal duplication and deletion events, suggesting that errors during protein synthesis promote the evolution of genome architecture. By altering the dosages of numerous, functionally related proteins simultaneously, these genetic changes introduced large phenotypic leaps that enabled rapid adaptation to mistranslation. Evolution increased the level of tolerance to mistranslation through acceleration of ubiquitin-proteasome–mediated protein degradation and protein synthesis. As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells. However, there was a strong evolutionary trade-off between adaptation to mistranslation and survival upon starvation: the evolved lines showed fitness defects and impaired capacity to degrade mature ribosomes upon nutrient limitation. Moreover, as a response to an enhanced energy demand of accelerated protein turnover, the evolved lines exhibited increased glucose uptake by selective duplication of hexose transporter genes. We conclude that adjustment of proteome homeostasis to mistranslation evolves rapidly, but this adaptation has several side effects on cellular physiology. Our work also indicates that

  5. 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.

  6. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions.

    PubMed

    Rubin, Mishaela R; Patsch, Janina M

    2016-01-01

    Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk. PMID:27019762

  7. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions

    PubMed Central

    Rubin, Mishaela R; Patsch, Janina M

    2016-01-01

    Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk. PMID:27019762

  8. 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

  9. Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture.

    PubMed

    Rauner, M; Föger-Samwald, U; Kurz, M F; Brünner-Kubath, C; Schamall, D; Kapfenberger, A; Varga, P; Kudlacek, S; Wutzl, A; Höger, H; Zysset, P K; Shi, G P; Hofbauer, L C; Sipos, W; Pietschmann, P

    2014-07-01

    Cathepsin S is a cysteine protease that controls adipocyte differentiation and has been implicated in vascular and metabolic complications of obesity. Considering the inverse relation of osteoblasts and adipocytes and their mutual precursor cell, we hypothesized that cathepsin S may also affect osteoblast differentiation and bone remodeling. Thus, the fat and bone phenotypes of young (3 months old) and aged (12 or 18 months old) cathepsin S knock-out (KO) and wild-type (WT) mice were determined. Cathepsin S KO mice had a normal body weight at both ages investigated, even though the amount of subscapular and gonadal fat pads was reduced by 20%. Further, cathepsin S deficiency impaired adipocyte formation (-38%, p<0.001), which was accompanied by a lower expression of adipocyte-related genes and a reduction in serum leptin, IL-6 and CCL2 (p<0.001). Micro-CT analysis revealed an unchanged trabecular bone volume fraction and density, while tissue mineral density was significantly lower in cathepsin S KO mice at both ages. Aged KO mice further had a lower cortical bone mass (-2.3%, p<0.05). At the microarchitectural level, cathepsin S KO mice had thinner trabeculae (-8.3%), but a better connected trabecular network (+24%). Serum levels of the bone formation marker type 1 procollagen amino-terminal-propeptide and osteocalcin were both 2-3-fold higher in cathepsin S KO mice as was the mineralized surface. Consistently, osteogenic differentiation was increased 2-fold along with an increased expression of osteoblast-specific genes. Interestingly, serum levels of C-terminal telopeptide of type I collagen were also higher (+43%) in cathepsin S KO mice as were histological osteoclast parameters and ex vivo osteoclast differentiation. Thus, cathepsin S deficiency alters the balance between adipocyte and osteoblast differentiation, increases bone turnover, and changes bone microarchitecture. Therefore, bone and fat metabolisms should be monitored when using cathepsin S

  10. 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

  11. The turnover of mineralized growth plate cartilage into bone may be regulated by osteocytes.

    PubMed

    Cox, Lieke G E; van Rietbergen, B; van Donkelaar, C C; Ito, K

    2011-06-01

    During endochondral ossification, growth plate cartilage is replaced with bone. Mineralized cartilage matrix is resorbed by osteoclasts, and new bone tissue is formed by osteoblasts. As mineralized cartilage does not contain any cells, it is unclear how this process is regulated. We hypothesize that, in analogy with bone remodeling, osteoclast and osteoblast activity are regulated by osteocytes, in response to mechanical loading. Since the cartilage does not contain osteocytes, this means that cartilage turnover during endochondral ossification would be regulated by the adjacent bone tissue. We investigated this hypothesis with an established computational bone adaptation model. In this model, osteocytes stimulate osteoblastic bone formation in response to the mechanical bone tissue loading. Osteoclasts resorb bone near randomly occurring microcracks that are assumed to block osteocyte signals. We used finite element modeling to evaluate our hypothesis in a 2D-domain representing part of the growth plate and adjacent bone. Cartilage was added at a constant physiological rate to simulate growth. Simulations showed that osteocyte signals from neighboring bone were sufficient for successful cartilage turnover, since equilibrium between cartilage remodeling and growth was obtained. Furthermore, there was good agreement between simulated bone structures and rat tibia histology, and the development of the trabecular architecture resembled that of infant long bones. Additionally, prohibiting osteoclast invasion resulted in thickened mineralized cartilage, similar to observations in a knock-out mouse model. We therefore conclude that it is well possible that osteocytes regulate the turnover of mineralized growth plate cartilage. PMID:21546025

  12. Paradoxical Response to Mechanical Unloading in Bone Loss, Microarchitecture, and Bone Turnover Markers

    PubMed Central

    Sun, Xiaodi; Yang, Kaiyun; Wang, Chune; Cao, Sensen; Merritt, Mackenzie; Hu, Yingwei; Xu, Xin

    2015-01-01

    Background: Sclerostin, encoded by the SOST gene, has been implicated in the response to mechanical loading in bone. Some studies demonstrated that unloading leads to up-regulated SOST expression, which may induce bone loss. Purpose: Most reported studies regarding the changes caused by mechanical unloading were only based on a single site. Considering that the longitudinal bone growth leads to cells of different age with different sensitivity to unloading, we hypothesized that bone turnover in response to unloading is site specific. Methods: We established a disuse rat model by sciatic neurectomy in tibia. In various regions at two time-points, we evaluated the bone mass and microarchitecture in surgically-operated rats and control rats by micro-Computed Tomography (micro-CT) and histology, sclerostin/SOST by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (qPCR), tartrate resistant acid phosphatase 5b (TRAP 5b) by ELISA and TRAP staining, and other bone markers by ELISA. Results: Micro-CT and histological analysis confirmed bone volume in the disuse rats was significantly decreased compared with those in the time-matched control rats, and microarchitecture also changed 2 and 8 weeks after surgery. Compared with the control groups, SOST mRNA expression in the diaphysis was down-regulated at both week 2 and 8. On the contrary, the percentage of sclerostin-positive osteocytes showed an up-regulated response in the 5 - 6 mm region away from the growth plate, while in the 2.5 - 3.5 mm region, the percentage was no significant difference. Nevertheless, in 0.5 - 1.5 mm region, the percentage of sclerostin-positive osteocytes decreased after 8 weeks, consistent with serum SOST level. Besides, the results of TRAP also suggested that the expression in response to unloading may be opposite in different sites or system. Conclusion: Our data indicated that unloading-induced changes in bone

  13. Role of oestrogen in the regulation of bone turnover at the menarche.

    PubMed

    Eastell, Richard

    2005-05-01

    The rise in oestrogen levels at menarche in girls is associated with a large reduction in bone turnover markers. This reduction reflects the closure of the epiphyseal growth plates, the reduction in periosteal apposition and endosteal resorption within cortical bone, and in bone remodelling within cortical and cancellous bone. Oestrogen promotes these changes, in part, by promoting apoptosis of chondrocytes in the growth plate and osteoclasts within cortical and cancellous bone. The period of early puberty is associated with an increased risk of fracture, particularly of the distal forearm, and this may be related to the high rate of bone turnover. A late menarche is a consistent risk factor for fracture and low bone mineral density in the postmenopausal period; models that might explain this association are considered. PMID:15845915

  14. 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

  15. Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women.

    PubMed

    Bhattacharyya, Sudeepa; Siegel, Eric R; Achenbach, Sara J; Khosla, Sundeep; Suva, Larry J

    2008-07-01

    Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the

  16. 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

  17. 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

  18. 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

  19. 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

  20. Short-Term Effects of TNF Inhibitors on Bone Turnover Markers and Bone Mineral Density in Rheumatoid Arthritis.

    PubMed

    Orsolini, Giovanni; Adami, Giovanni; Adami, Silvano; Viapiana, Ombretta; Idolazzi, Luca; Gatti, Davide; Rossini, Maurizio

    2016-06-01

    TNFα inhibitors (TNFαI) exert positive effects on disease activity in rheumatoid arthritis (RA). Bone involvement is a major determinant of functional impairment in this disease. Here we investigated the short-term effects of TNFαI therapy on bone metabolism and density. We studied 54 patients with RA starting a TNFαI biologic drug, in whom any factor known to interfere with bone metabolism was excluded or rigorously accounted for. We measured at baseline and after 6-month therapy bone turnover markers: N-propeptide of type I collagen (P1NP), and bone alkaline phosphates for bone formation and serum C-terminal telopeptide of type I collagen (CTX) for bone resorption. We also evaluated bone mineral density (BMD) at hip and lumbar by dual-energy X-ray absorptiometry. All bone markers rose significantly and these changes were not dependent on steroid dosage. A significant decrease in femoral neck BMD was also observed. These results indicate that TNFαI therapy in RA over 6 months is associated with an early increase in bone turnover and a decline in hip BMD. PMID:26887973

  1. 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

  2. Physiological and pathophysiological bone turnover - role of the immune system.

    PubMed

    Weitzmann, M Neale; Ofotokun, Ighovwerha

    2016-09-01

    Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration of bone structure and strength. Osteoporosis increases the risk of fragility fractures, a cause of substantial morbidity and mortality, especially in elderly patients. This imbalance between bone formation and bone resorption is brought about by natural ageing processes, but is frequently exacerbated by a number of pathological conditions. Of importance to the aetiology of osteoporosis are findings over the past two decades attesting to a deep integration of the skeletal system with the immune system (the immuno-skeletal interface (ISI)). Although protective of the skeleton under physiological conditions, the ISI might contribute to bone destruction in a growing number of pathophysiological states. Although numerous research groups have investigated how the immune system affects basal and pathological osteoclastic bone resorption, recent findings suggest that the reach of the adaptive immune response extends to the regulation of osteoblastic bone formation. This Review examines the evolution of the field of osteoimmunology and how advances in our understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures. PMID:27312863

  3. 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

  4. 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

  5. Influence of body weight on bone mass, architecture and turnover.

    PubMed

    Iwaniec, Urszula T; Turner, Russell T

    2016-09-01

    Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating the development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. Although the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

  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. Influence of Fatigue Loading and Bone Turnover on Bone Strength and Pattern of Experimental Fractures of the Tibia in Mice.

    PubMed

    Bonnet, Nicolas; Gerbaix, Maude; Ominsky, Michael; Ammann, Patrick; Kostenuik, Paul J; Ferrari, Serge L

    2016-07-01

    Bone fragility depends on bone mass, structure, and material properties, including damage. The relationship between bone turnover, fatigue damage, and the pattern and location of fractures, however, remains poorly understood. We examined these factors and their integrated effects on fracture strength and patterns in tibia. Adult male mice received RANKL (2 mg/kg/day), OPG-Fc (5 mg/kg 2×/week), or vehicle (Veh) 2 days prior to fatigue loading of one tibia by in vivo axial compression, with treatments continuing up to 28 more days. One day post fatigue, crack density was similarly increased in fatigued tibiae from all treatment groups. After 28 days, the RANKL group exhibited reduced bone mass and increased crack density, resulting in reduced bone strength, while the OPG-Fc group had greater bone mass and bone strength. Injury repair altered the pattern and location of fractures created by ex vivo destructive testing, with fractures occurring more proximally and obliquely relative to non-fatigued tibia. A similar pattern was observed in both non-fatigued and fatigued tibia of RANKL. In contrast, OPG-Fc prevented this fatigue-related shift in fracture pattern by maintaining fractures more distal and transverse. Correlation analysis showed that bone strength was predominantly determined by aBMD with minor contributions from structure and intrinsic strength as measured by nanoindentation and cracks density. In contrast, fracture location was predicted equally by aBMD, crack density and intrinsic modulus. The data suggest that not only bone strength but also the fracture pattern depends on previous damage and the effects of bone turnover on bone mass and structure. These observations may be relevant to further understand the mechanisms contributing to fracture pattern in long bone with different levels of bone remodeling, including atypical femur fracture. PMID:26945756

  8. Bone marrow capacity for bone cells and trabecular bone turnover in immobilized tibia after sciatic neurectomy in mice.

    PubMed

    Sakai, A; Nakamura, T; Tsurukami, H; Okazaki, R; Nishida, S; Tanaka, Y; Norimura, T; Suzuki, K

    1996-05-01

    Trabecular bone turnover and bone marrow capacity for the development of bone cells in the tibia were assessed after sciatic neurectomy (NX) in mice. The right hindlimbs of 6-week-old DDY mice were neurectomized and left hindlimbs were sham-operated and served as NX controls. Histomorphometrical analyses of the trabecular bone of the proximal tibia demonstrated the initial decrease in bone formation rate for the first 14 days and the subsequent increase in osteoclast surface for the next 14 days. The number of adherent stromal cells per tibia obtained for the NX limbs was reduced on days 7 and 10 postsurgically, and then recovered on day 12. However, the alkaline phosphatase activity of the cells was persistently depressed. The formation of osteoclast-like multinucleated cells in the marrow cultures obtained from NX limbs at days 10, 12, and 14 showed a significant increase in the medium containing parathyroid hormone (PTH). The number of colonies cultured for colony forming units-fibroblastic (CFU-f) that developed from the marrow cells did not differ in the NX and the contralateral limbs at any time during the period. On the other hand, the number of colonies cultured of colony forming units for granulocytes and macrophages (CFU-GM) was markedly increased for both the NX and the contralateral tibiae at days 12 and 14. This study clearly demonstrates that there are two stages in the development of osteopenia after NX. During the first 14 days, trabecular bone formation and number of marrow stromal cells are reduced. In the second 14 day period, the trabecular osteoclast number is increased and osteoclast formation from the bone marrow cells is enhanced in the presence of PTH. However, neither the CFU-f nor the CFU-GM assay could identify the changes in osteogenic or osteoclastogenic potential of the bone marrow. These in vitro assays provide limited information on the shifts in bone marrow cell lineages and the local environment producing osteopenia in the

  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. Histological evidence of increased turnover in bone from spontaneously hypertensive rats.

    PubMed

    Barbagallo, M; Quaini, F; Baroni, M C; Barbagallo, C M; Boiardi, L; Passeri, G; Arlunno, B; Delsignore, R; Passeri, M

    1991-03-01

    24 weeks-old spontaneously hypertensive male rats and normotensive genetic controls were subjected to: histomorphometry of the proximal tibiae, assay of mineral density of the femurs by dual photon absorptiometry, and measurement of the calcium content of the femoral bone ash by atomic absorption spectophotometry. Compared with the controls, the hypertensive rats showed osteopenia and increased bone turnover; their osteoid volumes and the surface area of both osteoclasts and osteoblasts were all increased. The data suggest that, during aging, spontaneously hypertensive rats both lose bone mass more rapidly and also have an increased skeletal metabolic rate with respect to the controls. PMID:1888878

  11. Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus.

    PubMed

    Gerdhem, P; Isaksson, A; Akesson, K; Obrant, Karl J

    2005-12-01

    Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility

  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. Elevated Bone Turnover in an Infantile Patient with Mucolipidosis II; No Association with Hyperparathyroidism

    PubMed Central

    Otomo, Takanobu; Yamamoto, Takehisa; Fujikawa, Yasuhiro; Shimotsuji, Tsunesuke; Ozono, Keiichi

    2011-01-01

    This present report concerns an infantile patient with mucolipidosis II, who showed transient cortical bone hyperostosis followed by severe osteopenia. The diagnosis of mucolipidosis II was made based on the leakage of lysosomal enzymes in serum and conditioned media of the patient's skin fibroblasts, low activity of lysosomal enzymes of the fibroblasts and mutation of c.2086_2089insC (p.L697fs) and c.3565C>T (p.R1189X) in the GNPTAB gene. Bone X-ray analysis demonstrated a periosteal reaction and elevated bone resorption at the age of 2 mo. Bone markers, including alkaline phosphatase, osteocalcin and urine deoxypyridinoline, also indicated a high turnover of bone metabolism; however, no apparent rickets-like changes and no increased levels of PTH were observed. Elevated bone resorption is possibly associated with the leakage of lysosomal enzyme from osteoclasts into bone matrices. Bone formation gradually reduced, and increased bone resorption persisted. This led to severe osteopenia at the age of 6 mo. Characteristic bone findings may contribute to early diagnosis of mucolipidosis II, but their pathogenesis remains to be clarified. PMID:23926388

  15. 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

  16. Effects of rhIGF-I administration on bone turnover during short-term fasting.

    PubMed Central

    Grinspoon, S K; Baum, H B; Peterson, S; Klibanski, A

    1995-01-01

    Insulin-like growth factor-I (IGF-I) is a nutritionally dependent bone trophic hormone which stimulates osteoblast function and collagen synthesis in vivo and in vitro. We hypothesized that in the fasting state, IGF-I levels would decline significantly and would establish a model in which we could investigate the effects of IGF-I administration on bone turnover. We therefore studied 14 normal women ages 19-33 (mean, 24 +/- 4 [SD] years) during a complete 10-d fast. After 4 d of fasting, subjects were randomized to receive rhIGF-I or placebo subcutaneously twice a day for 6 d. Bone turnover was assessed using specific markers of formation (osteocalcin and type I procollagen carboxyl-terminal propeptide [PICP]) and resorption (pyridinoline, deoxypyridinoline, type I collagen crosslinked N-telopeptide [N-telopeptide] and hydroxyproline). Serum levels of PICP and osteocalcin decreased from 143 +/- 52 to 60 +/- 28 ng/ml (P = 0.001) and from 7.6 +/- 5.4 to 4.2 +/- 3.1 ng/ml (P = 0.001) respectively with 4 d of fasting. Urinary excretion of pyridinoline and deoxypyridinoline decreased from 96 +/- 63 to 47 +/- 38 nmol/mmol creatinine (P < 0.05) and from 28 +/- 17 to 14 +/- 11 nmol/mmol creatinine (P < 0.05) respectively. Mean IGF-I levels decreased from 310 +/- 81 to 186 +/- 78 ng/ml (P = 0.001). In the second part of the experimental protocol, serum osteocalcin and PICP levels increased 5- and 3-fold, respectively with rhIGF-I administration and were significantly elevated compared with the placebo group at the end of treatment (20.9 +/- 17.3 vs. 5.9 +/- 6.4 ng/ml for osteocalcin [P < 0.05] and 188 +/- 45 vs. 110 +/- 37 ng/ml for PICP [P < 0.05]). In contrast, all four markers of bone resorption, including urinary pyridinoline, deoxypyridinoline, N-telopeptide and hydroxyproline were unchanged with rhIGF-I administration. This report is the first to demonstrate that bone turnover falls rapidly with acute caloric deprivation in normal women. RhIGF-I administration

  17. Familial resemblance of bone turnover rate in men aged 40 and over-the MINOS study.

    PubMed

    Nagy, Hoda; Feyt, Clément; Chapurlat, Roland; Szulc, Pawel

    2013-03-01

    Familial resemblance of bone mineral density (BMD) is well known in both sexes. Fewer data concern the familial resemblance of bone turnover markers (BTMs) and bone size in men. Our aim was to assess the correlation of BMD, bone size, BTM levels and hormones regulating bone turnover in 50 pairs of brothers aged ≥ 40 and 50 pairs of unrelated men matched for age, weight and height. BMD was measured at the lumbar spine, hip, forearm and whole body. We measured serum osteocalcin (OC), bone-specific alkaline phosphatase (bone ALP), N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) as well as urinary free and total deoxypyridinoline (DPD) and CTX-I. After adjustment for age, weight, bioavailable 17β-estradiol, and parathyroid hormone, all the BTMs (except bone ALP) were significantly correlated in the brothers (ICC = 0.36-0.64). Most of these correlations were significantly stronger than in the unrelated men. Bone size correlated significantly between the brothers (ICC = 0.55-0.65). These correlations were significantly stronger than in the unrelated men. BMD correlated between the brothers at most of the skeletal sites and, for some of them, more strongly than in the unrelated men. Serum levels of LDL-cholesterol and triglycerides were significantly correlated in the brothers, but not more strongly than in the unrelated men. BTM levels correlated independently in the brothers aged ≥ 40, when their shared environment was limited. These data suggest a substantial hereditary determinism of the BTM levels in men. PMID:23179229

  18. 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

  19. 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. PMID:25231881

  20. Accelerated Bone Repair After Plasma Laser Corticotomies

    PubMed Central

    Leucht, Philipp; Lam, Kentson; Kim, Jae-Beom; Mackanos, Mark A.; Simanovskii, Dmitrii M.; Longaker, Michael T.; Contag, Christopher H.; Schwettman, H Alan; Helms, Jill A.

    2007-01-01

    Objective: To reveal, on a cellular and molecular level, how skeletal regeneration of a corticotomy is enhanced when using laser-plasma mediated ablation compared with conventional mechanical tissue removal. Summary Background Data: Osteotomies are well-known for their most detrimental side effect: thermal damage. This thermal and mechanical trauma to adjacent bone tissue can result in the untoward consequences of cell death and eventually in a delay in healing. Methods: Murine tibial corticotomies were performed using a conventional saw and a Ti:Sapphire plasma-generated laser that removes tissue with minimal thermal damage. Our analyses began 24 hours after injury and proceeded to postsurgical day 6. We investigated aspects of wound repair ranging from vascularization, inflammation, cell proliferation, differentiation, and bone remodeling. Results: Histology of mouse corticotomy sites uncovered a significant difference in the onset of bone healing; whereas laser corticotomies showed abundant bone matrix deposition at postsurgical day 6, saw corticotomies only exhibited undifferentiated tissue. Our analyses uncovered that cutting bone with a saw caused denaturation of the collagen matrix due to thermal effects. This denatured collagen represented an unfavorable scaffold for subsequent osteoblast attachment, which in turn impeded deposition of a new bony matrix. The matrix degradation induced a prolonged inflammatory reaction at the cut edge to create a surface favorable for osteochondroprogenitor cell attachment. Laser corticotomies were absent of collagen denaturation, therefore osteochondroprogenitor cell attachment was enabled shortly after surgery. Conclusion: In summary, these data demonstrate that corticotomies performed with Ti:Sapphire lasers are associated with a reduced initial inflammatory response at the injury site leading to accelerated osteochondroprogenitor cell migration, attachment, differentiation, and eventually matrix deposition. PMID:17592303

  1. 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. PMID:27424935

  2. Estrogens modulate RANKL-RANK/osteoprotegerin mediated interleukin-6 effect on thyrotoxicosis-related bone turnover in mice.

    PubMed

    Mysliwiec, J; Zbucki, R; Nikolajuk, A; Mysliwiec, P; Kaminski, K; Bondyra, Z; Dadan, J; Gorska, M; Winnicka, M M

    2011-04-01

    Interleukin-6 has been shown to cause imbalance between bone resorption and formation in thyrotoxicosis. The aim of the present study was an attempt to estimate the influence of estrogens on thyrotoxicosis-related disturbances in bone turnover in relation to RANKL-RANK/osteoprotegerin system in IL-6 deficient mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6J (IL6-/-Kopf) (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1. WT controls, 2. IL6KO controls, 3. WT mice with thyrotoxicosis, 4. IL6KO mice with thyrotoxicosis, 5. WT ovariectomized, 6. IL6KO ovariectomized, 7. WT ovariectomized mice with thyrotoxicosis, and 8. IL6KO ovariectomized mice with thyrotoxicosis. Experimental model of menopause was evoked by bilateral ovariectomy carried out in 8-9 weeks old mice. Thyrotoxicosis was induced by intraperitoneal injection of levothyroxine at a dose of 1 μg/g daily over 21 days. The serum levels of TRACP5b, osteocalcin, OPG, and RANKL were determined by ELISA. RANKL serum concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, however, in a minor degree in IL6KO thyrotoxic mice as compared to wild-type animals. Osteoprotegerin serum levels were significantly increased in all thyrotoxic groups of mice except ovariectomized IL6KO animals. To sum up, the results of the present study suggest that IL-6 plays a key role in stimulation of RANKL-RANK/OPG system and this effect is strongly enhanced in conditions of accelerated bone turnover such as thyrotoxicosis and/or estrogen depletion. PMID:21332025

  3. Disordered-Eating Attitudes in Relation to Bone Mineral Density and Markers of Bone Turnover in Overweight Adolescents

    PubMed Central

    Schvey, Natasha A.; Tanofsky-Kraff, Marian; Yanoff, Lisa B.; Checchi, Jenna M.; Shomaker, Lauren B.; Brady, Sheila; Savastano, David M.; Ranzenhofer, Lisa M.; Yanovski, Susan Z.; Reynolds, James C.; Yanovski, Jack A.

    2009-01-01

    Purpose To examine the relationships between cognitive eating restraint and both bone mineral density (BMD) and markers of bone turnover in overweight adolescents. Methods 137 overweight (BMI 39.1±6.8 kg/m2) African American and Caucasian adolescent (age=14.4 ± 1.4y) girls (66.4%) and boys were administered the Eating Disorder Examination (EDE) interview and Eating Inventory (EI) questionnaire and underwent dual energy x-ray absorptiometry (DXA) to measure total lumbar spine BMD. Markers of bone formation (serum bone specific alkaline phosphatase and osteocalcin), bone resorption (24-hour urine N-telopeptides), and stress (urine free cortisol) were measured. Results After accounting for the contribution of demographics, height, weight, serum 25-hydroxyvitamin D, and depressive symptoms, adolescents’ weight concern, as assessed by interview, was a significant contributor to a model of urine free cortisol (β =.30, p <.05). Shape concern, as also assessed by interview, was significantly associated with lumbar spine bone mineral density (β =.−.15, p < 05). Dietary restraint was not a significant predictor in any of these models. Conclusions These findings suggest that among severely overweight adolescents, dissatisfaction with shape and weight may be salient stressors. Future research is required to illuminate the relationship between bone health and disordered-eating attitudes in overweight adolescents. PMID:19541247

  4. 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

  5. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    PubMed

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover. PMID:26487675

  6. 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

  7. 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.

  8. Comparative Proteome Analysis of hAT-MSCs Isolated from Chronic Renal Failure Patients with Differences in Their Bone Turnover Status

    PubMed Central

    Akpinar, Gurler; Tuncay, Mehmet; Aksoy, Ayça; Karaoz, Erdal

    2015-01-01

    The relationship between the stem cells and the bone turnover in uremic bone disease due to chronic renal failure (CRF) is not described. The aim of this study was to investigate the effect of bone turnover status on stem cell properties. To search for the presence of such link and shed some light on stem-cell relevant mechanisms of bone turnover, we carried out a study with mesenchymal stem cells. Tissue biopsies were taken from the abdominal subcutaneous adipose tissue of a CRF patient with secondary hyperparathyroidism with the high turnover bone disease. This patient underwent parathyroidectomy operation (PTX) and another sample was taken from this patient after PTX. A CRF patient with adynamic bone disease with low turnover and a healthy control were also included. Mesenchymal stem cells isolated from the subjects were analyzed using proteomic and molecular approaches. Except ALP activity, the bone turnover status did not affect common stem cell properties. However, detailed proteome analysis revealed the presence of regulated protein spots. A total of 32 protein spots were identified following 2D gel electrophoresis and MALDI-TOF/TOF analyzes. The identified proteins were classified into seven distinct groups and their potential relationship to bone turnover were discussed. Distinct protein expression patterns emerged in relation to the bone turnover status indicate a possible link between the stem cells and bone turnover in uremic bone disease due to CRF. PMID:26575497

  9. 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...

  10. 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

  11. 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

  12. 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

  13. Calcitropic hormones, bone turnover, and lead exposure among female smelter workers.

    PubMed

    Potula, Vijayalakshmi; Henderson, Alden; Kaye, Wendy

    2005-01-01

    To study the association between levels of lead in blood and bone among female former smelter workers in Bunker Hill, Idaho, the authors performed a longitudinal study using homeostatic regulators of calcium and biomarkers of bone turnover. The authors measured participants' blood lead levels (by means of a graphite furnace atomic absorption spectrophotometer) and tibia-bone lead levels (by means of the 109Cd K x-ray fluorescence system) in 1994 and again in 2000; serum ionized calcium, parathyroid hormone, osteocalcin, urinary deoxypyridinoline, pyridinoline, and 1, 25-dihydroxyvitamin D were measured. After controlling for weight and age, significant predictors of changes in blood lead levels from 1994 to 2000 in postmenopausal women were duration of employment, higher ionized calcium levels, alcohol consumption, and higher parathyroid hormone levels. Predictors of change in tibia-bone lead levels in the same group of women were employment in a technical job such as mining and higher urinary pyridinoline levels (p < .05). Changes in blood and bone lead levels over time were associated with increased bone resorption, especially among postmenopausal women. PMID:17214290

  14. Human Apolipoprotein E Isoforms differentially affect Bone Mass and Turnover in vivo

    PubMed Central

    Dieckmann, Marco; Beil, F. Timo; Mueller, Brigitte; Bartelt, Alexander; Marshall, Robert P.; Koehne, Till; Amling, Michael; Ruether, Wolfgang; Cooper, Jackie A.; Humphries, Steve E.; Herz, Joachim; Niemeier, Andreas

    2012-01-01

    The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3 and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12 week-old female knock-in mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced OPG/RANKL ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i.. Accordingly, histomorphometric and μCT analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n=21, n=80, n=55 respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p=0.02 for ε2/ε2 vs ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans. PMID:22991192

  15. Bone turnover in early rheumatoid arthritis. 2. Longitudinal bone density studies.

    PubMed Central

    Sambrook, P N; Ansell, B M; Foster, S; Gumpel, J M; Hesp, R; Reeve, J

    1985-01-01

    Serial measurements of bone mineral in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset and 19 age matched female controls were made in the radius by computed tomography and in the vertebrae by dual photon absorptiometry. Loss of trabecular bone from the distal radius was more rapid in RA (p = 0.0014), but there was no difference in the rate of loss of bone mineral from the radial midshaft or lumbar spine compared with the controls. This study is consistent with the hypothesis that the predominant form of bone loss early in the disease is the vicinity of affected joints. PMID:3876077

  16. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis.

    PubMed

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J

    2016-01-01

    BACKGROUND Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. MATERIAL AND METHODS The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. RESULTS While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. CONCLUSIONS Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID:27550548

  17. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis

    PubMed Central

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J.

    2016-01-01

    Background Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. Material/Methods The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. Results While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. Conclusions Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID:27550548

  18. Associations between Body Composition, Hormonal and Lifestyle Factors, Bone Turnover, and BMD

    PubMed Central

    Hammett-Stabler, Catherine A.; Renner, Jordan B.; Rubin, Janet E.

    2014-01-01

    Background The relative importance of body composition, lifestyle factors, bone turnover and hormonal factors in determining bone mineral density (BMD) is unknown. We studied younger postmenopausal women to determine whether modifiable or nonmodifiable risk factors for osteoporosis have stronger associations with BMD. Methods In multivariable linear regression models, we tested associations between non-bone body composition measures, self-reported measures of physical activity and dietary intake, urinary N-telopeptide (NTx), sex hormone concentrations, and BMD in 109 postmenopausal women aged 50 to 64 years, adjusting for current hormone therapy use and clinical risk factors for low BMD. Lean mass, fat mass and areal BMD (aBMD) at the lumbar spine, femoral neck, total hip and distal radius were measured using dual energy X-ray absorptiometry. Results Higher body weight and self-reported nonwhite race were independently associated with higher aBMD at the lumbar spine, femoral neck, total hip and distal radius. Lean and fat mass were not independently associated with aBMD. Older age and higher urinary NTx were independently associated with lower aBMD at the distal radius but not at weight-bearing sites. Sensitivity analyses demonstrated lack of an independent association between total daily protein or calorie intake and BMD. Conclusions BMD, weight and race were the most important determinants of aBMD at all sites. Older age and higher bone turnover were independently associated with lower aBMD at the distal radius. In a limited analysis, self-reported physical activity, dietary protein and calorie intake were not associated with aBMD after adjustment for the other variables. PMID:24707468

  19. 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.

  20. Effects of resistance training and protein supplementation on bone turnover in young adult women

    PubMed Central

    Mullins, Nicole M; Sinning, Wayne E

    2005-01-01

    Background The strength of aging bone depends on the balance between the resorption and formation phases of the remodeling process. The purpose of this study was to examine the interaction of two factors with the potential to exert opposing influences on bone turnover, resistance exercise training and high dietary protein intake. It was hypothesized that resistance training by young, healthy, untrained women with protein intakes near recommended levels (0.8 g·kg-1·d-1) would promote bone formation and/or inhibit bone resorption, and that subsequent supplementation to provide 2.4 g protein·kg-1·d-1 would reverse these effects. Methods Bone formation was assessed with serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and bone resorption with urinary calcium and deoxypyridinoline (DPD). Biochemical, strength, anthropometric, dietary, and physical activity data were obtained from 24 healthy, untrained, eumenorrheic women (18–29y) at baseline, after eight weeks of resistance training (3 d·wk-1, ~1 hr·d-1; 3 sets, 6–10 repetitions, 13 exercises, 75–85% maximum voluntary contraction), and after 12 weeks of resistance training and 10 days of protein/placebo supplementation. Subjects were randomized (double-blind) to either a high protein (HP) or training control (TC) group and, during the final 10 days, consumed either enough purified whey protein to bring daily protein intake to 2.4 g·kg-1·d-1, or an equivalent dose of isoenergetic, carbohydrate placebo. Results Strength, lean tissue mass, and DPD increased significantly in both groups over time, while percent body fat and BAP decreased (repeated measures ANOVA, p ≤ 0.05, Bonferroni correction). No significant changes were observed for serum OC or urinary calcium, and no significant group (TC, HP) × time (baseline, week 8, week 12) interactions emerged for any of the biochemical measures. Conclusion (1) Twelve weeks of high-intensity resistance training did not appear to enhance bone

  1. Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly men.

    PubMed

    Kahn, Arnold J; Halloran, Bernard; Wolkowitz, Owen; Brizendine, Louann

    2002-04-01

    In the present placebo-controlled, double-blind study, we assessed the effect of dehydroepiandrosterone (DHEA) supplementation (90 mg orally/d) on bone turnover in 43 healthy men, 56-80 yr old. Placebo or steroid was given for 6 months, followed by a 1-month washout period and then a further 6 months of the opposite agent. Serum samples were collected at baseline 3, 6, 7, and 13 months and assayed for procollagen peptide, bone-specific alkaline phosphatase, and osteocalcin, all markers of bone formation. Measurements were also made of serum cortisol, DHEA/DHEA-S, E2 and free and total T. First void, fasting urine was collected at baseline, 6, 7, and 13 months and assessed for deoxypyridinoline, a marker of bone resorption. Mean serum DHEA and DHEA-S levels in treated men were increased approximately 3-fold ( approximately 2.2 ng/ml to approximately 6 ng/ml) and 4.5-fold ( approximately 1000 ng/ml to approximately 4500 ng/ml), respectively, after 6 months and returned to baseline after washout. Similarly, circulating E2 concentrations were also increased 1.4-fold (from approximately 16-23 pg/ml; P < 0.001), a finding not observed with any other measured hormone. Bone marker levels remained remarkably constant at each sampling interval; procollagen peptide at approximately 8.0 ng/ml; bone-specific alkaline phosphatase at approximately 21.0 U/liter; deoxypyridinoline at approximately 4.5 nmol/mmol Cr. Osteocalcin showed a transient reduction from approximately 10.2- 6.2 ng/ml, P < 0.005 to P < 0.001, at 3 months, but this decline was observed in both treated and controls. Stratifying the marker levels by age or baseline DHEA/DHEA-S levels did not affect the findings. We conclude that oral DHEA does not affect bone turnover in middle-aged to elderly men when used for a 6-month period at doses targeted to restore circulating levels of the steroid to that seen in young adults. PMID:11932279

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

    PubMed

    Holloway, Leah; Moynihan, Sharon; Abrams, Steven A; Kent, Kyla; Hsu, Andrew R; Friedlander, Anne L

    2007-02-01

    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 chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72.2 (SD 6.4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0.05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0.05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0.05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0.887 +/- 0.102 v. 1.104 +/- 0.121 g/cm2; P < 0.01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density. PMID:17298707

  3. 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

  4. 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

  5. The Effect of Bed Rest on Bone Turnover in Young Women Hospitalized for Anorexia Nervosa: A Pilot Study

    PubMed Central

    DiVasta, Amy D.; Feldman, Henry A.; Quach, Ashley E.; Balestrino, Maria; Gordon, Catherine M.

