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Sample records for glucocorticoid-induced bone loss

  1. Bone ultrasonography in glucocorticoid-induced osteoporosis.

    PubMed

    Cepollaro, C; Gonnelli, S; Rottoli, P; Montagnani, A; Caffarelli, C; Bruni, D; Nikiforakis, N; Fossi, A; Rossi, S; Nuti, R

    2005-07-01

    Osteoporosis is one of the major complications of glucocorticoid (GC) therapy. Few data are available on the usefulness of quantitative ultrasound (QUS), a technique that could also theoretically provide information on bone structure, in the management of glucocorticoid-induced osteoporosis (GIO). This study aimed (1) to evaluate the ability of QUS in detecting bone impairment and in being associated with the prevalence of fragility fracture in GC patients; and (2) to assess whether QUS parameters, and particularly the graphic trace analysis of QUS signal at phalanges, show any peculiar pattern of GIO. We studied 192 patients (136 women and 56 men, mean age 56.7 +/- 14.2 years) on treatment with GCs for at least 6 months, and 192 sex- and age-matched controls. In all subjects, we measured bone mineral density (BMD) at lumbar spine and at femur by DXA, and ultrasound parameters at calcaneus and phalanges. All DXA and QUS parameters were significantly lower in GC patients than in controls and in fracture than in nonfracture GC patients. BMD at lumbar spine showed the best ability in discriminating GC patients with or without fractures. Among QUS parameters, stiffness showed a discriminatory ability significantly better than AD-SoS. BMD at lumbar spine and total femur, stiffness, and AD-SoS are able to predict the odds of fragility fracture event. QUS parameters of the postmenopausal GC patients (n = 105) and of the postmenopausal healthy controls (n = 101) were also compared with those obtained in a separate sample of 90 postmenopausal osteoporotic women (PMO). All parameters were significantly lower in GC patients and in PMO than in controls, without any significant difference between GC and PMO. Our findings show that QUS can be useful in the assessment of glucocorticoid-induced bone impairment. In addition, in this study we found no alteration in QUS parameters or in the graphic trace analysis which could differentiate between GIO and PMO. Further longitudinal

  2. Prophylactic pamidronate partially protects from glucocorticoid-induced bone loss in the mdx mouse model of Duchenne muscular dystrophy.

    PubMed

    Yoon, Sung-Hee; Chen, Jinghan; Grynpas, Marc D; Mitchell, Jane

    2016-09-01

    Glucocorticoids are extensively used to treat patients with Duchenne muscular dystrophy because of their ability to delay muscle damage, prolong ambulation and extend life. However, use of glucocorticoids significantly increases bone loss, fragility and fractures. To determine if antiresorptive bisphosphonates could prevent the effects of glucocorticoids on bone quality, we used dystrophic mdx mice treated with the glucocorticoid prednisone during 8weeks of rapid bone growth from 5 to 13weeks of age and treated some mice with the bisphosphonate pamidronate during the first two weeks of prednisone administration. Prednisone reduced long bone growth, decreased cortical bone thickness and area and decreased the strength of the femurs. Pamidronate treatment protected mice from cortical bone loss but did not increase bone strength. The combination of prednisone and pamidronate inhibited remodeling of metaphyseal trabecular bone with large numbers of trabeculae containing remnants of calcified cartilage. Prednisone improved muscle strength in the mdx mice and decreased serum creatine kinase with evidence of improved muscle histology and these effects were maintained in mice treated with pamidronate.

  3. Oxygen ultra-fine bubbles water administration prevents bone loss of glucocorticoid-induced osteoporosis in mice by suppressing osteoclast differentiation.

    PubMed

    Noguchi, T; Ebina, K; Hirao, M; Morimoto, T; Koizumi, K; Kitaguchi, K; Matsuoka, H; Iwahashi, T; Yoshikawa, H

    2017-03-01

    Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of glucocorti\\coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro. Ultra-fine bubbles (<200 nm in diameter) have several unique properties, and they are tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUB) on glucocorticoid-induced osteoporosis (GIO) model mice. Prednisolone (PSL, 5 mg) was subcutaneously inserted in 6-month-old male C57BL/6J mice, and 200 μl of saline, OUB-diluted saline, or nitrogen ultra-fine bubbles (NUB)-diluted saline was intraperitoneally injected three times per week for 8 weeks the day after operations. Mice were divided into four groups; (1) control, sham-operation + saline; (2) GIO, PSL + saline; (3) GIO + OUB, PSL + OUB saline; (4) GIO + NUB, PSL + NUB saline. The effects of OUB on osteoblasts and osteoclasts were examined by serially diluted OUB medium in vitro. Bone mass was significantly decreased in GIO [bone volume/total volume (%): control vs. GIO 12.6 vs. 7.9; p < 0.01] while significantly preserved in GIO + OUB (GIO vs. GIO + OUB 7.9 vs. 12.9; p < 0.05). In addition, tartrate-resistant acid phosphatase (TRAP)-positive cells in the distal femur [mean osteoclasts number/bone surface (mm(-1))] was significantly increased in GIO (control vs. GIO 6.8 vs. 11.6; p < 0.01) while suppressed in GIO + OUB (GIO vs. GIO + OUB 11.6 vs. 7.5; p < 0.01). NUB did not affect these parameters. In vitro experiments revealed that OUB significantly inhibited osteoclastogenesis by inhibiting RANK-TRAF6-c-Fos-NFATc1 signaling, RANK-p38 MAPK signaling, and TRAP/Cathepsin K/DC-STAMP mRNA expression in a concentration-dependent manner. OUB did not affect osteoblastogenesis in vitro. OUB prevent bone loss in GIO mice by inhibiting osteoclastogenesis.

  4. Strain dependent differences in glucocorticoid-induced bone loss between C57BL/6J and CD-1 mice

    PubMed Central

    Ersek, Adel; Santo, Ana I. Espirito; Vattakuzhi, Youridies; George, Saumya; Clark, Andrew R.; Horwood, Nicole J.

    2016-01-01

    We have investigated the effect of long-term glucocorticoid (GC) administration on bone turnover in two frequently used mouse strains; C57BL/6J and CD1, in order to assess the influence of their genetic background on GC-induced osteoporosis (GIO). GIO was induced in 12 weeks old female C57BL/6J and CD1 mice by subcutaneous insertion of long-term release prednisolone or placebo pellets. Biomechanical properties as assessed by three point bent testing revealed that femoral elasticity and strength significantly decreased in CD1 mice receiving GC, whereas C57BL/6J mice showed no differences between placebo and prednisolone treatment. Bone turnover assessed by microcomputer tomography revealed that contrary to C57BL/6J mice, prednisolone treated CD1 mice developed osteoporosis. In vitro experiments have underlined that, at a cellular level, C57BL/6J mice osteoclasts and osteoblasts were less responsive to GC treatment and tolerated higher doses than CD1 cells. Whilst administration of long-term release prednisolone pellets provided a robust GIO animal model in 12 weeks old CD1 mice, age matched C57BL/6J mice were not susceptible to the bone changes associated with GIO. This study indicates that for the induction of experimental GIO, the mouse strain choice together with other factors such as age should be carefully evaluated. PMID:27812009

  5. Prevention of glucocorticoid induced bone changes with beta-ecdysone.

    PubMed

    Dai, Weiwei; Jiang, Li; Lay, Yu-An Evan; Chen, Haiyan; Jin, Guoqin; Zhang, Hongliang; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

    2015-05-01

    Beta-ecdysone (βEcd) is a phytoecdysteroid found in the dry roots and seeds of the asteraceae and achyranthes plants, and is reported to increase osteogenesis in vitro. Since glucocorticoid (GC) excess is associated with a decrease in bone formation, the purpose of this study was to determine if treatment with βEcd could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8-10/group) were randomized to either placebo or slow release prednisolone pellets (3.3mg/kg/day) and treated with vehicle control or βEcd (0.5mg/kg/day) for 21days. GC treatment inhibited age-dependent trabecular gain and cortical bone expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at both the endosteal and periosteal surfaces. Mice treated with only βEcd significantly increased bone formation on the endosteal and periosteal bone surfaces, and increased cortical bone mass were their controls to compare to GC alone. Concurrent treatment of βEcd and GC completely prevented the GC-induced reduction in BFR, trabecular bone volume and partially prevented cortical bone loss. In vitro studies determined that βEcd prevented the GC increase in autophagy of the bone marrow stromal cells as well as in whole bone. In summary, βEcd prevented GC induced changes in bone formation, bone cell viability and bone mass. Additional studies are warranted of βEcd for the treatment of GC induced bone loss.