    2009-01-01

    Context: Malnourished adolescents with anorexia nervosa (AN) requiring medical hospitalization are at high risk for skeletal insults. Even short-term bed rest may further disrupt normal patterns of bone turnover. Objective: The objective of the study was to determine the effect of relative immobilization on bone turnover in adolescents hospitalized for AN. Design: This was a short-term observational study. Setting: The study was conducted at a tertiary care pediatric hospital. Study Participants: Twenty-eight adolescents with AN, aged 13–21 yr with a mean body mass index of 15.9 ± 1.8 kg/m2, were enrolled prospectively on admission. Intervention: As per standard care, all subjects were placed on bed rest and graded nutritional therapy. Main Outcome Measure: Markers of bone formation (bone specific alkaline phosphatase), turnover (osteocalcin), and bone resorption (urinary N-telopeptides NTx) were measured. Results: During the 5 d of hospitalization, serum osteocalcin increased by 0.24 ± 0.1 ng/ml · d (P = 0.02). Urine N-telopeptides reached a nadir on d 3, declining −6.9 ± 2.8 nm bone collagen equivalent per millimole creatinine (P = 0.01) but returned to baseline by d 5 (P > 0.05). Bone-specific alkaline phosphatase exhibited a decline that was strongly age dependent, being highly significant for younger subjects only [age 14 yr: −0.42 ± 0.11 (P = 0.0002); age 18 yr: −0.03 ± 0.08 (P = 0.68)]. Age had no effect on other outcome measures. Conclusion: Limitation of physical activity during hospitalization for patients with AN is associated with suppressed bone formation and resorption and an imbalance of bone turnover. Future interventional studies involving mechanical stimulation and/or weight-bearing activity are needed to determine whether medical protocols prescribing strict bed rest are appropriate. PMID:19223524

  6. 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

  7. 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

  8. 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...

  9. The type 2 deiodinase Thr92Ala polymorphism is associated with increased bone turnover and decreased femoral neck bone mineral density.

    PubMed

    Heemstra, Karen A; Hoftijzer, Hendrieke; van der Deure, Wendy M; Peeters, Robin P; Hamdy, Neveen A; Pereira, Alberto; Corssmit, Eleonora P; Romijn, Johannes A; Visser, Theo J; Smit, Johannes W

    2010-06-01

    The role of type 2 deiodinase (D2) in the human skeleton remains unclear. The D2 polymorphism Thr92Ala has been associated with lower enzymatic activity, which could result in lower local triiodothyronine (T(3)) availability in bone. We therefore hypothesized that the D2 Thr92Ala polymorphism may influence bone mineral density (BMD) and bone turnover. We studied 154 patients (29 men, 125 women: 79 estrogen-replete, 46 estrogen-deficient) with cured differentiated thyroid carcinoma. BMD and bone turnover markers [bone-specific alkaline phosphatase (BAP), cross-linking terminal C-telopeptide of type I collagen (CTX), procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked N-telopeptide of type I collagen (NTX)] were measured. Effects of the D2 Thr92Ala polymorphism on BMD and bone turnover markers were assessed by a linear regression model, with age, gender, estrogen state, body mass index (BMI), serum calcium, 25-hydroxyvitamin D, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and free triiodothyroxine (T(4)) as covariables. Sixty patients were wild type (Thr/Thr), 66 were heterozygous (Thr/Ala), and 28 were homozygous (Ala/Ala) for the D2 polymorphism. There were no significant differences in any covariables between the three genotypes. Subjects carrying the D2 Thr92Ala polymorphism had consistently lower femoral neck and total hip densities than wild-type subjects (p = .028), and this was accompanied by significantly higher serum P1NP and CTX and urinary NTX/creatinine levels. We conclude that in patients with cured differentiated thyroid carcinoma, the D2 Thr92Ala polymorphism is associated with a decreased femoral neck BMD and higher bone turnover independent of serum thyroid hormone levels, which points to a potential functional role for D2 in bone. PMID:20200941

  10. 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

  11. Increased intake of selected vegetables, herbs and fruit may reduce bone turnover in post-menopausal women.

    PubMed

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

    2015-04-01

    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

  12. Biochemical Markers of Bone Turnover and their Role in Osteoporosis Diagnosis: A Narrative Review.

    PubMed

    Khashayar, Patricia; Meybodi, Hamidreza Aghaei; Amoabediny, Ghassem; Larijani, Bagher

    2015-01-01

    Osteoporosis diagnosis, which is nowadays generally made based on bone mineral density (BMD) measurements, suffers from certain limitations. Thus it is believed that bone turnover markers (BTMs) can help improve osteoporosis detection. The shifting interest toward this topic made us perform a review to gather information on existing markers and their role in osteoporosis diagnosis. Based on the results, in this review, a list of existing markers and some of their characteristics is provided. Moreover, a brief explanation of different types of variability met while using these markers is also described. Finally some of the patents provided for the diagnosis of these markers are presented. While the use of BTMs in osteoporosis diagnosis has certain advantages over BMD and clinical risk assessment tools, more studies are needed before they can be used as a separate tool in this regard. It could be concluded that despite the fact that BTMs are better than BMD not only in monitoring treatment but also in identifying those at-risk, the diagnostic value of BTMs in predicting osteoporosis is low, and thus a model is needed to assess several BTMs at the same time with higher accuracy and lower variability to overcome this limitation. PMID:26246012

  13. 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

  14. Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa.

    PubMed

    Gordon, C M; Grace, E; Emans, S J; Goodman, E; Crawford, M H; Leboff, M S

    1999-01-01

    Bone loss is a serious consequence of anorexia nervosa (AN). Subnormal levels of serum dehydroepiandrosterone (DHEA) are seen in patients with AN and may be causally linked to their low bone density. We hypothesized that oral DHEA would decrease markers of bone resorption (urinary N-telopeptides [NTx]), and increase markers of bone formation (serum bone-specific alkaline phosphatase and osteocalcin [OC]). Fifteen young women (age 15-22 years) with AN were enrolled in a 3-month, randomized, double-blinded trial of 50, 100, or 200 mg of daily micronized DHEA. Blood and urinary levels of adrenal and gonadal steroids and bone turnover markers were measured. No adverse clinical side effects of DHEA were noted, and a 50 mg daily dose restored physiologic hormonal levels. At 3 months, NTx levels had decreased significantly in both the 50 mg (p = 0.018) and the 200 mg (p = 0.016) subgroups. OC levels simultaneously increased within treatment groups over time (p = 0.002). Eight out of 15 (53%) subjects had at least one menstrual cycle while on therapy. Short-term DHEA was well-tolerated and appears to normalize bone turnover in young women with AN. Resumption of menses in over half of subjects suggests that DHEA therapy may also lead to estradiol levels sufficient to stimulate the endometrium in this group of patients. PMID:9893076

  15. Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs

    PubMed Central

    Le Bloc'h, Jérôme; Leray, Véronique; Nazih, Hassan; Gauthier, Olivier; Serisier, Samuel; Magot, Thierry; Krempf, Michel; Nguyen, Patrick; Ouguerram, Khadija

    2015-01-01

    Aim Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin-Resistant dogs with increase plasma triglycerides. Methods HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured. Results NA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very-low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification. Conclusion NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile. PMID:26366727

  16. Osteogenic Effect of High-frequency Acceleration on Alveolar Bone

    PubMed Central

    Alikhani, M.; Khoo, E.; Alyami, B.; Raptis, M.; Salgueiro, J.M.; Oliveira, S.M.; Boskey, A.; Teixeira, C.C.

    2012-01-01

    Mechanical stimulation contributes to the health of alveolar bone, but no therapy using the osteogenic effects of these stimuli to increase alveolar bone formation has been developed. We propose that the application of high-frequency acceleration to teeth in the absence of significant loading is osteogenic. Sprague-Dawley rats were divided among control, sham, and experimental groups. The experimental group underwent localized accelerations at different frequencies for 5 min/day on the occlusal surface of the maxillary right first molar at a very low magnitude of loading (4 µε). Sham rats received a similar load in the absence of acceleration or frequency. The alveolar bone of the maxilla was evaluated by microcomputed tomography (µCT), histology, fluorescence microscopy, scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR imaging), and RT-PCR for osteogenic genes. Results demonstrate that application of high-frequency acceleration significantly increased alveolar bone formation. These effects were not restricted to the area of application, and loading could be replaced by frequency and acceleration. These studies propose a simple mechanical therapy that may play a significant role in alveolar bone formation and maintenance. PMID:22337699

  17. Turnover of bone marrow-derived cells in the irradiated mouse cornea

    PubMed Central

    Chinnery, Holly R; Humphries, Timothy; Clare, Adam; Dixon, Ariane E; Howes, Kristen; Moran, Caitlin B; Scott, Danielle; Zakrzewski, Marianna; Pearlman, Eric; McMenamin, Paul G

    2008-01-01

    In light of an increasing awareness of the presence of bone marrow (BM)-derived macrophages in the normal cornea and their uncertain role in corneal diseases, it is important that the turnover rate of these resident immune cells be established. The baseline density and distribution of macrophages in the corneal stroma was investigated in Cx3cr1gfp transgenic mice in which all monocyte-derived cells express enhanced green fluorescent protein (eGFP). To quantify turnover, BM-derived cells from transgenic eGFP mice were transplanted into whole-body irradiated wild-type recipients. Additionally, wild-type BM-derived cells were injected into irradiated Cx3cr1+/gfp recipients, creating reverse chimeras. At 2, 4 and 8 weeks post-reconstitution, the number of eGFP+ cells in each corneal whole mount was calculated using epifluorescence microscopy, immunofluorescence staining and confocal microscopy. The total density of myeloid-derived cells in the normal Cx3cr1+/gfp cornea was 366 cells/mm2. In BM chimeras 2 weeks post-reconstitution, 24% of the myeloid-derived cells had been replenished and were predominantly located in the anterior stroma. By 8 weeks post-reconstitution 75% of the myeloid-derived cells had been replaced and these cells were distributed uniformly throughout the stroma. All donor eGFP+ cells expressed low to moderate levels of CD45 and CD11b, with approximately 25% coexpressing major histocompatibility complex class II, a phenotype characteristic of previous descriptions of corneal stromal macrophages. In conclusion, 75% of the myeloid-derived cells in the mouse corneal stroma are replenished after 8 weeks. These data provide a strong basis for functional investigations of the role of resident stromal macrophages versus non-haematopoietic cells using BM chimeric mice in models of corneal inflammation. PMID:18540963

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD).

    PubMed

    Wölfl, Christoph; Schweppenhäuser, Daniela; Gühring, Thorsten; Takur, Caner; Höner, Bernd; Kneser, Ulrich; Grützner, Paul Alfred; Kolios, Leila

    2014-01-01

    The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD. PMID:24788647

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

    PubMed

    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 AND 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

  4. Accelerated soil carbon turnover under tree plantations limits soil carbon storage

    NASA Astrophysics Data System (ADS)

    Chen, Guangshui; Yang, Yusheng; Yang, Zhijie; Xie, Jinsheng; Guo, Jianfen; Gao, Ren; Yin, Yunfeng; Robinson, David

    2016-01-01

    The replacement of native forests by tree plantations is increasingly common globally, especially in tropical and subtropical areas. Improving our understanding of the long-term effects of this replacement on soil organic carbon (SOC) remains paramount for effectively managing ecosystems to mitigate anthropogenic carbon emissions. Meta-analyses imply that native forest replacement usually reduces SOC stocks and may switch the forest from a net sink to a net source of atmospheric carbon. Using a long-term chronosequence during which areas of subtropical native forest were replaced by Chinese fir, we show by direct measurement that plantations have significantly accelerated SOC turnover compared with native forest, an effect that has persisted for almost a century. The immediate stimulation of SOC decomposition was caused by warmer soil before the closure of the plantation’s canopy. Long-term reductions in SOC mean residence times were coupled to litter inputs. Faster SOC decomposition was associated with lower soil microbial carbon use efficiency, which was due to smaller litter inputs and reduced nutrient availabilities. Our results indicate a previously unelucidated control on long-term SOC dynamics in native forests and demonstrate a potential constraint on climate mitigation when such forests are replaced by plantations.

  5. Accelerated soil carbon turnover under tree plantations limits soil carbon storage.

    PubMed

    Chen, Guangshui; Yang, Yusheng; Yang, Zhijie; Xie, Jinsheng; Guo, Jianfen; Gao, Ren; Yin, Yunfeng; Robinson, David

    2016-01-01

    The replacement of native forests by tree plantations is increasingly common globally, especially in tropical and subtropical areas. Improving our understanding of the long-term effects of this replacement on soil organic carbon (SOC) remains paramount for effectively managing ecosystems to mitigate anthropogenic carbon emissions. Meta-analyses imply that native forest replacement usually reduces SOC stocks and may switch the forest from a net sink to a net source of atmospheric carbon. Using a long-term chronosequence during which areas of subtropical native forest were replaced by Chinese fir, we show by direct measurement that plantations have significantly accelerated SOC turnover compared with native forest, an effect that has persisted for almost a century. The immediate stimulation of SOC decomposition was caused by warmer soil before the closure of the plantation's canopy. Long-term reductions in SOC mean residence times were coupled to litter inputs. Faster SOC decomposition was associated with lower soil microbial carbon use efficiency, which was due to smaller litter inputs and reduced nutrient availabilities. Our results indicate a previously unelucidated control on long-term SOC dynamics in native forests and demonstrate a potential constraint on climate mitigation when such forests are replaced by plantations. PMID:26805949

  6. Accelerated soil carbon turnover under tree plantations limits soil carbon storage

    PubMed Central

    Chen, Guangshui; Yang, Yusheng; Yang, Zhijie; Xie, Jinsheng; Guo, Jianfen; Gao, Ren; Yin, Yunfeng; Robinson, David

    2016-01-01

    The replacement of native forests by tree plantations is increasingly common globally, especially in tropical and subtropical areas. Improving our understanding of the long-term effects of this replacement on soil organic carbon (SOC) remains paramount for effectively managing ecosystems to mitigate anthropogenic carbon emissions. Meta-analyses imply that native forest replacement usually reduces SOC stocks and may switch the forest from a net sink to a net source of atmospheric carbon. Using a long-term chronosequence during which areas of subtropical native forest were replaced by Chinese fir, we show by direct measurement that plantations have significantly accelerated SOC turnover compared with native forest, an effect that has persisted for almost a century. The immediate stimulation of SOC decomposition was caused by warmer soil before the closure of the plantation’s canopy. Long-term reductions in SOC mean residence times were coupled to litter inputs. Faster SOC decomposition was associated with lower soil microbial carbon use efficiency, which was due to smaller litter inputs and reduced nutrient availabilities. Our results indicate a previously unelucidated control on long-term SOC dynamics in native forests and demonstrate a potential constraint on climate mitigation when such forests are replaced by plantations. PMID:26805949

  7. Elevated carbon dioxide accelerates the spatial turnover of soil microbial communities.

    PubMed

    Deng, Ye; He, Zhili; Xiong, Jinbo; Yu, Hao; Xu, Meiying; Hobbie, Sarah E; Reich, Peter B; Schadt, Christopher W; Kent, Angela; Pendall, Elise; Wallenstein, Matthew; Zhou, Jizhong

    2016-02-01

    Although elevated CO2 (eCO2 ) significantly affects the α-diversity, composition, function, interaction and dynamics of soil microbial communities at the local scale, little is known about eCO2 impacts on the geographic distribution of micro-organisms regionally or globally. Here, we examined the β-diversity of 110 soil microbial communities across six free air CO2 enrichment (FACE) experimental sites using a high-throughput functional gene array. The β-diversity of soil microbial communities was significantly (P < 0.05) correlated with geographic distance under both CO2 conditions, but declined significantly (P < 0.05) faster at eCO2 with a slope of -0.0250 than at ambient CO2 (aCO2 ) with a slope of -0.0231 although it varied within each individual site, indicating that the spatial turnover rate of soil microbial communities was accelerated under eCO2 at a larger geographic scale (e.g. regionally). Both distance and soil properties significantly (P < 0.05) contributed to the observed microbial β-diversity. This study provides new hypotheses for further understanding their assembly mechanisms that may be especially important as global CO2 continues to increase. PMID:26414247

  8. Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children.

    PubMed

    Kocsis, I; Arató, A; Bodánszky, H; Szönyi, L; Szabó, A; Tulassay, T; Vásárhelyi, B

    2002-08-01

    Gastric proton pump inhibitors are widely used in the treatment of dyspeptic problems and for the eradication of H. pylori infection. Data are not available on whether omeprazole, a representative of proton pump inhibitors, influences the function of osteoclastic H+-pump in children. We studied the impact of short-term omeprazole administration on the biochemical parameters of bone turnover in pediatric patients. Urinary calcium excretion, serum total alkaline phosphatase activity, collagen type 1 crosslinked C-telopeptide, and osteocalcin levels were determined in 34 children [20 girls (9 prepubertal) and 14 boys (6 prepubertal)] before and after 2 weeks of omeprazole treatment at a dose of 20 mg/day. The measured parameters were within the healthy reference range in each patient. None of them altered during the study in any age or in any gender. We conclude that omeprazole, at a dose of 20 mg/day, does not significantly influence the investigated biochemical parameters of osteoclast and osteoblast function in pediatric patients. PMID:12200646

  9. 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. PMID:22438896

  10. 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

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

    PubMed Central

    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

  12. Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State

    PubMed Central

    Vestergaard, Peter; Støen, Ole-Gunnar; Swenson, Jon E.; Mosekilde, Leif; Heickendorff, Lene; Fröbert, Ole

    2011-01-01

    Background Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. Aim To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D2 and D3), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)2D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. Material and Methods We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. Results Serum 25-hydroxy-cholecalciferol (25OHD3) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p - 2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD2) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)2D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. Conclusions Dramatic changes were documented in the vitamin D3/D2 ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease. PMID:21731765

  13. [Bone formation and corticotomy-induced accelerated bone remodeling: can alveolar corticotomy induce bone formation?].

    PubMed

    Moreau, Nathan; Charrier, Jean-Baptiste

    2015-03-01

    Current orthodontic treatments must answer an increasing demand for faster yet as efficient treatments, especially in adult patients. These past years, the amelioration of orthodontic, anesthetic and orthognathic surgery techniques have allowed considerable improvement of orthodontico-surgical treatments and of adult orthodontic treatments. Alveolar corticotomy (an example of such techniques) accelerates orthodontic tooth movements by local modifications of bone metabolism, inducing a transient osteopenia. This osteopenia allows greater tooth movements than conventional techniques. Whereas there is a growing understanding of the underlying biological mechanisms of alveolar corticotomies, there is little data regarding the osteogenic potential of such technique. In the present article, we review the literature pertaining to alveolar corticotomies and their underlying biological mechanisms and present a clinical case underlining the osteogenic potential of the technique. PMID:25888047

  14. 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

  15. Bilateral atypical femoral subtrochanteric fractures in a premenopausal patient receiving prolonged bisphosphonate therapy: evidence of severely suppressed bone turnover

    PubMed Central

    Kondo, Naoki; Yoda, Takuya; Fujisawa, Junichi; Arai, Katsumitsu; Sakuma, Mayumi; Ninomiya, Hiroshi; Sano, Hiroshige; Endo, Naoto

    2015-01-01

    Summary We report a case of bilateral atypical femoral fractures that occurred in a patient who had been taking bisphosphonate long-term. A 36-year-old premenopausal female diagnosed with systemic lupus erythematosus and dermatomyositis had been treated with glucocorticoid and alendronate (5 mg/day) to prevent glucocorticoid-induced osteoporosis. She was taken to our hospital because she could not walk immediately after falling down from the standing position. A plain radiograph showed a subtrochanteric fracture of the left femur. Four months later, she fell again and sustained a contralateral subtrochanteric fracture. For each fracture, a femoral intramedullary nail was inserted. Delayed union was detected in both sides, and revision surgery with an iliac bone graft was required for implant breakage in the right side. Histomorphometric findings for the ilium revealed remarkably decreased osteoid volume with no osteoclasts and a minimally eroded surface, suggesting that bone turnover was severely suppressed. However, histology of the delayed union site revealed callus formation and some osteoclast appearance, suggesting that fracture healing was occurring. In total, it took 29 months (left) and 24 months (right) until fracture healing was achieved, showing delayed union. This case is extremely rare in that patient who presented with atypical femoral fractures in spite of her premenopausal status. The bone histomorphometric findings from this case suggest that severely suppressed bone turnover is associated with atypical femoral subtrochanteric fracture and can cause delayed union in patients treated with alendronate long-term. PMID:26811712

  16. Association of Blood Biomarkers of Bone Turnover in HIV-1 Infected Individuals Receiving Anti-Retroviral Therapy (ART)

    PubMed Central

    Aziz, Najib; Butch, Anthony W; Quint, Joshua J; Detels, Roger

    2015-01-01

    Objective To evaluate the association of bone turnover biomarkers with blood levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and other blood markers in HIV-1 infected men receiving anti-retroviral therapy (ART). Advances in the treatment of HIV-1 infection have extended the life span of HIV-1 infected individuals. However, these advances may come at the price of metabolic side effects and bone disorders, including premature osteopenia, osteoporosis and osteonecrosis. Methods Analyses of Ostase BAP, osteocalcin, and TRAP in blood were measured in three groups of MACS participants: 35 HIV-1 infected men on ART (A); 35 HIV-1- infected men not on ART (B); and 34 HIV-1 uninfected men (C). Results The mean and standard deviation results for groups A, B, and C were 19.7 ± 6.56, 17.2 ± 3.96, and 16.9 ± 5.78 for ostase BAP; 7.9 ± 9.53, 8.5 ± 8.30, and 5.5 ± 1.65 for osteocalcin; and 3.9 ± 1.04, 3.1 ± 0.81, and 2.5 ± 0.59 for TRAP, respectively. Simple and multivariate analyses showed significant differences in mean TRAP and BAP concentrations between the three groups. In addition strong correlations between blood levels of Ostase BAP and TRAP (r=0.570, p=0.0004), and between blood levels of Ostase BAP and PTH (r=0.436, P=0.0098) for HIV-1 infected men on ART were observed. Conclusion New strategies for measurement of blood and urine biochemical markers of bone formation and resorption during bone turnover can be useful for clinical monitoring of treatment of HIV-1 infected patients. Recently developed methods for measuring serum levels of TRAP and Ostase BAP represent superior laboratory tools for assessing the hyperactivity of osteoclasts, osteoblasts and bone loss in HIV-1 infected individuals receiving ART. Measurements of TRAP and BAP as bone turnover biomarkers are economical and are important for monitoring bone metabolism during ART and

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

    PubMed

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

    2016-04-01

    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

  18. Change of Bone Mineral Density and Biochemical Markers of Bone Turnover in Patients on Suppressive Levothyroxine Therapy for Differentiated Thyroid Carcinoma

    PubMed Central

    Kim, Chei Won; Hong, Seokbo; Oh, Se Hwan; Lee, Jung Jin; Han, Joo Young; Kim, So Hun; Nam, Moonsuk; Kim, Yong Seong

    2015-01-01

    Untreated hyperthyroidism and high-dose thyroid hormone are associated with osteoporosis, and increased bone mineral density (BMD) has been demonstrated in postmenopausal females with hypoparathyroidism. Studies on the effect of suppressive levothyroxine (LT4) therapy on BMD and bone metabolism after total thyroidectomy in patients with differentiated thyroid carcinoma have presented conflicting results, and few studies in relation to the status of hypoparathyroidism have been studied. One hundred postmenopausal women and 24 premenopausal women on LT4 suppression therapy were included in this study. BMD of lumbar spine and femur and bone turnover markers were measured at the baseline and during the follow-up period up to 18 months using dual energy X-ray absorptiometry. Biochemical marker of bone resorption was measured by urine deoxypyridinoline and bone formation by serum osteocalcin. The age ranged from 36 to 64 years old. Thyroid stimulating hormone (TSH) was suppressed during the study. The results showed that BMD of femur and lumbar spine were not significantly changed in both pre- and postmenopausal women except femur neck in postmenopausal women without hypoparathyroidism. Patients with hypoparathyroidism had higher BMD gain than those without hypoparathyroidism in total hip (1.25 vs. -1.18%, P=0.015). Biochemical markers of bone turnover, serum osteocalcin, and urine deoxypyridinoline did not show significant change. In conclusion, patients with well differentiated thyroid carcinoma are not at a great risk of bone loss after LT4 suppressive therapy. The state of hypoparathyroidism is associated with increased BMD, particularly in postmenopausal women. PMID:26389089

  19. 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...

  20. Evaluation of Markers of Bone Turnover During Lactation in African-Americans: A Comparison With Caucasian Lactation

    PubMed Central

    Carneiro, Raquel M.; Prebehalla, Linda; Tedesco, Mary Beth; Sereika, Susan M.; Gundberg, Caren M.; Stewart, Andrew F.

    2013-01-01

    Context: The African-American skeleton is resistant to PTH; whether it is also resistant to PTHrP and the hormonal milieu of lactation is unknown. Objectives: The objective of the study was to assess bone turnover markers in African-Americans during lactation vs Caucasians. Design and Participants: A prospective cohort study with repeated measures of markers of bone turnover in 60 African-American women (3 groups of 20: lactating, bottle feeding, and healthy controls), compared with historic Caucasian women. Setting: The study was conducted at a university medical center. Outcome Measures: Biochemical markers of bone turnover and calcium metabolism were measured. Results: 25-Hydroxyvitamin D (25-OHD) and PTH were similar among all 3 African-American groups, but 25-OHD was 30%–50% lower and PTH 2-fold higher compared with Caucasians (P < .001, P < .002), with similar 1,25 dihydroxyvitamin D [1,25(OH)2D] values. Formation markers [amino-terminal telopeptide of procollagen-1 (P1NP) and bone-specific alkaline phosphatase (BSAP)] increased significantly (2- to 3-fold) in lactating and bottle-feeding African-American women (P1NP, P < .001; BSAP, P < .001), as did resorption [carboxy-terminal telopeptide of collagen-1 (CTX) and serum amino-terminal telopeptide of collagen 1 (NTX), both P < .001]. P1NP and BSAP were comparable in African-American and Caucasian controls, but CTX and NTX were lower in African-American vs Caucasian controls. African-American lactating mothers displayed quantitatively similar increases in markers of bone formation but slightly lower increases in markers of resorption vs Caucasians (P = .036). Conclusions: Despite reported resistance to PTH, lactating African-American women have a significant increase in markers of bone resorption and formation in response the hormonal milieu of lactation. This response is similar to that reported in Caucasian women despite racial differences in 25-OHD and PTH. Whether this is associated with similar bone

  1. Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats

    PubMed Central

    Diwan, Ashish D; Leong, Anthony; Appleyard, Richard; Bhargav, Divya; Fang, Zhi Ming; Wei, Aiqun

    2013-01-01

    Background: Osteoporosis is characterized by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed and rates of implant failure are high with few biological treatment options available. This study aimed to determine whether a single dose of bone morphogenetic protein-7 (BMP-7) in a collagen/carboxy-methyl cellulose (CMC) composite enhanced fracture healing in an osteoporotic rat model. Materials and Methods: An open femoral midshaft osteotomy was performed in female rats 3 months post-ovarectomy. Rats were randomized to receive either BMP-7 composite (n = 30) or composite alone (n = 30) at the fracture site during surgery. Thereafter calluses were collected on days 12, 20 and 31. Callus cross-sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point. Results: There were statistically significant increases in bone mineral density and callus cross-section area at all time points in the BMP-7 group as compared to controls and biomechanical readings showed stronger bones at day 31 in the BMP-7 group. Histological and radiographic evaluation indicated significant acceleration of bony union in the BMP-7 group as compared to controls. Conclusion: This study demonstrated that BMP-7 accelerates fracture healing in an oestrogen-deficient environment in a rat femoral fracture healing model to scientific relevance level I. The use of BMP-7 composite could offer orthopedic surgeons an advantage over oestrogen therapy, enhancing osteoporotic fracture healing with a single, locally applied dose at the time of surgery, potentially overcoming delays in healing caused by the osteoporotic state. PMID:24379457

  2. The effect of age, sex hormones, and bone turnover markers on calcaneal quantitative ultrasonometry in healthy German men.

    PubMed

    Kyvernitakis, Ioannis; Saeger, Ulf; Ziller, Volker; Bauer, Thomas; Seker-Pektas, Berna; Hadji, Peyman

    2013-01-01

    The aim of this cross-sectional study was to determine the age-dependent variations of calcaneal quantitative ultrasonometry (QUS) and the association with sex hormones and biochemical bone turnover markers in a large sample of unselected healthy German men. Bone measurements are expected to behave differently among men and women. The speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcaneus were measured in 506 German men aged 20-79 yr (mean age: 45.7 yr). Additionally, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) as well as N-terminal propeptide of human procollagen type I (PINP), C-terminal telopeptide of type I collagen (ICTP), osteocalcin, bone-specific alkaline phosphatase, and CrossLaps were measured with standardized essays and correlated with the QUS results. The QUS results comprised an overall change of 12.4%, 3.2%, and 23.2% for BUA, SOS, and SI, respectively, between the 20-29 and 70-79 yr age groups (p ≤ 0.001). The annual rate of the age-related differences was 0.33% (standard deviation [SD]: 0.31), 0.06% (SD: 0.08), and 0.53% (SD: 0.56) for BUA, SOS, and SI, respectively. Testosterone and DHEA-S were significantly associated with QUS parameters and increasing age, whereas SHBG showed an age-related increase and was inversely related with QUS values (p < 0.05). Bone turnover markers present lower values gradually, and we found a significant correlation between carboxy-terminal collagen crosslinks (CTX), osteocalcin (OC), bone alkaline phosphatase (BAP), and QUS variables (p < 0.05). PMID:23582469

  3. 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

  4. 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

  5. Is gastrectomy-induced high turnover of bone with hyperosteoidosis and increase of mineralization a typical osteomalacia?

    PubMed

    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

  6. Bioeffects of micron-size magnesium particles on inflammatory cells and bone turnover in vivo and in vitro.

    PubMed

    Guo, Chengzhi; Li, Jian; She, Chang; Shao, Xiangzhi; Teng, Bin; Feng, Jing; Zhang, Jian V; Ren, Pei-Gen

    2016-07-01

    Magnesium (Mg) is a promising biodegradable metal offering many potential advantages over current scaffold technologies. Many studies have reported on the corrosion characteristics the Mg and its bioeffects in vitro and in vivo, but there are few studies on the biological effects of the corrosive products of Mg - the micron-size Mg particles (MgMPs). In this study, the effects of size-selected commercial MgMPs on bone turnover and macrophages were investigated in vivo and in vitro. We found that MgMPs were susceptible to engulfment by macrophages, leading to cell lysis, likely resulting from H2 gas production. We also found that the inflammatory cytokines IL-1, IL-6, and TNF-α were induced more strongly by titanium particles (TiMPs) group than by either MgMPs or control. Examination of the expression of bone remodeling markers revealed that MgMPs are beneficial for bone regeneration. Micro-CT scanning indicated that, 30 days postimplantation, unlike TiMPs, MgMPs had no adverse effect on either bone quality or quantity. We have investigated the bioeffects of micron-size MgMPs in vivo and in vitro, and our results indicate that MgMPs may promote bone regeneration without inducing inflammation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 923-931, 2016. PMID:25976168

  7. 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

  8. Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion

    PubMed Central

    Mousiolis, Athanasios C.; Rapti, Eleni; Grammatiki, Maria; Yavropoulou, Maria; Efstathiou, Maria; Foroglou, Nikolaos; Daniilidis, Michalis; Kotsa, Kalliopi

    2016-01-01

    Abstract Increased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state. We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor. Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas. PMID:26765410

  9. Bacterial and enchytraeid abundance accelerate soil carbon turnover along a lowland vegetation gradient in interior Alaska

    USGS Publications Warehouse

    Waldrop, M.P.; Harden, Jennifer W.; Turetsky, M.R.; Petersen, D.G.; McGuire, A.D.; Briones, M.J.I.; Churchill, A.C.; Doctor, D.H.; Pruett, L.E.

    2012-01-01

    Boreal wetlands are characterized by a mosaic of plant communities, including forests, shrublands, grasslands, and fens, which are structured largely by changes in topography and water table position. The soil associated with these plant communities contain quantitatively and qualitatively different forms of soil organic matter (SOM) and nutrient availability that drive changes in biogeochemical cycling rates. Therefore different boreal plant communities likely contain different soil biotic communities which in turn affect rates of organic matter decomposition. We examined relationships between plant communities, microbial communities, enchytraeids, and soil C turnover in near-surface soils along a shallow topographic soil moisture and vegetation gradient in interior Alaska. We tested the hypothesis that as soil moisture increases along the gradient, surface soils would become increasingly dominated by bacteria and mesofauna and have more rapid rates of C turnover. We utilized bomb radiocarbon techniques to infer rates of C turnover and the 13C isotopic composition of SOM and respired CO2 to infer the degree of soil humification. Soil phenol oxidase and peroxidase enzyme activities were generally higher in the rich fen compared with the forest and bog birch sites. Results indicated greater C fluxes and more rapid C turnover in the surface soils of the fen sites compared to the wetland forest and shrub sites. Quantitative PCR analyses of soil bacteria and archaea, combined with enchytraeid counts, indicated that surface soils from the lowland fen ecosystems had higher abundances of these microbial and mesofaunal groups. Fungal abundance was highly variable and not significantly different among sites. Microbial data was utilized in a food web model that confirmed that rapidly cycling systems are dominated by bacterial activity and enchytraeid grazing. However, our results also suggest that oxidative enzymes play an important role in the C mineralization process in

  10. Effect of Neoadjuvant Chemotherapy on the Serum Levels of Bone Turnover Markers in Women with Early-Stage Breast Cancer

    PubMed Central

    Chen, YangYang; Xu, GuoBin; Yang, Feng

    2015-01-01

    Background To evaluate effects of neoadjuvant chemotherapy on the bone turnover markers of preoperational breast cancer patients. Methods Forty-one breast cancer patients (29 premenopausal and 12 postmenopausal) and 60 healthy women (30 premenopausal and 30 postmenopausal) aged 30-64 years, were evaluated for their bone status. Serum levels of the bone formation markers PINP and BAP, as well as the resorption markers ICTP and β-Crosslaps in addition to E2, FSH, 25(OH)D and PTH were measured at the initial diagnosis and at 24 hours after each four chemotherapy cycles. BMD T-scores were determined in 12 patients 6 months after the neoadjuvant chemotherapies. Results The baseline levels of both bone formation and resorption markers in premenopausal patients were higher than in premenopausal healthy women (p<0.05), while no statistic difference was observed between postmenopausal patients and postmenopausal healthy women. Regardless of the menopausal status, chemotherapy increased the ICTP and β-Crosslaps levels (p<0.05), but decreased the BAP and PINP levels (p<0.05), the later one significantly more with Taxane medication (p<0.01, p<0.05). Chemotherapy caused significant decreases of 25(OH)D levels in premenopausal (p<0.01) and postmenopausal (p<0.05) patients, however, did not affect the PTH concentrations. In premenopausal patients the E2 level decreased, while the FSH level increased after chemotherapy (p<0.05). Patients with pronounced ICTP and β-Crosslaps combined with reduced BAP and PINP serum concentrations after neoadjuvant chemotherapies were prone to develop osteoporosis 6 month later. Conclusions Neoadjuvant chemotherapy appeared to promote bone resorption and inhibit bone formation in both postmenopausal and premenopausal early-stage breast patients. PMID:25923354

  11. 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

  12. 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

  13. 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

  14. Circulating concentrations of vitamin E isomers: Association with bone turnover and arterial stiffness in post-menopausal women.