  6. Prevention of glucocorticoid induced bone changes with beta-ecdysone

    PubMed Central

    Dai, Weiwei; Jiang, Li; Lay, Yu-An Evan; Chen, Haiyan; Jin, Guoqin; Zhang, Hongliang; Kot, Alex; Ritchie, Robert O.; Lane, Nancy E.; Yao, Wei

    2015-01-01

    Beta-ecdysone (βEcd) is a phytoecdysteroid found in the dry roots and seeds of the asteraceae and achyranthes plants, and is reported to increase osteogenesis in vitro. Since glucocorticoid (GCs) excess is associated with a decrease in bone formation, the purpose of this study was to determine if treatment with βEcd could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8-10/group) were randomized to either placebo or slow release prednisolone pellets (3.3mg/kg/d) and treated with vehicle control or βEcd (0.5mg/kg/d) for 21 days. GC treatment inhibited age-dependent trabecular gain and cortical bone expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at both the endosteal and periosteal surfaces. Mice treated with only βEcd significantly increased bone formation on endosteal and periosteal bone surfaces, and increased cortical bone mass were their controls to compare to GC alone. Concurrent treatment of βEcd and GC completely prevented the GC-induced reduction in BFR, trabecular bone volume and partially prevented cortical bone loss. In vitro studies determined that βEcd prevented the GC increase in autophagy of the bone marrow stromal cells as well as in whole bone. In summary, βEcd prevented GC induced changes in bone formation, bone cell viability and bone mass. Additional studies are warranted of βEcd for the treatment of GC induced bone loss. PMID:25585248

  7. Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition

    USDA-ARS?s Scientific Manuscript database

    Glucocorticoids (GCs) have both anabolic and catabolic effects on bone. However, no GC anabolic effect mediator has been identified to date. In this report, we provide the first evidence that glucocorticoid-induced leucine zipper (GILZ), a GC anti-inflammatory effect mediator, can enhance bone forma...

  8. Risedronate, an effective treatment for glucocorticoid-induced bone loss in CKD patients with or without concomitant active vitamin D (PRIUS-CKD).

    PubMed

    Fujii, Naohiko; Hamano, Takayuki; Mikami, Satoshi; Nagasawa, Yasuyuki; Isaka, Yoshitaka; Moriyama, Toshiki; Horio, Masaru; Imai, Enyu; Hori, Masatsugu; Ito, Takahito

    2007-06-01

    Recent post hoc analysis proved the efficacy and tolerability of risedronate in osteoporotic patients with renal impairment, but the combination of active vitamin D in chronic kidney disease (CKD) patients taking glucocorticoids remains unknown. We conducted a prospective study enrolling 114 CKD patients (creatinine clearance > or =30 ml/min/1.73 m(2)) receiving glucocorticoid therapy for > or =6 months. Eighty-eight subjects who had received active vitamin D (aVD) were randomly assigned to either a group treated with aVD only (group A), or to a group also receiving risedronate 2.5 mg/day (group B). The remaining patients (group C) received risedronate only. After 1 year 100 subjects were analysed. Risedronate was effective on the lumbar spine, but not on the femoral neck. The lumbar bone mineral density (BMD) significantly increased by 2.8 and 2.5% in groups B and C, respectively, but decreased by 1.0% in group A. Serum N-terminal telopeptides of type I collagen (S-NTX) and bone alkaline phosphatase (ALP) fell significantly in groups B and C at 3 and 6 months, respectively, while in group A S-NTX remained unchanged and bone ALP significantly increased. There was no significant difference between groups B and C regarding BMD and bone markers. The reduction rate of S-NTX (bone ALP) at 6 months predicted the increase in lumbar BMD at 1 year with a sensitivity of 73% (34%) and a specificity of 46.2% (100%). Risedronate is effective in increasing BMD with or without aVD in CKD patients receiving long-term glucocorticoid therapy. Bone markers are of some use in predicting the response to anti-resorptive therapy.

  9. A joined role of canopy and reversal cells in bone remodeling--lessons from glucocorticoid-induced osteoporosis.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Hauge, Ellen-Margrethe; Bollerslev, Jens; Delaissé, Jean-Marie

    2015-04-01

    Successful bone remodeling demands that osteoblasts restitute the bone removed by osteoclasts. In human cancellous bone, a pivotal role in this restitution is played by the canopies covering the bone remodeling surfaces, since disruption of canopies in multiple myeloma, postmenopausal- and glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e., uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces. In postmenopausal osteoporosis, this concept is supported by the coincidence between the absence of canopies and scarcity of cells on reversal surfaces together with abortion of the remodeling cycle. Here we tested whether this concept holds true in glucocorticoid-induced osteoporosis. A histomorphometric analysis of iliac crest biopsies from patients exposed to long-term glucocorticoid treatment revealed a subpopulation of reversal surfaces corresponding to the characteristics of arrest found in postmenopausal osteoporosis. Importantly, these arrested reversal surfaces were devoid of canopy coverage in almost all biopsies, and their prevalence correlated with a deficiency in bone forming surfaces. Taken together with the other recent data, the functional link between canopies, reversal surface activity, and the extent of bone formation surface in postmenopausal- and glucocorticoid-induced osteoporosis, supports a model where bone restitution during remodeling demands recruitment of osteoprogenitors from the canopy onto reversal surfaces. These data suggest that securing the presence of functional local osteoprogenitors deserves attention in the search of strategies to prevent the bone loss that occurs during bone remodeling in pathological situations.

  10. ACTH protects against glucocorticoid-induced osteonecrosis of bone.

    PubMed

    Zaidi, Mone; Sun, Li; Robinson, Lisa J; Tourkova, Irina L; Liu, Li; Wang, Yujuan; Zhu, Ling-Ling; Liu, Xuan; Li, Jianhua; Peng, Yuanzhen; Yang, Guozhe; Shi, Xingming; Levine, Alice; Iqbal, Jameel; Yaroslavskiy, Beatrice B; Isales, Carlos; Blair, Harry C

    2010-05-11

    We report that adrenocorticotropic hormone (ACTH) protects against osteonecrosis of the femoral head induced by depot methylprednisolone acetate (depomedrol). This therapeutic response likely arises from enhanced osteoblastic support and the stimulation of VEGF by ACTH; the latter is largely responsible for maintaining the fine vascular network that surrounds highly remodeling bone. We suggest examining the efficacy of ACTH in preventing human osteonecrosis, a devastating complication of glucocorticoid therapy.

  11. Glucocorticoid-induced osteonecrosis.

    PubMed

    Weinstein, Robert S

    2012-04-01

    Awareness of the need for prevention of glucocorticoid-induced fractures is growing, but glucocorticoid administration is often overlooked as the most common cause of nontraumatic osteonecrosis. Glucocorticoid-induced osteonecrosis develops in 9-40% of patients receiving long-term therapy although it may also occur with short-term exposure to high doses, after intra-articular injection, and without glucocorticoid-induced osteoporosis. The name, osteonecrosis, is misleading because the primary histopathological lesion is osteocyte apoptosis. Apoptotic osteocytes persist because they are anatomically unavailable for phagocytosis and, with glucocorticoid excess, decreased bone remodeling retards their replacement. Glucocorticoid-induced osteocyte apoptosis, a cumulative and unrepairable defect, uniquely disrupts the mechanosensory function of the osteocyte-lacunar-canalicular system and thus starts the inexorable sequence of events leading to collapse of the femoral head. Current evidence indicates that bisphosphonates may rapidly reduce pain, increase ambulation, and delay joint collapse in patients with osteonecrosis.

  12. Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis.

    PubMed

    Mohamad Asri, Siti Fadziyah; Mohd Ramli, Elvy Suhana; Soelaiman, Ima Nirwana; Mat Noh, Muhamad Alfakry; Abdul Rashid, Abdul Hamid; Suhaimi, Farihah

    2016-11-15

    Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration (p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.

  13. Effects of glucocorticoid-induced osteoporosis on bone tissue of rats with experimental periodontitis.

    PubMed

    Sousa, Luzia Hermínia Teixeira; Moura, Eveline Valeriano; Queiroz, Ana Larissa; Val, Danielle; Chaves, Hellíada; Lisboa, Mario; Furlaneto, Flávia; Brito, Gerly Anne; Goes, Paula

    2017-05-01

    To evaluate the effects of osteoporosis induced by glucocorticoid (GIOP) on bone tissue of rats with experimental periodontitis (EP). 48 male Wistar rats divided into groups: Naïve, EP, GIOP and GIOP+EP. Rats of GIOP and GIOP+EP groups received 7mg/kg of dexamethasone intramuscularly once a week for 5 weeks. Following, EP and GIOP+EP groups were subjected to ligature-induced periodontitis. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic, radiographic, micro-tomographic and microscopic analysis of alveolar bone loss (ABL). Blood samples were collected for determination of bone-specific alkaline phosphatase (BALP) levels and the right femurs were removed for radiographic and biomechanical analysis. EP caused ABL and reduced BALP levels (p<0,05), but it did not change the architecture or biomechanics of femur, compared to Naïve. GIOP did not cause ABL, but it significantly decreased alveolar bone mineral density (ABMD), bone percentage and trabecular thickness (Tb.Th) and increased alveolar bone porosity (p<0.05) and significantly reduced BALP serum levels, as well as radiographic density and Young's module of femur, compared to Naïve. There was a greater ABL in group GIOP+EP when compared to EP (p<0.05). GIOP+EP caused a greater decrease on ABMD, Tb.Th, bone percentage and increased bone porosity (p<0.05) and also presented a significant reduction in BALP levels (p<0.05), in radiographic density and in Young's module of femur compared to EP (p<0.05). GIOP can potentiate the destructive effects of EP on alveolar bone and alter the systemic bone loss, by promoting bone resorption and reducing osteoblast activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3.

    PubMed

    Bhandaru, Madhuri; Kempe, Daniela S; Rotte, Anand; Capuano, Paola; Pathare, Ganesh; Sopjani, Mentor; Alesutan, Ioana; Tyan, Leonid; Huang, Dan Yang; Siraskar, Balasaheb; Judenhofer, Martin S; Stange, Gerti; Pichler, Bernd J; Biber, Jürg; Quintanilla-Martinez, Leticia; Wagner, Carsten A; Pearce, David; Föller, Michael; Lang, Florian

    2011-07-01

    Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. Coexpression of SGK3 and sodium-phosphate cotransporter IIa significantly enhanced the phosphate-induced current in Xenopus oocytes. In sgk3 knockout and wild-type mice on a standard diet, fluid intake, glomerular filtration and urine flow rates, and urinary calcium ion excretion were similar. However, fractional urinary phosphate excretion was slightly but significantly larger in the knockout than in wild-type mice. Plasma calcium ion, phosphate concentration, and plasma parathyroid hormone levels were not significantly different between the two genotypes, but plasma calcitriol and fibroblast growth factor 23 concentrations were significantly lower in the knockout than in wild-type mice. Moreover, bone density was significantly lower in the knockouts than in wild-type mice. Histological analysis of the femur did not show any differences in cortical bone but there was slightly less prominent trabecular bone in sgk3 knockout mice. Thus, SGK3 has a subtle but significant role in the regulation of renal tubular phosphate transport and bone density.

  15. [Randomized controlled trials for the prevention and treatment of glucocorticoid-induced osteoporosis].

    PubMed

    Suzuki, Yasuo

    2006-11-01

    The effectiveness of drug therapy for the prevention or treatment of glucocorticoid-induced osteoporosis has been reported. Especially, the beneficial effects of bisphosphonates (etidoronate, alendronate, and risedronate) to prevent bone loss and fractures have been confirmed by the large-scale, multicenter, double-blind, randomized controlled trials in terms of both primary and secondary prevention. This article reviews the results of recent randomized prospective trials using bisphosphonates in glucocorticoid-induced osteoporosis.

  16. Neuropeptide Y mediates glucocorticoid-induced osteoporosis and marrow adiposity in mice.

    PubMed

    Wang, F-S; Lian, W-S; Weng, W-T; Sun, Y-C; Ke, H-J; Chen, Y-S; Ko, J-Y

    2016-09-01

    Increased neuropeptide Y (NPY) expression occurred in the glucocorticoid-induced osteoporotic skeleton. NPY knockout mice exhibited a minor response to the glucocorticoid-mediated exacerbation of bone accretion and fatty marrow pathogenesis. NPY deletion restored SITR1 signaling and enhanced PPARγ ubiquitination of bone tissue, an alternative strategy for ameliorating glucocorticoid-induced skeletal deterioration. Glucocorticoid excess is observed to worsen the pathogenesis of osteoporosis and fatty marrow. This study was undertaken to investigate the contribution of neuropeptide Y (NPY) to glucocorticoid-induced bone loss and marrow adiposity. NPY knockout and wild-type mice were administered methylprednisolone for four consecutive weeks. Bone mineral density, microarchitecture, and calcein-labeled mineral acquisition were quantified by μCT, dual energy X-ray absorptiometry, and histomorphometry. Expression of osteogenic and adipogenic markers and acetylation states of PPARγ were detected by RT-quantitative PCR, immunoprecipitation, and immunoblotting. High NPY levels were associated with glucocorticoid-induced trabecular bone deterioration and marrow fat accumulation. Mice lacking NPY had high bone mass concomitant with spacious trabecular and cortical bone microstructure. NPY deletion shielded skeletal tissues from the glucocorticoid-induced impediment of bone mass, trabecular morphometric characteristics, mineral accretion activity, and fatty marrow development. Ex vivo, NPY deficiency sustained osteogenic differentiation capacity and curtailed the glucocorticoid-mediated escalation of adipocyte formation reactions of primary bone-marrow mesenchymal cells. NPY deletion appeared to modulate Y1 and Y2 receptors, sirtuin 1, ERK, and p38 signaling pathways, an effect that facilitated hypoacetylation and ubiquitination of adipogenic transcription factor PPARγ in the skeletal tissues exposed to glucocorticoid stress. NPY mediates the glucocorticoid-induced

  17. Bone Tissue Properties Measurement by Reference Point Indentation in Glucocorticoid-Induced Osteoporosis.

    PubMed

    Mellibovsky, Leonardo; Prieto-Alhambra, Daniel; Mellibovsky, Fernando; Güerri-Fernández, Roberto; Nogués, Xavier; Randall, Connor; Hansma, Paul K; Díez-Perez, Adolfo

    2015-09-01

    Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment-induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation technique could detect bone tissue property changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium + vitamin D (Ca+D) supplements or anti-osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring bone material strength index (BMSi). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA). Although Ca+D-treated patients exhibited substantial and significant deterioration, risedronate-treated patients exhibited no significant change, and both denosumab- and teriparatide-treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared with baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to our knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids.

  18. GLUCOCORTICOID-INDUCED BONE DISEASE: MECHANISMS AND IMPORTANCE IN PEDIATRIC PRACTICE

    PubMed Central

    Sarinho, Emanuel Sávio Cavalcanti; Melo, Verônica Maria Pinho Pessoa

    2017-01-01

    ABSTRACT Objective: To describe mechanisms by which glucocorticoids cause osteoporosis, with fracture risk, combining this learning with a possible professional behavior change. Data sources: A systematic search on SciELO, PubMed, Scopus, and Medline databases was carried out for consensus, review articles, including systematic reviews and meta-analysis, which were published in English, between 2000 and 2016. Keywords used on the search were the following: glucocorticoids, fractures, osteoporosis, bone health, vitamin D, children, and adolescents. Data synthesis: The review was divided into four topics: 1) introduction, with a brief focus on pediatric fractures; 2) osteoporosis in children and adolescents, highlighting it as a silent cause of fractures; 3) glucocorticoids and secondary bone disease, describing deleterious mechanisms of this steroids group on bone structure; 4) molecular effects of glucocorticoids excess on bone, with details about the harmful mechanisms on bone molecular level. Conclusions: Glucocorticoids excess determines early bone disease, favoring the occurrence of fractures. Thus, a child or an adolescent who uses glucocorticoids, especially systemically and chronically, but also repeats cycles at high cumulative doses of the medication, needs care and guidance related to bone health at the onset of treatment. On the other hand, the presence of fractures, even if related to trauma, can be a sign of underlying and unknown bone fragility, which may be secondary to the use of glucocorticoids and/or vitamin D deficiency. PMID:28977339