    PubMed

    Hampson, G; Edwards, S; Sankaralingam, A; Harrington, D J; Voong, K; Fogelman, I; Frost, M L

    2015-12-01

    The effects of vitamin E on cardiovascular and bone health are conflicting with beneficial and detrimental findings reported. To investigate this further, we carried out a cross-sectional study to determine the relationship between circulating concentrations of the 2 vitamin E isomers, α- and γ-tocopherol (TP) with bone turnover and arterial stiffness. Two hundred and seventy eight post-menopausal women with mean age [SD] 60.9 [6.0] years were studied. Fasting serum α-TP and γ-TP, bone turnover markers; procollagen type 1 amino-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), total cholesterol (TC) and triglycerides (TG) were measured. Pulse wave velocity (PWV) and central augmentation index (AI) as markers of arterial stiffness were also determined. A positive correlation was observed between α-TP and γ-TP (r=0.14, p=0.022). A significant negative association between α-TP and P1NP only was seen in multiple linear regression analysis following adjustment for serum TC and TG (p=0.016). In a full multi-linear regression model, following correction for age, years since menopause, smoking habits, alcohol intake, use of calcium supplements, BMI, PTH, serum calcium, and estimated glomerular filtration rate (eGFR), the association between α-TP and P1NP remained significant (p=0.011). We did not observe any significant association between γ-TP or α-TP/γ-TP ratio with P1NP or CTX. P1NP was significantly lower in subjects with α-TP concentrations of >30 μmol/L (α-TP >30 μmol/L; P1NP: 57.5 [20.7], α-TP<30 μmol/L; P1NP: 65.7 [24.9] μg/L, p=0.005). PWV was significantly associated with α-TP/γ-TP ratio (p=0.04) but not with serum α-TP or γ-TP in a full multi-linear regression model adjusting for serum lipids, age, and blood pressure. The data suggest that high serum concentrations of α-TP may have a negative effect on bone formation. The balance of α-TP and γ-TP may be important in maintaining

  15. Effect of acceleration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    NASA Astrophysics Data System (ADS)

    Suzuki, S.; Kitamura, K.; Nemoto, N.; Shimizu, S.; Wada, W.; Kondo, K.; Tabata, T.; Sodeyama, S.; Ijiri, I.; Hattori, H.

    It is well known that hypo-gravity and hyper-gravity influence bone metabolism However basic data concerning the mechanism are a few because no in vitro model system of human bone is available Human bone consists of osteoblasts osteoclasts and the bone matrix No technique for the co-culture of these components has ever been developed Fish scale is a calcified tissue that contains osteoblasts osteoclasts and bone matrix all of which are similar to those found in human bone Recently we developed a new in vitro model system using goldfish scale This system can simultaneously detect the activities of both scale osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers Using this system we analyzed the bone metabolism under acceleration with a custom-made G-load apparatus Osteoclastic activity in the goldfish scales was suppressed under low-acceleration 0 5-G while osteoblastic activity did not change under this acceleration Under high-acceleration 6-G however the osteoblastic activity of the scales increased In addition the osteoclastic activity of the scales decreased These results suggest that both osteoblastic and osteoclastic activities are regulated by the strength of acceleration Therefore we strongly believe that our in vitro system is useful for analysis of bone metabolism under acceleration

  16. 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...

  17. 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

  18. The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

    PubMed Central

    Tejero, Sergio; Cejudo, Pilar; Quintana-Gallego, E.; Sañudo, Borja; Oliva-Pascual-Vaca, A.

    2016-01-01

    ABSTRACT Background Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral density (BMD) were determined by dual energy X-ray absorptiometry and bone metabolism markers ALP, P1NP, PICP, and ß-CrossLaps. PA monitoring was assessed for 5 consecutive days using a portable device. Exercise capacity was also determined. Serum 25-hydroxyvitamin D and vitamin K were also determined in all participants. Results Fifty patients (median age: 24.4 years; range: 16-46) were included. BMI had positive correlation with all BMD parameters, with Spearman’s coefficients ranging from 0.31 to 0.47. Total hip bone mineral density and femoral neck BMD had positive correlation with the daily time spent on moderate PA (>4.8 metabolic equivalent-minutes/day; r=0.74, p<0.001 and r=0.72 p<0.001 respectively), daily time spent on vigorous PA (>7.2 metabolic equivalent-minutes/day; r=0.45 p<0.001), body mass index (r=0.44, p=0.001), and muscle mass in limbs (r=0.41, p=0.004). Levels of carboxy-terminal propeptide of type 1 collagen were positively associated with the daily time spent on moderate (r=0.33 p=0.023) and vigorous PA (r=0.53, p<0.001). Conclusions BMI and the daily time spent on moderate PA were found to be correlated with femoral neck BMD in CF patients. The association between daily PA and biochemical markers of bone formation suggests that the level of daily PA may be linked to bone health in this patient group. Further research is needed to confirm these findings. PMID:27437711

  19. 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

  20. 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

  1. 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

  2. Biochemical Markers of Bone Turnover in Patients with β-Thalassemia Major: A Single Center Study from Southern Pakistan

    PubMed Central

    Sultan, Sadia; Irfan, Syed Mohammed; Ahmed, Syed Ijlal

    2016-01-01

    Objectives. Skeletal complications in β-homozygous thalassemic patients are uncommon but often debilitating, even amongst children and adolescent patients with well maintained transfusion and chelation therapy. The aim is to evaluate the biochemical markers of bone turnover in regularly transfused thalassemic patients and its possible correlations with demographic data and hematological and biochemical markers. Methods. In this prospective cross-sectional study, 36 β-thalassemia major patients were enrolled from March 2012 to March 2014. All patients underwent complete blood counts, LFTs, serum ferritin, serum calcium, phosphorus, serum albumin, alkaline phosphatase, 25-OH vitamin D, and parathormone (PTH) levels. Results. There were 17 males and 19 females with mean age of 12.56 ± 5.9 years. Hypocalcemia and hypophosphatemia were seen in 66.6% and 19.4%, respectively, while 25-OH vitamin D deficiency was present in 72.2% of thalassemic children and adolescents. Hypoparathyroidism was seen in 13.8% while hyperparathyroidism was detected in 8.3% of patients. There was direct correlation between serum phosphorus and ferritin levels (P < 0.05). No correlation was found between indirect bilirubin and skeletal parameters, calcium and parathyroid hormone (P > 0.05). Conclusions. Biochemical profile is significantly altered in patients with β-thalassemia major and bone associated biochemical abnormalities like hypocalcaemia, 25-OH vitamin D deficiency, and hypophosphatemia are not uncommon in Pakistani patients with thalassemia major. PMID:27006658

  3. 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

  4. 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.

  5. 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.

  6. Associations between Systemic Markers of Bone Turnover or Bone Mineral Density and Anti-Resorptive Agent-Related Osteonecrosis of the Jaw in Patients Treated with Anti-Resorptive Agents

    PubMed Central

    Tohashi, Kazuhito; Nakabayashi, Motoki; Kodani, Isamu; Kidani, Kazunori; Ryoke, Kazuo

    2016-01-01

    Background Some previous studies have examined anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) prediction using systemic markers of bone turnover as risk factors. Radiographic imaging is also effective at detecting ARONJ. In this study, computed tomography (CT)-derived bone mineral density (BMD) values and the levels of systemic markers of bone turnover were evaluated, and then each parameter was compared between patients that developed ARONJ and those who did not after treatment with systemic anti-resorptive agents. The aim of this study was to determine whether systemic markers of bone turnover and/or BMD values can be used to predict the risk of ARONJ Methods The subjects’ serum levels of cross-linked N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) (systemic markers of bone turnover) were measured. BMD was calibrated to CT values using a medical imaging phantom. Then, the subjects’ BMD were assessed using quantitative computed tomography. Fifty-six patients who had received systemic anti-resorptive agents were included in this study. Thirty-two of the patients developed ARONJ after receiving the drugs whereas the remaining 24 did not. Results No correlation was observed between the serum levels of the systemic markers of bone turnover and the incidence of ARONJ. On the other hand, the ARONJ patients exhibited higher mandibular BMD values than the control group. BMD was not associated with healing or the clinical stage of ARONJ. Conclusion These results suggest that increased mandibular BMD values are associated with ARONJ. Furthermore, mandibular BMD might serve as a novel marker for predicting the risk of ARONJ in patients that are taking anti-resorptive agents and are about to undergo tooth extraction. Accordingly, mandibular BMD could be a useful tool for aiding risk assessments and guiding treatment decisions. PMID:27046950

  7. 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...

  8. A novel peptide-modified and gene-activated biomimetic bone matrix accelerating bone regeneration.

    PubMed

    Pan, Haitao; Zheng, Qixin; Yang, Shuhua; Guo, Xiaodong; Wu, Bin; Zou, Zhenwei; Duan, Zhixia

    2014-08-01

    The osteogenic differentiation of bone marrow stromal cells (BMSCs) can be regulated by systemic or local growth factor, especially by transforming growth factor beta 1 (TGF-β1). However, how to maintain the bioactivity of exogenous TGF-β1 is a great challenge due to its short half-life time. The most promising solution is to transfer TGF-β1 gene into seed cells through transgenic technology and then transgenic cells to continuously secret endogenous TGF-β1 protein via gene expression. In this study, a novel non-viral vector (K)16GRGDSPC was chemically linked to bioactive bone matrices PLGA-[ASP-PEG]n using cross-linker to construct a novel non-viral gene transfer system. TGF-β1 gene was incubated with this system and subsequently rabbit-derived BMSCs were co-cultured with this gene-activated PLGA-[ASP-PEG]n, while co-cultured with PLGA-[ASP-PEG]n modified with (K)16GRGDSPC only and original PLGA-[ASP-PEG]n as control. Thus we fabricated three kinds of composites: Group A (BMSCs-TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); Group B (BMSCs-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); and Group C (BMSCs-PLGA-[ASP-PEG]n composite). TGF-β1 and other osteogenic phenotype markers of alkaline phosphatase, osteocalcin, osteopontin and type I collagen in Group A were all significantly higher than the other two groups ex vivo. In vivo, 15-mm long segmental rabbit bone defects were created and randomly implanted the aforementioned composites separately, and then fixed with plate-screws. The results demonstrated that the implants in Group A significantly accelerated bone regeneration compared with the other implants based on X-rays, histological and biomechanical examinations. Therefore, we conclude this novel peptide-modified and gene-activated biomimetic bone matrix of TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n is a very promising scaffold biomaterial for accelerating bone regeneration. PMID:24115366

  9. Effects of a herbal extract on the bone density, strength and markers of bone turnover of mature ovariectomized rats.

    PubMed

    Xu, Min; Dick, Ian M; Day, Robert; Randall, Drew; Prince, Richard L

    2003-01-01

    For many decades, the Chinese have been using herbal medications to treat bone diseases. To examine effects of an extract of ten medicinal herbs on estrogen deficiency bone loss, ten-month-old female rats were randomly divided into three groups: ovariectomized (OVX), OVX treated with herbs (OVX-M) 4 ml/day by gavage, and OVX treated with estrogen (OVX-E) 10 mg subcutaneously (s.c.) twice per week. The bone mineral density (BMD) of the left femur (fBMD), spine (sBMD) and global body (gBMD) were measured at baseline and at 4, 8 and 12 weeks using a Hologic QDR 2000 dual-energy X-ray densitometer. Tibial strength was tested using the Instron Model 5566 electro-mechanical testing machine. The urinary pyridinoline creatinine ratio (Pyd/Cr), deoxypyridinoline creatinine ratio (Dpd/Cr), plasma alkaline phosphatase (ALP), calcium (CA), phosphorus (P) and albumin (ALB) were also determined. Uterine weight was determined at 12 weeks. The results showed that percent changes of fBMD in the OVX (n = 9), OVX-E (n = 8) and OVX-M (n = 8) rats at the 12-week time point were -11.8 +/- 4.6(c), 1.8 +/- 3.1(a), -7.6 +/- 1.9(abc) (p < 0.05-0.001, a: vs. OVX, b: vs. OVX-E, c: vs. baseline); sBMD were -10.7 +/- 4.6(c), -0.3 +/- 5.5(a), -5.9 +/- 3.5(abc); and gBMD were -4.8 +/- 2.3(c), 0.1 +/- 2.4(a), -2.7 +/- 2.6(abc), respectively. Further, the tibia maximum breaking stress and flexural modulus of elasticity in OVX-M rats (295 +/- 33(a), 18,194 +/- 3,264(a)) were significantly higher (p < 0.005-0.001) than that in OVX rats (189 +/- 83, 10,309 +/- 4,930), and similar to OVX-E rats (298 +/- 35(a), 18,766 +/- 2,620(a)). Additionally, the herbal extract reduced the urinary Pyd/Cr, Dpd/Cr and plasma ALP increment followed OVX and was not associated with a rise in uterine weight. In conclusion, the herbal extract demonstrated a therapeutic effect to inhibit bone resorption and to reduce estrogen-dependent bone loss without uterine stimulation. It may have potential as a new approach in

  10. 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.

  11. Salivary bone turnover markers in healthy pre- and postmenopausal women: daily and seasonal rhythm.

    PubMed

    Pellegrini, Gretel G; Gonzales Chaves, Macarena M S; Fajardo, Maria A; Ponce, Graciela M; Toyos, Gloria I; Lifshitz, Fima; Friedman, Silvia M; Zeni, Susana N

    2012-04-01

    No studies had investigated circadian and circannual rhythms of bone biomarkers in whole saliva. We evaluated the salivary daily and seasonal rhythm of carboxy-terminal telopeptide of type I collagen (CTX) and bone alkaline phosphatase (b-ALP). Forty clinical and oral healthy ambulatory pre- and postmenopausal women from two southern Argentine cities: Comodoro Rivadavia (latitude 45º S) and Ushuaia (latitude 54º S) were included in the study. CTX levels were evaluated in serum, urine, and saliva, and b-ALP levels were measured in serum and saliva. In both groups of women, salivary CTX showed a maximum percentage of change early in the morning (80%) and a minimum in the late afternoon (45%), similarly to the pattern observed in urinary samples. No daily rhythm was observed in serum or salivary b-ALP. 25-Hydroxyvitamin D levels decreased in winter vs. summer (p < 0.01) without differences between the two studied groups. Conversely, parathormone reached higher levels in winter (p < 0.05) which induced a slight non-significant increment in salivary CTX and b-ALP levels. The results showed that, as in serum and urinary samples, salivary CTX exhibits daily and a slight seasonal rhythmicity. Whole non-stimulated saliva is a useful tool to detect several oral and systemic diseases because it has important advantages compared to serum and urinary samples. Then, it may also be a promising sample to test changes in bone metabolism contributing to diagnose and to monitor the therapy of several metabolic bone diseases. PMID:21431857

  12. 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

  13. Short-term immobilization-induced cancellous bone loss is limited to regions undergoing high turnover and/or modeling in mature rats.

    PubMed

    Shen, V; Liang, X G; Birchman, R; Wu, D D; Healy, D; Lindsay, R; Dempster, D W

    1997-07-01

    remodeling sites when a high turnover state is provided by either estrogen or dietary calcium deficiency. These results suggest that the presence of a risk factor, such as immobilization, which in the short-term causes inhibition of bone formation, does not predispose the skeleton to rapid cancellous bone loss except when accompanied by modeling or high turnover. PMID:9213010

  14. 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. PMID:24604866

  15. 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…

  16. 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

  17. MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer

    PubMed Central

    Wen, Jing; Fu, Jianhua; Ling, Yihong; Zhang, Wei

    2016-01-01

    The migration and invasion inhibitory protein (MIIP) has been discovered recently to have inhibitory functions in cell proliferation and migration. Overexpression of MIIP reduced the intracellular steady-state level of epidermal growth factor receptor (EGFR) protein in lung cancer cells with no effect on EGFR mRNA expression compared to that in the control cells. This MIIP-promoted EGFR protein degradation was reversed by proteasome and lysosome inhibitors, suggesting the involvement of both proteasomal and lysosomal pathways in this degradation. This finding was further validated by pulse-chase experiments using 35S-methionine metabolic labeling. We found that MIIP accelerates EGFR protein turnover via proteasomal degradation in the endoplasmic reticulum and then via the lysosomal pathway after its entry into endocytic trafficking. MIIP-stimulated downregulation of EGFR inhibits downstream activation of Ras and blocks the MEK signal transduction pathway, resulting in inhibition of cell proliferation. The negative correlation between MIIP and EGFR protein expression was validated in lung adenocarcinoma samples. Furthermore, the higher MIIP protein expression predicts a better overall survival of Stage IA-IIIA lung adenocarcinoma patients who underwent radical surgery. These findings reveal a new mechanism by which MIIP inhibits cell proliferation. PMID:26824318

  18. CD33 responses are blocked by SOCS3 through accelerated proteasomal-mediated turnover.

    PubMed

    Orr, Selinda J; Morgan, Nuala M; Elliott, Joanne; Burrows, James F; Scott, Christopher J; McVicar, Daniel W; Johnston, James A

    2007-02-01

    CD33 is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family of inhibitory receptors and a therapeutic target for acute myeloid leukemia (AML). CD33 contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2. How CD33 expression is regulated is unclear. Suppressor of cytokine signaling 3 (SOCS3) is expressed in response to cytokines, LPS, and other PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signaling. In this study, using peptide pull-down experiments, we found that SOCS3 can specifically bind to the phosphorylated ITIM of CD33. Additionally, following cross-linking SOCS3 can recruit the ECS E3 ligase resulting in accelerated proteasomal degradation of both CD33 and SOCS3. Our data suggest that the tyrosine motifs in CD33 are not important for internalization, while they are required for degradation. Moreover, SOCS3 inhibited the CD33-induced block on cytokine-induced proliferation. This is the first receptor shown to be degraded by SOCS3 and where SOCS3 and its target protein are degraded concomitantly. Our findings clearly suggest that during an inflammatory response, the inhibitory receptor CD33 is lost by this mechanism. Moreover, this has important clinical implications as tumors expressing SOCS3 may be refractory to alpha-CD33 therapy. PMID:17008544

  19. Supplementation with calcium and short-chain fructo-oligosaccharides affects markers of bone turnover but not bone mineral density in postmenopausal women.

    PubMed

    Slevin, Mary M; Allsopp, Philip J; Magee, Pamela J; Bonham, Maxine P; Naughton, Violetta R; Strain, J J; Duffy, Maresa E; Wallace, Julie M; Mc Sorley, Emeir M

    2014-03-01

    This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444. PMID

  20. Reference intervals of bone turnover markers in healthy premenopausal women: results from a cross-sectional European study.

    PubMed

    Eastell, Richard; Garnero, Patrick; Audebert, Christine; Cahall, David L

    2012-05-01

    Robust validated reference intervals for bone turnover markers (BTMs) are required to assess fracture risk and effectiveness of therapy. However, there are currently limited reference intervals for BTMs in premenopausal women, especially comparing manual and automated assays. This study determined the BTM reference intervals using automated and manual assays, compared the results obtained from two different assays, and evaluated the factors that may affect BTM levels. This was a cross-sectional registry study in 194 healthy, premenopausal, European Caucasian women aged 35 to 39years from France (n=98) and Denmark (n=96). Two independent specialized laboratories, one in France (Synarc) and the other in Denmark (Nordic Bioscience), analyzed blood and urine samples from each woman for BTM levels. The type of assay used in this study significantly affected the reference intervals obtained for serum cross-linked C-terminal telopeptide of type I collagen (sCTX) and urinary cross-linked N-terminal telopeptides of type I collagen (uNTX/Cr; both P<0.001), but not for serum procollagen type I amino-terminal propeptide (PINP; P=0.28). The Serum Crosslaps® ELISA; Microtitre-plate based ELISA; Metra BAP EIA; and UniQ® PINP RIA assays yielded higher BTM reference values. The reference intervals for the BTMs, as measured with Serum β-Crosslaps, Elecsys® 2010 Systems; VITROS® ECI System; Ostase®, Access® Immunoassay System; and Total PINP, Elecsys® 2010 Systems assays, were 0.111-0.791ng/mL for sCTX, 12.3-59.7nmol BCE/mmol creatinine for uNTX/Cr, 5.8-17.5ng/mL for bone alkaline phosphatase (ALP), and 17.3-83.4ng/mL for PINP, respectively. When measured with Serum Crosslaps® ELISA, Microtitre-plate based ELISA, Metra BAP EIA, and UniQ® PINP RIA, the reference intervals were 0.177-0.862ng/mL for sCTX, 22.6-95.7nmol BCE/mmol creatinine for uNTX/Cr, 14.8-38.8U/L for bone ALP, and 19.5-75.2ng/mL for PINP, respectively. The clinical interpretation of the BTMs of a subject

  1. Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins.

    PubMed

    Scacchi, Massimo; Danesi, Leila; Cattaneo, Agnese; Sciortino, Giovanna; Radin, Raffaella; Ambrogio, Alberto Giacinto; Vitale, Giovanni; D'Angelo, Emanuela; Mirra, Nadia; Zanaboni, Laura; Arvigo, Marica; Boschetti, Mara; Ferone, Diego; Marzullo, Paolo; Baldini, Marina; Cassinerio, Elena; Cappellini, Maria Domenica; Persani, Luca; Cavagnini, Francesco

    2016-08-01

    Previous evidence supports a role for growth hormone (GH)-insulin-like growth factor (IGF)-I deficiency in the pathophysiology of osteopenia/osteoporosis in adult thalassemia. Moreover, serum IGF-II has never been studied in this clinical condition. Thus, we elected to study the GH secretory status and the levels of circulating somatomedins, correlating these parameters with bone mineral density (BMD) and biochemical markers of bone turnover. A hundred and thirty-nine normal weight adult thalassemic patients (72 men and 67 women) were studied. Lumbar and femoral neck BMD were measured in 106/139 patients. Sixty-eight patients underwent growth hormone releasing hormone plus arginine testing. Measurement of baseline IGF-I and IGF-II was performed in all patients, while osteocalcin, C-terminal telopeptide of type I collagen (CTx), and urinary cross-linked N-telopeptides of type I collagen (NTx) were assayed in 95 of them. Femoral and lumbar osteoporosis/Z score below the expected range for age were documented in 61.3 and in 56.6 % of patients, respectively. Severe GH deficiency (GHD) was demonstrated in 27.9 % of cases, whereas IGF-I SDS was low in 86.3 %. No thalassemic patients displayed circulating levels of IGF-II below the reference range. GH peaks were positively correlated with femoral, but not lumbar, Z score. No correlations were found between GH peaks and osteocalcin, CTx and NTx. GH peaks were positively correlated with IGF-I values, which in their turn displayed a positive correlation with osteocalcin, CTx, and NTx. No correlations emerged between IGF-I values and either femoral or lumbar Z scores. No correlations were found between IGF-II and any of the following parameters: GH peaks, osteocalcin, CTx, NTx, femoral Z score, and lumbar Z score. Our study, besides providing for the first time evidence of a normal IGF-II production in thalassemia, contributes to a better understanding of the involvement of the somatotropin-somatomedin axis in the

  2. 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

  3. Serum biochemical markers of bone turnover in healthy infants and children.

    PubMed

    Tommasi, M; Bacciottini, L; Benucci, A; Brocchi, A; Passeri, A; Saracini, D; D'Agata, A; Cappelli, G

    1996-01-01

    Serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D] were measured in 241 normal infants and children (134 males and 107 females aged 1.9 months-14 years, 1.8 months-12 years, respectively). Regarding the analysis of data for children above 2 yrs, we chose data with the following normalization: data/body surface x standard body surface, to eliminate biological variations not exclusively related to chronological age. The increase in serum OC occurred at the expected age of growth spurts in both sexes: in the first year of life OC values (mean +/- SD) were 82.6 +/- 34.3 and 60.2 +/- 32.9 OC ng/ml in males and females, respectively; during puberty, peak values occurred at the age of 10-12 yrs in girls (76.6 +/- 25.8) and at the age of 12-14 yrs in boys (113 +/- 48.3). Furthermore, significant positive correlations with age were found for males from 2 to 14 yrs (p < 0.00001) and for females from 2 to 12 yrs (p < 0.001). Elevated levels of BAP occurred in the first year, 70.4 +/- 28.2 and 71.8 +/- 28.5, and in the second year, 69.4 +/- 26.7 and 67.4 +/- 33.8 ng/ml, for males and females, respectively. For children older than 2 yrs, a positive correlation with age (p < 0.01) was found for females only, with a peak value of 67.2 +/- 13.9 at the age of 10-12 yrs. For ages 2-14 yrs the reference values (mean +/- 2SD) were 15.5 - 90.3 and 17.2 - 95.2 ng/ml for males and females, respectively. The highest PICP levels (1354 +/- 680 ng/ml in males and 1041 +/- 766 in females) were observed in infants less than 1 year of age, decreasing by about 60% at the age of 2. There was no significant change in serum PICP for children older than 2 yrs with values covering a range (mean +/- 2SD) of 52 - 544 and 18 - 546 ng/ml in males and females, respectively. Similarly, the highest ICTP values were seen in

  4. High-acceleration whole body vibration stimulates cortical bone accrual and increases bone mineral content in growing mice.

    PubMed

    Gnyubkin, Vasily; Guignandon, Alain; Laroche, Norbert; Vanden-Bossche, Arnaud; Malaval, Luc; Vico, Laurence

    2016-06-14

    Whole body vibration (WBV) is a promising tool for counteracting bone loss. Most WBV studies on animals have been performed at acceleration <1g and frequency between 30 and 90Hz. Such WBV conditions trigger bone growth in osteopenia models, but not in healthy animals. In order to test the ability of WBV to promote osteogenesis in young animals, we exposed seven-week-old male mice to vibration at 90Hz and 2g peak acceleration for 15min/day, 5 days/week. We examined the effects on skeletal tissues with micro-computed tomography and histology. We also quantified bone vascularization and mechanosensitive osteocyte proteins, sclerostin and DMP1. Three weeks of WBV resulted in an increase of femur cortical thickness (+5%) and area (+6%), associated with a 25% decrease of sclerostin expression, and 35% increase of DMP1 expression in cortical osteocytes. Mass-structural parameters of trabecular bone were unaltered in femur or vertebra, while osteoclastic parameters and bone formation rate were increased at both sites. Three weeks of WBV resulted in higher blood vessel numbers (+23%) in the distal femoral metaphysis. After 9-week WBV, we have not observed the difference in structural cortical or trabecular parameters. However, the tissue mineral density of cortical bone was increased by 2.5%. Three or nine weeks of 2g/90Hz WBV treatment did not affect longitudinal growth rate or body weight increase under our experimental conditions, indicating that these are safe to use. These results validate a potential of 2g/90Hz WBV to stimulate trabecular bone cellular activity, accelerate cortical bone growth, and increase bone mineral density. PMID:27178020

  5. Locally administered T cells from mice immunized with lipopolysaccharide (LPS) accelerate LPS-induced bone resorption.

    PubMed

    Ozaki, Yukio; Ukai, Takashi; Yamaguchi, Masayuki; Yokoyama, Miho; Haro, Esperanza R Ayón; Yoshimoto, Mayumi; Kaneko, Takashi; Yoshinaga, Miho; Nakamura, Hirotaka; Shiraishi, Chiaki; Hara, Yoshitaka

    2009-06-01

    T cells play important roles in bone destruction and osteoclastogenesis and are found in chronic destructive bone lesions. Lipopolysaccharide (LPS) is one of several pathological factors involved in inflammatory bone destruction. We previously described the importance of T cells in the inflammatory bone resorption that occurs after repeated LPS administration. However, whether local or systemic T cells are important for inflammatory bone resorption and whether immunization of host animals influences bone resorption remain unclear. The present study examines the effects of local extant T cells from LPS-immunized mice on LPS-induced bone resorption. T cells from LPS-immunized or non-immunized mice were injected together with LPS into the gingival tissues of mice with severe combined immunodeficiency disease that lack both T and B cells. We histomorphometrically evaluated bone resorption at sites of T cell injections and examined the influence of T cells from LPS-immunized mice on osteoclastogenesis in vitro. We found that locally administered T cells from LPS-immunized but not non-immunized mice accelerated LPS-induced bone resorption in vivo. Moreover, T cells from LPS-immunized mice increased osteoclastogenesis in vitro induced by receptor activator of NF-kappa B ligand and LPS and anti-tumor necrosis factor (TNF)-alpha antibody inhibited this increase. These results demonstrated that local extant T cells accelerate inflammatory bone resorption. Furthermore, T cells from LPS-immunized mice appear to elevate LPS-induced bone resorption using TNF-alpha. PMID:19437611

  6. NAT8L (N-Acetyltransferase 8-Like) Accelerates Lipid Turnover and Increases Energy Expenditure in Brown Adipocytes*

    PubMed Central

    Pessentheiner, Ariane R.; Pelzmann, Helmut J.; Walenta, Evelyn; Schweiger, Martina; Groschner, Lukas N.; Graier, Wolfgang F.; Kolb, Dagmar; Uno, Kyosuke; Miyazaki, Toh; Nitta, Atsumi; Rieder, Dietmar; Prokesch, Andreas; Bogner-Strauss, Juliane G.

    2013-01-01

    NAT8L (N-acetyltransferase 8-like) catalyzes the formation of N-acetylaspartate (NAA) from acetyl-CoA and aspartate. In the brain, NAA delivers the acetate moiety for synthesis of acetyl-CoA that is further used for fatty acid generation. However, its function in other tissues remained elusive. Here, we show for the first time that Nat8l is highly expressed in adipose tissues and murine and human adipogenic cell lines and is localized in the mitochondria of brown adipocytes. Stable overexpression of Nat8l in immortalized brown adipogenic cells strongly increases glucose incorporation into neutral lipids, accompanied by increased lipolysis, indicating an accelerated lipid turnover. Additionally, mitochondrial mass and number as well as oxygen consumption are elevated upon Nat8l overexpression. Concordantly, expression levels of brown marker genes, such as Prdm16, Cidea, Pgc1α, Pparα, and particularly UCP1, are markedly elevated in these cells. Treatment with a PPARα antagonist indicates that the increase in UCP1 expression and oxygen consumption is PPARα-dependent. Nat8l knockdown in brown adipocytes has no impact on cellular triglyceride content, lipogenesis, or oxygen consumption, but lipolysis and brown marker gene expression are increased; the latter is also observed in BAT of Nat8l-KO mice. Interestingly, the expression of ATP-citrate lyase is increased in Nat8l-silenced adipocytes and BAT of Nat8l-KO mice, indicating a compensatory mechanism to sustain the acetyl-CoA pool once Nat8l levels are reduced. Taken together, our data show that Nat8l impacts on the brown adipogenic phenotype and suggests the existence of the NAT8L-driven NAA metabolism as a novel pathway to provide cytosolic acetyl-CoA for lipid synthesis in adipocytes. PMID:24155240

  7. THE INFLUENCE OF THYROID FUNCTION AND BONE TURNOVER ON LIPOPROTEIN PROFILE IN YOUNG PHYSICALLY ACTIVE MEN WITH DIFFERENT INSULIN SENSITIVITY

    PubMed Central

    Lutosławska, G.; Czajkowska, A.; Tkaczyk, J.; Mazurek, K.; Tomaszewski, P.

    2014-01-01

    Physical activity induces changes in the endocrine system. Previous data indicated that changes in insulin secretion and the tissue response to this hormone are very important for energy metabolism. It is believed that they are accompanied by changes in lipid metabolism, but factors contributing to this process are still disputed. The aim of this study was to assess interactions among insulin sensitivity, thyroid function, a bone turnover marker and serum lipid profile in young physically active men. Eighty-seven physical education students, aged 18-23 years, participated in the study. We measured serum levels of glucose, lipids, insulin, thyroid-stimulating hormone (TSH), osteocalcin and anthropometric parameters. Insulin sensitivity was determined using homeostatic model assessment for insulin resistance (HOMA-IR). The median value of HOMA-IR (1.344) was used to divide the study population into Group A (above the median) and Group B (below the median). Men from both groups did not differ in anthropometric parameters or in daily physical activity. Triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were higher in Group A (P < 0.05). TSH and osteocalcin levels were similar in males with different HOMA-IR. Multiple regression analysis for TSH and osteocalcin showed that in Group A these hormones had no effect on plasma lipoproteins. However, in Group B they significantly determined the variation of plasma TC and low-density lipoprotein cholesterol (LDL-C) levels (in about 28% and 29%, respectively). We concluded that TSH and osteocalcin are involved in determination of a more healthy lipid profile at a certain level of insulin sensitivity. PMID:24899778

  8. The influence of thyroid function and bone turnover on lipoprotein profile in young physically active men with different insulin sensitivity.

    PubMed

    Kęska, A; Lutosławska, G; Czajkowska, A; Tkaczyk, J; Mazurek, K; Tomaszewski, P

    2014-06-01

    Physical activity induces changes in the endocrine system. Previous data indicated that changes in insulin secretion and the tissue response to this hormone are very important for energy metabolism. It is believed that they are accompanied by changes in lipid metabolism, but factors contributing to this process are still disputed. The aim of this study was to assess interactions among insulin sensitivity, thyroid function, a bone turnover marker and serum lipid profile in young physically active men. Eighty-seven physical education students, aged 18-23 years, participated in the study. We measured serum levels of glucose, lipids, insulin, thyroid-stimulating hormone (TSH), osteocalcin and anthropometric parameters. Insulin sensitivity was determined using homeostatic model assessment for insulin resistance (HOMA-IR). The median value of HOMA-IR (1.344) was used to divide the study population into Group A (above the median) and Group B (below the median). Men from both groups did not differ in anthropometric parameters or in daily physical activity. Triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were higher in Group A (P < 0.05). TSH and osteocalcin levels were similar in males with different HOMA-IR. Multiple regression analysis for TSH and osteocalcin showed that in Group A these hormones had no effect on plasma lipoproteins. However, in Group B they significantly determined the variation of plasma TC and low-density lipoprotein cholesterol (LDL-C) levels (in about 28% and 29%, respectively). We concluded that TSH and osteocalcin are involved in determination of a more healthy lipid profile at a certain level of insulin sensitivity. PMID:24899778

  9. 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

    High bone turnover, evidenced by high serum osteocalcin (OC) concentration, is indicated as risk of fracture in old age. However, low bone turnover has been reported in patients with type 2 diabetes (T2D) who also have high fracture risk. Poor glycemic control indicated by higher glycated hemoglobin levels (HbA1c) has been associated with lower serum OC in older Caucasian and Asian patients with T2D. There remains a gap in knowledge about effects of T2D on bone turnover status in Hispanic populations. We report bone turnover in association with glycemic control in 72 older (greater than or equal to 50 years) men (N=21) and women (N=51) from the Cameron County Hispanic Cohort (CCHC) in Texas. Prevalence of T2D is about 30 percent in this cohort who live in health disparity due to poor access to health care. Separate multivariable linear regression models were conducted to determine association between high/diabetic levels of HbA1c (less than 6.5 normal versus greater than or equal to 6.5 high) and serum OC after controlling for age, body mass index (BMI, greater than 30 obese versus less than 30 non-obese), visceral fat, femoral neck BMD and serum concentrations of creatinine, calcium, and vitamin D for men and women. Interaction effects were assessed while developing final multivariable model to identify factors that modify the association between HbA1c and OC. Subjects were 66 plus or minus 9 (mean plus or minus Standard Deviation) years for men and 67 plus or minus 8 years for women. HbA1c was 8.0 plus or minus 2.0 for men and 7.8 plus or minus 2.0 for women. There were no significant differences for BMI, femoral neck BMD, serum calcium or 25-hydroxyvitamin D concentrations between men and women. High HbA1c was significantly associated with lower OC levels in men in both age groups (mean difference in OC between high vs. low HbA1c [95 percent confidence interval] for older group (greater than or equal to 65 years) was minus 9.51 (minus 16.36 to minus 2.65) and

  10. Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate.