  19. Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density

    PubMed Central

    Grahnemo, Louise; Jochems, Caroline; Andersson, Annica; Engdahl, Cecilia; Ohlsson, Claes; Islander, Ulrika; Carlsten, Hans

    2015-01-01

    Treatment with anti-inflammatory glucocorticoids is associated with osteoporosis. Many of the treated patients are postmenopausal women, who even without treatment have an increased risk of osteoporosis. Lymphocytes have been shown to play a role in postmenopausal and arthritis-induced osteoporosis, and they are targeted by glucocorticoids. The aim of this study was to investigate the mechanisms behind effects of glucocorticoids on bone during health and menopause, focusing on lymphocytes. Female C57BL/6 or SCID mice were therefore sham-operated or ovariectomized and 2 weeks later treatment with dexamethasone (dex), the nonsteroidal anti-inflammatory drug carprofen, or vehicle was started and continued for 2.5 weeks. At the termination of experiments, femurs were phenotyped using peripheral quantitative computed tomography and high-resolution micro-computed tomography, and markers of bone turnover were analyzed in serum. T and B lymphocyte populations in bone marrow and spleen were analyzed by flow cytometry. Dex-treated C57BL/6 mice had increased trabecular bone mineral density, but lower cortical content and thickness compared with vehicle-treated mice. The dex-treated mice also had lower levels of bone turnover markers and markedly decreased numbers of spleen T and B lymphocytes. In contrast, these effects could not be repeated when mice were treated with the nonsteroidal anti-inflammatory drug carprofen. In addition, dex did not increase trabecular bone in ovariectomized SCID mice lacking functional T and B lymphocytes. In contrast to most literature, the results from this study indicate that treatment with dex increased trabecular bone density, which may indicate that this effect is associated with corticosteroid-induced alterations of the lymphocyte populations. PMID:25359897

  20. Targeting osteoblastic casein kinase-2 interacting protein-1 to enhance Smad-dependent BMP signaling and reverse bone formation reduction in glucocorticoid-induced osteoporosis

    PubMed Central

    Liu, Jin; Lu, Changwei; Wu, Xiaohao; Zhang, Zongkang; Li, Jie; Guo, Baosheng; Li, Defang; Liang, Chao; Dang, Lei; Pan, Xiaohua; Peng, Songlin; Lu, Aiping; Zhang, Baoting; Zhang, Ge

    2017-01-01

    The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment. Further, the reduced bone formation in GIO mice could not only be prevented by osteoblasts-specific Ckip-1 ablation, but also be attenuated after osteoblasts-specific Smad1 overexpression. Moreover, osteoblasts-targeting CKIP-1 siRNA treatment also attenuated the bone formation reduction in GIO mice. These study suggest that the highly expressed CKIP-1 in osteoblasts could suppress the Smad-dependent BMP signaling and contribute to the bone formation reduction in GIO. Targeting osteoblastic CKIP-1 would be a novel bone anabolic strategy for GIO patients. PMID:28128304

  1. Glucocorticoid-induced loss of DNA methylation in non-neuronal cells and potential involvement of DNMT1 in epigenetic regulation of Fkbp5.

    PubMed

    Yang, Xiaoju; Ewald, Erin R; Huo, Yuqing; Tamashiro, Kellie L; Salvatori, Roberto; Sawa, Akira; Wand, Gary S; Lee, Richard S

    2012-04-13

    Glucocorticoids may play a significant role in the etiology of neuropsychiatric illnesses. Abnormalities in plasma cortisol levels, glucocorticoid sensitivity, and HPA-axis function often accompany clinical symptoms of stress-related illnesses such as PTSD and depression. Of particular interest are genetic association studies that link single nucleotide polymorphisms of HPA-axis genes with illnesses only in the context of an early-life trauma exposure such as child abuse. These studies suggest that dysregulation of HPA-axis function can have lasting repercussions in shaping mood and anxiety, long after termination of the traumatic experience. As persistent glucocorticoid-induced loss of DNA methylation in FK506 binding protein 5 (Fkbp5) was previously observed in the hippocampus and blood and in the neuronal cell line HT-22, we asked whether these epigenetic alterations occur in non-neuronal, HPA-axis relevant cells. We used the pituitary adenoma cell line AtT-20 to demonstrate that the intronic enhancer region of Fkbp5 undergoes loss of DNA methylation in response to dexamethasone treatment in a dose-dependent manner. We also focused on the mouse hippocampal dentate gyrus to test whether these changes would be enriched in a region implicated in the HPA-axis stress response, neurogenesis, and synaptic plasticity. We observed an increase in enrichment of DNA methylation loss in the dentate gyrus, as compared to whole hippocampal tissues that were similarly treated with glucocorticoids. We then asked whether DNA methyltransferase 1 (Dnmt1), a methyltransferase enzyme involved in maintaining DNA methylation following cell division, is involved in the observed epigenetic alterations. We found a dose-dependent decrease of Dnmt1 expression in the AtT-20 cells following dexamethasone treatment, and a similar decrease in corticosterone-treated mouse hippocampus. Taken together, we provide evidence that these glucocorticoid-induced epigenetic alterations have a broader

  2. IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse

    PubMed Central

    Zhang, Yuan-yuan; Yang, Hui-lin

    2016-01-01

    Osteoporosis is one of the most prevalent skeletal system diseases. It is characterized by a decrease in bone mass and microarchitectural changes in bone tissue that lead to an attenuation of bone resistance and susceptibility to fracture. Vertebral fracture is by far the most prevalent osteoporotic fracture. In the musculoskeletal system, osteoblasts, originated from bone marrow stromal cells (BMSC), are responsible for osteoid synthesis and mineralization. In osteoporosis, BMSC osteogenic differentiation is defective. However, to date, what leads to the defective BMSC osteogenesis in osteoporosis remains an open question. In the current study, we made attempts to answer this question. A mouse model of glucocorticoid-induced osteoporosis (GIO) was established and BMSC were isolated from vertebral body. The impairment of osteogenesis was observed in BMSC of osteoporotic vertebral body. The expression profiles of thirty-six factors, which play important roles in bone metabolisms, were compared through antibody array between normal and osteoporotic BMSC. Significantly higher secretion level of IL-6 was observed in osteoporotic BMSCs compared with normal control. We provided evidences that IL-6 over-secretion impaired osteogenesis of osteoporotic BMSC. Further, it was observed that β-catenin activity was inhibited in response to IL-6 over-secretion. More importantly, in vivo administration of IL-6 neutralizing antibody was found to be helpful to rescue the osteoporotic phenotype of mouse vertebral body. Our study provides a deeper insight into the pathophysiology of osteoporosis and identifies IL-6 as a promising target for osteoporosis therapy. PMID:27128729

  3. Glucocorticoid-Induced Osteoporosis

    MedlinePlus

    ... Positions Letters to Policy Makers State Advocacy State Societies Letters to Policy Makers State Advocacy Key Issues ... D supplements can help prevent loss of bone mass. Calcium alone is not effective. A rheumatologist can ...

  4. Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism

    PubMed Central

    Yang, Nianlan; Baban, Babak; Isales, Carlos M.; Shi, Xing-Ming

    2015-01-01

    Bone marrow is a reservoir for regulatory T (Treg) cells, but how Treg cells are regulated in that environment remains poorly understood. We show that expression of glucocorticoid (GC)-induced leucine zipper (GILZ) in bone marrow mesenchymal lineage cells or bone marrow-derived mesenchymal stem cells (BMSCs) increases the production of Treg cells via a mechanism involving the up-regulation of developmental endothelial locus-1 (Del-1), an endogenous leukocyte-endothelial adhesion inhibitor. We found that the expression of Del-1 is increased ∼4-fold in the bone tissues of GILZ transgenic (Tg) mice, and this increase is coupled with a significant increase in the production of IL-10 (2.80 vs. 0.83) and decrease in the production of IL-6 (0.80 vs. 2.33) and IL-12 (0.25 vs. 1.67). We also show that GILZ-expressing BMSCs present antigen in a way that favors Treg cells. These results indicate that GILZ plays a critical role mediating the crosstalk between BMSCs and Treg in the bone marrow microenvironment. These data, together with our previous findings that overexpression of GILZ in BMSCs antagonizes TNF-α-elicited inflammatory responses, suggest that GILZ plays important roles in bone-immune cell communication and BMSC immune suppressive functions.—Yang, N., Baban, B., Isales, C. M., Shi, X.-M. Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism. PMID:26038125

  5. An appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

    PubMed

    Lekamwasam, S; Adachi, J D; Agnusdei, D; Bilezikian, J; Boonen, S; Borgström, F; Cooper, C; Perez, A Diez; Eastell, R; Hofbauer, L C; Kanis, J A; Langdahl, B L; Lesnyak, O; Lorenc, R; McCloskey, E; Messina, O D; Napoli, N; Obermayer-Pietsch, B; Ralston, S H; Sambrook, P N; Silverman, S; Sosa, M; Stepan, J; Suppan, G; Wahl, D A; Compston, J E

    2012-01-01

    The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

  6. Management of glucocorticoid-induced osteoporosis.

    PubMed

    Rizzoli, R; Adachi, J D; Cooper, C; Dere, W; Devogelaer, J P; Diez-Perez, A; Kanis, J A; Laslop, A; Mitlak, B; Papapoulos, S; Ralston, S; Reiter, S; Werhya, G; Reginster, J Y

    2012-10-01

    This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48 weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines.

  7. Menopause and Bone Loss

    MedlinePlus

    Fact Sheet & Menopause Bone Loss How are bone loss and menopause related? Throughout life your body keeps a balance between the ... lose bone faster than it can be replaced. Menopause—the time when menstrual periods end, which usually ...

  8. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: A review of glucocorticoid pharmacology and bone health.

    PubMed

    Caplan, Avrom; Fett, Nicole; Rosenbach, Misha; Werth, Victoria P; Micheletti, Robert G

    2017-01-01

    Systemic glucocorticoids are an essential therapy for a range of conditions, but their multiple side effects can produce significant morbidity for patients. The objective of this review is to discuss these side effects while addressing 3 questions: 1) What dose and duration of glucocorticoid therapy should prompt concern for individual side effects?; 2) How should clinicians counsel patients about these complications?; and 3) How can these problems be prevented or managed? To accomplish these objectives, we have created a series of tables and algorithms based on a review of relevant data to guide counseling, prophylaxis, and management of 11 glucocorticoid side effects. The first article in this 4-part continuing medical education series begins with a review of glucocorticoid pharmacology followed by a discussion of bone health (ie, osteoporosis and osteonecrosis).

  9. Medicines and Bone Loss

    MedlinePlus

    ... studies also show that drinking a lot of alcohol might weaken bones. Questions to ask your doctor • Do any of my medicines cause bone loss? • Are there different medicines I can take? • Do I need a bone density test? • What should I do to protect my ...

  10. Glucocorticoid-Induced Osteoporosis

    MedlinePlus

    ... may weaken your bones. If you take an equivalent doss of prednisone at greater than 7.5 ... glucocorticoid medicine should: Be physically active and do weight-bearing exercises, like walking, most days each week. ...

  11. Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis.

    PubMed

    Ramli, Elvy Suhana Mohd; Suhaimi, Farihah; Asri, Siti Fadziyah Mohamad; Ahmad, Fairus; Soelaiman, Ima Nirwana

    2013-05-01

    Rapid onset of bone loss is a frequent complication of systemic glucocorticoid therapy which may lead to fragility fractures. Glucocorticoid action in bone depends upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Regulations of 11β-HSD1 activity may protect the bone against bone loss due to excess glucocorticoids. Glycyrrhizic acid (GCA) is a potent inhibitor of 11β-HSD. Treatment with GCA led to significant reduction in bone resorption markers. In this study we determined the effect of GCA on 11β-HSD1 activity in bones of glucocorticoid-induced osteoporotic rats. Thirty-six male Sprague-Dawley rats (aged 3 months and weighing 250-300 g) were divided randomly into groups of ten. (1) G1, sham operated group; (2) G2, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral vehicle normal saline vehicle; and (3) G3, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral GCA 120 mg/kg/day The results showed that GCA reduced plasma corticosterone concentration. GCA also reduced serum concentration of the bone resorption marker, pyridinoline and induced 11β-HSD1 dehydrogenase activity in the bone. GCA improved bone structure, which contributed to stronger bone. Therefore, GCA has the potential to be used as an agent to protect the bone against glucocorticoid induced osteoporosis.

  12. Glucocorticoid-induced osteoporosis: who to treat with what agent?

    PubMed

    Rizzoli, René; Biver, Emmanuel

    2015-02-01

    Among the adverse events of glucocorticoid treatment are bone loss and fractures. Despite available, effective preventive measures, many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated for bone health and fracture risk. Populations with, or at risk of, glucocorticoid-induced osteoporosis (GIOP) to target for these measures are defined on the basis of dose and duration of glucocorticoid therapy and bone mineral density. That patients with GIOP should be treated as early as possible is generally agreed upon; however, diversity remains in intervention thresholds and management guidelines. The FRAX(®) algorithm provides a 10-year probability of fracture that can be adjusted according to glucocorticoid dose. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. Available anti-osteoporotic therapies such as anti-resorptives including bisphosphonates and the bone anabolic agent teriparatide are effective for the management of GIOP. Prevention with calcium and vitamin D supplementation is less effective than specific anti-osteoporotic treatment. Anti-osteoporotic treatment should be stopped at the time of glucocorticoid cessation, unless the patient remains at increased risk of fracture.

  13. Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone Properties in Glucocorticoid-Induced Osteoporosis.

    PubMed

    Sequetto, Priscila L; Gonçalves, Reggiani V; Pinto, Aloísio S; Oliveira, Maria G A; Maldonado, Izabel R S C; Oliveira, Tânia T; Novaes, Rômulo D

    2017-10-01

    By using an experimental model of dexamethasone-induced osteoporosis we investigated the effects of different therapeutic schemes combining sodium alendronate (SA) and simvastatin on bone mineral and protein composition, microstructural and mechanical remodeling. Wistar rats were randomized into eight groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg, respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea, especially in non-treated animals, which showed severe osteoporosis. Dexamethasone also induced bone microstructural fragility and reduced mechanical resistance, which were associated with a marked depletion in mineral mass, collagenous and non-collagenous protein levels in cortical and cancellous bone. Although SA has attenuated osteoporosis severity, the effectiveness of drug therapy was enhanced combining alendronate and simvastatin. The restoration in serum parameters, organic and inorganic bone mass, and mechanical behavior showed a dose-dependent effect that was potentially related to the complementary mechanisms by which each drug acts to induce bone anabolism, accelerating tissue repair.

  14. Effect of Pulsed Electromagnetic Field on Bone Formation and Lipid Metabolism of Glucocorticoid-Induced Osteoporosis Rats through Canonical Wnt Signaling Pathway

    PubMed Central

    Jiang, Yuan; Gou, Hui; Wang, Sanrong; Zhu, Jiang; Tian, Si; Yu, Lehua

    2016-01-01

    Pulsed electromagnetic field (PEMF) has been suggested as a promising method alternative to drug-based therapies for treating osteoporosis (OP), but the role of PEMF in GIOP animal models still remains unknown. This study was performed to investigate the effect of PEMF on bone formation and lipid metabolism and further explored the several important components and targets of canonical Wnt signaling pathway in GIOP rats. After 12 weeks of intervention, bone mineral density (BMD) level of the whole body increased significantly, serum lipid levels decreased significantly, and trabeculae were thicker in GIOP rats of PEMF group. PEMF stimulation upregulated the mRNA and protein expression of Wnt10b, LRP5, β-catenin, OPG, and Runx2 and downregulated Axin2, PPAR-γ, C/EBPα, FABP4, and Dkk-1. The results of this study suggested that PEMF stimulation can prevent bone loss and improve lipid metabolism disorders in GIOP rats. Canonical Wnt signaling pathway plays an important role in bone formation and lipid metabolism during PEMF stimulation. PMID:26941827

  15. Glucocorticoid-induced osteoporosis: 2013 update.

    PubMed

    Mazzantini, M; Di Munno, O

    2014-07-28

    Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoid-induced osteoporosis (GIO). A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX) intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF) and the European Calcified Tissue Society (ECTS) published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis.