    PubMed

    Williams, Donald S; McCracken, Paul J; Purcell, Mona; Pickarski, Maureen; Mathers, Parker D; Savitz, Alan T; Szumiloski, John; Jayakar, Richa Y; Somayajula, Sangeetha; Krause, Stephen; Brown, Keenan; Winkelmann, Christopher T; Scott, Boyd B; Cook, Lynn; Motzel, Sherri L; Hargreaves, Richard; Evelhoch, Jeffrey L; Cabal, Antonio; Dardzinski, Bernard J; Hangartner, Thomas N; Duong, Le T

    2013-10-01

    Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months. The study consisted of four groups: L-ODN (2 mg/kg, daily p.o.), H-ODN (8/4 mg/kg daily p.o.), ALN (15 μg/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, p<0.001), spine trabecular vBMD (13.7%, p<0.001), femoral neck (FN) integral (int) vBMD (9.0%, p<0.001) and sub-trochanteric proximal femur (SubTrPF) int vBMD, (6.4%, p<0.001) compared to baseline. L-ODN significantly increased FN cortical thickness (Ct.Th) and cortical bone mineral content (Ct.BMC) by 22.5% (p<0.001) and 21.8% (p<0.001), respectively, and SubTrPF Ct.Th and Ct.BMC by 10.9% (p<0.001) and 11.3% (p<0.001) respectively. Compared to ALN, L-ODN significantly increased FN Ct. BMC by 8.7% (p<0.05), and SubTrPF Ct.Th by 7.6% (p<0.05) and Ct.BMC by 6.2% (p<0.05). H-ODN showed no additional efficacy compared to L-ODN in OVX-monkeys in prevention mode. Taken together, the results from this study have demonstrated that administration of ODN at levels which approximate clinical exposure in OVX-monkeys had comparable efficacy to ALN in

  11. Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion: A Case Report.

    PubMed

    Mousiolis, Athanasios C; Rapti, Eleni; Grammatiki, Maria; Yavropoulou, Maria; Efstathiou, Maria; Foroglou, Nikolaos; Daniilidis, Michalis; Kotsa, Kalliopi

    2016-01-01

    Increased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state.We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor.Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas. PMID:26765410

  12. Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks

    PubMed Central

    Tebas, Pablo; Kumar, Princy; Hicks, Charles; Granier, Catherine; Wynne, Brian; Min, Sherene; Pappa, Keith

    2015-01-01

    Objective: Antiretroviral therapy initiation has been linked to bone mineral density and bone biomarker changes. We assessed long-term bone turnover biomarker effects over 144 weeks in patients initiating dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC) versus efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Methods: Patients randomized in SINGLE received DTG (50 mg once daily) + ABC/3TC or fixed-dose combination EFV/FTC/TDF. We evaluated vitamin D serum levels and bone turnover markers (BTMs), including type 1 collagen cross-linked C-telopeptide (CTx), osteocalcin, bone-specific alkaline phosphatase (BSAP), and procollagen type 1 N-terminal propeptide (P1NP), at baseline and weeks 48, 96, and 144. Results: Among the 833 enrolled patients (68% white, 85% men), baseline median age was 35 years (range 18–85), median CD4+ was 338 cells/μl, and median BMI was 24 kg/m2. Fifty-three percent of patients smoked, and 6% reported baseline vitamin D use, with no meaningful differences between groups. Relative to baseline, CTx, osteocalcin, BSAP, and P1NP increased; vitamin D decreased in both groups at weeks 48, 96, and 144. Changes from baseline typically peaked at weeks 48 or 96 and for the four analytes, excluding vitamin D, with the EFV/FTC/TDF group having significantly greater changes from baseline at all time points. Conclusion: DTG + ABC/3TC in antiretroviral therapy-naive patients resulted in significantly lower increases in BTMs (CTx, osteocalcin, BSAP, P1NP) compared with EFV/FTC/TDF over 144 weeks. The observed changes are consistent with results from other smaller, randomized trials. These differences in BTMs likely correlate with changes in bone mineral density over time. PMID:26355674

  13. Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

    NASA Astrophysics Data System (ADS)

    Ma, Honglei; Zhang, Feng; Zhu, Yu; Xiao, Yanhua; Wazir, Abrar

    2014-02-01

    The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3-L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.

  14. High-Frequency Acceleration: Therapeutic Tool to Preserve Bone following Tooth Extractions.

    PubMed

    Alikhani, M; Lopez, J A; Alabdullah, H; Vongthongleur, T; Sangsuwon, C; Alikhani, M; Alansari, S; Oliveira, S M; Nervina, J M; Teixeira, C C

    2016-03-01

    A common problem in clinical dentistry is the significant and rapid bone loss that occurs after tooth extraction. Currently there is no solution for the long-term preservation of alveolar bone. Previously, we showed that high-frequency acceleration (HFA) has an osteogenic effect on healthy alveolar bone. However, it is not known if HFA can preserve alveolar bone after extraction without negatively affecting wound healing. The purpose of this study was to evaluate the effect of HFA on alveolar bone loss and the rate of bone formation after tooth extraction. Eighty-five adult Sprague-Dawley rats were divided into 3 groups: control, static (static load), and HFA. In all groups, the maxillary right third molar was extracted. The HFA group received HFA for 5 min/d, applied through the second molar. The static group received the same magnitude of static load. The control group did not receive any stimulation. Some animals received fluorescent dyes at 26 and 54 d. Samples were collected on days 0, 7, 14, 28, and 56 for fluorescence microscopy, micro-computed tomography, histology, RNA, and protein analyses. We found that HFA increased bone volume in the extraction site and surrounding alveolar bone by 44% when compared with static, while fully preserving alveolar bone height and width long-term. These effects were accompanied by increased expression of osteogenic markers and intramembranous bone formation and by decreased expression of osteoclastic markers and bone resorption activity, as well as decreased expression of many inflammatory markers. HFA is a noninvasive safe treatment that can be used to prevent alveolar bone loss and/or accelerate bone healing after tooth extraction. PMID:26672126

  15. Milk extracellular vesicles accelerate osteoblastogenesis but impair bone matrix formation.

    PubMed

    Oliveira, Marina C; Arntz, Onno J; Blaney Davidson, Esmeralda N; van Lent, Peter L E M; Koenders, Marije I; van der Kraan, Peter M; van den Berg, Wim B; Ferreira, Adaliene V M; van de Loo, Fons A J

    2016-04-01

    The claimed beneficial effect of milk on bone is still a matter for debate. Recently extracellular vesicles (EVs) that contain proteins and RNA were discovered in milk, but their effect on bone formation has not yet been determined. We demonstrated previously that bovine milk-derived EVs (BMEVs) have immunoregulatory properties. Our aim was to evaluate the effect of BMEVs on osteogenesis by mice and human mesenchymal stem cells (hMSCs). Oral delivery of two concentrations of BMEVs to female DBA/1J mice during 7weeks did not alter the tibia trabecular bone area; however, the osteocytes number increased. In addition, the highest dose of BMEVs markedly increased the woven bone tissue, which is more brittle. The exposure of hMSCs to BMEVs during 21days resulted in less mineralization but higher cell proliferation. Interestingly BMEVs reduced the collagen production, but enhanced the expression of genes characteristic for immature osteoblasts. A kinetic study showed that BMEVs up-regulated many osteogenic genes within the first 4days. However, the production of type I collagen and expression of its genes (COL1A1 and COL1A2) were markedly reduced at days 21 and 28. At day 28, BMEVs again lead to higher proliferation, but mineralization was significantly increased. This was associated with increased expression of sclerostin, a marker for osteocytes, and reduced osteonectin, which is associated to bone matrix formation. Our study adds BMEVs to the list of milk components that can affect bone formation and may shed new light on the contradictory claims of milk on bone formation. PMID:27012623

  16. Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.

    PubMed

    Greenspan, S L; Parker, R A; Ferguson, L; Rosen, H N; Maitland-Ramsey, L; Karpf, D B

    1998-09-01

    Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary

  17. Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation

    PubMed Central

    Mehdikhani-Nahrkhalaji, Mehdi; Fathi, Mohammad Hossein; Mortazavi, Vajihesadat; Mousavi, Sayed Behrouz; Akhavan, Ali; Haghighat, Abbas; Hashemi-Beni, Batool; Razavi, Sayed Mohammad; Mashhadiabbas, Fatemeh

    2015-01-01

    Background: The aim of this study was to evaluate the interaction of bioactive and biodegradable poly (lactide-co-glycolide)/bioactive glass/hydroxyapatite (PBGHA) and poly (lactide-co-glycolide)/bioactive glass (PBG) nanocomposite coatings with bone. Materials and Methods: Sol-gel derived 58S bioactive glass nanoparticles, 50/50 wt% poly (lactic acid)/poly (glycolic acid) and hydroxyapatite nanoparticles were used to prepare the coatings. The nanocomposite coatings were characterized by scanning electron microscopy, X-ray diffraction and atomic force microscopy. Mechanical stability of the prepared nanocomposite coatings was studied during intramedullary implantation of coated Kirschner wires (K-wires) into rabbit tibia. Titanium mini-screws coated with nanocomposite coatings and without coating were implanted intramedullary in rabbit tibia. Bone tissue interaction with the prepared nanocomposite coatings was evaluated 30 and 60 days after surgery. The non-parametric paired Friedman and Kruskal-Wallis tests were used to compare the samples. For all tests, the level of significance was P < 0.05. Results: The results showed that nanocomposite coatings remained stable on the K-wires with a minimum of 96% of the original coating mass. Tissue around the coated implants showed no adverse reactions to the coatings. Woven and trabecular bone formation were observed around the coated samples with a minimum inflammatory reaction. PBG nanocomposite coating induced more rapid bone healing than PBGHA nanocomposite coating and titanium without coating (P < 0.05). Conclusion: It was concluded that PBG nanocomposite coating provides an ideal surface for bone formation and it could be used as a candidate for coating dental and orthopedic implants. PMID:25709681

  18. Systemic treatment with strontium ranelate accelerates the filling of a bone defect and improves the material level properties of the healing bone.

    PubMed

    Zacchetti, Giovanna; Dayer, Romain; Rizzoli, René; Ammann, Patrick

    2014-01-01

    Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days) or vehicle for 4, 8, or 12 weeks (10 rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT) and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively. PMID:25243150

  19. Runx2 Overexpression in Bone Marrow Stromal Cells Accelerates Bone Formation in Critical-Sized Femoral Defects

    PubMed Central

    Wojtowicz, Abigail M.; Templeman, Kellie L.; Hutmacher, Dietmar W.; Guldberg, Robert E.

    2010-01-01

    The repair of large nonunions in long bones remains a significant clinical problem due to high failure rates and limited tissue availability for auto- and allografts. Many cell-based strategies for healing bone defects deliver bone marrow stromal cells (BMSCs) to the defect site to take advantage of the inherent osteogenic capacity of this cell type. However, many factors, including donor age and ex vivo expansion of the cells, cause BMSCs to lose their differentiation ability. To overcome these limitations, we have genetically engineered BMSCs to constitutively overexpress the osteoblast-specific transcription factor Runx2. In the present study, we examined Runx2-modified BMSCs, delivered via polycaprolactone scaffolds loaded with type I collagen meshes, in critical-sized segmental defects in rats compared to unmodified cells, cell-free scaffolds, and empty defects. Runx2 expression in BMSCs accelerated healing of critical-sized defects compared to unmodified BMSCs and defects receiving cell-free treatments. These findings provide an accelerated method for healing large bone defects, which may reduce recovery time and the need for external fixation of critical-sized defects. PMID:20412027

  20. Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critical-sized femoral defects.

    PubMed

    Wojtowicz, Abigail M; Templeman, Kellie L; Hutmacher, Dietmar W; Guldberg, Robert E; García, Andrés J

    2010-09-01

    The repair of large nonunions in long bones remains a significant clinical problem due to high failure rates and limited tissue availability for auto- and allografts. Many cell-based strategies for healing bone defects deliver bone marrow stromal cells (BMSCs) to the defect site to take advantage of the inherent osteogenic capacity of this cell type. However, many factors, including donor age and ex vivo expansion of the cells, cause BMSCs to lose their differentiation ability. To overcome these limitations, we have genetically engineered BMSCs to constitutively overexpress the osteoblast-specific transcription factor Runx2. In the present study, we examined Runx2-modified BMSCs, delivered via polycaprolactone scaffolds loaded with type I collagen meshes, in critical-sized segmental defects in rats compared to unmodified cells, cell-free scaffolds, and empty defects. Runx2 expression in BMSCs accelerated healing of critical-sized defects compared to unmodified BMSCs and defects receiving cell-free treatments. These findings provide an accelerated method for healing large bone defects, which may reduce recovery time and the need for external fixation of critical-sized defects. PMID:20412027

  1. 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

  2. Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

    SciTech Connect

    Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P. )

    1988-11-01

    Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which {sup 45}Ca release from {sup 45}Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with {sup 45}Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke.

  3. Acute effects of a single session of aerobic exercise with or without weight-lifting on bone turnover in healthy young women.

    PubMed

    Tosun, Aliye; Bölükbaşi, Nesrin; Cingi, Elif; Beyazova, Mehmet; Unlü, Mustafa

    2006-01-01

    This study aimed to investigate the acute effects of exercise on bone turnover and to determine whether brisk walking with or without weight-lifting makes a difference on bone metabolism. Nine healthy women performed two exercise bouts: brisk walking on a treadmill for 30 min (E), and similar exercise carrying 5 kg of weight in a backpack (WE). Serum parathyroid hormone (PTH), osteocalcin (OC), calcitonin (CT), procollagen type 1 carboxy terminal propeptide (PICP), procollagen type 1 amino terminal propeptide (PINP), type 1 collagen carboxy terminal telopeptide (ICTP), total alkaline phosphatase (ALP), and urine deoxypyridinoline (D-Pyr) levels were studied. Resting values served as control. Significant variances were observed only in serum ALP and PTH values. Variances in ALP values within subjects after exercise were statistically significant (analysis of variance in repeated measurements [AVRM], P=0.000). E caused a significant decrease, while WE caused a significant increase in ALP values at the 24th h (Bonferroni pairwise comparisons tests [BPC t-test]: P=0.028, P=0.000, respectively). Variances in PTH values within subjects after exercise were statistically significant (AVRM, P=0.029), while diurnal variation was not significant (P=0.981). E caused significant alterations in PTH levels (an increase at the 30th min, turned towards baseline at the 45th min) (BPC t-test, P=0.007). WE also caused alterations in PTH levels, though insignificant (BPC t-test, P=1.00). Brisk walking for 30 min has stimulating effects on bone turnover by various mechanisms without any additive effect of weight bearing. PMID:17039311

  4. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    NASA Technical Reports Server (NTRS)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (<10 µg/dL) have indicated associations of blood lead level with lower cognitive test scores in children, later onset of puberty in girls, and increased blood pressure and cardiovascular mortality rates in adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although 95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  5. In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice

    PubMed Central

    Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

    2014-01-01

    We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208

  6. 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

  7. 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...

  8. Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy.

    PubMed

    Murakami, H; Nakamura, T; Tsurukami, H; Abe, M; Barbier, A; Suzuki, K

    1994-09-01

    To evaluate the effects of tiludronate on the mass, structure, and turnover of cancellous bone regions in immobilized rat tibiae, we performed a 4 week dosing experiment. The right hindlimbs of 84 Sprague-Dawley rats (5 weeks old) wee neurectomized or sham operated. Animals were assigned to seven groups (n = 12 each); group 1 was sham operated, and groups 2-7 were neurectomized. Groups 1 and 2 were given vehicle only (distilled water), and groups 3, 4, and 5 were given tiludronate orally at doses of 25, 50, and 100 mg/kg body weight (BW)/day, respectively, throughout the experimental period. Group 6 was given 100 mg/kg BW/day of the agent for the first 2 weeks only, and group 7 received vehicle only for the first 2 weeks and then 100 mg/kg BW/day of the agent for the last 2 weeks. After tetracycline labeling was performed, the right tibiae were removed from the animals and processed to yield undecalcified sections. Histomorphometry was performed in the epiphyseal, primary, and secondary spongiosa of the proximal tibia. In group 2, trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly decreased in the primary and secondary spongiosae, but this did not occur in the epiphyseal spongiosa. Osteoid surface (OS/BS) was decreased and osteoclast surface (Oc.S/BS) was increased in the secondary spongiosa. Tiludronate increased BV/TV and Tb.N in the primary spongiosa by reducing the values for the parameters of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS). Osteoid surface in this region was not decreased by the agent. In groups 4 and 5, tiludronate prevented bone loss in the secondary spongiosa by reducing both OS/BS and Oc.S/BS. In group 6, BV/TV in the primary spongiosa was maintained at the level of group 1, but Oc.S/BS and Oc.N/BS were elevated. In the secondary spongiosa, bone mass was preserved and the reduction in these parameters was maintained. In group 7, however, BV/TV was increased in the primary spongiosa as a result of a

  9. 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. PMID:24869977

  10. Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects.

    PubMed

    Kitami, Megumi; Kaku, Masaru; Rocabado, Juan Marcelo Rosales; Ida, Takako; Akiba, Nami; Uoshima, Katsumi

    2016-09-01

    Considering the increased interest in cell-based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti-apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3-E1 osteoblastic cells from H2 O2 -induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27-overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4-week of transplantation, both control cell- and Hsp27 overexpressed cell-transplanted groups showed significantly higher new bone formation in comparison with cell-free gel-transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4-week but did not differentiate into bone-forming osteoblasts. In conclusion, cell-containing collagen gel accelerated calvarial bone defect healing in comparison with cell-free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation-based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974-1982, 2016. © 2016 Wiley Periodicals, Inc. PMID:26754153

  11. Low level laser therapy accelerates bone healing in spinal cord injured rats.

    PubMed

    Medalha, Carla Christina; Santos, Ana Lúcia Yaeko Silva; Veronez, Suellen de Oliveira; Fernandes, Kelly Rossetti; Magri, Angela Maria Paiva; Renno, Ana Claudia Muniz

    2016-06-01

    Bone loss occurs rapidly and consistently after the occurrence of a spinal cord injury (SCI), leading to a decrease in bone mineral density (BMD) and a higher risk of fractures. In this context, the stimulatory effects of low level laser therapy (LLLT) also known as photobiomodulation (PBM) have been highlighted, mainly due to its osteogenic potential. The aim of the present study was to evaluate the effects of LLLT on bone healing using an experimental model of tibial bone defect in SCI rats. Twenty-four female Wistar rats were randomly divided into 3 groups: Sham group (SG), SCI control group (SC) and SCI laser treated group (SL). Two weeks after the induction of the SCI, animals were submitted to surgery to induce a tibial bone defect. Treatment was performed 3days a week, for 2weeks, at a single point over the area of the injury, using an 808nm laser (30mW, 100J/cm(2); 0.028cm(2), 1.7W/cm², 2.8J). The results of the histological and morphometric evaluation demonstrated that the SL group showed a larger amount of newly formed bone compared to the SC group. Moreover, a significant immunoexpression of runt-related transcription factor 2 (RUNX2) was observed in the SL group. There was no statistical difference in the biomechanical evaluation. In conclusion, the results suggest that LLLT accelerated the process of bone repair in rats with complete SCI. PMID:27077555

  12. 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

  13. RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

    NASA Technical Reports Server (NTRS)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1979-01-01

    The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

  14. Effects of a deficient magnesium supply during the dry period on bone turnover of dairy cows at parturition.

    PubMed

    van Mosel, M; van 't Klooster, A T; Wouterse, H S

    1991-10-01

    The bone activity and bone mineral content in rib bones resected from 33 dairy cows between 3 and 8 h after parturition were measured, and the effects upon them of a deficient supply of dietary magnesium (Mg) during the last seven weeks of pregnancy were studied. The cows were fed a diet containing either 0.22% magnesium (low Mg) or 0.82% magnesium (high Mg) in the dry matter (DM), and the potassium content of both rations was increased to approximately 4.1% in the DM to reduce the absorption of magnesium. In the cows fed the low-Mg diet a fall in plasma Mg concentration was observed. In the low-Mg, low-parity cows the plasma Mg concentrations at parturition were higher than in the low-Mg, high-parity cows, i.e. 0.83 mmol/l and 0.54 mmol/l, respectively. After parturition four cows in the low-Mg, high-parity group showed clinical signs of hypocalcaemia but none of the other groups did so. The bone formation in low-parity cows was significantly (P less than 0.05) affected by Mg supply, with higher percentages of both trabecular surface covered by osteoid and osteoid volume in the low-Mg group. In the high-parity cows no significant differences in bone formation were found between the low- and high-Mg groups. An inadequate Mg supply resulted in a significantly (P less than 0.05) higher Ca content in the bone ash of low-parity cows and a significantly (P less than 0.05) higher bone ash percentage in the bone of high-parity cows. PMID:1776234

  15. Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

    PubMed

    Tikhonova, Maria A; Ting, Che-Hao; Kolosova, Nataliya G; Hsu, Chao-Yu; Chen, Jian-Horng; Huang, Chi-Wen; Tseng, Ging-Ting; Hung, Ching-Sui; Kao, Pan-Fu; Amstislavskaya, Tamara G; Ho, Ying-Jui

    2015-10-31

    Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis. PMID:26387656

  16. Effects of suppression of estrogen action by the p450 aromatase inhibitor letrozole on bone mineral density and bone turnover in pubertal boys.

    PubMed

    Wickman, Sanna; Kajantie, Eero; Dunkel, Leo

    2003-08-01

    The essential role of estrogen (E) in regulation of developing peak bone mass in males was confirmed when young adult men were described who cannot respond to or produce E because of defective E receptor alpha or P-450 aromatase enzyme, respectively. These men had significantly reduced bone mineral density (BMD) despite normal or supranormal androgen concentrations, and E administration improved BMD in the men with aromatase deficiency, whereas testosterone (T) was ineffective. Because new P450 aromatase inhibitors may prove to be potential drugs in various growth disorders, the effect of suppression of E action on developing peak bone mass has to be closely evaluated. In this study, we explored the effects of suppression of E synthesis on bone metabolism in pubertal boys. A total of 23 boys with constitutional delay of puberty were randomized to receive T and placebo or T and a specific and potent P450 aromatase inhibitor, letrozole. We determined BMD in the lumbar spine and the femoral neck. Bone resorption was studied by measuring the serum concentration of cross-linked carboxyterminal telopeptide of type I collagen by two different methods (CTx and ICTP), and bone formation by determining the serum concentrations of carboxyterminal propeptide of type I procollagen (PICP), osteocalcin, and alkaline phosphatase. We demonstrated previously that, during treatment with T and placebo, the concentrations of androgens and E increased. During treatment with T and letrozole, the E concentrations remained at the pretreatment level, but the androgen concentrations increased; the increase in the T concentration was more than 5-fold higher than during treatment with T and placebo. We did not observe any significant differences in the changes in bone mineral content, BMD, or bone mineral apparent density, an estimate of true volumetric BMD, between the treated groups. Lumbar spine bone mineral apparent density increased in both treated groups; but in the T- plus letrozole

  17. 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

  18. 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...

  19. 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 ...

  20. Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

    PubMed

    Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

    2015-05-01

    Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

  1. Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

    PubMed Central

    Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

    2015-01-01

    Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

  2. 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

  3. Chinese Bone Turnover Marker Study: Reference Ranges for C-Terminal Telopeptide of Type I Collagen and Procollagen I N-Terminal Peptide by Age and Gender

    PubMed Central

    Li, Mei; Li, Yan; Deng, Weimin; Zhang, Zhenlin; Deng, Zhongliang; Hu, Yingying; Xia, Weibo; Xu, Ling

    2014-01-01

    Background Bone formation marker procollagen I N-terminal peptide (PINP) and resorption marker C-terminal telopeptide of type I collagen (β-CTX) are useful biomarkers for differential diagnosis and therapeutic evaluation of osteoporosis, but reference values are required. Methods The multi-center, cross-sectional Chinese Bone Turnover Marker Study included 3800 healthy volunteers in 5 Chinese cities. Serum PINP, β-CTX, parathyroid hormone (PTH) and 25OHD levels were measured by chemiluminescence assay. Lumbar spine and proximal femur BMD were measured by dual-energy X-ray absorptiometry. Serum PINP and β-CTX levels were assessed by age, gender, weight, recruitment latitude, levels of PTH and 25OHD. Results Subjects (n = 1436, M∶F, 500∶936; mean age 50.6±19.6 years) exhibited non-normally distributed PINP and β-CTX peaking between 15–19 years, gradually declining throughout adulthood, elevating within 10 years of postmenopause, and then declining by age 70. In women between the age of 30 and menopause, median PINP and β-CTX levels were 40.42 (95% CI: 17.10–102.15) and 0.26 (95% CI: 0.08–0.72) ng/mL, respectively. β-CTX and PINP were positively linearly correlated (r = 0.599, P<0.001). β-CTX correlated positively (r = 0.054 and 0.093) and PINP correlated negatively (r = −0.012 and −0.053) with 25OHD and PTH (P<0.05). Conclusions We established Chinese reference ranges for PINP and CTX. Chinese individuals exhibited high serum PINP and β-CTX levels between 15 and 19 years of age and at menopause, which gradually declined after 70 years of age. PMID:25117452

  4. Geminivirus Activates ASYMMETRIC LEAVES 2 to Accelerate Cytoplasmic DCP2-Mediated mRNA Turnover and Weakens RNA Silencing in Arabidopsis

    PubMed Central

    Ye, Jian; Yang, Junyi; Sun, Yanwei; Zhao, Pingzhi; Gao, Shiqiang; Jung, Choonkyun; Qu, Jing; Fang, Rongxiang; Chua, Nam-Hai

    2015-01-01

    Aberrant viral RNAs produced in infected plant cells serve as templates for the synthesis of dsRNAs. The derived virus-related small interfering RNAs (siRNA) mediate cleavage of viral RNAs by post-transcriptional gene silencing (PTGS), thus blocking virus multiplication. Here, we identified ASYMMETRIC LEAVES2 (AS2) as a new component of plant P body complex which mediates mRNA decapping and degradation. We found that AS2 promotes DCP2 decapping activity, accelerates mRNA turnover rate, inhibits siRNA accumulation and functions as an endogenous suppressor of PTGS. Consistent with these findings, as2 mutant plants are resistant to virus infection whereas AS2 over-expression plants are hypersensitive. The geminivirus nuclear shuttle protein BV1 protein, which shuttles between nuclei and cytoplasm, induces AS2 expression, causes nuclear exit of AS2 to activate DCP2 decapping activity and renders infected plants more sensitive to viruses. These principles of gene induction and shuttling of induced proteins to promote mRNA decapping in the cytosol may be used by viral pathogens to weaken antiviral defenses in host plants. PMID:26431425

  5. Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2.

    PubMed

    Lang, Elisabeth; Bissinger, Rosi; Fajol, Abul; Salker, Madhuri S; Singh, Yogesh; Zelenak, Christine; Ghashghaeinia, Mehrdad; Gu, Shuchen; Jilani, Kashif; Lupescu, Adrian; Reyskens, Kathleen M S E; Ackermann, Teresa F; Föller, Michael; Schleicher, Erwin; Sheffield, William P; Arthur, J Simon C; Lang, Florian; Qadri, Syed M

    2015-01-01

    The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk(-/-)) and corresponding wild-type mice (msk(+/+)). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk(-/-) and msk(+/+) mice, but reticulocyte count was significantly increased in msk(-/-) mice. Cell membrane PS exposure was similar in untreated msk(-/-) and msk(+/+) erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk(-/-) erythrocytes than in msk(+/+) erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk(-/-) erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk(-/-) mice. The spleens from msk(-/-) mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk(+/+) mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice. PMID:26611568

  6. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups.

    PubMed Central

    Burch, Jane; Rice, Stephen; Yang, Huiqin; Neilson, Aileen; Stirk, Lisa; Francis, Roger; Holloway, Paul; Selby, Peter; Craig, Dawn

    2014-01-01

    BACKGROUND There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. OBJECTIVES We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. DATA SOURCES We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. REVIEW METHODS A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax, MSD), risedronate (Actonel, Warner Chilcott Company), zolendronate (Zometa, Novartis)], raloxifene (Evista, Eli Lilly and Company Ltd), strontium ranelate (Protelos, Servier Laboratories Ltd), denosumab (Prolia, Amgen Ltd) or teriparatide (Forsteo, Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs

  7. Accelerated bone mineral loss following a hip fracture: a prospective longitudinal study.

    PubMed

    Dirschl, D R; Henderson, R C; Oakley, W C

    1997-07-01

    The purpose of this prospective study was to monitor the bone mineral density (BMD) of the lumbar spine and contralateral femoral neck in the first year following an osteoporosis-related fracture of the hip. Eighty-three elderly patients (mean age 77 years) who had sustained a hip fracture had determinations of BMD made at the time of fracture; 49 of these patients were available for reassessment of BMD 1 year later. The change in BMD was correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, mental status, and routine serologies. The mean decrease in BMD in the year following fracture was 5.4% from the contralateral femoral neck and 2.4% from the lumbar spine. Calcium intake correlated with the loss of BMD from the femoral neck (p = 0.015), but not the lumbar spine. Patients with daily calcium intakes of less than 500 mg/day had a more than 10% decrease in femoral neck BMD in the year following their hip fracture. Serum 1,25-dihydroxy vitamin D level correlated with loss of MBD from the lumbar spine (p = 0.001), but not from the femoral neck. There was no correlation between the loss of bone mineral from either measurement site and age, sex, level of ambulation, or mental status. The loss of BMD from the femoral neck in the year following a hip fracture is more than five times that reported in the nonfractured population. This accelerated rate of loss can have drastic consequences in an elderly population already exhibiting osteopenia and propensity to fall. Investigation of pharmacologic or other interventions in the first critical year following a hip fracture may potentially blunt this accelerated rate of bone loss and lessen the risk of subsequent fractures. PMID:9213011

  8. 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 ...

  9. Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover.

    PubMed

    Scillitani, A; Dicembrino, F; Chiodini, I; Minisola, S; Fusilli, S; Di Giorgio, A; Garrubba, M; D'Aloiso, L; Frusciante, V; Torlontano, M; Modoni, S; Trischitta, V; Trischitta, V; Carnevale, V

    2002-10-01

    menopause as predictor variables and GSU or OC or U-DPD as dependent variables. The significant partial regression coefficients ( r) were: in TT, free triiodothyronine (fT3) with GSU ( r = 0.37; p<0.005), Ln OC ( r = 0.30; p = NS), Ln U-DPD ( r = 0.76; p<0.0001), respectively; in PHPT, PTH with GSU ( r = 0.74; p<0.001), Ln OC ( r = 0.50; p<0.05), Ln U-DPD ( r = 0.64; p<0.001); in CS Ln urinary free cortisol with OC ( r = -0.68; p<0.001) and U-DPD ( r = 0.66; p<0.05). Our data suggest that GSU could represent a valuable clinical tool for evaluating bone turnover rate in PHPT, CS, TT but not in AC. The behavior of GSU and OC and U-DPD is non-uniform in disorders characterized by a marked uncoupling between bone formation and resorption. PMID:12378373

  10. DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism

    PubMed Central

    Chen, Qian; Liu, Kai; Robinson, Andria R.; Clauson, Cheryl L.; Blair, Harry C.; Robbins, Paul D.; Niedernhofer, Laura J.; Ouyang, Hongjiao

    2013-01-01

    Advanced age is one of the most important risk factors for osteoporosis. Accumulation of oxidative DNA damage has been proposed to contribute to age-related deregulation of osteoblastic and osteoclastic cells. ERCC1 (Excision Repair Cross Complementary group 1)-XPF (Xeroderma Pigmentosum Group F) is an evolutionarily conserved structure-specific endonuclease that is required for multiple DNA repair pathways. Inherited mutations affecting expression of ERCC1-XPF cause a severe progeroid syndrome in humans, including early onset of osteopenia and osteoporosis, or anomalies in skeletal development. Herein, we used progeroid ERCC1-XPF deficient mice, including Ercc1-null (Ercc1−/−) and hypomorphic (Ercc1−/Δ) mice, to investigate the mechanism by which DNA damage leads to accelerated bone aging. Compared to their wild-type littermates, both Ercc1−/− and Ercc1−/Δ mice display severe, progressive osteoporosis caused by reduced bone formation and enhanced osteoclastogenesis. ERCC1 deficiency leads to atrophy of osteoblastic progenitors in the bone marrow stromal cell (BMSC) population. There is increased cellular senescence of BMSCs and osteoblastic cells, as characterized by reduced proliferation, accumulation of DNA damage and a senescence-associated secretory phenotype (SASP). This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as IL-6, TNFα, and RANKL and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis. Furthermore, we found that the transcription factor NF-κB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice. Importantly, we demonstrated that haploinsufficiency of the p65 NF-κB subunit partially rescued the osteoporosis phenotype of Ercc1−/Δ mice. Finally, pharmacological inhibition of the NF-κB signaling via an IKK inhibitor reversed cellular senescence and SASP in Ercc1−/Δ BMSCs. These results demonstrate that DNA damage drives

  11. Role of Polymer Architecture on the Activity of Polymer-Protein Conjugates for the Treatment of Accelerated Bone Loss Disorders.

    PubMed

    Tucker, Bryan S; Stewart, Jon D; Aguirre, J Ignacio; Holliday, L Shannon; Figg, C Adrian; Messer, Jonathan G; Sumerlin, Brent S

    2015-08-10

    Polymers of similar molecular weights and chemical constitution but varying in their macromolecular architectures were conjugated to osteoprotegerin (OPG) to determine the effect of polymer topology on protein activity in vitro and in vivo. OPG is a protein that inhibits bone resorption by preventing the formation of mature osteoclasts from the osteoclast precursor cell. Accelerated bone loss disorders, such as osteoporosis, rheumatoid arthritis, and metastatic bone disease, occur as a result of increased osteoclastogenesis, leading to the severe weakening of the bone. OPG has shown promise as a treatment in bone disorders; however, it is rapidly cleared from circulation through rapid liver uptake, and frequent, high doses of the protein are necessary to achieve a therapeutic benefit. We aimed to improve the effectiveness of OPG by creating OPG-polymer bioconjugates, employing reversible addition-fragmentation chain transfer polymerization to create well-defined polymers with branching densities varying from linear, loosely branched to densely branched. Polymers with each of these architectures were conjugated to OPG using a "grafting-to" approach, and the bioconjugates were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The OPG-polymer bioconjugates showed retention of activity in vitro against osteoclasts, and each bioconjugate was shown to be nontoxic. Preliminary in vivo studies further supported the nontoxic characteristics of the bioconjugates, and measurement of the bone mineral density in rats 7 days post-treatment via peripheral quantitative computed tomography suggested a slight increase in bone mineral density after administration of the loosely branched OPG-polymer bioconjugate. PMID:26151628

  12. Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.

    PubMed

    Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

    2014-10-01

    Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05μg/kg) or ALF (0.2 or 0.4μg/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05μg/kg group were comparable to those of the ALF 0.2μg/kg group. ELD 0.05μg/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (p<0.001) and the ALF 0.2μg/kg group (p<0.05) evaluated by 3-point bending test. The cortical area of the mid-femur in the ELD 0.05μg/kg group but not the ALF 0.2μg/kg group was significantly higher than those of the vehicle control group (p<0.001). Bone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05μg/kg) was greater than that by ALF (0.2μg/kg). In contrast, in the femoral periosteal surface, ELD 0.05μg/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (p<0.05, p<0.01, respectively), whereas ALF 0.2μg/kg did not alter these parameters. These results indicate that ELD improved the biomechanical properties of femoral cortical bone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24189542

  13. 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

  14. Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

    PubMed

    Keeney, Michael; Chung, Michael T; Zielins, Elizabeth R; Paik, Kevin J; McArdle, Adrian; Morrison, Shane D; Ransom, Ryan C; Barbhaiya, Namrata; Atashroo, David; Jacobson, Gunilla; Zare, Richard N; Longaker, Michael T; Wan, Derrick C; Yang, Fan

    2016-08-01

    Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016. PMID:27059085

  15. A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization.

    PubMed

    Kawakami, Yohei; Ii, Masaaki; Matsumoto, Tomoyuki; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Akimaru, Hiroshi; Mifune, Yutaka; Shoji, Taro; Fukui, Tomoaki; Asahi, Michio; Kurosaka, Masahiro; Asahara, Takayuki

    2013-09-01

    Lnk, an intracellular adapter protein, is expressed in hematopoietic cell lineages, which has recently been proved as an essential inhibitory signaling molecule for stem cell self-renewal in the stem cell factor-c-Kit signaling pathway with enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. Moreover, the therapeutic potential of hematopoietic stem/endothelial progenitor cells (EPCs) for fracture healing has been demonstrated with mechanistic insight into vasculogenesis/angiogenesis and osteogenesis enhancement in the fracture sites. We report here, Lnk siRNA-transfected endothelial commitment of c-kit+/Sca-1+/lineage- subpopulations of bone marrow cells have high EPC colony-forming capacity exhibiting endothelial markers, VE-Cad, VEGF and Ang-1. Lnk siRNA-transfected osteoblasts also show highly osteoblastic capacity. In vivo, locally transfected Lnk siRNA could successfully downregulate the expression of Lnk at the fracture site up to 1 week, and radiological and histological examination showed extremely accelerated fracture healing in Lnk siRNA-transfected mice. Moreover, Lnk siRNA-transfected mice exhibited sufficient therapeutic outcomes with intrinstic enhancement of angiogenesis and osteogenesis, specifically, the mice demonstrated better blood flow recovery in the sites of fracture. In our series of experiments, we clarified that a negatively regulated Lnk system contributed to a favorable circumstance for fracture healing by enhancing vasculogenesis/angiogenesis and osteogenesis. These findings suggest that downregulation of Lnk system may have the clinical potential for faster fracture healing, which contributes to the reduction of delayed unions or non-unions. PMID:23897412

  16. Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone.