  16. Breast Cancer and Bone Loss

    MedlinePlus

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  17. Breast Cancer and Bone Loss

    MedlinePlus

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  18. Glucocorticoid-Induced Osteoporosis and Osteonecrosis

    PubMed Central

    Weinstein, Robert S.

    2012-01-01

    SYNOPSIS Glucocorticoid administration is the most common cause of secondary osteoporosis and the leading cause of nontraumatic osteonecrosis. In patients receiving long-term therapy, glucocorticoids induce fractures in 30 to 50% and osteonecrosis in 9 to 40%. This article reviews glucocorticoid-induced osteoporosis and osteonecrosis addressing the risk factors, pathogenesis, evaluation, treatment, and uncertainties in the clinical management of these disorders. PMID:22877431

  19. Adenosine Receptor Stimulation Improves Glucocorticoid-Induced Osteoporosis in a Rat Model.

    PubMed

    Pizzino, Gabriele; Irrera, Natasha; Galfo, Federica; Oteri, Giacomo; Atteritano, Marco; Pallio, Giovanni; Mannino, Federica; D'Amore, Angelica; Pellegrino, Enrica; Aliquò, Federica; Anastasi, Giuseppe P; Cutroneo, Giuseppina; Squadrito, Francesco; Altavilla, Domenica; Bitto, Alessandra

    2017-01-01

    Glucocorticoid-induced osteoporosis (GIO) is a secondary cause of bone loss. Bisphosphonates approved for GIO, might induce jaw osteonecrosis; thus additional therapeutics are required. Adenosine receptor agonists are positive regulators of bone remodeling, thus the efficacy of adenosine receptor stimulation for treating GIO was tested. In a preventive study GIO was induced in Sprague-Dawley rats by methylprednisolone (MP) for 60 days. Animals were randomly assigned to receive polydeoxyribonucleotide (PDRN), an adenosine A2 receptor agonist, or PDRN and DMPX (3,7-dimethyl-1-propargylxanthine, an A2 antagonist), or vehicle (0.9% NaCl). Another set of animals was used for a treatment study, following the 60 days of MP-induction rats were randomized to receive (for additional 60 days) PDRN, or PDRN and DMPX (an adenosine A2 receptor antagonist), or zoledronate (as control for gold standard treatment), or vehicle. Control animals were administered with vehicle for either 60 or 120 days. Femurs were analyzed after treatments for histology, imaging, and breaking strength analysis. MP treatment induced severe bone loss, the concomitant use of PDRN prevented the developing of osteoporosis. In rats treated for 120 days, PDRN restored bone architecture and bone strength; increased b-ALP, osteocalcin, osteoprotegerin and stimulated the Wnt canonical and non-canonical pathway. Zoledronate reduced bone resorption and ameliorated the histological features, without significant effects on bone formation. Our results suggest that adenosine receptor stimulation might be useful for preventing and treating GIO.

  20. PKCβII-mediated cross-talk of TRPV1/CB2 modulates the glucocorticoid-induced osteoclast overactivity.

    PubMed

    Bellini, Giulia; Torella, Marco; Manzo, Iolanda; Tortora, Chiara; Luongo, Livio; Punzo, Francesca; Colacurci, Nicola; Nobili, Bruno; Maione, Sabatino; Rossi, Francesca

    2017-01-01

    In this study, we investigated the role of the endovanilloid/endocannabinoid system in the glucocorticoid-induced osteoclast overactivity. Receptorial and enzymatic component of the endovanilloid/endocannabinoid system are expressed in bone cells, and dysregulated when bone mass is reduced. Moreover, blockade or desensitization of vanilloid receptor 1 (TRPV1) and/or stimulation of cannabinoid receptor 2 (CB2) are beneficial for reducing number and activity of the bone cells modulating resorption, the osteoclasts. We have treated in vitro healthy woman derived osteoclasts with methylprednisolone in presence or not of CB2 or TRPV1 agonists/antagonists, analysing the effect on osteoclast function and morphology through a multidisciplinary approach. Moreover, a treatment with a protein kinase C inhibitor to evaluate osteoclast activity and endovanilloid/endocannabinoid component expression levels was performed in osteoclasts derived from healthy subjects in presence of not of methylprednisolone. Our results show, for the first time, that the endovanilloid/endocannabinoid system is dysregulated by the treatment with methylprednisolone, that the osteoclast activity is increased and that pharmacological compounds stimulating CB2 or inhibiting TRPV1 might reduce, possible inhibiting protein kinase C beta II, the methylprednisolone-induced osteoclast over-activation, suggesting their therapeutic use for protecting from the glucocorticoid-induced bone mass loss.

  1. Inducible models of bone loss.

    PubMed

    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions. Copyright © 2014 John Wiley & Sons, Inc.

  2. What causes bone loss?

    MedlinePlus

    ... more calcium than normal in the urine Certain habits can affect your bones. Drinking alcohol. Too much alcohol can damage your bones. It can also put you at risk of falling and breaking a bone. Smoking. Men and women who smoke ...

  3. MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation.

    PubMed

    Ko, Jih-Yang; Chuang, Pei-Chin; Ke, Huei-Jin; Chen, Yu-Shan; Sun, Yi-Chih; Wang, Feng-Sheng

    2015-12-01

    Glucocorticoid treatment reportedly increases the morbidity of osteoporotic or osteonecrotic disorders. Exacerbated bone acquisition and escalated marrow adipogenesis are prominent pathological features of glucocorticoid-mediated skeletal disorders. MicroRNAs reportedly modulate tissue metabolism and remodeling. This study was undertaken to investigate the biological roles of microRNA-29a (miR-29a) in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis. Transgenic mice overexpressing miR-29a precursor or wild-type mice were given methylprednisolone. Bone mass, microarchitecture and histology were assessed by dual energy X-ray absorptiometry, μCT and histomorphometry. Differential gene expression and signaling components were delineated by quantitative RT-PCR and immunoblotting. Glucocorticoid treatment accelerated bone loss and marrow fat accumulation in association with decreased miR-29a expression. The miR-29a transgenic mice had high bone mineral density, trabecular microarchitecture and cortical thickness. miR-29a overexpression mitigated the glucocorticoid-induced impediment of bone mass, skeletal microstructure integrity and mineralization reaction and attenuated fatty marrow histopathology. Ex vivo, miR-29a increased osteogenic differentiation capacity and alleviated the glucocorticoid-induced promotion of adipocyte formation in primary bone-marrow mesenchymal progenitor cell cultures. Through inhibition of histone deacetylase 4 (HDAC4) expression, miR-29a restored acetylated Runx2 and β-catenin abundances and reduced RANKL, leptin and glucocorticoid receptor expression in glucocorticoid-mediated osteoporosis bone tissues. Taken together, glucocorticoid suppression of miR-29a signaling disturbed the balances between osteogenic and adipogenic activities, and thereby interrupted bone formation and skeletal homeostasis. miR-29a inhibition of HDAC4 stabilized the acetylation state of Runx2 and β-catenin that ameliorated the

  4. Space Radiation and Bone Loss

    PubMed Central

    Willey, Jeffrey S.; Lloyd, Shane A.J.; Nelson, Gregory A.; Bateman, Ted A.

    2011-01-01

    Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within the irradiated volume. The resulting suppression of bone formation and a general state of low bone-turnover is thought to be the primary contributor to bone loss and eventual fracture. Recent investigations using mouse models have identified a rapid, but transient, increase in osteoclast activity immediately after irradiation with both spaceflight and clinically-relevant radiation qualities and doses. Together with a chronic suppression of bone formation after radiation exposure, this acute skeletal damage may contribute to long-term deterioration of bone quality, potentially increasing fracture risk. Direct evidence for the damaging effects of radiation on human bone are primarily demonstrated by the increased incidence of fractures at sites that absorb high doses of radiation during cancer therapy: exposures are considerably higher than what could be expected during spaceflight. However, both the rapidity of bone damage and the chronic nature of the changes appear similar between exposure scenarios. This review will outline our current knowledge of space and clinical exploration exposure to ionizing radiation on skeletal health. PMID:22826632

  5. Space Radiation and Bone Loss.

    PubMed

    Willey, Jeffrey S; Lloyd, Shane A J; Nelson, Gregory A; Bateman, Ted A

    2011-01-01

    Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within the irradiated volume. The resulting suppression of bone formation and a general state of low bone-turnover is thought to be the primary contributor to bone loss and eventual fracture. Recent investigations using mouse models have identified a rapid, but transient, increase in osteoclast activity immediately after irradiation with both spaceflight and clinically-relevant radiation qualities and doses. Together with a chronic suppression of bone formation after radiation exposure, this acute skeletal damage may contribute to long-term deterioration of bone quality, potentially increasing fracture risk. Direct evidence for the damaging effects of radiation on human bone are primarily demonstrated by the increased incidence of fractures at sites that absorb high doses of radiation during cancer therapy: exposures are considerably higher than what could be expected during spaceflight. However, both the rapidity of bone damage and the chronic nature of the changes appear similar between exposure scenarios. This review will outline our current knowledge of space and clinical exploration exposure to ionizing radiation on skeletal health.