    PubMed

    Cole, J M; Wood, J C; Lopes, N C; Poder, K; Abel, R L; Alatabi, S; Bryant, J S J; Jin, A; Kneip, S; Mecseki, K; Symes, D R; Mangles, S P D; Najmudin, Z

    2015-01-01

    A bright μm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 μm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications. PMID:26283308

  17. Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone

    NASA Astrophysics Data System (ADS)

    Cole, J. M.; Wood, J. C.; Lopes, N. C.; Poder, K.; Abel, R. L.; Alatabi, S.; Bryant, J. S. J.; Jin, A.; Kneip, S.; Mecseki, K.; Symes, D. R.; Mangles, S. P. D.; Najmudin, Z.

    2015-08-01

    A bright μm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 μm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications.

  18. Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

    PubMed Central

    Gupta, Himadri S.; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi

    2012-01-01

    The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth. PMID:23091616

  19. Alternate light sources in the detection of bone after an accelerated fire: a pilot study.

    PubMed

    Gallant, Amber S

    2013-01-01

    This study examines the ability of alternate light sources to detect bone that has been exposed to fire when identification of bone remains is difficult to ascertain. It is intended as a tool for fire investigators to quickly determine whether an area should be considered a forensic scene. After being subjected to a test burn, pig bones were viewed and photographed with the use of a laser, and later compared with a UV light source. A secondary study observing stages of a human cremation was conducted to assess how various levels of burnt flesh affect the ability of bone to fluoresce utilizing a laser. Both studies demonstrated success in detecting bone while fluorescing with a molten lava type of appearance that has the potential to distinguish bone from its surrounding environment. Limitations and recommendations are discussed by the author including the need for future studies to expand on this research. PMID:22994928

  20. Acid-sensing ion channel 3 or P2X2/3 is involved in the pain-like behavior under a high bone turnover state in ovariectomized mice.

    PubMed

    Kanaya, Kumiko; Iba, Kousuke; Abe, Yasuhisa; Dohke, Takayuki; Okazaki, Shunichiro; Matsumura, Tadaki; Yamashita, Toshihiko

    2016-04-01

    We have recently demonstrated that pathological changes leading to increased bone resorption by osteoclast activation are related to the induction of pain-like behavior in ovariectomized (OVX) mice. In addition, bisphosphonate and the antagonist of transient receptor potential vanilloid type 1 (TRPV1), an acid-sensing nociceptor, improved the threshold value of pain-like behaviors accompanying an improvement in the acidic environment in the bone tissue based on osteoclast inactivation. The aim of this study was to evaluate the effect of (i) an inhibitor of vacuolar H(+) -ATPase, known as an proton pump, (ii) an antagonist of acid-sensing ion channel (ASIC) 3, as another acid-sensing nociceptor, and (iii) the P2X2/3 receptor, as an ATP-ligand nociceptor, on pain-like behavior in OVX mice. This inhibitor and antagonists were found to improve the threshold value of pain-like behavior in OVX mice. These results indicated that the skeletal pain accompanying osteoporosis is possibly associated with the acidic microenvironment and increased ATP level caused by osteoclast activation under a high bone turnover state. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:566-573, 2016. PMID:26340235

  1. [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. PMID:26728527

  2. A modified PMMA cement (Sub-cement) for accelerated fatigue testing of cemented implant constructs using cadaveric bone.

    PubMed

    Race, Amos; Miller, Mark A; Mann, Kenneth A

    2008-10-20

    Pre-clinical screening of cemented implant systems could be improved by modeling the longer-term response of the implant/cement/bone construct to cyclic loading. We formulated bone cement with degraded fatigue fracture properties (Sub-cement) such that long-term fatigue could be simulated in short-term cadaver tests. Sub-cement was made by adding a chain-transfer agent to standard polymethylmethacrylate (PMMA) cement. This reduced the molecular weight of the inter-bead matrix without changing reaction-rate or handling characteristics. Static mechanical properties were approximately equivalent to normal cement. Over a physiologically reasonable range of stress-intensity factor, fatigue crack propagation rates for Sub-cement were higher by a factor of 25+/-19. When tested in a simplified 2 1/2-D physical model of a stem-cement-bone system, crack growth from the stem was accelerated by a factor of 100. Sub-cement accelerated both crack initiation and growth rate. Sub-cement is now being evaluated in full stem/cement/femur models. PMID:18774136

  3. Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.

    PubMed

    Sugamori, Yasutaka; Mise-Omata, Setsuko; Maeda, Chizuko; Aoki, Shigeki; Tabata, Yasuhiko; Murali, Ramachandran; Yasuda, Hisataka; Udagawa, Nobuyuki; Suzuki, Hiroshi; Honma, Masashi; Aoki, Kazuhiro

    2016-08-01

    Both W9 and OP3-4 were known to bind the receptor activator of NF-κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide-induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3-4 accelerated BMP-2-induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL-binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP-2-induced bone regeneration by the RANKL-binding peptides. PMID:27345003

  4. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

    PubMed

    Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

    2015-05-01

    During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

  5. Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean

    2008-01-01

    The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

  6. Use of calcium, folate, and vitamin D₃-fortified milk for 6 months improves nutritional status but not bone mass or turnover, in a group of Australian aged care residents.

    PubMed

    Grieger, Jessica A; Nowson, Caryl A

    2009-07-01

    In residential care, inadequate calcium and folate intakes and low serum vitamin D (25(OH)D) concentrations are common. We assessed whether daily provision of calcium, folate, and vitamin D₃-fortified milk for 6 months improved nutritional status (serum micronutrients), bone quality (heel ultrasound), bone turnover markers (parathyroid hormone, C-terminal collagen I telopeptide, terminal propeptide of type I procollagen), and/or muscle strength and mobility in a group of Australian aged care residents. One hundred and seven residents completed the study (mean (SD) age: 79.9 (10.1) years; body weight: 68.4 (15.4) kg). The median (inter-quartile range) volume of fortified milk consumed was 160 (149) ml/day. At the end of the study, the median daily vitamin D intake increased to 10.4 (8.7) μg (P < .001), which is 70% of the adequate intake (15 μg); and calcium density (mg/MJ) was higher over the study period compared with baseline (161 ± 5 mg/MJ vs. 142 ± 4 mg/MJ, P < .001). Serum 25(OH)D concentrations increased by 23 ± 2 nmol/L (83 (107)%, P < .001), yet remained in the insufficient range (mean 45 ± 2 nmol/L). Consumption of greater than the median intake of milk (160 ml/day) (n = 54, 50%) increased serum 25(OH)D levels into the adequate range (53 ± 2 nmol/L) and reduced serum parathyroid hormone by 24% (P = .045). There was no effect on bone quality, bone turnover markers, muscle strength, or mobility. Consumption of fortified milk increased dietary vitamin D intake and raised serum 25(OH)D concentrations, but not to the level thought to reduce fracture risk. If calcium-fortified milk also was used in cooking and milk drinks, this approach could allow residents to achieve a dietary calcium intake close to recommended levels. A vitamin D supplement would be recommended to ensure adequate vitamin D status for all residents. PMID:21184368

  7. High-intensity Nd:YAG laser accelerates bone regeneration in calvarial defect models.

    PubMed

    Kim, Kwansik; Kim, In Sook; Cho, Tae Hyung; Seo, Young-Kwon; Hwang, Soon Jung

    2015-08-01

    High-power pulsed lasers have been recently regarded to be anabolic to bone, but in vivo evidence is still lacking. This study aimed to investigate the capacity of bone repair using a high-power, Q-switched, pulsed, neodymium-doped yttrium aluminium garnet (Nd:YAG) laser, using bilateral calvarial defect models having non-critical sized, 5 mm (rat) or 8 mm (rabbit) diameter. One of the bilateral defects, which were all filled with collagen sponge or left empty, was irradiated with a Nd:YAG laser once every 2 days for 2 weeks at a constant total fluence rate (344 J/cm(2) ), output power (0.75 W), pulse repetition rate (15 pps) and wavelength (1064 nm) and examined for the laser effect. The same experimental scheme was designed using a rabbit calvarial defect model implanted with sponge, which was explored for the dose effect of output power at 0.75 and 3 W with the same quantities of the other parameters. New bone formation was evaluated by micro-computed tomography-based analysis and histological observation at 4 weeks after surgery. Laser irradiation significantly increased new bone formation by approximately 45%, not only in the sponge-filled defects of rats but also when the defects were left empty, compared to the non-irradiated group. Consistently, both doses of output power (0.75 and 3 W) enhanced new bone formation, but there was no significant difference between the two doses. This study is one of the first to demonstrate the beneficial effect of Nd:YAG lasers on the regeneration of bone defects which were left empty or filled with collagen sponge, suggesting its great potential in postoperative treatment targeting local bone healing. PMID:24254743

  8. Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study

    PubMed Central

    Kulachote, Noratep; Sirisreetreerux, Norachart; Chanplakorn, Pongsthorn; Fuangfa, Praman; Suphachatwong, Chanyut; Wajanavisit, Wiwat

    2016-01-01

    Background. Delayed union and nonunion are common complications in atypical femoral fractures (AFFs) despite having good fracture fixation. Demineralized bone matrix (DBM) is a successfully proven method for enhancing fracture healing of the long bone fracture and nonunion and should be used in AFFs. This study aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs) fixation with and without DBM. Materials and Methods. A prospective study was conducted on 9 ST-AFFs patients using DBM (DBM group) during 2013-2014 and compared with a retrospective consecutive case series of ST-AFFs patients treated without DBM (2010–2012) (NDBM group, 9 patients). All patients were treated with the same standard guideline and followed up until fractures completely united. Postoperative outcomes were then compared. Results. DBM group showed a significant shorter healing time than NDBM group (28.1 ± 14.4 versus 57.9 ± 36.8 weeks, p = 0.04). Delayed union was found in 4 patients (44%) in DBM group compared with 7 patients (78%) in NDBM group (p > 0.05). No statistical difference of nonunion was demonstrated between both groups (DBM = 1 and NDBM = 2, p > 0.05). Neither postoperative infection nor severe local tissue reaction was found. Conclusions. DBM is safe and effective for accelerating the fracture healing in ST-AFFx and possibly reduces nonunion after fracture fixation. Trial registration number is TCTR20151021001. PMID:27022610

  9. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket

    PubMed Central

    Nishida, Erika; Miyaji, Hirofumi; Kato, Akihito; Takita, Hiroko; Iwanaga, Toshihiko; Momose, Takehito; Ogawa, Kosuke; Murakami, Shusuke; Sugaya, Tsutomu; Kawanami, Masamitsu

    2016-01-01

    Graphene oxide (GO) consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1 µg/mL GO scaffold were, respectively, approximately 2.5-fold and 1.4-fold greater than those of the control. Particularly, the infiltration of ED2-positive (M2) macrophages and blood vessels were prominent in the GO scaffold. Dog bone-formation tests showed that 1 µg/mL GO scaffold implantation enhanced bone formation. New bone formation following GO scaffold implantation was enhanced fivefold compared to that in control subjects. These results suggest that GO was biocompatible and had high bone-formation capability for the scaffold

  10. Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

    PubMed

    Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

    2015-10-01

    G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. PMID:25917236

  11. Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.

    PubMed

    DeMambro, Victoria E; Le, Phuong T; Guntur, Anyonya R; Maridas, David E; Canalis, Ernesto; Nagano, Kenichi; Baron, Roland; Clemmons, David R; Rosen, Clifford J

    2015-11-01

    Previously, we reported sexually dimorphic bone mass and body composition phenotypes in Igfbp2(-/-) mice (-/-), where male mice exhibited decreased bone and increased fat mass, whereas female mice displayed increased bone but no changes in fat mass. To investigate the interaction between IGF-binding protein (IGFBP)-2 and estrogen, we subjected Igfbp2 -/- and +/+ female mice to ovariectomy (OVX) or sham surgery at 8 weeks of age. At 20 weeks of age, mice underwent metabolic cage analysis and insulin tolerance tests before killing. At harvest, femurs were collected for microcomputed tomography, serum for protein levels, brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT) adipose depots for histology, gene expression, and mitochondrial respiration analysis of whole tissue. In +/+ mice, serum IGFBP-2 dropped 30% with OVX. In the absence of IGFBP-2, OVX had no effect on preformed BAT; however, there was significant "browning" of the IWAT depot coinciding with less weight gain, increased insulin sensitivity, lower intraabdominal fat, and increased bone loss due to higher resorption and lower formation. Likewise, after OVX, energy expenditure, physical activity and BAT mitochondrial respiration were decreased less in the OVX-/- compared with OVX+/+. Mitochondrial respiration of IWAT was reduced in OVX+/+ yet remained unchanged in OVX-/- mice. These changes were associated with significant increases in Fgf21 and Foxc2 expression, 2 proteins known for their insulin sensitizing and browning of WAT effects. We conclude that estrogen deficiency has a profound effect on body and bone composition in the absence of IGFBP-2 and may be related to changes in fibroblast growth factor 21. PMID:26230658

  12. The effect of accelerated, brace free, rehabilitation on bone tunnel enlargement after ACL reconstruction using hamstring tendons: a CT study.

    PubMed

    Vadalà, Antonio; Iorio, Raffaele; De Carli, Angelo; Argento, Giuseppe; Di Sanzo, Vincenzo; Conteduca, Fabio; Ferretti, Andrea

    2007-04-01

    The mechanism of bone tunnel enlargement following anterior cruciate ligament (ACL) reconstruction is not yet clearly understood. Many authors hypothesized that aggressive rehabilitation protocols may be a potential factor for bone tunnel enlargement, especially in reconstructions performed with hamstrings autograft. The purpose of this study was to evaluate the effect of a brace free rehabilitation on the tunnel enlargement after ACL reconstruction using doubled semitendinosus and gracilis tendons (DGST): our hypothesis was that early post-operative knee motion increase the diameters of the tibial and femoral bone tunnels. Forty-five consecutive patients undergoing ACL reconstruction for chronic ACL deficiency were selected. All patients were operated by the same surgeon using autologous DGST and the same fixation devices. Patients with associated ligaments injuries and or severe chondral damage were excluded. The patients were randomly assigned to enter the control group (group A, standard post-operative rehabilitation) and the study group (group B, brace free accelerated rehabilitation). A CT scan was used to exactly determine the diameters of both femoral and tibial tunnels at various levels of lateral femoral condyle and proximal tibia, using a previously described method [17]. Measurements were done by an independent radiologist in a blinded fashion the day after the operation and at a mean follow-up of 10 months (range 9-11). Statistical analysis was performed using paired t-test. The mean femoral tunnel diameter increased significantly from 9.04 +/- 0.05 (post-operative) to 9.30 +/- 0.8 mm (follow-up) in group A and from 9.04 +/- 0.03 to 9.94 +/- 1.12 mm in group B. The mean tibial tunnel diameter increased significantly from 9.03 +/- 0.04 to 10.01 +/- 0.80 mm in group A and from 9.04 +/- 0.03 to 10.60 +/- 0.78 mm in group B. The increase in femoral and tunnel diameters observed in the study group was significantly higher than that observed in the control

  13. Loss of milk fat globule-epidermal growth factor 8 (MFG-E8) in mice leads to low bone mass and accelerates ovariectomy-associated bone loss by increasing osteoclastogenesis.

    PubMed

    Sinningen, Kathrin; Albus, Elise; Thiele, Sylvia; Grossklaus, Sylvia; Kurth, Thomas; Udey, Mark C; Chavakis, Triantafyllos; Hofbauer, Lorenz C; Rauner, Martina

    2015-07-01

    Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts inflammation-modulatory effects. Recently, it has been implicated in osteoclastogenesis and the pathogenesis of inflammatory periodontal bone loss, but its role in physiological bone homeostasis is still not well defined. Here, we evaluated the influence of MFG-E8 on osteoblasts and osteoclasts and its impact on bone remodeling in healthy and ovariectomized mice as a model for post-menopausal osteoporosis. Total and trabecular bone mineral densities at the lumbar spine in 6-week-old MFG-E8 KO mice were reduced by 11% (p < 0.05) and 17% (p < 0.01), respectively, as compared to wild-type (WT) mice. Accordingly, serum levels of the bone formation marker P1NP were decreased by 37% (p < 0.01) in MFG-E8 KO mice as were the ex vivo mineralization capacity and expression of osteoblast genes (Runx2, alkaline phosphatase, osteocalcin) in MFG-E8 KO osteoblasts. In contrast, serum bone resorption markers CTX1 and TRAP5b were increased by 30% and 60% (p < 0.05), respectively, in MFG-E8 KO mice. Furthermore, bone marrow macrophages from MFG-E8-KO mice differentiated more effectively into osteoclasts, as compared to WT cells. MFG-E8-deficient osteoclasts displayed increased bone resorption ex vivo, which could be reversed by the presence of recombinant MFG-E8. To determine the significance of the enhanced osteoclastogenesis in MFG-E8 KO mice, we performed an ovariectomy, which is associated with bone loss due to increased osteoclast activity. Indeed, MFG-E8 KO mice lost 12% more trabecular bone density than WT mice after ovariectomy. Together, these data indicate that MFG-E8 controls steady-state and pathological bone turnover and may therefore represent a new target gene in the treatment of bone diseases. PMID:25868798

  14. Acceleration and holographic studies on different types of dynamization of external fixators of the bones

    NASA Astrophysics Data System (ADS)

    Podbielska, Halina; Kasprzak, Henryk T.; Voloshin, Arkady S.; Pennig, Dietmar; von Bally, Gert

    1992-08-01

    The unilateral axially dynamic fixator (Orthofix) was mounted on a sheep tibial shaft. Three fixation modes: static, dynamic controlled, and dynamic free were examined by means of double exposure holographic interferometry. Simultaneously, the acceleration was measured by an accelerometer and displayed on the monitor together with loading characteristics. The first exposure was made before the acting force was applied to the tibia plateau. The second one after the moment when the acceleration wave started to propagate through the specimen. We stated that in the case of dynamization less torsion occurs at the fracture site. So far, we have not been able to determine any correlation between results of holographic and accelerometric measurements.

  15. Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

    SciTech Connect

    Arioka, Masaki; Takahashi-Yanaga, Fumi; Sasaki, Masanori; Yoshihara, Tatsuya; Morimoto, Sachio; Takashima, Akihiko; Mori, Yoshihide; Sasaguri, Toshiyuki

    2013-11-01

    Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β{sup +/−} mice. •The cortical and trabecular bone volumes were increased in GSK-3β{sup +/−} mice. •Regeneration of a partial bone defect was accelerated in GSK-3β{sup +/−} mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β{sup +/−}). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β{sup +/−} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β{sup +/−} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β{sup +/−} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β{sup +/−} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.

  16. [Bone histomorphometry;A role of evaluation for bone quality and mechanical strength].

    PubMed

    Yamamoto, Noriaki; Takahashi, Hideaki; Shimakura, Taketoshi

    2016-01-01

    Bone histomorphometry is defined as a quantitative evaluation of bone remodeling and bone turnover. Bone remodeling is the important mechanism for calcium metabolism and mechanical usage. The changes of bone remodeling in special condition with metabolic bone disease or osteoporosis agents have the effectiveness on bone mechanical strength. PMID:26728526

  17. Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.

    PubMed

    Min, Jouha; Choi, Ki Young; Dreaden, Erik C; Padera, Robert F; Braatz, Richard D; Spector, Myron; Hammond, Paula T

    2016-04-26

    Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic. PMID:26923427

  18. Characterization of multiple SPS knockout mutants reveals redundant functions of the four Arabidopsis sucrose phosphate synthase isoforms in plant viability, and strongly indicates that enhanced respiration and accelerated starch turnover can alleviate the blockage of sucrose biosynthesis.

    PubMed

    Bahaji, Abdellatif; Baroja-Fernández, Edurne; Ricarte-Bermejo, Adriana; Sánchez-López, Ángela María; Muñoz, Francisco José; Romero, Jose M; Ruiz, María Teresa; Baslam, Marouane; Almagro, Goizeder; Sesma, María Teresa; Pozueta-Romero, Javier

    2015-09-01

    We characterized multiple knock-out mutants of the four Arabidopsis sucrose phosphate synthase (SPSA1, SPSA2, SPSB and SPSC) isoforms. Despite their reduced SPS activity, spsa1/spsa2, spsa1/spsb, spsa2/spsb, spsa2/spsc, spsb/spsc, spsa1/spsa2/spsb and spsa2/spsb/spsc mutants displayed wild type (WT) vegetative and reproductive morphology, and showed WT photosynthetic capacity and respiration. In contrast, growth of rosettes, flowers and siliques of the spsa1/spsc and spsa1/spsa2/spsc mutants was reduced compared with WT plants. Furthermore, these plants displayed a high dark respiration phenotype. spsa1/spsb/spsc and spsa1/spsa2/spsb/spsc seeds poorly germinated and produced aberrant and sterile plants. Leaves of all viable sps mutants, except spsa1/spsc and spsa1/spsa2/spsc, accumulated WT levels of nonstructural carbohydrates. spsa1/spsc leaves possessed high levels of metabolic intermediates and activities of enzymes of the glycolytic and tricarboxylic acid cycle pathways, and accumulated high levels of metabolic intermediates of the nocturnal starch-to-sucrose conversion process, even under continuous light conditions. Results presented in this work show that SPS is essential for plant viability, reveal redundant functions of the four SPS isoforms in processes that are important for plant growth and nonstructural carbohydrate metabolism, and strongly indicate that accelerated starch turnover and enhanced respiration can alleviate the blockage of sucrose biosynthesis in spsa1/spsc leaves. PMID:26259182

  19. Overexpression of DMP1 Accelerates Mineralization and Alters Cortical Bone Biomechanical Properties in Vivo

    PubMed Central

    Bhatia, Ankush; Albazzaz, Michael; Espinoza Orías, Alejandro A.; Inoue, Nozomu; Miller, Lisa M.; Acerbo, Alvin; George, Anne; Sumner, Dale R.

    2011-01-01

    Dentin matrix protein-1 (DMP1) is a key regulator of biomineralization. Here, we examine changes in structural, geometric, and material properties of cortical bone in a transgenic mouse model overexpressing DMP1. Micro-computed tomography and three-point bending were performed on 90 femora of wild type and transgenic mice at 1, 2, 4, and 6 months. Fourier transform infrared imaging was performed at 2 months. We found that the transgenic femurs were longer (p<0.01), more robust in cross-section (p<0.05), stronger (p<0.05), but had less post-yield strain and displacement (p<0.01), and higher tissue mineral density (p<0.01) than the wild type femurs at 1 and 2 months. At 2 months, the transgenic femurs also had a higher mineral-to-matrix ratio (p<0.05) and lower carbonate substitution (p<0.05) compared to wild type femurs. These findings indicate that increased mineralization caused by overexpressing DMP1 led to increased structural cortical bone properties associated with decreased ductility during the early post-natal period. PMID:22100074

  20. 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

  1. [Effects of antiresorptive therapy on the structural and material properties of bone strength].

    PubMed

    Kishimoto, Hideaki

    2016-01-01

    Bone strength depends on its structural and material properties. Structural properties are determined by the size and shape of bone and also the microarchitecture. Material properties are determined by mineral crystallinity, collagen structure and microdamage in bone. The strength of bone is adapted to the needs of physical activities by biologic mechanisms, bone modeling and remodeling. The deterioration of bone strength in postmenopausal women is characterized by a trabecular bone deficit with poor trabecular connectivity and followed by a cortical bone deficit with trabeculation of endocortical bone and intracortical porosity due to accelerated bone remodeling. In high turnover osteoporosis antiresorptive therapy is effective in preventing the structural deficit and in increasing the stiffness and the toughness(bone strength)by increasing the mean degree of mineralization of bone tissue through the prolongation of secondary mineralization. But the long-term use of strong antiresorber, i.e. bisphosphonate or denosumab, would result in highly mineralized bone and disturbed repair of microcracks by inhibition of bone remodeling. Intermittent use or discontinuation of strong antiresorber after about 3-5 years of administration could be recommended to avoid the deterioration of bone strength. PMID:26728537

  2. 5. Accelerated Fracture Healing Targeting Periosteal Cells: Possibility of Combined Therapy of Low-Intensity Pulsed Ultrasound (LIPUS), Bone Graft, and Growth Factor (bFGF).

    PubMed

    Uchida, Kentaro; Urabe, Ken; Naruse, Koji; Mikuni-Takagaki, Yuko; Inoue, Gen; Takaso, Masashi

    2016-08-01

    We have studied the mechanism of fracture healing, and the effect of LIPUS, bone graft and growth factor on accelerating fracture healing. We present here the results of our research. To examine callus formation cells in fracture healing, we made marrow GFP chimera mice and a fracture model of marrow mesenchymal stem cell GFP chimera mice. It was demonstrated that periosteal cells were essential for callus formation. We focused on periosteal cells and examined the effect of LIPUS. In an in vitro experiment using a cultured part of the femur, LIPUS promoted ossification of the periosteal tissue. Further, LIPUS accelerated VEGF expression in the experiment using the femoral fracture model of mice. From these results, it was suggested that activation of periosteal cells might play a role in the fracture healing mechanism of LIPUS. Next, we discussed the possibility of combined therapy of LIPUS, bone graft and growth factor. Therapy involving the topical administration of bFGF using a controlled release system and bone graft could promote callus formation. In addition, LIPUS was able to promote membranaceous ossification after the bone graft. It was suggested that combined therapy of LIPUS, bone graft and bFGF could be a new option for treating fractures. PMID:27441766

  3. Toxicokinetics of bone lead.

    PubMed Central

    Rabinowitz, M B

    1991-01-01

    This article discusses bone as a source of lead to the rest of the body and as a record of past lead exposure. Bone lead levels generally increase with age at rates dependent on the skeletal site and lead exposure. After occupational exposure, the slow decline in blood lead, a 5- to 19-year half-life, reflects the long skeletal half-life. Repeated measurements of bone lead demonstrate the slow elimination of lead from bone. Stable isotope ratios have revealed many details of skeletal uptake and subsequent release. The bulk turnover rates for compact bone are about 2% per year and 8% for spine. Turnover activity varies with age and health. Even though lead approximates calcium, radium, strontium, barium, fluorine, and other bone seekers, the rates for each are different. A simple, two-pool (bone and blood) kinetic model is presented with proposed numerical values for the changes in blood lead levels that occur with changes in turnover rates. Two approaches are offered to further quantify lead turnover. One involves a study of subjects with known past exposure. Changes in the ratio of blood lead to bone lead with time would reflect the course of bone lead availability. Also, stable isotopes and subjects who move from one geographical area to another offer opportunities. Sequential isotope measurements would indicate how much of the lead in blood is from current exposure or bone stores, distinct from changes in absorption or excretion. PMID:2040248

  4. Acceleration of segmental bone regeneration in a rabbit model by strontium-doped calcium polyphosphate scaffold through stimulating VEGF and bFGF secretion from osteoblasts.

    PubMed

    Gu, Zhipeng; Zhang, Xu; Li, Li; Wang, Qiguang; Yu, Xixun; Feng, Ting

    2013-01-01

    The development of suitable bioactive three-dimensional scaffold for the promotion of bone regeneration is critical in bone tissue engineering. The purpose of this study was to investigate in vivo osteogenesis of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds for bone repair, as well as the relationship between osteogenic properties of SCPP scaffolds and the secretion of bFGF and VEGF from osteoblasts stimulated by SCPP. Besides, the advantages of scaffolds seeded with mesenchymal stem cells (MSCs) for bone repair were also studied. Firstly, the bone repair evaluation of scaffolds was performed on a rabbit segmental bony defects model over a period of 16 weeks by histology combined with X-ray microradiography. And then, in order to avoid the influence from the other factors such as hypoxia which emerge in vivo study and affect the secretion of VEGF and bFGF from host cells, human osteoblast-like cells (MG63) were seeded to SCPP, CPP and HA scaffolds in vitro to determine the ability of these scaffolds to stimulate the secretion of angiogenic growth factors (VEGF and bFGF) from MG63 and further explore the reason for the better osteogenic properties of SCPP scaffolds. The histological and X-ray microradiographic results showed that the SCPP scaffolds presented better osteogenic potential than CPP and HA scaffolds, when combined with MSCs, the SCPP scaffolds could further accelerate the bone repair. And the amounts of VEGF measured by ELISA assay in SCPP, CPP and HA groups after cultured for 7 days were about 364.989 pg/mL, 244.035 pg/mL and 232.785 pg/mL, respectively. Accordingly, the amounts of bFGF were about 27.085 pg/mL, 15.727 pg/mL and 8.326 pg/mL. The results revealed that the SCPP scaffolds significantly enhanced the bFGF and VEGF secretion compared with other scaffolds. The results presented in vivo and in vitro study demonstrated that the SCPP could accelerate bone formation through stimulating the secretion of VEGF and bFGF from

  5. Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice.

    PubMed

    Hasegawa-Ishii, Sanae; Inaba, Muneo; Li, Ming; Shi, Ming; Umegaki, Hiroyuki; Ikehara, Susumu; Shimada, Atsuyoshi

    2016-04-01

    Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction. PMID:25577138

  6. Vascular Calcification and Renal Bone Disorders

    PubMed Central

    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

  7. 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

  8. Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway.

    PubMed

    Li, Na; Zhang, Min; Drummen, Gregor P C; Zhao, Yu; Tan, Yin Fen; Luo, Su; Qu, Xiao Bo

    2016-01-01

    Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone injury and/or in scaffolds for bone replacement strategies. Finally, isolation of SDA-Col I from deer antler represents a renewable, green, and uncomplicated way to obtain a biomedically valuable therapeutic. PMID:27066099

  9. Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway

    PubMed Central

    Li, Na; Zhang, Min; Drummen, Gregor P. C.; Zhao, Yu; Tan, Yin Fen; Luo, Su; Qu, Xiao Bo

    2016-01-01

    Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone injury and/or in scaffolds for bone replacement strategies. Finally, isolation of SDA-Col I from deer antler represents a renewable, green, and uncomplicated way to obtain a biomedically valuable therapeutic. PMID:27066099

  10. Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain

    PubMed Central

    KATSUYAMA, HIRONOBU; FUSHIMI, SHIGEKO; YAMANE, KUNIKAZU; WATANABE, YOKO; SHIMOYA, KOICHIRO; OKUYAMA, TOSHIKO; KATSUYAMA, MIDORI; SAIJOH, KIYOFUMI; TOMITA, MASAFUMI

    2015-01-01

    Vitamin K2 (VK2) has been used as a therapeutic agent for osteoporosis, since it has been suggested to be able to reduce the frequency of fractures by improving bone quality; however, bone turnover is strictly regulated by various cytokines and hormones. In the present study, the effect of menaquinone-4 (MK-4) on bone turnover was investigated using the senescence-accelerated mouse prone 6 (SAMP6) strain. Since water-immersion restraint stress (WRS) causes a significant decrease in bone mineral density (BMD), WRS was used as the bone resorption model in the SAMP6 strain. Six-week-old SAMP6 male mice were divided into the following three groups: Control, WRS and WRS + MK-4. WRS was performed for 6 h per day, 5 times a week, for 4 weeks. Following WRS, MK-4 (30 mg/kg) was injected subcutaneously 3 times a week for 4 weeks. No growth retardation was observed in the WRS groups as compared with the control group. In the WRS groups, the BMD was significantly lower than that in the control group. The levels of bone formation and resorption markers were increased in the WRS groups, indicating that WRS reduced the BMD by promoting high bone turnover. A bone histomorphometrical examination showed that the trabecular (Tb) bone mass in the secondary spongiosa at the distal femur was significantly reduced in the WRS mice, and this reduction was abrogated by MK-4 treatment. Specifically, the Tb bone reduction was caused by the activation of osteoclasts (Ocs), and Oc activity was suppressed by MK-4. The number of osteoblasts and the mineral apposition rate were significantly increased in the WRS and WRS + MK-4 mice, suggesting that WRS triggered a significantly higher mineral apposition rate. These results indicate that MK-4 can induce recovery from the bone mineral loss caused by WRS treatment. Further studies are required to clarify the association between bone quality and MK-4. PMID:26622403

  11. Acceleration of Bone Repair in NOD/SCID Mice by Human Monoosteophils, Novel LL-37-Activated Monocytes

    PubMed Central

    Zhang, Zhifang; Shively, John E.

    2013-01-01

    Background An incomplete understanding of bone forming cells during wound healing and ectopic calcification has led to a search for circulating cells that may fulfill this function. Previously, we showed that monoosteophils, a novel lineage of calcifying/bone-forming cells generated by treatment of monocytes with the natural peptide LL-37, are candidates. In this study, we have analyzed their gene expression profile and bone repair function. Methods and Findings Human monoosteophils can be distinguished from monocytes, macrophages and osteoclasts by their unique up-regulation of integrin α3 and down-regulation of CD14 and CD16. Monoosteophils express high mRNA and protein levels of SPP1 (osteopontin), GPNMB (osteoactivin), CHI3L1 (cartilage glycoprotein-39), CHIT1 (Chitinase 1), MMP-7, CCL22 and MAPK13 (p38MAPKδ). Monocytes from wild type, but not MAPK13 KO mice are also capable of monoosteophil differentiation, suggesting that MAPK13 regulates this process. When human monoosteophils were implanted in a freshly drilled hole in mid-diaphyseal femurs of NOD/SCID mice, significant bone repair required only 14 days compared to at least 24 days in control treated injuries. Conclusion Human derived monoosteophils, characterized as CD45+α3+α3β+CD34−CD14−BAP (bone alkaline phosphatase)− cells, can function in an animal model of bone injury. PMID:23844045

  12. 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 ...

  13. Toward accelerated bone regeneration by altering poly(D,L-lactic-co-glycolic) acid porogen content in calcium phosphate cement.

    PubMed

    van Houdt, C I A; Preethanath, R S; van Oirschot, B A J A; Zwarts, P H W; Ulrich, D J O; Anil, S; Jansen, J A; van den Beucken, J J J P

    2016-02-01

    This work aimed to compare in vitro degradation of dense PLGA microspheres and milled PLGA particles as porogens within CPC, considering that the manufacturing of milled PLGA is more cost-effective when compared with PLGA microspheres. Additionally, we aimed to examine the effect of porogen amount within CPC/PLGA on degradation and bone formation. Our in vitro results showed no differences between both forms of PLGA particles (as porogens in CPC; spherical for microspheres, irregular for milled) regarding morphology, porosity, and degradation. Using milled PLGA as porogens within CPC/PLGA, we evaluated the effect of porogen amount on degradation and bone forming capacity in vivo. Titanium landmarks surrounded by CPC/PLGA with 30 and 50 wt % PLGA, were implanted in forty femoral bone defects of twenty male Wistar rats. Histomorphometrical results showed a significant temporal decrease in the amount of CPC, for both formulas, and confirmed that 50 wt % PLGA degrades faster than 30 wt%, and allows for a 1.5-fold higher amount of newly formed bone. Taken together, this study demonstrated that (i) milled PLGA particles perform equal to PLGA microspheres, and (ii) tuning of the PLGA content in CPC/PLGA is a feasible approach to leverage material degradation and bone formation. PMID:26454146

  14. Proteomics in bone research.

    PubMed

    Zhang, Hengwei; Recker, Robert; Lee, Wai-Nang Paul; Xiao, Gary Guishan

    2010-02-01

    Osteoporosis is prevalent among the elderly and is a major cause of bone fracture in this population. Bone integrity is maintained by the dynamic processes of bone resorption and bone formation (bone remodeling). Osteoporosis results when there is an imbalance of the two counteracting processes. Bone mineral density, measured by dual-energy x-ray absorptiometry has been the primary method to assess fracture risk for decades. Recent studies demonstrated that measurement of bone turnover markers allows for a dynamic assessment of bone remodeling, while imaging techniques, such as dual-energy x-ray absorptiometry, do not. The application of proteomics has permitted discoveries of new, sensitive, bone turnover markers, which provide unique information for clinical diagnosis and treatment of patients with bone diseases. This review summarizes the recent findings of proteomic studies on bone diseases, properties of mesenchymal stem cells with high expansion rates and osteoblast and osteoclast differentiation, with emphasis on the role of quantitative proteomics in the study of signaling dynamics, biomarkers and discovery of therapeutic targets. PMID:20121480

  15. Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats

    PubMed Central

    Jackson, M.A.; Iwaniec, U.T.; Turner, R.T.; Wronski, T.J.; Kalra, S.P.

    2011-01-01

    Estrogen deficiency results in accelerated bone turnover with a net increase in bone resorption. Subcutaneous administration of leptin attenuates bone loss in ovariectomized (ovx) rats by reducing bone resorption. However, in addition to its direct beneficial effects, leptin has been reported to have indirect (central nervous system-mediated) antiosteogenic effects on bone, which may limit the efficacy of elevated serum leptin to prevent estrogen deficiency-associated bone loss. The present study evaluated the long-term effects of increased hypothalamic leptin transgene expression, using recombinant adeno-associated virus-leptin (rAAV-Lep) gene therapy, on bone mass, architecture, and cellular endpoints in sexually mature ovx Sprague-Dawley rats. Ovx rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained for 10 weeks. Additional controls consisted of ovary-intact rats and ovx rats pair-fed to rAAV-Lep rats. Lumbar vertebrae were analyzed by micro-computed tomography and tibiae by histomorphometry. Cancellous bone volume was lower and osteoclast perimeter, osteoblast perimeter, and bone marrow adipocyte density were greater in ovx rats compared to ovary-intact controls. In contrast, differences among ovx groups were not detected for any endpoint evaluated. In conclusion, whereas estrogen deficiency resulted in marked cancellous osteopenia, increased bone turnover and marrow adiposity, increasing hypothalamic leptin transgene expression in ovx rats had neither detrimental nor beneficial effects on bone mass, architecture, or cellular endpoints. These findings demonstrate that the antiresorptive effects of subcutaneous leptin administration in ovx rats are mediated through leptin targets in the periphery. PMID:21640774

  16. Bone Appetit: The Role of Food and Nutrition in Building and Maintaining Strong Bones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone is a living, dynamic, metabolically active tissue. It under goes a process of constant renewal throughout life, through a process called bone turnover in which cells called osteoclasts remove old or damaged bone, and cells called osteoblasts make new bone to replace it. A healthy, balanced di...

  17. Osteoporosis and bone metabolic parameters in dependence upon calcium intake through milk and milk products.

    PubMed

    Stracke, H; Renner, E; Knie, G; Leidig, G; Minne, H; Federlin, K

    1993-09-01

    The bone mineral content of young adults as well as of osteoporotic patients and age-matched controls without bone disease was measured by single-photon absorptiometry. A retrospective nutrition survey was additionally made to study the relationship between bone mineral content and calcium intake in different periods of life. The bone mineral content and bone mineral density of young adults is directly related to the calcium intake through milk and dairy products. The osteoporotics had a significantly lower bone mineral content than the controls. Calcium intake through milk and milk products in childhood and adolescence had been significantly lower in the patients than in the controls, whereas in the later periods of life (20-30 years prior to the study and at the time of the study) there were no significant differences between the calcium intakes of the two groups. It was also found that an adequate intake of calcium protected against increased bone resorption, as evidenced in particular by the reduced levels of serum osteocalcin, a parameter of bone turnover. In conclusion it can be stated that the data support the hypothesis that adequate calcium intake through milk and milk products in childhood and adolescence is a decisive marker for obtaining a maximum bone mass (peak adult bone mass) and for the prevention of osteoporosis. Furthermore, it can be stated that increased calcium intake in the later years may not reduce the accelerated risk of osteoporosis resulting from inadequate calcium intake during childhood and adolescence. PMID:8243426

  18. Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA.

    PubMed

    Mroue, Kamal H; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H; Morris, Michael D; Ramamoorthy, Ayyalusamy

    2014-07-01

    Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA=Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the (1)H T1 values were calculated from data collected by (1)H spin-inversion recovery method detected in natural-abundance (13)C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the (1)H T1 values can be successfully reduced by a factor of 3.5 using as low as 10mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the (13)C CPMAS spectra. These results obtained from (13)C-detected CPMAS experiments were further confirmed using (1)H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans. PMID:24881032

  19. Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA

    NASA Astrophysics Data System (ADS)

    Mroue, Kamal H.; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H.; Morris, Michael D.; Ramamoorthy, Ayyalusamy

    2014-07-01

    Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the 1H T1 values were calculated from data collected by 1H spin-inversion recovery method detected in natural-abundance 13C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the 1H T1 values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the 13C CPMAS spectra. These results obtained from 13C-detected CPMAS experiments were further confirmed using 1H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans.

  20. Acceleration of Natural-Abundance Solid-State MAS NMR Measurements on Bone by Paramagnetic Relaxation from Gadolinium-DTPA

    PubMed Central

    Mroue, Kamal H.; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H.; Morris, Michael D.; Ramamoorthy, Ayyalusamy

    2014-01-01

    Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylenetriamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the 1H T1 values were calculated from data collected by 1H spin-inversion recovery method detected in natural-abundance 13C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the 1H T1 values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the 13C CPMAS spectra. These results obtained from 13C-detected CPMAS experiments were further confirmed using 1H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans. PMID:24881032

  1. SIRT6 deficiency culminates in low-turnover osteopenia.

    PubMed

    Sugatani, Toshifumi; Agapova, Olga; Malluche, Hartmut H; Hruska, Keith A

    2015-12-01

    Deficiency of Sirtuin 6 (SIRT6), a chromatin-related deacetylase, in mice reveals severe premature aging phenotypes including osteopenia. However, the underlying molecular mechanisms of SIRT6 in bone metabolism are unknown. Here we show that SIRT6 deficiency in mice produces low-turnover osteopenia caused by impaired bone formation and bone resorption, which are mechanisms similar to those of age-related bone loss. Mechanistically, SIRT6 interacts with runt-related transcription factor 2 (Runx2) and osterix (Osx), which are the two key transcriptional regulators of osteoblastogenesis, and deacetylates histone H3 at Lysine 9 (H3K9) at their promoters. Hence, excessively elevated Runx2 and Osx in SIRT6(-/-) osteoblasts lead to impaired osteoblastogenesis. In addition, SIRT6 deficiency produces hyperacetylation of H3K9 in the promoter of dickkopf-related protein 1 (Dkk1), a potent negative regulator of osteoblastogenesis, and osteoprotegerin, an inhibitor of osteoclastogenesis. Therefore, the resulting up-regulation of Dkk1 and osteoprotegerin levels contribute to impaired bone remodeling, leading to osteopenia with a low bone turnover in SIRT6-deficient mice. These results establish a new link between SIRT6 and bone remodeling that positively regulates osteoblastogenesis and osteoclastogenesis. PMID:26189760

  2. Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice

    PubMed Central

    Rey, Jose R. Caeiro; Cervino, Eduardo Vaquero; Rentero, Maria Luz; Crespo, Emilio Calvo; Álvaro, Angel Oteo; Casillas, Marta

    2009-01-01

    Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium. This is a review article summarizing its mechanism, effects on bone and its applicability in traumatology clinical practice. In postmenopausal osteoporosis, this drug has been proven to decrease accelerated bone turnover, increase bone mineral density (BMD), and to structurally recover bone, decreasing the risk of vertebral fractures and the risk of non-vertebral fractures in patients with previous, severe vertebral fractures. Moreover, raloxifene appears to lower the risk of invasive breast cancer. Raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis. We can therefore conclude that raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis, while reducing the risk of breast cancer when used at the indicated dose of 60 mg/day and with a low incidence of side effects. PMID:19516920

  3. 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…

  4. Effect of gamma radiation and accelerated aging on the mechanical and thermal behavior of HDPE/HA nano-composites for bone tissue regeneration

    PubMed Central

    2013-01-01

    Background The replacement of hard tissues demands biocompatible and sometimes bioactive materials with properties similar to those of bone. Nano-composites made of biocompatible polymers and bioactive inorganic nano particles such as HDPE/HA have attracted attention as permanent bone substitutes due to their excellent mechanical properties and biocompatibility. Method The HDPE/HA nano-composite is prepared using melt blending at different HA loading ratios. For evaluation of the degradation by radiation, gamma rays of 35 kGy, and 70 kGy were used to irradiate the samples at room temperature in vacuum. The effects of accelerated ageing after gamma irradiation on morphological, mechanical and thermal properties of HDPE/HA nano-composites were measured. Results In Vitro test results showed that the HDPE and all HDPE/HA nano-composites do not exhibit any cytotoxicity to WISH cell line. The results also indicated that the tensile properties of HDPE/HA nano-composite increased with increasing the HA content except fracture strain decreased. The dynamic mechanical analysis (DMA) results showed that the storage and loss moduli increased with increasing the HA ratio and the testing frequency. Finally, it is remarked that all properties of HDPE/HA is dependent on the irradiation dose and accelerated aging. Conclusion Based on the experimental results, it is found that the addition of 10%, 20% and 30% HA increases the HDPE stiffness by 23%, 44 and 59% respectively. At the same time, the G’ increased from 2.25E11 MPa for neat HDPE to 4.7E11 MPa when 30% HA was added to the polymer matrix. Also, significant improvements in these properties have been observed due to irradiation. Finally, the overall properties of HDPE and its nano-composite properties significantly decreased due to aging and should be taken into consideration in the design of bone substitutes. It is attributed that the developed HDPE/HA nano-composites could be a good alternative material for bone tissue

  5. 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…

  6. Occupational stress and employee turnover.

    PubMed

    Bridger, Robert S; Day, Andrea J; Morton, Kate

    2013-01-01

    Questionnaire data captured in January-March 2007 were examined in relation to turnover in males and females during the next five years. In general, most of the workplace stressors (such as role conflict or peer support) were not antecedents of turnover in any group. Junior personnel with psychological strain in 2007 had an increased risk of turnover in the next five years. Low commitment to the service in 2007 increased the odds of turnover in male and female juniors and in female officers. Female juniors with less effective skills for coping with stress and who exercised less frequently on a weekly basis were more likely to leave. An incidental finding was that the odds of turnover were three times greater in female officers with children than in female officers with no children. Stress management interventions focusing on effective coping and sports and exercise participation which are targeted appropriately may improve retention. PMID:24047248

  7. [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

  8. Cell Line IDG-SW3 Replicates Osteoblast-to-Late-Osteocyte Differentiation in vitro and Accelerates Bone Formation in vivo

    PubMed Central

    Woo, Stacey M.; Rosser, Jennifer; Dusevich, Vladimir; Kalajzic, Ivo; Bonewald, Lynda F.

    2011-01-01

    Osteocytes are the most abundant cells in bone yet are the most challenging to study as they are embedded in a mineralized matrix. We generated a clonal cell line called IDG-SW3 (for Immortomouse/Dmp1-GFP-SW3) from long bone chips from mice carrying a Dmp1 promoter driving GFP crossed with the Immortomouse, which expresses a thermolabile SV40 large T-antigen regulated by IFN-γ. Cells from these mice can be expanded at 33°C in the presence of IFN-γ and then allowed to resume their original phenotype at 37°C in the absence of IFN-γ. IDG-SW3 cells are Dmp1-GFP-negative and T-antigen-positive under immortalizing conditions but Dmp1-GFP-positive and T-antigen-negative under osteogenic conditions. Like osteoblasts, they express alkaline phosphatase and produce and mineralize a type I collagen matrix containing calcospherulites. Like early osteocytes, they express E11/gp38, Dmp1, MEPE, and Phex. Like late osteocytes, they develop a dendritic morphology and express SOST/sclerostin and FGF23, regulated by PTH and 1,25-dihydroxyvitamin-D3. When cultured on 3D matrices, they express Dmp1-GFP and sclerostin. When the 3D cultures are implanted in calvarial defects in vivo, they accelerate bone healing. This cell line should prove useful for studying osteoblast-to-osteocyte transition, mechanisms for biomineralization, osteocyte function, and regulation of SOST/sclerostin and FGF23. PMID:21735478

  9. Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats.

    PubMed

    Balmayor, Elizabeth R; Geiger, Johannes P; Aneja, Manish K; Berezhanskyy, Taras; Utzinger, Maximilian; Mykhaylyk, Olga; Rudolph, Carsten; Plank, Christian

    2016-05-01

    Limitations associated to the use of growth factors represent a major hurdle to musculoskeletal regeneration. On the one hand, they are needed to induce neo-tissue formation for the substitution of a necrotic or missing tissue. On the other hand, these factors are used in supraphysiological concentrations, are short lived and expensive and result in many side effects. Here we develop a gene transfer strategy based on the use of chemically modified mRNA (cmRNA) coding for human bone morphogenetic protein 2 (hBMP-2) that is non-immunogenic and highly stable when compared to unmodified mRNA. Transfected stem cells secrete hBMP-2, show elevated alkaline phosphatase levels and upregulated expression of RunX2, ALP, Osterix, Osteocalcin, Osteopontin and Collagen Type I genes. Mineralization was induced as seen by positive Alizarin red staining. hBMP-2 cmRNA transfected human fat tissue also yielded an osteogenic response in vitro as indicated by expression of hBMP-2, RunX2, ALP and Collagen Type I. Delivering hBMP-2 cmRNA to a femur defect in a rat model results in new bone tissue formation as early as 2 weeks after application of very low doses. Overall, our studies demonstrate the feasibility and therapeutic potential of a new cmRNA-based gene therapy strategy that is safe and efficient. When applied clinically, this approach could overcome BMP-2 growth factor associated limitations in bone regeneration. PMID:26923361

  10. [Morphological analysis of bone dynamics and metabolic bone disease. Histomorphometric concepts of bone remodeling and modeling].

    PubMed

    Takahashi, Hideaki E

    2011-04-01

    In tissue level turnover of bone cells, bone remodeling shows a sequential events of activation, resorption, reversal and formation. This may be observed as secondary osteons in the cortical bone and trabecular packets in the cancellous bone. Microcracks are repaired by targeted remodeling, and calcium is released by non-targeted remodeling. In macromodeling, a macroscopic size of a bone increases with growth, without changing its basic figure. In micromodelimg, a shift of trabecula, a minishift, is biomechnically controlled. New lamellar bone is added parallel to compressive and tensile force, and bone resorption occurs at the opposite surface of formation. In minimodeling new lamellar bone is formed with a sequence of activation, then directly formation, without scalloping at the cement line between newly formed bone and its basic bone. PMID:21447918

  11. Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis

    PubMed Central

    2010-01-01

    Introduction To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. Methods In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. Results 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. Conclusions In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year. PMID:20482894

  12. 3H-tetracycline as a proxy for 41Ca for measuring dietary perturbations of bone resorption

    NASA Astrophysics Data System (ADS)

    Weaver, Connie; Cheong, Jennifer; Jackson, George; Elmore, David; McCabe, George; Martin, Berdine

    2007-06-01

    Our group is interested in evaluating early effects of dietary interventions on bone loss. Postmenopausal women lose bone following reduction in estrogen which leads to increased risk of fracture. Traditional means of monitoring bone loss and effectiveness of treatments include changes in bone density, which takes 6 months to years to observe effects, and changes in biochemical markers of bone turnover, which are highly variable and lack specificity. Prelabeling bone with 41Ca and measuring urinary 41Ca excretion with accelerator mass spectrometry provides a sensitive, specific, and rapid approach to evaluating effectiveness of treatment. To better understand 41Ca technology as a tool for measuring effective treatments on reducing bone resorption, we perturbed bone resorption by manipulating dietary calcium in rats. We used 3H-tetracycline (3H-TC) as a proxy for 41Ca and found that a single dose is feasible to study bone resorption. Suppression of bone resorption, as measured by urinary 3H-TC, by dietary calcium was observed in rats stabilized after ovariectomy, but not in recently ovariectomized rats.

  13. [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

  14. 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

  15. 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

  16. High bone turnover assessed by 18F-fluoride PET/CT in the spine and sacroiliac joints of patients with ankylosing spondylitis: comparison with inflammatory lesions detected by whole body MRI

    PubMed Central

    2012-01-01

    Background This study compares the frequency and distribution of increased activity on 18 F-fluoride PET/CT with the presence of bone marrow edema on whole-body MR imaging in the spine and sacroiliac joints (SIJ) of patients with active ankylosing spondylitis (AS). Methods Ten patients (6 men and 4 women), between 30 and 58 years old (median 44) with active AS, were prospectively examined with both whole-body MRI and 18 F-fluoride PET/CT. Patients fulfilled modified NY criteria and had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of at least 4. Increased radiotracer uptake in PET/CT and bone marrow edema in whole-body MRI of spine and SIJ was evaluated independently by two blinded observers for each modality. Kappa statistics were used to compare interobserver agreement as well as scores of consensus reading of the two imaging modalities. Results Analysis of interobserver agreement for PET/CT yielded a kappa value of 0.68 for spinal lesions and of 0.88 for SIJ lesions. The corresponding kappa values for the MRI modality were 0.64 and 0.93, respectively. More spinal lesions were detected by MRI in comparison to PET/CT (68 vs. 38), whereas a similar number of SIJ quadrants scored positive in both modalities (19 vs. 17). Analysis of agreement of lesion detection between both imaging modalities yielded a kappa value of only 0.25 for spinal lesions and of 0.64 for SIJ lesions. Conclusion Increased 18 F-fluoride uptake in PET/CT is only modestly associated with bone marrow edema on MRI in the spine and SIJ of patients with AS, suggesting different aspects of bone involvement in AS. PMID:22788874

  17. 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

  18. PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Haider, Adnan; Gupta, Kailash Chandra; Kang, Inn-Kyu

    2014-06-01

    The development of tissue engineering in the field of orthopedic surgery is booming. Two fields of research in particular have emerged: approaches for tailoring the surface properties of implantable materials with osteoinductive factors as well as evaluation of the response of osteogenic cells to these fabricated implanted materials (hybrid material). In the present study, we chemically grafted insulin onto the surface of hydroxyapatite nanorods (nHA). The insulin-grafted nHAs (nHA-I) were dispersed into poly(lactide-co-glycolide) (PLGA) polymer solution, which was electrospun to prepare PLGA/nHA-I composite nanofiber scaffolds. The morphology of the electrospun nanofiber scaffolds was assessed by field emission scanning electron microscopy (FESEM). After extensive characterization of the PLGA/nHA-I and PLGA/nHA composite nanofiber scaffolds by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM), the PLGA/nHA-I and PLGA/nHA (used as control) composite nanofiber scaffolds were subjected to cell studies. The results obtained from cell adhesion, alizarin red staining, and Von Kossa assay suggested that the PLGA/nHA-I composite nanofiber scaffold has enhanced osteoblastic cell growth, as more cells were proliferated and differentiated. The fact that insulin enhanced osteoblastic cell proliferation will open new possibilities for the development of artificial scaffolds for bone tissue regeneration.

  19. Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification.

    PubMed

    Jeong, Claire G; Zhang, Huina; Hollister, Scott J

    2012-08-01

    As articular cartilage is avascular, and mature chondrocytes do not proliferate, cartilage lesions have a limited capacity for regeneration after severe damage. The treatment of such damage has been challenging due to the limited availability of autologous healthy cartilage and lengthy and expensive cell isolation and expansion procedures. Hence, the use of bone morphogenetic protein-2 (BMP-2), a potent regulator of chondrogenic expression, has received considerable attention in cartilage and osteochondral tissue engineering. However, the exact role of BMP-2 in cartilage repair has been postulated to promote both cartilage formation and subsequent cartilage degradation through hypertrophy and endochondral ossification. Furthermore, it is likely that the manner in which BMP-2 is presented to chondrocytes will influence the physiologic pathway (repair vs. degeneration). This study investigates the relative influence of BMP-2 on cartilage matrix and potential subsequent bone matrix production using primary chondrocytes seeded on designed 3D polycaprolactone (PCL) scaffolds with chemically conjugated BMP-2. The results show that chemically conjugated BMP-2 PCL scaffolds can promote significantly greater cartilage regeneration from seeded chondrocytes both in vitro and in vivo compared with untreated scaffolds. Furthermore, our results demonstrate that the conjugated BMP-2 does not particularly accelerate endochondral ossification even in a readily permissible and highly vascular in vivo environment compared with untreated PCL scaffolds. This study not only reveals the potential use of the BMP-2 conjugation delivery method for enhanced cartilage tissue formation but also gives new insights for the effects of conjugated BMP-2 on cartilage regeneration and osteochondral ossification. PMID:22615065

  20. Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.

    PubMed

    Kuang, G M; Yau, W P; Lu, W W; Chiu, K Y

    2013-07-01

    We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft. PMID:23814244

  1. Eating disorders and bone.

    PubMed

    Tomlinson, Dale; Morgan, Sarah L

    2013-01-01

    Low bone mineral density (BMD) is a frequent and often-overlooked consequence of eating disorders, in particular anorexia nervosa and eating disorders associated with the female athlete triad. The causes of low BMD are multifactorial and include low peak bone mass accrual, accelerated bone resorption, and changes in bone microarchitecture. Early diagnosis and interventions focused on nutritional rehabilitation and weight gain reduce the risk of further BMD deficits and fractures. PMID:24094471

  2. 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

  3. The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice

    PubMed Central

    Vinik, Yaron; Shatz-Azoulay, Hadas; Vivanti, Alessia; Hever, Navit; Levy, Yifat; Karmona, Rotem; Brumfeld, Vlad; Baraghithy, Saja; Attar-Lamdar, Malka; Boura-Halfon, Sigalit; Bab, Itai; Zick, Yehiel

    2015-01-01

    Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins. DOI: http://dx.doi.org/10.7554/eLife.05914.001 PMID:25955862

  4. The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice.

    PubMed

    Vinik, Yaron; Shatz-Azoulay, Hadas; Vivanti, Alessia; Hever, Navit; Levy, Yifat; Karmona, Rotem; Brumfeld, Vlad; Baraghithy, Saja; Attar-Lamdar, Malka; Boura-Halfon, Sigalit; Bab, Itai; Zick, Yehiel

    2015-01-01

    Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins. PMID:25955862

  5. Corticision: A Flapless Procedure to Accelerate Tooth Movement.

    PubMed

    Park, Young Guk

    2016-01-01

    Orthodontic tooth movement results from applied forces to the teeth evoking cellular responses in the teeth and their surrounding tissues, including the periodontal ligament, alveolar bone and gingiva. It is advantageous for the orthodontist to be well informed of the detailed process of the biological events that unfold during tooth movement, since some of these details may differ from one person to another due to biological differences such as periodontal metabolism or alveolar bone density. This led us to emphasize that orthodontics is a field of endeavor where the integration of mechanics and biology is materialized, and to affirm the fact that tooth movement is conducted in individual human beings, each composed of a unique and intricate physiological system. Biological variations may be the foundation of the differences that are frequently observed in the outcomes of orthodontic treatment in particular with reference to treatment duration between patients with similar malocclusions and who were treated identically. A wide diversity of clinical trials has been carried out to control the tissue resistance to facilitate orthodontic tooth movement, which involves biomechanical, pharmaceutical, surgical, electrical regimens or tissue engineering technology. The term 'Corticision' is a neologism which indicates 'cortical bone incision'. It is a minimally invasive periodontal procedure without flap elevation, thus accelerating tooth movement with an enhanced turnover rate of the surrounding structures. This chapter introduces the technical procedure, and the biological background of how such a minor surgical procedure can receive the accelerated tooth movement with impunity and thereby shorten the duration of treatment. PMID:26599124

  6. Turnover in the Advancement Profession

    ERIC Educational Resources Information Center

    Iarrobino, Jon D.

    2006-01-01

    Recruitment and retention is an area with which most organizations are concerned. Excessive turnover has exorbitant costs and wastes valuable time. Institutions of higher education are no exception. One of the most vital operations in nonprofit colleges and universities is its Office of Institutional Advancement. More and more, an institution of…

  7. 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. PMID:26859106

  8. Peripheral Leptin Regulates Bone Formation

    PubMed Central

    Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

    2012-01-01

    Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

  9. 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

  10. Reader's digest of the pathophysiology of bone metastases.

    PubMed

    Gruber, Reinhard

    2012-09-01

    Bone metastases are a process originally proposed as the "seed and soil theory" in the eighteenth century. Tumor cell disseminating from patients with breast or prostate cancer typically use the bony environment to grow outside the primary tumor location. The severe clinical consequences of bone metastasis such as pain, fractures, and hypercalcemia result from a serious misbalance of bone turnover. Most bone metastases cause catabolic changes of bone turnover. The severity of bone resorption is associated with tumor growth, suggesting the existence of a vicious cycle that needs to be interrupted. Osteoblastic metastasis showing signs of osteosclerotic lesions are observed in prostate cancer. Understanding the pathophysiology of bone metastases and their detrimental consequence provide the scientific basis for therapeutic interventions at various levels including homing of tumors to bone, survival and growth of the tumor cell in the bone niche, and the mechanisms causing bone destruction. PMID:22797871

  11. Bone health in eating disorders.

    PubMed

    Zuckerman-Levin, N; Hochberg, Z; Latzer, Y

    2014-03-01

    Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health. Low bone mineral density (BMD) with ED is caused by failure to accrue peak bone mass in adolescence and bone loss in young adulthood. Although ED patients diagnosed with bone loss may be asymptomatic, some suffer bone pains and have increased incidence of fractures. Adolescents with ED are prone to increased prevalence of stress fractures, kyphoscoliosis and height loss. The clinical picture of the various EDs involves endocrinopathies that contribute to impaired bone health. Anorexia nervosa (AN) is characterized by low bone turnover, with relatively higher osteoclastic (bone resorptive) than osteoblastic (bone formation) activity. Bone loss in AN occurs in both the trabecular and cortical bones, although the former is more vulnerable. Bone loss in AN has been shown to be influenced by malnutrition and low weight, reduced fat mass, oestrogen and androgen deficiency, glucocorticoid excess, impaired growth hormone-insulin-like growth factor 1 axis, and more. Bone loss in AN may not be completely reversible despite recovery from the illness. Treatment modalities involving hormonal therapies have limited effectiveness, whereas increased caloric intake, weight gain and resumption of menses are essential to improved BMD. PMID:24165231

  12. Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase.

    PubMed

    Sekiguchi, Hiroyuki; Uchida, Kentaro; Inoue, Gen; Matsushita, Osamu; Saito, Wataru; Aikawa, Jun; Tanaka, Keisuke; Fujimaki, Hisako; Miyagi, Masayuki; Takaso, Masashi

    2016-06-01

    Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016. PMID:26833780

  13. Chronic Teacher Turnover in Urban Elementary Schools

    ERIC Educational Resources Information Center

    Guin, Kacey

    2004-01-01

    This study examines the characteristics of elementary schools that experience chronic teacher turnover and the impacts of turnover on a school's working climate and ability to effectively function. Based on evidence from staff climate surveys and case studies, it is clear that high turnover schools face significant organizational challenges.…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. Benchmarking of homogeneous electrocatalysts: overpotential, turnover frequency, limiting turnover number.

    PubMed

    Costentin, Cyrille; Passard, Guillaume; Savéant, Jean-Michel

    2015-04-29

    In relation to contemporary energy challenges, a number of molecular catalysts for the activation of small molecules, mainly based on transition metal complexes, have been developed. The time has thus come to develop tools allowing the benchmarking of these numerous catalysts. Two main factors of merit are addressed. One involves their intrinsic catalytic performances through the comparison of "catalytic Tafel plots" relating the turnover frequency to the overpotential independently of the characteristics of the electrochemical cell. The other examines the effect of deactivation of the catalyst during the course of electrolysis. It introduces the notion of the limiting turnover number as a second key element of catalyst benchmarking. How these two factors combine with one another to control the course of electrolysis is analyzed in detail, leading to procedures that allow their separate estimation from measurements of the current, the charge passed, and the decay of the catalyst concentration. Illustrative examples from literature data are discussed. PMID:25757058

  19. Calvarial doughnut lesions associated with high-turnover osteoporosis presenting in childhood.

    PubMed

    Stock, J L; Coderre, J A; Overdorf, J H; Fitzpatrick, L A; Shapiro, J R

    1999-01-01

    Osteogenesis imperfecta and juvenile osteoporosis are two well-described syndromes of osteoporosis presenting in childhood. There are also several references in the radiology literature to calvarial doughnut lesions (CDLs), areas of radiolucency surrounded by a dense and well-defined area of sclerotic bone, either as an incidental finding or associated with childhood fracture. We have characterized the metabolic abnormalities in a 13-yr-old boy with CDLs and multiple fractures and followed him during his progression through puberty. The patient's paternal grandmother; father; and paternal aunt, uncle, and first cousin were similarly affected, and a mandibular lesion in the uncle was pathologically described as fibrous dysplasia. The subject's physical examination was significant for bony protuberances of the skull and normal hearing, sclearal hue, dentition, and joint flexibility. Radiographs revealed calvarial CDLs and osteopenia which was confirmed by bone mineral density (BMD) testing. Biochemical markers of bone formation and resorption were elevated compared to normal adult and a transiliac crest bone biopsy confirmed high-turnover osteoporosis. Over 6 yr, with no specific therapy, BMD gradually normalized, but the CDLs increased in size, bone turnover remained elevated by biochemical markers, and he continued to fracture. The subject's affected father and maternal grandmother had normal BMD and no history of adult fracture. CDLs with high-turnover osteoporosis should be considered in the differential diagnosis of pediatric osteoporosis. During puberty the BMD normalizes but the high-turnover state persists, and the propensity to fracture eventually decreases in older affected adults. The CDLs may be a variant of fibrous dysplasia, and further study is necessary in order to elucidate the stimulus for increased bone turnover and the familial nature of this syndrome. PMID:23547313

  20. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  1. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  2. Turnover: strategies for staff retention.

    PubMed

    SnowAntle, S

    1990-01-01

    This discussion has focused on a number of areas where organizations may find opportunities for more effectively managing employee retention. Given the multitude of causes and consequences, there is no one quick fix. Effective management of employee retention requires assessment of the entire human resources process, that is, recruitment, selection, job design, compensation, supervision, work conditions, etc. Regular and systematic diagnosis of turnover and implementation of multiple strategies and evaluation are needed (Mobley, 1982). PMID:10106673

  3. Supervisory Turnover in Outpatient Substance Abuse Treatment

    PubMed Central

    Knight, Danica K.; Broome, Kirk M.; Edwards, Jennifer R.; Flynn, Patrick M.

    2009-01-01

    Staff turnover is a significant issue within substance abuse treatment, with implications for service delivery and organizational health. This study examined factors associated with turnover among supervisors in outpatient substance abuse treatment. Turnover was conceptualized as being an individual response to organizational-level influences, and predictors represent aggregate program measures. Participants included 532 staff (including 467 counselors and 65 clinical/program directors) from 90 programs in four regions of the USA. Using logistic regression, analyses of structural factors indicated that programs affiliated with a parent organization and those providing more counseling hours to clients had higher turnover rates. When measures of job attitudes were included, only parent affiliation and collective appraisal of satisfaction were related to turnover. Subsequent analyses identified a trend toward increased supervisory turnover when satisfaction was low following the departure of a previous supervisor. These findings suggest that organizational-level factors can be influential in supervisory turnover. PMID:19949883

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

    PubMed

    Zhang, Jian; Lazarenko, Oxana P; Blackburn, Michael L; Badger, Thomas M; Ronis, Martin J J; Chen, Jin-Ran

    2013-06-01

    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-induced bone loss is associated with profound decreases in collagen 1 and Sirt1. This was accompanied by increases in expression and activity of the senescence marker collagenase and expression of p16/p21 in bone. Feeding a diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only prior to puberty [postnatal day 21 (PND21) to PND34] prevents OVX-induced effects on expression of these molecules at PND68. In order to provide more evidence and gain a better understanding on the association between bone collagen matrix and resident bone cell fate, in vitro studies on the cellular senescence pathway using primary calvarial cells and three cell lines (ST2 cells, OB6, and MLO-Y4) were conducted. We found that senescence was inhibited by collagen in a dose-response manner. Treatment of cells with serum from OVX rats accelerated osteoblastic cell senescence pathways, but serum from BB-fed OVX rats had no effect. In the presence of low collagen or treatment with OVX rat serum, ST2 cells exhibited higher potential to differentiate into adipocytes. Finally, we demonstrated that bone cell senescence is associated with decreased Sirt1 expression and activated p53, p16, and p21. These results suggest that (1) a significant prevention of OVX-induced bone cell senescence from adult rats can occur after only 14 days consumption of a BB-containing diet immediately prior to puberty, and (2) the molecular mechanisms underlying this effect involves, at least in part, prevention of collagen degradation. PMID:22555620

  5. Assessment of bone formation and bone resorption in osteoporosis: a comparison between tetracycline-based iliac histomorphometry and whole body /sup 85/Sr kinetics

    SciTech Connect

    Reeve, J.; Arlot, M.E.; Chavassieux, P.M.; Edouard, C.; Green, J.R.; Hesp, R.; Tellez, M.; Meunier, P.J.

    1987-12-01

    Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption.

  6. Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.

    PubMed

    Collette, Nicole M; Yee, Cristal S; Hum, Nicholas R; Murugesh, Deepa K; Christiansen, Blaine A; Xie, LiQin; Economides, Aris N; Manilay, Jennifer O; Robling, Alexander G; Loots, Gabriela G

    2016-07-01

    Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1(-/-)) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1(-/-) cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1(-/-) mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1(-/-) 5day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1(-/-) mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum. PMID:27102547

  7. 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...

  8. Consensus on the utility of bone markers in the malignant bone disease setting.

    PubMed

    Coleman, Robert; Costa, Luis; Saad, Fred; Cook, Richard; Hadji, Peyman; Terpos, Evangelos; Garnero, Patrick; Brown, Janet; Body, Jean-Jacques; Smith, Matthew; Lee, Ker-Ai; Major, Pierre; Dimopoulos, Meletios; Lipton, Allan

    2011-12-01

    Biochemical markers of bone turnover provide insight into ongoing rates of skeletal metabolism and tumor-bone interactions in patients with malignant bone disease. This article reviews the available recent evidence assessing the potential of bone markers for detecting and monitoring malignant bone lesions in patients with advanced cancers, and for assessing overall skeletal health and response to antiresorptive therapies in patients at all stages of cancer progression. Most data thus far are for urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in predicting risks of skeletal morbidity and death and monitoring response to zoledronic acid in patients with bone metastases. Ongoing studies are evaluating such correlations for other markers and therapies. Emerging evidence suggests that bone markers may help identify patients at high risk for bone metastasis or bone lesion progression, thereby allowing improved follow-up. Results from ongoing clinical trials evaluating such potential applications of bone markers are awaited. PMID:21411334

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

    PubMed

    Obermayer-Pietsch, B; Schwetz, V

    2016-06-01

    Laboratory analyses of biochemical markers for bone and mineral metabolism can play a key role in the assessment of patients with osteoporosis. They may help to assess bone turnover in the diagnostic work-up and aid decision-making as well as selection of pharmaceutical therapy options. Recent publications on therapy response have shown that biochemical markers of bone turnover are valuable tools for the evaluation of therapy success in individual osteoporosis patients and the assessment of bone mineral density gain during therapy. PMID:27146404

  10. Revisiting nurse turnover costs: adjusting for inflation.

    PubMed

    Jones, Cheryl Bland

    2008-01-01

    Organizational knowledge of nurse turnover costs is important, but gathering these data frequently may not always be feasible in today's fast-paced and complex healthcare environment. The author presents a method to inflation adjust baseline nurse turnover costs using the Consumer Price Index. This approach allows nurse executives to gain current knowledge of organizational nurse turnover costs when primary data collection is not practical and to determine costs and potential savings if nurse retention investments are made. PMID:18157000

  11. 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 ...