  6. Protection From Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin.

    PubMed

    Sato, Amy Y; Cregor, Meloney; Delgado-Calle, Jesus; Condon, Keith W; Allen, Matthew R; Peacock, Munro; Plotkin, Lilian I; Bellido, Teresita

    2016-10-01

    Excess of glucocorticoids, either due to disease or iatrogenic, increases bone resorption and decreases bone formation and is a leading cause of osteoporosis and bone fractures worldwide. Improved therapeutic strategies are sorely needed. We investigated whether activating Wnt/β-catenin signaling protects against the skeletal actions of glucocorticoids, using female mice lacking the Wnt/β-catenin antagonist and bone formation inhibitor Sost. Glucocorticoids decreased the mass, deteriorated the microarchitecture, and reduced the structural and material strength of bone in wild-type (WT), but not in Sost(-/-) mice. The high bone mass exhibited by Sost(-/-) mice is due to increased bone formation with unchanged resorption. However, unexpectedly, preservation of bone mass and strength in Sost(-/-) mice was due to prevention of glucocorticoid-induced bone resorption and not to restoration of bone formation. In WT mice, glucocorticoids increased the expression of Sost and the number of sclerostin-positive osteocytes, and altered the molecular signature of the Wnt/β-catenin pathway by decreasing the expression of genes associated with both anti-catabolism, including osteoprotegerin (OPG), and anabolism/survival, such as cyclin D1. In contrast in Sost(-/-) mice, glucocorticoids did not decrease OPG but still reduced cyclin D1. Thus, in the context of glucocorticoid excess, activation of Wnt/β-catenin signaling by Sost/sclerostin deficiency sustains bone integrity by opposing bone catabolism despite markedly reduced bone formation and increased apoptosis. This crosstalk between glucocorticoids and Wnt/β-catenin signaling could be exploited therapeutically to halt resorption and bone loss induced by glucocorticoids and to inhibit the exaggerated bone formation in diseases of unwanted hyperactivation of Wnt/β-catenin signaling. © 2016 American Society for Bone and Mineral Research.

  7. Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose.

    PubMed

    Dobrowolski, Piotr; Tomaszewska, Ewa; Muszyński, Siemowit; Blicharski, Tomasz; Pierzynowski, Stefan G

    2017-04-01

    Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength ( P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13-45%) decreased compared to the control ( P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2

  8. Glucocorticoid-induced apoptosis and cellular mechanisms of myopathy.

    PubMed

    Dirks-Naylor, Amie J; Griffiths, Carrie L

    2009-10-01

    Glucocorticoid-induced myopathy is a common side effect of chronic glucocorticoid therapy. Several mechanisms are currently being examined as ways in which glucocorticoid-induced myopathy occurs. These include apoptotic signaling through mitochondrial-mediated and Fas-mediated apoptosis, the role of the proteosome, the suppression of the IGF-1 signaling, and the role of ceramide in glucocorticoid-induced apoptosis and myopathy. It is difficult to differentiate which mechanism may be the initiating event responsible for the induction of apoptosis; however, all of the mechanisms play a vital role in glucocorticoid-induced myopathy.

  9. Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review.

    PubMed

    Zhang, Zhida; Ren, Hui; Shen, Gengyang; Qiu, Ting; Liang, De; Yang, Zhidong; Yao, Zhensong; Tang, Jingjing; Jiang, Xiaobing; Wei, Qiushi

    2016-12-01

    Glucocorticoid-induced postmenopausal osteoporosis is a severe osteoporosis, with high risk of major osteoporotic fractures. This severe osteoporosis urges more extensive and deeper basic study, in which suitable animal models are indispensable. However, no relevant review is available introducing this model systematically. Based on the recent studies on GI-PMOP, this brief review introduces the GI-PMOP animal model in terms of its establishment, evaluation of bone mass and discuss its molecular mechanism. Rat, rabbit and sheep with their respective merits were chosen. Both direct and indirect evaluation of bone mass help to understand the bone metabolism under different intervention. The crucial signaling pathways, miRNAs, osteogenic- or adipogenic- related factors and estrogen level may be the predominant contributors to the development of glucocorticoid-induced postmenopausal osteoporosis.

  10. Aromatase Inhibitors and Bone Loss

    PubMed Central

    PEREZ, EDITH A.; M., Serene; Durling, Frances C.; WEILBAECHER, KATHERINE

    2009-01-01

    The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor–positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment–related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score < −2.5) and considered on an individual basis for those with osteopenia (T score < −1). Modifiable lifestyle behaviors including adequate calcium and vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor–positive breast cancer. PMID:16986348

  11. Aromatase inhibitors and bone loss.

    PubMed

    Perez, Edith A; Weilbaecher, Katherine

    2006-08-01

    The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor-positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment-related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score < -2.5) and considered on an individual basis for those with osteopenia (T score < -1). Modifiable lifestyle behaviors including adequate calcium and vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor-positive breast cancer.

  12. Vertebral histomorphometry in a child with glucocorticoid-induced osteoporosis.

    PubMed

    Hatakeyama, Yuji; Miyakoshi, Naohisa; Kasukawa, Yuji; Watanabe, Arata; Hirayama, Masashi; Senma, Seietsu; Ono, Iwao; Shimada, Yoichi

    2012-08-01

    Vertebral fractures are an under-recognized problem in children with glucocorticoid-induced osteoporosis (GIO). They cause severe back pain and spinal column deformity with a decrease of quality of life. For evaluating the bone mass, bone mineral density measurements have been widely carried out using dual energy X-ray absorptiometry. However, bone histomorphometric analyses of GIO in children are scarce. Bone histomorphometric analyses of vertebral bodies have not been reported. Our aim is to report the first bone histomorphometric data for vertebrae from an autopsied child with GIO. A 15-year-old girl with systemic lupus erythematosus was started on a daily oral dose of 10 mg of prednisolone at 6 years of age. She presented with back pain from 12 years of age. Magnetic resonance imaging at 14 years of age showed a compression fracture of the first lumbar (L1) vertebral body. At 15 years of age, she died of heart failure owing to pulmonary hypertension. Collapsed (L1) and non-collapsed (seventh thoracic vertebrae; T7) vertebral bodies were autopsied for bone histomorphometry and compared. T7 showed severe osteoporosis (bone volume, 4.99%; trabecular thickness, 59 µm; trabecular separation, 1,134 µm). Compared with T7, L1 showed increased bone volume (33.9%) and trabecular thickness (77 µm), and decreased trabecular separation (156 µm) owing to the impact of the vertebral fracture. The bone formation and bone resorption parameters were comparable between the two vertebrae. These histological findings suggest that severe osteoporosis developed after long-term glucocorticoid administration, and that the remodeling activities were similar in the fractured and non-fractured vertebrae.