  12. 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.

  13. 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.

  14. 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…

  15. Ultrasound simulation in bone.

    PubMed

    Kaufman, Jonathan J; Luo, Gangming; Siffert, Robert S

    2008-01-01

    The manner in which ultrasound interacts with bone is of key interest in therapy and diagnosis alike. These may include applications directly to bone, as, for example, in treatment to accelerate the healing of bone fractures and in assessment of bone density in osteoporosis, or indirectly in diagnostic imaging of soft tissue with interest in assessing exposure levels to nearby bone. Because of the lack of analytic solutions to virtually every "practical problem" encountered clinically, ultrasound simulation has become a widely used technique for evaluating ultrasound interactions in bone. This paper provides an overview of the use of ultrasound simulation in bone. A brief description of the mathematical model used to characterize ultrasound propagation in bone is first provided. A number of simulation examples are then presented that explain how simulation may be utilized in a variety of practical configurations. The focus of this paper in terms of examples presented is on diagnostic applications in bone, and, in particular, for assessment of osteoporosis. However, the use of simulation in other areas of interest can easily be extrapolated from the examples presented. In conclusion, this paper describes the use of ultrasound simulation in bone and demonstrates the power of computational methods for ultrasound research in general and tissue and bone applications in particular. PMID:18599409

  16. Employee Turnover among Full-time Public Librarians.

    ERIC Educational Resources Information Center

    Rubin, Richard

    1989-01-01

    A study of employee turnover in 31 public libraries in the American Midwest established baseline turnover rates and examined the relationship of gender to turnover behavior. Findings showed that: turnover rates are low compared to other occupations; and turnover rates of males and females are similar. (28 references) (Author/MES)

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

    PubMed

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

    2014-01-01

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

  18. 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.

  19. Assembly and Turnover of Short Actin Filaments by the Formin INF2 and Profilin*

    PubMed Central

    Gurel, Pinar S.; A, Mu; Guo, Bingqian; Shu, Rui; Mierke, Dale F.; Higgs, Henry N.

    2015-01-01

    INF2 (inverted formin 2) is a formin protein with unique biochemical effects on actin. In addition to the common formin ability to accelerate actin nucleation and elongation, INF2 can also sever filaments and accelerate their depolymerization. Although we understand key attributes of INF2-mediated severing, we do not understand the mechanism by which INF2 accelerates depolymerization subsequent to severing. Here, we show that INF2 can create short filaments (<60 nm) that continuously turn over actin subunits through a combination of barbed end elongation, severing, and WH2 motif-mediated depolymerization. This pseudo-steady state condition occurs whether starting from actin filaments or monomers. The rate-limiting step of the cycle is nucleotide exchange of ADP for ATP on actin monomers after release from the INF2/actin complex. Profilin addition has two effects: 1) to accelerate filament turnover 6-fold by accelerating nucleotide exchange and 2) to shift the equilibrium toward polymerization, resulting in longer filaments. In sum, our findings show that the combination of multiple interactions of INF2 with actin can work in concert to increase the ATP turnover rate of actin. Depending on the ratio of INF2:actin, this increased flux can result in rapid filament depolymerization or maintenance of short filaments. We also show that high concentrations of cytochalasin D accelerate ATP turnover by actin but through a different mechanism from that of INF2. PMID:26124273

  20. Bone Remodeling Under Pathological Conditions.

    PubMed

    Xiao, Wenmei; Li, Shuai; Pacios, Sandra; Wang, Yu; Graves, Dana T

    2016-01-01

    Bone is masterfully programmed to repair itself through the coupling of bone formation following bone resorption, a process referred to as coupling. In inflammatory or other conditions, the balance between bone resorption and bone formation shifts so that a net bone loss results. This review focuses on four pathologic conditions in which remodeling leads to net loss of bone, postmenopausal osteoporosis, arthritis, periodontal disease, and disuse bone loss, which is similar to bone loss associated with microgravity. In most of these there is an acceleration of the resorptive process due to increased formation of bone metabolic units. This initially leads to a net bone loss since the time period of resorption is much faster than the time needed for bone formation that follows. In addition, each of these processes is characterized by an uncoupling that leads to net bone loss. Mechanisms responsible for increased rates of bone resorption, i.e. the formation of more bone metabolic units, involve enhanced expression of inflammatory cytokines and increased expression of RANKL. Moreover, the reasons for uncoupling are discussed which range from a decrease in expression of growth factors and bone morphogenetic proteins to increased expression of factors that inhibit Wnt signaling. PMID:26599114

  1. 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

  2. Biophotonics and Bone Biology

    NASA Technical Reports Server (NTRS)

    Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

    2004-01-01

    One of the more-serious side effects of extended space flight is an accelerated bone loss [Bioastronautics Critical Path Roadmap, http://research.hq.nasa.gov/code_u/bcpr/index.cfm]. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It shows that an extrapolation of the microgravity induced bone loss rates to longer time scales, such as a 2.5 year round-trip to Mars (6 months out at 0 g, 1.5 year stay on Mars at 0.38 g, 6 months back at 0 g), could severely compromise the skeletal system of such a person.

  3. Employee Turnover: An Empirical and Methodological Assessment.

    ERIC Educational Resources Information Center

    Muchinsky, Paul M.; Tuttle, Mark L.

    1979-01-01

    Reviews research on the prediction of employee turnover. Groups predictor variables into five general categories: attitudinal (job satisfaction), biodata, work-related, personal, and test-score predictors. Consistent relationships between common predictor variables and turnover were found for four categories. Eight methodological problems/issues…

  4. 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…

  5. 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…

  6. 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…

  7. Predicting Employee Turnover from Communication Networks.

    ERIC Educational Resources Information Center

    Feeley, Thomas H.; Barnett, George A.

    1997-01-01

    Investigates three social network models of employee turnover: a structural equivalence model, a social influence model, and an erosion model. Administers a communication network questionnaire to all 170 employees of an organization. Finds support for all three models of turnover, with the erosion model explaining more of the variance than do the…

  8. Mitochondrial Turnover in the Heart

    PubMed Central

    Gustafsson, Åsa B.

    2010-01-01

    Mitochondrial quality control is increasingly recognized as an essential element in maintaining optimally functioning tissues. Mitochondrial quality control depends upon a balance between biogenesis and autophagic destruction. Mitochondrial dynamics (fusion and fission) allows for the redistribution of mitochondrial components. We speculate that this permits sorting of highly functional components into one end of a mitochondrion, while damaged components are segregated at the other end, to be jettisoned by asymmetric fission followed by selective mitophagy. Ischemic preconditioning requires autophagy/mitophagy, resulting in selective elimination of damaged mitochondria, leaving behind a population of robust mitochondria with a higher threshold for opening of the mitochondrial permeability transition pore. In this review we will consider the factors that regulate mitochondrial biogenesis and destruction, the machinery involved in both processes, and the biomedical consequences associated with altered mitochondrial turnover. PMID:21147177

  9. 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

  10. [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. PMID:26412727

  11. Bone Metabolism in Adolescents with Anorexia Nervosa

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often begins in the adolescent years, and decreased rates of bone mass accrual at this critical time are therefore also concerning for deficits in peak bone mass. Factors contributing to low bone density and decreased rates of bone accrual include alterations in body composition such as low BMI and lean body mass, and hormonal alterations such as hypogonadism, a nutritionally acquired resistance to growth hormone and low levels of IGF-1, relative hypercortisolemia, low levels of leptin, and increased adiponectin (for fat mass) and peptide YY. Therapeutic strategies include optimizing weight and menstrual recovery, and adequate calcium and vitamin D replacement. Oral estrogen-progesterone combination pills are not effective in increasing bone density in adolescents with AN. RhIGF-1 increases levels of bone formation markers in the short-term, while long-term effects remain to be determined. Bisphosphonates act by decreasing bone resorption, and are not optimal for use in adolescents with AN, in whom the primary defect is low bone formation. PMID:21301203

  12. Accelerated bone ingrowth by local delivery of Zinc from bioactive glass: oxidative stress status, mechanical property, and microarchitectural characterization in an ovariectomized rat model

    PubMed Central

    Samira, Jbahi; Saoudi, Monji; Abdelmajid, Kabir; Hassane, Oudadesse; Treq, Rebai; Hafed, Efeki; Abdelfatteh, Elfeki; Hassib, Keskes

    2015-01-01

    Background Synthetic bone graft substitutes such as bioactive glass (BG) material are developed in order to achieve successful bone regeneration. Zn plays an important role in the proper bone growth, development, and maintenance of healthy bones. Aims This study aims to evaluate in vivo the performance therapy of zinc-doped bioactive glass (BG-Zn) and its applications in biomedicine. Methods Female Wistar rats were ovariectomized. BG and BG-Zn were implanted in the femoral condyles of Wistar rats and compared to that of control group. Grafted bone tissues were carefully removed to evaluate the oxidative stress status, histomorphometric profile, mechanical property, and mineral bone distribution by using inductively coupled plasma optical emission spectrometry. Results A significant decrease of thiobarbituric acid–reactive substances was observed after BG-Zn implantation. Superoxide dismutase, catalase (CAT), and glutathione peroxidase (GPx) activities significantly increased in ovariectomized group implanted with Zinc-doped bioactive glass (OVX-BG-Zn) as compared to ovariectomized group implanted with bioactive glass (OVX-BG). An improved mechanical property was noticed in contact of OVX-BG-Zn (39±6 HV) when compared with that of OVX-BG group (26±9 HV). After 90 days of implantation, the histomorphometric analysis showed that trabecular thickness (Tb.Th) and trabecular number (Tb.N) were significantly increased with 28 and 24%, respectively, in treated rats of OVX-BG-Zn group as compared to those of OVX-BG groups. Trabecular separation (Tb.Sp) and trabecular bone pattern factor (TBPf) were significantly decreased in OVX-BG-Zn group with 29.5 and 54% when compared with those of OVX-BG rat groups. On the other hand, a rise in Ca and P ion concentrations in the implanted microenvironment was shown and lead to the formation/deposition of Ca-P phases. The ratio of pyridinoline [Pyr] to dihydroxylysinonorleucine [DHLNL] cross-links was normalized to the control level

  13. Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.

    PubMed

    Kuipers, Allison L; Kammerer, Candace M; Pratt, J Howard; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

    2016-05-01

    Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (bothP<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. PMID:26975710

  14. [The assessment of bone quality in lifestyle-related diseases].

    PubMed

    Yamauchi, Mika

    2016-01-01

    Type 2 diabetes mellitus(DM)and other lifestyle-related diseases are associated with an increased risk of bone quality deterioration-type osteoporosis. The deterioration of bone quality in type 2 DM involves factors such as qualitative changes of collagens, reduction in bone turnover, narrow cortical bone diameter, increased cortical bone porosity, and destruction of trabecular bone microarchitecture. In mild to moderate chronic kidney disease and chronic obstructive pulmonary disease, the factors involved are thought to be hyperhomocysteinemia and deterioration of trabecular bone microarchitecture as well as cortical bone structure. Investigations of the usefulness of bone quality assessment using approaches such as the following are under way : biocheminal markers such as pentosidine and homocysteine, bone structure assessment methods such as hip structure analysis, trabecular bone score, and high-resolution peripheral quantitative computed tomography. PMID:26728532

  15. Bone Diseases

    MedlinePlus

    ... also avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... Bones can also develop cancer and infections Other bone diseases, which are caused by poor nutrition, genetics, or ...

  16. Bone Grafts

    MedlinePlus

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  17. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility.

    PubMed

    Karim, Lamya; Vashishth, Deepak

    2012-01-01

    Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC). Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks). The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage. PMID:22514706

  18. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo

    NASA Astrophysics Data System (ADS)

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-04-01

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01439e

  19. 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

  20. 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

  1. Improvements to Kramers turnover theory

    NASA Astrophysics Data System (ADS)

    Pollak, Eli; Ankerhold, Joachim

    2013-04-01

    The Kramers turnover problem, that is, obtaining a uniform expression for the rate of escape of a particle over a barrier for any value of the external friction was solved in the 1980s. Two formulations were given, one by Mel'nikov and Meshkov (MM) [V. I. Mel'nikov and S. V. Meshkov, J. Chem. Phys. 85, 1018 (1986), 10.1063/1.451844], which was based on a perturbation expansion for the motion of the particle in the presence of friction. The other, by Pollak, Grabert, and Hänggi (PGH) [E. Pollak, H. Grabert, and P. Hänggi, J. Chem. Phys. 91, 4073 (1989), 10.1063/1.456837], valid also for memory friction, was based on a perturbation expansion for the motion along the collective unstable normal mode of the particle. Both theories did not take into account the temperature dependence of the average energy loss to the bath. Increasing the bath temperature will reduce the average energy loss. In this paper, we analyse this effect, using a novel perturbation theory. We find that within the MM approach, the thermal energy gained from the bath diverges, the average energy gain becomes infinite implying an essential failure of the theory. Within the PGH approach increasing the bath temperature reduces the average energy loss but only by a finite small amount of the order of the inverse of the reduced barrier height. Then, this does not seriously affect the theory. Analysis and application for a cubic potential and Ohmic friction are presented.

  2. Bone metabolism during pregnancy.

    PubMed

    Salles, Jean Pierre

    2016-06-01

    During pregnancy, mineral concentrations, of calcium and phosphorus in particular, are maintained at a high level in fetal blood so that the developing skeleton may accrete adequate mineral content. The placenta actively transports minerals for this purpose. Maternal intestinal absorption increases in order to meet the fetal demand for calcium, which is only partly dependent on calcitriol. Mineral regulation is essentially dependent on parathyroid hormone (PTH) and PTH-related protein (PTHrP). The calcium-sensing receptor (CaSR) regulates PTH and PTHrP production. If calcium intake is insufficient, the maternal skeleton will undergo resorption due to PTHrP. After birth, a switch from fetal to neonatal homeostasis occurs through increase in PTH and calcitriol, and developmental adaptation of the kidneys and intestines with bone turnover contributing additional mineral to the circulation. Calcium absorption becomes progressively active and dependent on calcitriol. The postnatal skeleton can transiently present with osteoposis but adequate mineral diet usually allows full restoration. Cases of primary osteoporosis must be identified. Loss of trabecular mineral content occurs during lactation in order to provide calcium to the newborn. This programmed bone loss is dependent on a "brain-breast-bone" circuit. The physiological bone resorption during reproduction does not normally cause fractures or persistent osteoporosis. Women who experience fracture are likely to have other causes of bone loss. PMID:27157104

  3. Biophotonics and Bone Biology

    NASA Technical Reports Server (NTRS)

    Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

    2004-01-01

    One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

  4. Hypercalciuric Bone Disease

    NASA Astrophysics Data System (ADS)

    Favus, Murray J.

    2008-09-01

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

  5. Plagued by Turnover? Train Your Managers.

    ERIC Educational Resources Information Center

    Dobbs, Kevin

    2000-01-01

    Dissatisfaction with managers is a major cause of employee turnover The Charles Schwab Corporation surveys employees annually and holds employee focus groups and online town meetings. The information is used for the coaching and training of department heads. (JOW)

  6. Coping with Turnovers in School Food Service.

    ERIC Educational Resources Information Center

    Pannell, Dorothy V.

    1988-01-01

    Labor shortages, cost increases, and turnover have prompted Fairfax County Schools, Virginia, food service managers to offer training programs and recruitment bonuses, to use more convenience foods, and to price out every service. (MLF)

  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. 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

  9. Effect of nutritional substrate on sulfolipids metabolic turnover in isolated renal tubules from rat

    PubMed Central

    NAGAI, Ken-ichi; TADANO-ARITOMI, Keiko; NIIMURA, Yukio; ISHIZUKA, Ineo

    2008-01-01

    Effects of a glycolytic (glucose) and a gluconeogenic renal nutritional substrate (glutamine) on metabolic turnover of sulfolipids, determined as [35S]sulfate incorporation, were compared in renal tubules prepared from well-fed rats. The results showed that the effects of glucose and glutamine, at nearly physiological serum concentration, are quite contrary to each other. Glucose increased the turnover rates of relatively long chain ganglio-series sulfoglycolipids (Gg3Cer II3-sulfate and Gg4Cer II3,IV3-bis-sulfate) (1.7 to 2.4-fold), but not of cholesterol 3-sulfate (0.9-fold). In contrast, glutamine accelerated the turnover rates of relatively short chain sulfoglycolipids (glucosyl sulfatide, galactosyl sulfatide and lactosyl sulfatide) (1.3 to 2.7-fold), as well as cholesterol 3-sulfate (2.4-fold). The possible mechanism which causes these marked differences is also discussed. PMID:18941285

  10. 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. PMID:15877902

  11. [Bone metabolic markers and diagnosis of abnormal bone and calcium metabolism].

    PubMed

    Fukunaga, M; Sone, T

    2001-07-01

    Bone metabolic markers increase in blood or urine, when bone formation or bone resorption accelerates. Reference values of bone metabolic markers are determined in male or female, and in pre- or post-menopause, respectively. Values of bone metabolic markers in most patients with primary osteoporosis were distributed within a reference value, mean+/-1.96 SD. When measured values exceeded a reference values, we should survey a possibility of abnormal calcium or bone metabolism such as primary hyperparathyroidism, renal osteodystrophy, hyperthyroidism and Paget's disease of bone or bone metastasis associated with malignant tumor. PMID:15775589

  12. 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

  13. Zinc-deficient rats have more limited bone recovery during repletion than diet-restricted rats.

    PubMed

    Hosea, Heather J; Taylor, Carla G; Wood, Trisha; Mollard, Rebecca; Weiler, Hope A

    2004-04-01

    The objective of this study was to investigate the effects of dietary zinc deficiency and diet restriction on bone development in growing rats, and to determine whether any adverse effects could be reversed by dietary repletion. Weanling rats were fed either a zinc-deficient diet ad libitum (ZD; <1 mg zinc/kg) or nutritionally complete diet (30 mg zinc/kg) either ad libitum (CTL) or pair-fed to the intake of the ZD group (DR; diet-restricted) for 3 weeks (deficiency phase) and then all groups were fed the zinc-adequate diet ad libitum for 3, 7, or 23 days (repletion phase). Excised femurs were analyzed for bone mineral density (BMD) using dual-energy x-ray absorptiometry, and plasma was analyzed for markers of bone formation (osteocalcin) and resorption (Ratlaps). After the deficiency phase, ZD had lower body weight and reduced femur BMD, zinc, and phosphorus concentrations compared with DR; and these parameters were lower in DR compared with CTL. Femur calcium concentrations were unchanged among the groups. Reduced plasma osteocalcin in ZD and elevated plasma Ratlaps in DR suggested that zinc deficiency limits bone formation while diet restriction accelerates bone resorption activity. After 23 days of repletion, femur size, BMD, and zinc concentrations remained lower in ZD compared with DR and CTL. Body weight and femur phosphorus concentrations remained lower in both ZD and DR compared with CTL after repletion. There were no differences in plasma osteocalcin concentrations after the repletion phase, but the plasma Ratlaps concentrations remained elevated in DR compared with CTL. In summary, both ZD and DR lead to osteopenia during rapid growth, but the mechanisms appear to be due to reduced modeling in ZD and higher turnover in DR. Zinc deficiency was associated with a greater impairment in bone development than diet restriction, and both deficiencies limited bone recovery during repletion in growing rats. PMID:15044713

  14. Spatial turnover in the global avifauna

    PubMed Central

    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

    2007-01-01

    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. PMID:17472910

  15. On gigahertz spectral turnovers in pulsars

    NASA Astrophysics Data System (ADS)

    Rajwade, K.; Lorimer, D. R.; Anderson, L. D.

    2016-01-01

    Pulsars are known to emit non-thermal radio emission that is generally a power-law function of frequency. In some cases, a turnover is seen at frequencies around 100 MHz. Kijak et al. have reported the presence of a new class of `Gigahertz Peaked Spectrum' (GPS) pulsars that show spectral turnovers at frequencies around 1 GHz. We apply a model based on free-free thermal absorption to explain these turnovers in terms of surrounding material such as the dense environments found in H II regions, pulsar wind nebulae, or in cold, partially ionized molecular clouds. We show that the turnover frequency depends on the electron temperature of the environment close to the pulsar, as well as the emission measure along the line of sight. We fitted this model to the radio fluxes of known GPS pulsars and show that it can replicate the GHz turnover. From the thermal absorption model, we demonstrate that normal pulsars would exhibit a GPS-like behaviour if they were in a dense environment. We discuss the application of this model in the context of determining the population of neutron stars within the central parsec of the Galaxy. We show that a non-negligible fraction of this population might exhibit high-frequency spectral turnovers, which has implications on the detectability of these sources in the Galactic Centre.

  16. Doxorubicin enhances nucleosome turnover around promoters.

    PubMed

    Yang, Fan; Kemp, Christopher J; Henikoff, Steven

    2013-05-01

    Doxorubicin is an anthracycline DNA intercalator that is among the most commonly used anticancer drugs. Doxorubicin causes DNA double-strand breaks in rapidly dividing cells, although whether it also affects general chromatin properties is unknown. Here, we use a metabolic labeling strategy to directly measure nucleosome turnover to examine the effect of doxorubicin on chromatin dynamics in squamous cell carcinoma cell lines derived from genetically defined mice. We find that doxorubicin enhances nucleosome turnover around gene promoters and that turnover correlates with gene expression level. Consistent with a direct action of doxorubicin, enhancement of nucleosome turnover around promoters gradually increases with time of exposure to the drug. Interestingly, enhancement occurs both in wild-type cells and in cells lacking either the p53 tumor suppressor gene or the master regulator of the DNA damage response, ATM, suggesting that doxorubicin action on nucleosome dynamics is independent of the DNA damage checkpoint. In addition, another anthracycline drug, aclarubicin, shows similar effects on enhancing nucleosome turnover around promoters. Our results suggest that anthracycline intercalation promotes nucleosome turnover around promoters by its effect on DNA topology, with possible implications for mechanisms of cell killing during cancer chemotherapy. PMID:23602475

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

    PubMed Central

    2013-01-01

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

  18. Ultraviolet-accelerated formation of bone-like apatite on oxidized Ti-24Nb-4Zr-7.9Sn alloy

    NASA Astrophysics Data System (ADS)

    Chen, Min-Fang; Zhang, Jing; You, Chen

    2013-12-01

    A novel method has been developed to rapidly deposit bone-like apatite with the assistance of ultraviolet (UV) light irradiation on the nanostructured titania in the simulated body fluid (SBF). The process has three main steps: Ti-24Nb-4Zr-7.9Sn alloy was heated at 650°C for 3 h, UV-light illumination in air for 4 h and soaking in the SBF for 3 d. A titania coating consisted of main rutile formed on the thermal oxidized Ti-24Nb-4Zr-7.9Sn alloy. The UV not only converted the rutile surface from hydrophilic to hydrophobic but also stimulated high surface activity. After 4 h UV illumination, the contents of Ti3+ and hydroxyl groups on the oxidized sample were increased, while that of lattice O decreased. After 3 d of soaking in the SBF, a compact and uniform layer of carbonated hydroxyapatite (CHA) particles was formed on the UV-illuminated rutile surface whereas there was a few of HA to be viewed on the surface of as-oxidized Ti-24Nb-4Zr-7.9Sn alloy. Our study demonstrates a simple, fast and cost-effective technique for growing bone-like apatite on titanium alloys.

  19. 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

  20. Addressing employee turnover and retention: keeping your valued performers.

    PubMed

    McConnell, Charles R

    2011-01-01

    Employee turnover and employee retention are inextricably linked; to control turnover is to enhance retention. Turnover is a relatively simple concept; however, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some that can be corrected and some that cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role; every improvement in turnover is a direct improvement in retention, with eventual positive effects on the bottom line. PMID:21808181

  1. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  2. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  3. 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

  4. 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

  5. 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...

  6. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change Over Time Matters

    PubMed Central

    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

  7. 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

  8. A decade of bisphosphonate bone complications: what it has taught us about bone physiology.

    PubMed

    Marx, Robert E

    2014-01-01

    While the AIDS epidemic of the 1980s taught the medical and dental professions much about immune cells and the immune system's cellular relationships, the bisphosphonate-induced osteonecrosis epidemic of the past decade has taught these same professions much about bone turnover, bone cell cross talk, the response and functional relationship of bone cells to loading, and drug effects on cellular dynamic relationships. The present article explores the literature as well as both evidence- and experience-based data to discuss known bone pathologies and physiologic mechanisms as well as uncover new findings: (1) bone remodeling is the mechanism by which bone adapts to loading stresses, termed either bone modeling or Wolff's law, and it is also the mechanism for bone renewal; (2) osteoclastic bone resorption triggers bone renewal at a rate of about 0.7%/day by its release of growth factors; (3) bisphosphonates prevent the renewal of old and injured bone, thus making it brittle and more likely to fracture over time; (4) bisphosphonates have a half-life in bone of 11 years because of their irreversible binding to bone via their central carbon atom; (5) when administered intravenously, bisphosphonate loads bone and accumulates in bone 142.8 times faster than when administered orally; (6) osteoclastic resorption of bisphosphonate-loaded bone results in osteoclast death in which the cell bursts, releasing the bisphosphonate molecules to reenter the local bone or bone marrow in a re-dosing effect; (7) endosteal osteoblasts are dependent on the osteoclastic resorption/growth factor release/new bone formation mechanism of bone renewal, whereas periosteal osteoblasts are not; and (8) it is likely that endosteal osteoblasts and periosteal osteoblasts have different cell membrane receptors and arise from separate embryologic niches. PMID:24683588

  9. Bone scan

    MedlinePlus

    ... scan is an imaging test used to diagnose bone diseases and find out how severe they are. How ... a 3-phase bone scan. To evaluate metastatic bone disease, images are taken only after the 3- to ...

  10. 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 ...

  11. Bone scan

    MedlinePlus

    A bone scan is an imaging test used to diagnose bone diseases and find out how severe they are. ... A bone scan involves injecting a very small amount of radioactive material (radiotracer) into a vein. The substance travels through ...

  12. Bone Density

    MedlinePlus

    ... bone health. It compares your bone density, or mass, to that of a healthy person who is ... Whether your osteoporosis treatment is working Low bone mass that is not low enough to be osteoporosis ...

  13. 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 ...

  14. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  15. Turnover of Grassland Roots in Mountain Ecosystems Revealed by Their Radiocarbon Signature: Role of Temperature and Management

    PubMed Central

    Leifeld, Jens; Meyer, Stefanie; Budge, Karen; Sebastia, Maria Teresa; Zimmermann, Michael; Fuhrer, Juerg

    2015-01-01

    Root turnover is an important carbon flux component in grassland ecosystems because it replenishes substantial parts of carbon lost from soil via heterotrophic respiration and leaching. Among the various methods to estimate root turnover, the root’s radiocarbon signature has rarely been applied to grassland soils previously, although the value of this approach is known from studies in forest soils. In this paper, we utilize the root’s radiocarbon signatures, at 25 plots, in mountain grasslands of the montane to alpine zone of Europe. We place the results in context of a global data base on root turnover and discuss driving factors. Root turnover rates were similar to those of a subsample of the global data, comprising a similar temperature range, but measured with different approaches, indicating that the radiocarbon method gives reliable, plausible and comparable results. Root turnover rates (0.06–1.0 y-1) scaled significantly and exponentially with mean annual temperatures. Root turnover rates indicated no trend with soil depth. The temperature sensitivity was significantly higher in mountain grassland, compared to the global data set, suggesting additional factors influencing root turnover. Information on management intensity from the 25 plots reveals that root turnover may be accelerated under intensive and moderate management compared to low intensity or semi-natural conditions. Because management intensity, in the studied ecosystems, co-varied with temperature, estimates on root turnover, based on mean annual temperature alone, may be biased. A greater recognition of management as a driver for root dynamics is warranted when effects of climatic change on belowground carbon dynamics are studied in mountain grasslands. PMID:25734640

  16. Climate change amplifies gross nitrogen turnover in montane grasslands of Central Europe both in summer and winter seasons

    NASA Astrophysics Data System (ADS)

    Chen, Zhe; Wang, Changhui; Unteregelsbacher, Sebastian; Lu, Haiyan; Gschwendtner, Silvia; Gasche, Rainer; Kolar, Allison; Schloter, Michael; Butterbach-Bahl, Klaus; Dannenmann, Michael

    2016-04-01

    The carbon and nitrogen rich soils of montane grasslands are exposed to above average warming and to altered precipitation patterns as a result of global change. In order to investigate the consequences of climatic change for soil nitrogen turnover, we translocated intact plant-soil mesocosms along an elevational gradient. Following three years of equilibration, we monitored the dynamics of gross nitrogen turnover and ammonia oxidizing microbes over an entire year. Gross nitrogen turnover and gene levels of ammonia oxidizing bacteria (AOB) and archaea (AOA) showed pronounced seasonal dynamics. While both summer and winter periods equally contributed to cumulative annual N turnover, the highest gross N turnover and abundance of ammonia oxidizers were observed in frozen soil of climate change sites due to physical liberation of organic substrates and their rapid turnover in the unfrozen soil water film. The control site never experienced soil freezing due to a significant insulating snowpack. Climate change conditions accelerated gross N mineralization by 250% on average. The AOB community benefited more from increased soil ammonium production under climate change conditions than the AOA community and thus accounted for a significant increase in gross nitrification rates. Climate change impacts were restricted to the 2-6 cm topsoil and rarely occurred at 12-16 cm depth, where generally much lower N turnover was observed. Mineralization pulses in a changing climate may result in soil organic matter loss with their associated negative impacts on key soil functions. In this context, N cycling processes in frozen soil can be a hot spot for gross N turnover and thus be of paramount importance for understanding seasonal patterns, annual sum of N turnover and possible climate change feedbacks.

  17. Climate change amplifies gross nitrogen turnover in montane grasslands of Central Europe in both summer and winter seasons.

    PubMed

    Wang, Changhui; Chen, Zhe; Unteregelsbacher, Sebastian; Lu, Haiyan; Gschwendtner, Silvia; Gasche, Rainer; Kolar, Allison; Schloter, Michael; Kiese, Ralf; Butterbach-Bahl, Klaus; Dannenmann, Michael

    2016-09-01

    The carbon- and nitrogen-rich soils of montane grasslands are exposed to above-average warming and to altered precipitation patterns as a result of global change. To investigate the consequences of climatic change for soil nitrogen turnover, we translocated intact plant-soil mesocosms along an elevational gradient, resulting in an increase of the mean annual temperature by approx. 2 °C while decreasing precipitation from approx. 1500 to 1000 mm. Following three years of equilibration, we monitored the dynamics of gross nitrogen turnover and ammonia-oxidizing bacteria (AOB) and archaea (AOA) in soils over an entire year. Gross nitrogen turnover and gene levels of AOB and AOA showed pronounced seasonal dynamics. Both summer and winter periods equally contributed to cumulative annual N turnover. However, highest gross N turnover and abundance of ammonia oxidizers were observed in frozen soil of the climate change site, likely due to physical liberation of organic substrates and their rapid turnover in the unfrozen soil water film. This effect was not observed at the control site, where soil freezing did not occur due to a significant insulating snowpack. Climate change conditions accelerated gross nitrogen mineralization by 250% on average. Increased N mineralization significantly stimulated gross nitrification by AOB rather than by AOA. However, climate change impacts were restricted to the 2-6 cm topsoil and rarely occurred at 12-16 cm depth, where generally much lower N turnover was observed. Our study shows that significant mineralization pulses occur under changing climate, which is likely to result in soil organic matter losses with their associated negative impacts on key soil functions. We also show that N cycling processes in frozen soil can be hot moments for N turnover and thus are of paramount importance for understanding seasonal patterns, annual sum of N turnover and possible climate change feedbacks. PMID:27173913

  18. Progesterone and Bone: Actions Promoting Bone Health in Women

    PubMed Central

    Seifert-Klauss, Vanadin; Prior, Jerilynn C.

    2010-01-01

    Estradiol (E2) and progesterone (P4) collaborate within bone remodelling on resorption (E2) and formation (P4). We integrate evidence that P4 may prevent and, with antiresorptives, treat women's osteoporosis. P4 stimulates osteoblast differentiation in vitro. Menarche (E2) and onset of ovulation (P4) both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD) related to subclinical ovulatory disturbances (SODs). Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to P4 deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P4 in postmenopausal women with increased bone turnover. However, 5 studies of E2-MPA co-therapy show greater BMD increases versus E2 alone. P4 fracture data are lacking. P4 prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD. PMID:21052538

  19. 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

  20. An investigation of the neutron flux in bone-fluorine phantoms comparing accelerator based in vivo neutron activation analysis and FLUKA simulation data

    NASA Astrophysics Data System (ADS)

    Mostafaei, F.; McNeill, F. E.; Chettle, D. R.; Matysiak, W.; Bhatia, C.; Prestwich, W. V.

    2015-01-01

    We have tested the Monte Carlo code FLUKA for its ability to assist in the development of a better system for the in vivo measurement of fluorine. We used it to create a neutron flux map of the inside of the in vivo neutron activation analysis irradiation cavity at the McMaster Accelerator Laboratory. The cavity is used in a system that has been developed for assessment of fluorine levels in the human hand. This study was undertaken to (i) assess the FLUKA code, (ii) find the optimal hand position inside the cavity and assess the effects on precision of a hand being in a non-optimal position and (iii) to determine the best location for our γ-ray detection system within the accelerator beam hall. Simulation estimates were performed using FLUKA. Experimental measurements of the neutron flux were performed using Mn wires. The activation of the wires was measured inside (1) an empty bottle, (2) a bottle containing water, (3) a bottle covered with cadmium and (4) a dry powder-based fluorine phantom. FLUKA was used to simulate the irradiation cavity, and used to estimate the neutron flux in different positions both inside, and external to, the cavity. The experimental results were found to be consistent with the Monte Carlo simulated neutron flux. Both experiment and simulation showed that there is an optimal position in the cavity, but that the effect on the thermal flux of a hand being in a non-optimal position is less than 20%, which will result in a less than 10% effect on the measurement precision. FLUKA appears to be a code that can be useful for modeling of this type of experimental system.

  1. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  2. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  3. Risk factors, endothelial cell turnover and lipid transport in atherogenesis.

    PubMed

    Lin, S J

    1996-11-01

    transendothelial macromolecular transport, which may have some implications in increasing lipid entry and thus, accelerating atherogenesis. Animal experiments were performed in adult male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) normotensive rats, and Sprague-Dawley (SD) rats. SHRs were used as hypertensive group with WKY rats as normotensive control. SD rats were given nicotine at a dose of 5 mg/Kg body wt/ day in their drinking water to mimic smoking effect over a period of 6 weeks. Diabetes was induced in SD rats by single intraperitoneal injection of 60 mg/Kg body wt of streptozotocin. The duration of diabetes was 6 weeks. Also, SD rats were fed a diet containing 5% cholesterol for 6 weeks to induce hyperlipidemia. Age-matched rats of comparable number served as control for each experimental group. In en face preparations of thoracic aorta, mitotic endothelial cells were identified by hematoxylin staining, immunoglobulin G-containing dying or dead endothelial cells were detected by an indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was visualized and quantified by fluorescence microscopy. The results showed that SHR, chronic oral nicotine-treated rats, diabetic, rats, and hyperlipidemic rats, when compared to control rats, had higher values for the frequency of endothelial cell death and the number density of EBA leaky foci in the aorta. These findings suggested that hypertension, cigarette smoking, diabetes mellitus, and hyperlipidemia become risk factors in atherogenesis by increasing the rate of arterial endothelial cell turnover and the associated endothelial cell turnover and the to the consequent enhanced entry of atherogenic lipoproteins into the arterial wall and accelerated atherogenesis. PMID:9037845

  4. Surgically Assisted Orthodontics: Use of Piezocision in a Case of Oligodontia to Accelerate the Rate of Tooth Movement.

    PubMed

    Sabrish, Sharanya; Pattabiraman, Vinod; Rizvi, Syed Omar Aziz; Kumar, Shravan

    2016-01-01

    Conventionally the use of surgical assisted tooth movement is to hasten orthodontic tooth movement. In this article, a case of 13 year-old male with oligodontia has been described in whom piezocision has been used to improve bone turnover and remodeling in long standing edentulous spaces which have less medullary bone and more cortical bone. PMID:27319046

  5. Dendritic Cell Depletion and Repopulation in the Lung after Irradiation and Bone Marrow Transplantation in Mice

    PubMed Central

    Hahn, Ines; Klaus, Anna; Maus, Regina; Christman, John W.; Welte, Tobias

    2011-01-01

    Dendritic cells (DCs) are essential for innate and adaptive immunity, but are purported to exhibit variable radiosensitivity in response to irradiation in various bone marrow transplantation (BMT) protocols. To address this controversy, we analyzed the magnitude of depletion and repopulation of both lung CD11bpos DC and CD103pos DC subsets in response to irradiation and BMT in a murine model. In our study, CD45.2pos donor bone marrow cells were transplanted into irradiated CD45.1pos recipient mice to examine the depletion of recipient DC subsets and the repopulation of donor DC subsets. We observed an apoptosis-mediated and necrosis-mediated depletion (> 90%) of the recipient CD103pos DC subset, and only a 50–60% depletion of recipient CD11bpos DCs from lung parenchymal tissue on Days 3 and 5, whereas recipient alveolar and lung macrophages were much less radiosensitive, showing an approximately 50% depletion by Days 14–21 after treatment. A repopulation of lung tissue with donor DC subsets had occurred by Days 10 and 28 for CD11bpos DCs and CD103pos DCs, whereas alveolar and lung macrophages were repopulated by 6 and 10 weeks after treatment. Furthermore, the infection of mice with Streptococcus pneumoniae further accelerated the turnover of lung DCs and lung macrophage subsets. Our data illustrate the vulnerability of lung CD103pos DCs and CD11bpos DCs to irradiation, and indicate that an accelerated turnover of lung DC subsets occurs, relative to pulmonary and lung macrophages. Our findings may have important implications in the development of adjuvant immune-stimulatory protocols that could reduce the risk of opportunistic infections in patients undergoing BMT. PMID:21177980

  6. 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

  7. Modeling of Trabecular Bone and Lamina Dura Following Selective Alveolar Decortication in Rats

    PubMed Central

    Sebaoun, Jean-David; Kantarci, Alpdogan; Turner, John W.; Carvalho, Roberto S.; Van Dyke, Thomas E.; Ferguson, Donald J.

    2008-01-01

    Background: Modifying the balance between resorption and apposition through selectively injuring the cortical plate of the alveolus has been an approach to speed tooth movement and is referred to as periodontally accelerated osteogenic orthodontics. The aim of this study was to investigate the alveolar response to corticotomy as a function of time and proximity to the surgical injury in a rat model. Methods: Maxillary buccal and lingual cortical plates were injured in 36 healthy adult rats adjacent to the upper left first molars. Twenty-four animals were euthanized at 3, 7, or 11 weeks. In one group, the maxillae were removed and stripped of soft tissues, and histomorphometric analysis was performed to study alveolar spongiosa and periodontal ligament (PDL) modeling dynamics. Catabolic activity was analyzed with tartrate-resistant acid phosphatase–positive osteoclasts and preosteoclasts. Anabolic actions were measured using a fluorescent vital bone stain series followed by sacrifice at 30 and 51 days. To further analyze the new bone formation, a separate group of animals were fed with calcein fluorescent stain and processed for non-decalcified fluorescent stain histology. Results: At 3 weeks, the surgery group had significantly (P <0.05) less calcified spongiosa bone surface, greater periodontal ligament surface, higher osteoclast number, and greater lamina dura apposition width. The catabolic activity (osteoclast count) and anabolic activity (apposition rate) were three-fold greater, calcified spongiosa decreased by two-fold, and PDL surface increased by two-fold. Surgical injury to the alveolus that induced a significant increase in tissue turnover by week 3 dissipated to a steady state by postoperative week 11. The impact of the injury was localized to the area immediately adjacent to the decortication injury. Conclusion: Selective alveolar decortication induced increased turnover of alveolar spongiosa, and the activity was localized; dramatic escalation of

  8. Mitochondrial protein turnover: methods to measure turnover rates on a large scale

    PubMed Central

    Chan, X’avia CY; Black, Caitlin M; Lin, Amanda J; Ping, Peipei; Lau, Edward

    2016-01-01

    Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. PMID:25451168

  9. 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. PMID:26585891

  10. Short bones

    MedlinePlus

    Short bones in the human body are often cube-like, their length, width, and height are all about the same. Short bones include the carpal bones of the hands and wrist, and the tarsal bones of the feet and ankles.

  11. Bioactive Silica Nanoparticles Reverse Age-Associated Bone Loss in Mice

    PubMed Central

    Vikulina, Tatyana; Roser-Page, Susanne; Lee, Jin-Kyu; Beck, George R.

    2015-01-01

    We recently reported that in vitro, engineered 50 nm spherical silica nanoparticles promote the differentiation and activity of bone building osteoblasts but suppress that of bone-resorbing osteoclasts. Furthermore, these nanoparticles promote bone accretion in young mice in vivo. In the present study the capacity of these nanoparticles to reverse bone loss in aged mice, a model of human senile osteoporosis, was investigated. Aged mice received nanoparticles weekly and bone mineral density (BMD), bone structure, and bone turnover was quantified. Our data revealed a significant increase in BMD, bone volume, and biochemical markers of bone formation. Biochemical and histological examinations failed to identify any abnormalities caused by nanoparticle administration. Our studies demonstrate that silica nanoparticles effectively blunt and reverse age-associated bone loss in mice by a mechanism involving promotion of bone formation. The data suggest that osteogenic silica nanoparticles may be a safe and effective therapeutic for counteracting age-associated bone loss. PMID:25680544

  12. 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

  13. A Turnover Model for the Mexican Maquiladoras.

    ERIC Educational Resources Information Center

    Maertz, Carl P.; Stevens, Michael J.; Campion, Michael A.

    2003-01-01

    From interviews with 47 Mexican maquiladora workers, a model of voluntary turnover was created and compared with models from the United States, Canada, England, and Australia. Despite similarities, the cultural and economic environment affected the precise content of antecedents in the Mexican model. (Contains 63 references.) (SK)

  14. 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…

  15. 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

  16. 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…

  17. 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…

  18. Cusp catastrophe model of employee turnover.

    PubMed

    Sheridan, J E; Abelson, M A

    1983-09-01

    A cusp catastrophe model is developed to explain job turnover of nursing employees. The temporal dynamics of the catastrophe model suggest that leavers experience lower organization commitment than do stayers prior to termination. Leavers' perceptions of job tension and commitment appear to cross the threshold levels prior to the termination dates. PMID:10262614

  19. 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…

  20. 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'…

  1. Costing Child Protective Services Staff Turnover.

    ERIC Educational Resources Information Center

    Graef, Michelle I.; Hill, Erick L.

    2000-01-01

    Details process of determining a child welfare agency's actual dollar costs directly attributed to protective services staff turnover, using the agency's human resources database and interviews with administrative personnel. Provides formulas and process for calculating specific cost elements due to employee separation, replacement, and training.…

  2. 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…

  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. Looking for a Challenge? Watch That Labour Turnover!

    ERIC Educational Resources Information Center

    Wilkinson, Roderick

    1975-01-01

    Low labor turnover is an essential factor in the success of an enterprise. Steps in dealing with the turnover problem include: establish the objective, get the facts, decide what to do, take action, and check results. (MW)

  5. Staff turnover: occasional friend, frequent foe, and continuing frustration.

    PubMed

    McConnell, C R

    1999-09-01

    Turnover appears to be a relatively simple concept. However, considerable confusion results when discussing turnover because of differences in how it is defined--what is counted, how it is counted, and how the rate of turnover is expressed. Turnover is also costly, although not enough attention is paid to turnover's cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some which can be corrected and some which cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role. PMID:10747463

  6. A concept analysis of turnover intention: implications for nursing management.

    PubMed

    Takase, Miyuki

    2010-01-01

    This paper provides a review and concept analysis of turnover intention. The aim was to promote Nurse Managers' understanding of the meanings and mechanisms of turnover intention, which could help them counteract nurse turnover. Sixty-six papers published between January 1998 and August 2007 were collected from CINAHL, PubMed, and PsycINFO databases, and were subjected to Rogers' concept analysis. The results showed that turnover intention is a multi-stage process involving the voluntary departure of employees from their current position, and is triggered by negative psychological responses to internal/external job context. These psychological responses evolve into withdrawal cognition and behaviours, and lead to actual turnover. To prevent nurse turnover, Nurse Managers should closely observe the internal and external causes of turnover, and the stage of nurses' turnover intention. PMID:20394269

  7. Work-Related Variables and Turnover Intention among Registered Nurses.

    ERIC Educational Resources Information Center

    Pooyan, Abdullah; And Others

    1990-01-01

    Health institutions have become more interested in the causes of job turnover among registered nurses. Proper management of job turnover can improve the financial health and long-term survival of health care institutions. (Author)

  8. Impact of lanthanum carbonate on cortical bone in dialysis patients with adynamic bone disease.

    PubMed

    Yajima, Aiji; Inaba, Masaaki; Tominaga, Yoshihiro; Tanaka, Motoko; Otsubo, Shigeru; Nitta, Kosaku; Ito, Akemi; Satoh, Shigeru

    2013-04-01

    Among the most serious problems in patients with chronic kidney disease (CKD) is fragility of cortical bone caused by cortical thinning and increased cortical porosity; the cortical fragility is sometimes irreversible, with fractures generally initiating from cortical bone. Therefore, development of treatments for problems of cortical bone is urgently desired. Cortical bone has the three surfaces, including the periosteal surface, intracortical spaces and endocortical surface. Bone turnover at the endocortical surface and intracortical resorption spaces are increased as compared with that at cancellous surface. Bone growth sometimes depends on apposition at the periosteal surface. We treated hyperphosphatemia in two hemodialysis patients with adynamic bone disease with 750-1500 mg/day of lanthanum carbonate, which is a non-calcium containing phosphate binder; the treatment resulted in a decrease of the serum phosphorus levels (P levels), without significant change of the serum intact parathyroid hormone levels. We now report that treatment of these patients with lanthanum carbonate increased mineralization of the periosteal surface, increased bone mass within the intracortical resorption spaces and increased mineralization of the minimodeling surface at the endocortical surface. In addition, woven bone volume in cortical bone was decreased and mineralization of bone units, namely, osteons, was increased. Although these findings were not observed across all surfaces of the cortical bone in the patients, it is expected that lanthanum carbonate would increase the cortical stability in CKD patients, with consequent reduction in the fracture rate in these patients. PMID:23586512

  9. Gaussian Process Modeling of Protein Turnover.

    PubMed

    Rahman, Mahbubur; Previs, Stephen F; Kasumov, Takhar; Sadygov, Rovshan G

    2016-07-01

    We describe a stochastic model to compute in vivo protein turnover rate constants from stable-isotope labeling and high-throughput liquid chromatography-mass spectrometry experiments. We show that the often-used one- and two-compartment nonstochastic models allow explicit solutions from the corresponding stochastic differential equations. The resulting stochastic process is a Gaussian processes with Ornstein-Uhlenbeck covariance matrix. We applied the stochastic model to a large-scale data set from (15)N labeling and compared its performance metrics with those of the nonstochastic curve fitting. The comparison showed that for more than 99% of proteins, the stochastic model produced better fits to the experimental data (based on residual sum of squares). The model was used for extracting protein-decay rate constants from mouse brain (slow turnover) and liver (fast turnover) samples. We found that the most affected (compared to two-exponent curve fitting) results were those for liver proteins. The ratio of the median of degradation rate constants of liver proteins to those of brain proteins increased 4-fold in stochastic modeling compared to the two-exponent fitting. Stochastic modeling predicted stronger differences of protein turnover processes between mouse liver and brain than previously estimated. The model is independent of the labeling isotope. To show this, we also applied the model to protein turnover studied in induced heart failure in rats, in which metabolic labeling was achieved by administering heavy water. No changes in the model were necessary for adapting to heavy-water labeling. The approach has been implemented in a freely available R code. PMID:27229456

  10. 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;…

  11. 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…

  12. 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

  13. 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…

  14. Job Turnover and Job Satisfaction among Nursing Home Aides.

    ERIC Educational Resources Information Center

    Waxman, Howard M.; And Others

    1984-01-01

    Interviewed 234 aides in seven nursing homes concerning job turnover rate, job satisfaction, and perception of milieu. A positive association found between turnover rate and aides' perceptions of the homes' order, organization, and control suggested that job turnover would lessen with more involvement in the decision-making process. (JAC)

  15. Employee Turnover in the Federal Government. A Special Study.

    ERIC Educational Resources Information Center

    Musell, R. Mark

    A study of employee turnover in the Federal government showed that in 1984, about 195,000 full-time, nonpostal Federal workers with permanent appointments left Federal jobs or transferred to other Federal agencies--representing a turnover rate of 11.5 percent. The turnover was about three percentage points higher for white-collar workers than for…

  16. 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…

  17. Job Satisfaction, Commitment, Withdrawal Cognitions and Turnover: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Kerber, Kenneth W.; Campbell, James P.

    Recent research on organizational turnover has examined the validity of the turnover decision process, in particular, the model of employee turnover proposed by Mobley (1977). This study followed-up on a previous (Kerber and Campbell, 1986) study of new employees of a large computer company in which participants completed a questionnaire that…

  18. 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

  19. 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

  20. 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 ...

  1. High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

    PubMed Central

    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

  2. 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

  3. 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

  4. Effects of myokines on bone.

    PubMed

    Kaji, Hiroshi

    2016-01-01

    The links between muscle and bone have been recently examined because of the increasing number of patients with osteoporosis and sarcopenia. Myokines are skeletal muscle-derived humoral cytokines and growth factors, which exert physiological and pathological functions in various distant organs, including the regulation of glucose, energy and bone metabolism. Myostatin is a crucial myokine, the expression of which is mainly limited to muscle tissues. The inhibition of myostatin signaling increases bone remodeling, bone mass and muscle mass, and it may provide a target for the treatment of both sarcopenia and osteoporosis. As myostatin is involved in osteoclast formation and bone destruction in rheumatoid arthritis, myostatin may be a target myokine for the treatment of accelerated bone resorption and joint destruction in rheumatoid arthritis. Numerous other myokines, including transforming growth factor-β, follistatin, insulin-like growth factor-I, fibroblast growth factor-2, osteoglycin, FAM5C, irisin, interleukin (IL)-6, leukemia inhibitory factor, IL-7, IL-15, monocyte chemoattractant protein-1, ciliary neurotrophic factor, osteonectin and matrix metalloproteinase 2, also affect bone cells in various manners. However, the effects of myokines on bone metabolism are largely unknown. Further research is expected to clarify the interaction between muscle and bone, which may lead to greater diagnosis and the development of the treatment for muscle and bone disorders, such as osteoporosis and sarcopenia. PMID:27579164

  5. 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. PMID:10296903

  6. Turnover intention in new graduate nurses: a multivariate analysis

    PubMed Central

    Beecroft, Pauline C; Dorey, Frederick; Wenten, Madé

    2008-01-01

    Title Turnover intention in new graduate nurses: a multivariate analysis Aim This paper is a report of a study to determine the relationship of new nurse turnover intent with individual characteristics, work environment variables and organizational factors and to compare new nurse turnover with actual turnover in the 18 months of employment following completion of a residency. Background Because of their influence on patient safety and health outcomes nurse turnover and turnover intent have received considerable attention worldwide. When nurse staffing is inadequate, especially during nursing shortages, unfavourable clinical outcomes have been documented. Method Prospective data collection took place from 1999 to 2006 with 889 new paediatric nurses who completed the same residency. Scores on study instruments were related to likelihood of turnover intent using logistic regression analysis models. Relationships between turnover intent and actual turnover were compared using Kaplan–Meier survivorship. Results The final model demonstrated that older respondents were more likely to have turnover intent if they did not get their ward choice. Also higher scores on work environment and organizational characteristics contributed to likelihood that the new nurse would not be in the turnover intent group. These factors distinguish a new nurse with turnover intent from one without 79% of the time. Increased seeking of social support was related to turnover intent and older new graduates were more likely to be in the turnover intent group if they did not get their ward choice. Conclusion When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds against turnover intent decrease. What is already known about this topic There is concern in many countries about nurse turnover and the resulting effects on patient safety and quality of care. Decreasing ability to recruit experienced nurses has increased the emphasis on

  7. Plasma accelerators

    SciTech Connect

    Ruth, R.D.; Chen, P.

    1986-03-01

    In this paper we discuss plasma accelerators which might provide high gradient accelerating fields suitable for TeV linear colliders. In particular we discuss two types of plasma accelerators which have been proposed, the Plasma Beat Wave Accelerator and the Plasma Wake Field Accelerator. We show that the electric fields in the plasma for both schemes are very similar, and thus the dynamics of the driven beams are very similar. The differences appear in the parameters associated with the driving beams. In particular to obtain a given accelerating gradient, the Plasma Wake Field Accelerator has a higher efficiency and a lower total energy for the driving beam. Finally, we show for the Plasma Wake Field Accelerator that one can accelerate high quality low emittance beams and, in principle, obtain efficiencies and energy spreads comparable to those obtained with conventional techniques.

  8. 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.

  9. Bone tumor

    MedlinePlus

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  10. 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 ...

  11. 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

  12. Bone Balance within a Cortical BMU: Local Controls of Bone Resorption and Formation

    PubMed Central

    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

  13. Health Care Workplace Discrimination and Physician Turnover

    PubMed Central

    Nunez-Smith, Marcella; Pilgrim, Nanlesta; Wynia, Matthew; Desai, Mayur M.; Bright, Cedric; Krumholz, Harlan M.; Bradley, Elizabeth H.

    2013-01-01

    Objective To examine the association between physician race/ethnicity, workplace discrimination, and physician job turnover. Methods Cross-sectional, national survey conducted in 2006–2007 of practicing physicians [n = 529] randomly identified via the American Medical Association Masterfile and The National Medical Association membership roster. We assessed the relationships between career racial/ethnic discrimination at work and several career-related dependent variables, including 2 measures of physician turnover, career satisfaction, and contemplation of career change. We used standard frequency analyses, odds ratios and χ2 statistics, and multivariate logistic regression modeling to evaluate these associations. Results Physicians who self-identified as nonmajority were significantly more likely to have left at least 1 job because of workplace discrimination (black, 29%; Asian, 24%; other race, 21%; Hispanic/Latino, 20%; white, 9%). In multivariate models, having experienced racial/ethnic discrimination at work was associated with high job turnover [adjusted odes ratio, 2.7; 95% CI, 1.4–4.9]. Among physicians who experienced work-place discrimination, only 45% of physicians were satisfied with their careers (vs 88% among those who had not experienced workplace discrimination, p value < .01], and 40% were con-templating a career change (vs 10% among those who had not experienced workplace discrimination, p value < .001). Conclusion Workplace discrimination is associated with physician job turnover, career dissatisfaction, and contemplation of career change. These findings underscore the importance of monitoring for workplace discrimination and responding when opportunities for intervention and retention still exist. PMID:20070016

  14. 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.

  15. 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.

  16. Bone cement

    PubMed Central

    Vaishya, Raju; Chauhan, Mayank; Vaish, Abhishek

    2013-01-01

    The knowledge about the bone cement is of paramount importance to all Orthopaedic surgeons. Although the bone cement had been the gold standard in the field of joint replacement surgery, its use has somewhat decreased because of the advent of press-fit implants which encourages bone in growth. The shortcomings, side effects and toxicity of the bone cement are being addressed recently. More research is needed and continues in the field of nanoparticle additives, enhanced bone–cement interface etc. PMID:26403875

  17. Bone Analyzer

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The danger of disuse osteoporosis under weightless condition in space led to extensive research into measurements of bone stiffness and mass by the Biomedical Research Division of Ames and Stanford University. Through its Technology Utilization Program, NASA funded an advanced SOBSA, a microprocessor-controlled bone probe system. SOBSA determines bone stiffness by measuring responses to an electromagnetic shaker. With this information, a physician can identify bone disease, measure deterioration and prescribe necessary therapy. The system is now undergoing further testing.

  18. 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

  19. Persistence of the fluoroquinolone antibiotic difloxacin in soil and lacking effects on nitrogen turnover.

    PubMed

    Rosendahl, Ingrid; Siemens, Jan; Kindler, Reimo; Groeneweg, Joost; Zimmermann, Judith; Czerwinski, Sonja; Lamshöft, Marc; Laabs, Volker; Wilke, Berndt-Michael; Vereecken, Harry; Amelung, Wulf

    2012-01-01

    The environmental risks caused by the use of fluoroquinolone antibiotics in human therapeutics and animal husbandry are associated with their persistence and (bio)accessibility in soil. To assess these aspects, we administered difloxacin to pigs and applied the contaminated manure to soil. We then evaluated the dissipation and sequestration of difloxacin in soil in the absence and presence of plants within a laboratory trial, a mesocosm trial, and a field trial. A sequential extraction yielded antibiotic fractions of differing binding strength. We also assessed the antibiotic's effects on nitrogen turnover in soil (potential nitrification and denitrification). Difloxacin was hardly (bio)accessible and was very persistent under all conditions studied (dissipation half-life in bulk soil, >217 d), rapidly forming nonextractable residues. Although varying environmental conditions did not affect persistence, dissipation was accelerated in soil surrounding plant roots. Effects on nitrogen turnover were limited due to the compound's strong binding and small (bio)accessibility despite its persistence. PMID:22751072

  20. 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 ...

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

    PubMed

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

    2013-08-01

    Various biochemical markers help to evaluate the state of bone turnover in humans and could be used during the peri-parturient period in dairy cows when calcium (Ca) metabolism changes dramatically. To investigate this, the peri-partum characteristics of serum bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were investigated. Both serum BAP activity and urinary DPD concentrations were increased and demonstrated wide variability in younger animals, and these findings were consistent with other bone turnover markers. Around the time of parturition, serum Ca concentration and serum BAP activity in multiparous cows were significantly lower than in primiparous cows, but urinary DPD concentration was unchanged. The use of BAP as a bone formation marker appears to be valuable for evaluating bone remodelling status in cows, but the specificity of the test needs to be confirmed. The DPD/BAP ratio around parturition demonstrated a clear difference in bone turnover status between the two parity groups with multiparous cows demonstrating increased signs of bone resorption compared with primiparous cows, corresponding to the Ca requirement for milk production. In future studies, the applicability of the ratio of bone resorption marker to bone formation marker should be evaluated for bone turnover assessment. PMID:23422881

  2. Bone and body mass changes during space flight

    NASA Astrophysics Data System (ADS)

    Schneider, V.; Oganov, V.; LeBlanc, A.; Rakmonov, A.; Taggart, L.; Bakulin, A.; Huntoon, C.; Grigoriev, A.; Varonin, L.

    Long duration space flight has shown us that humans have significant bone loss and mineral changes because they are living in microgravity. Skylab and the longer Salyut and Mir missions, are providing us useful data and allowing us to explore the mechanism involved in skeletal turnover. Bone redistribution occurs throughout space flight with bone loss predominately in the weight bearing bones of posture and locomotion. The primary health hazards which may occur during space flight induced by skeletal changes include signs and symptoms of hypercalcemia, and the risk of kidney stones and metastatic calcification. After flight lengthy recovery of bone mass and the possible increase in the risk of bone fracture should be considered. Continued research studies are being directed toward determining the mechanisms by which bone is lost in space and developing more effective countermeasures by both the US (Schneider and McDonald, 1984 and Schneider, LeBlanc & Huntoon, 1993) and Russian (Grigoriev et. al., 1989) space programs.

  3. 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

  4. Dynamic aspects of voluntary turnover: an integrated approach to curvilinearity in the performance-turnover relationship.

    PubMed

    Becker, William J; Cropanzano, Russell

    2011-03-01

    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 downward performance change may increase the likelihood of organizational separation. Drawing on decision theory, we propose and test an integrative framework. This approach incorporates both of these earlier models. Specifically, we argue that individuals are most likely to voluntarily exit when they are below-average performers who are also experiencing a downward performance change. Furthermore, the interaction between this downward change and performance partially accounts for the curvilinear relationship proposed by the push-pull model. Findings from a longitudinal field study supported this integrative theory. PMID:20853945

  5. 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.

  6. 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...

  7. 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

  8. Selenoprotein P is the essential selenium transporter for bones.

    PubMed

    Pietschmann, Nicole; Rijntjes, Eddy; Hoeg, Antonia; Stoedter, Mette; Schweizer, Ulrich; Seemann, Petra; Schomburg, Lutz

    2014-05-01

    Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations. PMID:24626785

  9. Sequential extracts of human bone show differing collagen synthetic rates.

    PubMed

    Babraj, J; Cuthbertson, D J; Rickhuss, P; Meier-Augenstein, W; Smith, K; Bohé, J; Wolfe, R R; Gibson, J N A; Adams, C; Rennie, M J

    2002-04-01

    Type I collagen is the major bone protein. Little is known quantitatively about human bone collagen synthesis in vivo, despite its importance for the understanding of bone formation and turnover. Our aim was to develop a method that could be used for the physiological and pathophysiological investigation of human bone collagen synthesis. We have carried out preliminary studies in patients undergoing hip replacement and in pigs to validate the use of the flooding dose method using (13)C- or (15)N-labelled proline and we have now refined our techniques to allow them to be used in a normal clinical or physiological setting. The results show that the application of a flooding dose causes bone free-proline labelling to equilibrate with that of blood in pigs and human beings, so that only 150 mg of bone will provide enough sample to prepare and measure the labelling of three fractions of bone collagen (dissolved in NaCl, acetic acid and pepsin/acetic acid) which have the same relative labelling (1.0:0.43:0.1) as measured by GC-combustion-isotope ratio MS. The rates of incorporation were substantially faster than in skeletal muscle samples taken at the same time. The results suggest that different fractions of human bone collagen turnover at markedly higher rates than had been previously considered. This approach should allow us to discover how growth and development, food, activity and drugs affect bone collagen turnover and to measure the effects on it of ageing and bone disease. PMID:12023825

  10. Organizational commitment and turnover of nursing home administrators.

    PubMed

    Castle, Nicholas G

    2006-01-01

    In this investigation, the associations between organizational commitment (OC), intent-to-turnover, and actual turnover of a large sample of nursing home administrators (NHAs) are examined. Data used come from a mail survey, from which 632 responses were received from the NHAs (response rate = 63%). The one-year turnover rate of NHAs was 39 percent, and in almost all cases (87%) these NHAs had also exhibited low OC scores. The intent-to-turnover results show thinking about quitting comes before searching for a new position, which in turn both comes before the intention to quit. Multivariate analyses show work overload has a strong and robust association with both intent-to-turnover and turnover of NHAs, and may indicate that NHAs are leaving their positions because they are understaffed. PMID:16648695

  11. The implications of linking the dynamic performance and turnover literatures.

    PubMed

    Sturman, M C; Trevor, C O

    2001-08-01

    This article examines how the literatures of dynamic performance and the performance-turnover relationship inform each other. The nonrandom performance turnover relationship suggests that dynamic performance studies may be biased by their elimination of participants who do not remain for the entire study period. The authors demonstrated that the performance slopes of those who leave an organization differ from the performance slopes of those who remain. This finding suggests that studies of the performance-turnover relationship need to consider employee performance trends when predicting turnover. Replicating and extending the research of D. A. Harrison, M. Virick, and S. William (1996), the authors found that performance changes from the previous month and performance trends measured over a longer time period explained variance in voluntary turnover beyond current performance. Finally, the authors showed that performance trends interacted with current performance in the prediction of voluntary turnover. PMID:11519652

  12. 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

  13. Protein turnover in Azotobacter vinelandii during encystment and germination.

    PubMed

    Ruppen, M E; Garner, G; Sadoff, H L

    1983-12-01

    Protein turnover occurs during differentiation of Azotobacter vinelandii 12837 to the extent of 50% during encystment and 7% during germination. The addition of rifampin at the initiation of encystment prevents encystment and inhibits turnover. In germinating cysts, protein turnover is essential owing to an apparent lack of certain amino acid biosynthetic enzymes. The capacity to synthesize sulfur-containing amino acids from inorganic precursors is regained about halfway through the germination process. PMID:6643391

  14. Short-range intercellular calcium signaling in bone.

    PubMed

    Jørgensen, Niklas Rye

    2005-01-01

    The regulation of bone turnover is a complex and finely tuned process. Many factors regulate bone remodeling, including hormones, growth factors, cytokines etc. However, little is known about the signals coupling bone formation to bone resorption, and how mechanical forces are translated into biological effects in bone. Intercellular calcium waves are increases in intracellular calcium concentration in single cells, subsequently propagating to adjacent cells, and can be a possible mechanism for the coupling of bone formation to bone resorption. The aim of the present studies was to investigate whether bone cells are capable of communicating via intercellular calcium signals, and determine by which mechanisms the cells propagate the signals. First, we found that osteoblastic cells can propagate intercellular calcium transients upon mechanical stimulation, and that there are two principally different mechanisms for this propagation. One mechanism involves the secretion of a nucleotide, possibly ATP, acting in an autocrine action to purinergic P2Y2 receptors on the neighboring cells, leading to intracellular IP3 generation and subsequent release of calcium from intracellular stores. The other mechanism involves the passage of a small messenger through gap junctions to the cytoplasm of the neighboring cells, inducing depolarization of the plasma membrane with subsequent opening of membrane bound voltage-operated calcium channels. Next, we found that osteoblasts can propagate these signals to osteoclasts as well. We demonstrated that paracrine action of ATP was responsible for the wave propagation, but now the purinergic P2X7 receptor was involved. Thus, the studies demonstrate that calcium signals can be propagated not only among osteoblasts, but also between osteoblasts and osteoclasts in response to mechanical stimulation. Thus, intercellular calcium signaling can be a mechanism by which mechanical stimuli on bone are translated into biological signals in bone cells

  15. [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. PMID:26946704

  16. Turnover intentions and voluntary turnover: the moderating roles of self-monitoring, locus of control, proactive personality, and risk aversion.

    PubMed

    Allen, David G; Weeks, Kelly P; Moffitt, Karen R

    2005-09-01

    This article explores moderators of the relationship between turnover intentions and turnover behavior to better explain why some employees translate intentions into behavior and other employees do not. Individual differences in self-monitoring, locus of control, proactive personality, and risk aversion were examined. Results indicate that self-monitoring and risk aversion moderate the intentions-turnover link. Specifically, the relationship between turnover intentions and turnover is stronger for low self-monitors and those lower in risk aversion. Locus of control moderated the relationship in 1 of 2 samples such that the relationship was stronger for those with an internal locus of control. Proactive personality, however, did not directly moderate the relationship between intentions and turnover behaviors. PMID:16162070

  17. 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.

  18. Cytoplasmic mRNA turnover and ageing

    PubMed Central

    Borbolis, Fivos; Syntichaki, Popi

    2015-01-01

    Messenger RNA (mRNA) turnover that determines the lifetime of cytoplasmic mRNAs is a means to control gene expression under both normal and stress conditions, whereas its impact on ageing and age-related disorders has just become evident. Gene expression control is achieved at the level of the mRNA clearance as well as mRNA stability and accessibility to other molecules. All these processes are regulated by cis-acting motifs and trans-acting factors that determine the rates of translation and degradation of transcripts. Specific messenger RNA granules that harbor the mRNA decay machinery or various factors, involved in translational repression and transient storage of mRNAs, are also part of the mRNA fate regulation. Their assembly and function can be modulated to promote stress resistance to adverse conditions and over time affect the ageing process and the lifespan of the organism. Here, we provide insights into the complex relationships of ageing modulators and mRNA turnover mechanisms. PMID:26432921

  19. 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

  20. Management of Minerals and Bone Disorders after Kidney Transplantation

    PubMed Central

    Kalantar-Zadeh, Kamyar; Molnar, Miklos Z; Kovesdy, Csaba P.; Mucsi, Istvan; Bunnapradist, Suphamai

    2012-01-01

    Purpose of review Mineral and bone disorders (MBD), inherent complications of moderate and advanced chronic kidney disease (CKD), occur frequently in kidney transplant recipients. However, much confusion exists about clinical application of diagnostic tools and preventive or treatment strategies to correct bone loss or mineral disarrays in transplanted patients. We have reviewed the recent evidence about prevalence and consequences of MBD in kidney transplant recipients and examined diagnostic, preventive and therapeutic options to this end. Recent findings Low turnover bone disease occurs more frequently after kidney transplantation according to bone biopsy studies. The risk of fracture is high, especially in the first several months after kidney transplantation. Alterations in minerals (calcium, phosphorus and magnesium) and biomarkers of bone metabolism (PTH, alkaline phosphatase, vitamin D and FGF-23) are observed with varying impact on post-transplant outcomes. Calcineurin inhibitors are linked to osteoporosis, whereas steroid therapy may lead to both osteoporosis and varying degrees of osteonecrosis. Sirolimus and everolimus might have a bearing on osteoblasts proliferation and differentiation or decreasing osteoclast mediated bone resorption. Selected pharmacologic interventions for treatment of MBD in transplant patients include steroid withdrawal, the use of bisphosphonates, vitamin D derivatives, calcimimetics, teriparatide, calcitonin and denosumab. Summary MBD following kidney transplantation is common and characterized by loss of bone volume and mineralization abnormalities often leading to low turnover bone disease. Although there are no well-established therapeutic approaches for management of MBD in renal transplant recipients, clinicians should continue individualizing therapy as needed. PMID:22614626

  1. 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

  2. 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

  3. Effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats.

    PubMed

    Iwamoto, Jun; Yeh, James K; Takeda, Tsuyoshi

    2003-04-01

    We examined the effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats. Ninety male Sprague-Dawley rats, 3 months of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control (BLC), age-matched intact control (IN), IN+vitamin K2 administration (K), orchidectomy (ORX), ORX+K, unilateral sciatic neurectomy (NX), NX+K, ORX+NX (ONX), and ONX+K. Vitamin K2 (menatetrenone) was administered orally twice a week at a dose of 30 mg/kg each. After 10 weeks of feeding, the tibial shaft and proximal tibia were processed for cortical and cancellous bone histomorphometric analyses, respectively. An ORX-induced reduction in maturation-related cortical bone gain and ORX-induced cancellous bone loss were attributable to increased endocortical and trabecular bone turnover, respectively. NX- and ONX-induced reductions in maturation-related cortical bone gain were attributable to decreased periosteal bone formation and increased endocortical bone turnover, while NX- and ONX-induced cancellous bone loss was attributable to increased bone resorption and decreased bone formation. ORX-induced cancellous bone loss was more pronounced when combined with immobilization. Vitamin K2 administration did not significantly alter any parameters in IN rats. Vitamin K2 administration in ORX rats suppressed endocortical bone resorption and trabecular bone turnover, retarding a reduction in maturation-related cortical bone gain and cancellous bone loss. This effect on cancellous bone loss was primarily because of prevention of a reduction of trabecular thickness. Vitamin K2 administration in NX and ONX rats suppressed bone resorption and stimulated bone formation (mineralization), with retardation of a reduction of trabecular thickness without any significant effect on cancellous bone mass, and suppressed endocortical bone resorption, retarding a reduction in maturation-related cortical bone gain

  4. Raman spectroscopy of bone metastasis

    NASA Astrophysics Data System (ADS)

    Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

    2012-02-01

    Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

  5. 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.

  6. Bone health in cerebral palsy and introduction of a novel therapy

    PubMed Central

    Scheinberg, Morton Aaron; Golmia, Ricardo Prado; Sallum, Adriana Maluf Elias; Pippa, Maria Guadalupe Barbosa; Cortada, Aline Pinheiros dos Santos; da Silva, Telma Gomes

    2015-01-01

    ABSTRACT Objective To assess the bone health status of children with cerebral palsy and the therapeutic effect of denosumab in a subgroup of children with cerebral palsy and decreased bone mass. Methods Children with cerebral palsy were evaluated according to their motor disability score (classification system gross motor functions III to V), bone density and bone turnover markers. Dual X-ray energy absorption was used to measure the lumbar spine, and total body, except the head. Thereafter a group of children with cerebral palsy and osteoporosis was treated with denosumab, a fully human monoclonal antibody. Bone turnover markers were measured before and three months after treatment. Results Reduction in bone mineral density was observed, particularly in children with greater impairment evaluated by the motor score. Decreased bone turnover markers were found in a selected group of children three months after exposure to denosumab. Conclusion Bone loss was present in children with