  13. Vitamin K2 Prevents Glucocorticoid-induced Osteonecrosis of the Femoral Head in Rats.

    PubMed

    Zhang, Yue-Lei; Yin, Jun-Hui; Ding, Hao; Zhang, Wei; Zhang, Chang-Qing; Gao, You-Shui

    2016-01-01

    Glucocorticoid medication is one of the most common causes of atraumatic osteonecrosis of the femoral head (ONFH), and vitamin K2 (VK2) has been shown to play an important and beneficial role in bone metabolism. In this study, we hypothesized that VK2 could decrease the incidence of glucocorticoid-induced ONFH in a rat model. Using in vitro studies, we investigated how bone marrow-derived stem cells in the presence of methylprednisolone proliferate and differentiate, specifically examining osteogenic-related proteins, including Runx2, alkaline phosphatase and osteocalcin. Using in vivo studies, we established glucocorticoid-induced ONFH in rats and investigated the preventive effect of VK2. We employed micro-CT scanning, angiography of the femoral head, and histological and immunohistochemical analyses, which demonstrated that VK2 yielded beneficial effects for subchondral bone trabecula. In conclusion, VK2 is an effective antagonist for glucocorticoid on osteogenic progenitors. The underlying mechanisms include acceleration of BMSC propagation and promotion of bone formation-associated protein expression, which combine and contribute to the prevention of glucocorticoid-induced ONFH in rats.

  14. Effects of Atorvastatin on Periodontitis of Rats Subjected to Glucocorticoid-Induced Osteoporosis.

    PubMed

    Sousa, Luzia Hermínia; Linhares, Eveline V M; Alexandre, Joanna Trycia; Lisboa, Mario Roberto; Furlaneto, Flávia; Freitas, Raul; Ribeiro, Isabela; Val, Danielle; Marques, Mirna; Chaves, Hellíada Vasconcelos; Martins, Conceição; Brito, Gerly A C; Goes, Paula

    2016-10-01

    Atorvastatin (ATV) has shown pleiotropic effects on bone tissue, and osteoporosis can aggravate periodontitis. Thus, the effects of ATV on experimental periodontitis (EP) in rats subjected to glucocorticoid-induced osteoporosis (GIOP) was assessed. Male Wistar rats were divided into the following groups: 1) naive; 2) EP; 3) GIOP + EP; and 4) ATV. Groups GIOP + EP and ATV received 7 mg/kg dexamethasone intramuscularly once per week for 5 weeks, and the others received saline (SAL). Groups EP, GIOP + EP, and ATV were submitted to EP by ligature around the maxillary left second molars for 11 days. Group ATV received 27 mg/kg ATV orally, and the others received SAL 30 minutes before EP. Periodontium was analyzed by macroscopy, microtomography, and histopathology; by immunohistochemical examination of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), wingless (WNT) 10b, dickkopf-related protein 1 (DKK-1), and β-catenin; and by enzyme-linked immunosorbent assay analysis of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL10, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Leukogram, liver and kidney enzymes, and bone-specific alkaline phosphatase (BALP) serum levels were evaluated. ATV decreased bone loss, reduced MPO, TNF-α, IL-1β, IL-6, and IL-8, and increased IL-10, GSH, SOD, and CAT levels. ATV reduced RANKL and DKK-1 and increased OPG, WNT10b, and β-catenin expressions and BALP activity. ATV reduced inflammation, oxidative stress, and bone loss in rats with EP and GIOP, with participation of the WNT signaling pathway.

  15. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip.

    PubMed

    Weinstein, R S; Nicholas, R W; Manolagas, S C

    2000-08-01

    An increase in osteoblast and osteocyte apoptosis has been demonstrated in mice and humans receiving glucocorticoids and may be involved in the pathogenesis of the associated osteonecrosis. To examine the spatial relationship between osteocyte apoptosis and glucocorticoid-induced osteonecrosis, we determined the prevalence of osteocyte apoptosis in whole femoral heads obtained from patients who underwent prosthetic hip replacement because of osteonecrosis due to chronic glucocorticoid treatment (n = 5), alcoholism (n = 3), and trauma (n = 1) as well as in femoral neck cores from patients with sickle cell disease (n = 5). Abundant apoptotic osteocytes and cells lining cancellous bone were found juxtaposed to the subchondral fracture crescent in femurs from the patients with glucocorticoid excess. In contrast, apoptotic bone cells were absent from the specimens taken from patients with trauma or sickle cell disease and were rare with alcohol abuse. These results indicate that glucocorticoid-induced osteonecrosis is a misnomer. The bone is not necrotic; instead, it shows prominent apoptosis of cancellous lining cells and osteocytes. Glucocorticoid-induced osteocyte apoptosis, a cumulative and irreparable defect, could uniquely disrupt the mechanosensory function of the osteocyte network and thus start the inexorable sequence of events leading to collapse of the femoral head.

  16. Regulation of bone mineral loss during lactation

    NASA Technical Reports Server (NTRS)

    Brommage, R.; Deluca, H. F.

    1985-01-01

    The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

  17. Regulation of bone mineral loss during lactation

    NASA Technical Reports Server (NTRS)

    Brommage, R.; Deluca, H. F.

    1985-01-01

    The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

  18. Weight loss, weight regain and bone health.

    PubMed

    Pines, Amos

    2012-08-01

    The ideal body image for women these days is being slim but, in the real world, obesity becomes a major health problem even in the developing countries. Overweight, but also underweight, may have associated adverse outcomes in many bodily systems, including the bone. Only a few studies have investigated the consequences of intentional weight loss, then weight regain, on bone metabolism and bone density. It seems that the negative impact of bone loss is not reversed when weight partially rebounds following the end of active intervention programs. Thus the benefits and risks of any weight loss program should be addressed individually, and monitoring of bone parameters is recommended.

  19. Weight loss and bone mineral density.

    PubMed

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

    2014-10-01

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

  20. Bed Rest and Immobilization: Risk Factors for Bone Loss

    MedlinePlus

    ... weightlessness and immobility can result in bone loss. Space travel has provided significant research data on the subject of weightlessness and bone loss. Astronauts exposed to the microgravity of space experience significant bone loss, leaving their bones weak ...

  1. Glucocorticoid-induced osteoporosis: an update on effects and management.

    PubMed

    Buehring, Bjoern; Viswanathan, Ravi; Binkley, Neil; Busse, William

    2013-11-01

    Glucocorticoids remain a cornerstone of guideline-based management of persistent asthma and allergic diseases. Glucocorticoid-induced osteoporosis (GIO) is the most common iatrogenic cause of secondary osteoporosis and an issue of concern for physicians treating patients with inhaled or oral glucocorticoids either continuously or intermittently. Patients with GIO experience fragility fractures at better dual-energy x-ray absorptiometry T-scores than those with postmenopausal or age-related osteoporosis. This might be explained, at least in part, by the effects of glucocorticoids not only on osteoclasts but also on osteoblasts and osteocytes. Effective options to detect and manage GIO exist, and a management algorithm has been published by the American College of Rheumatology to provide treatment guidance for clinicians. This review will summarize GIO epidemiology and pathophysiology and assess the role of inhaled and oral glucocorticoids in asthmatic adults and children, with particular emphasis on the effect of such therapies on bone health. Lastly, we will review the American College of Rheumatology GIO guidelines and discuss diagnostic and therapeutic strategies to mitigate the risk of GIO and fragility fractures.

  2. Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

    USDA-ARS?s Scientific Manuscript database

    Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

  3. Proresorptive actions of FSH and bone loss.

    PubMed

    Zaidi, Mone; Blair, Harry C; Iqbal, Jameel; Zhu, Ling Ling; Kumar, T Rajendra; Zallone, Alberta; Sun, Li

    2007-11-01

    We review studies that propose follicle-stimulating hormone (FSH) as a physiologic stimulator of osteoclastic bone resorption. We hypothesize that, in addition to low estrogen, a rising FSH contributes to the increased bone resorption and bone loss in hypergonadism. This is of particular relevance to the perimenopausal transition, wherein profound bone loss is accompanied by trabecular perforations in the face of high FSH and normal estrogen levels. Potential therapeutic implications include the development of antagonists to both circulating FSH and its osteoclastic receptor.

  4. Prevent and cure disuse bone loss

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.

    1994-01-01

    Anabolic agents like parathyroid hormone and postagladin E-like substances were studied in dogs and rats to determine their effectiveness in the prevention and cure of bone loss due to immobilization. It was determined that postagladin E2 administration prevented immobilization while at the same time it added extra bone in a dose responsive manner. Although bone mass returns, poor trabecular architecture remains after normal ambulation recovery from immobilization. Disuse related bone loss and poor trabecular architecture were cured by post-immobilization postagladin E2 treatment.

  5. Preventive effects of Polygonum multiflorum on glucocorticoid-induced osteoporosis in rats.

    PubMed

    Zhou, Manru; Li, Jin; Wu, Jingkai; Yang, Yajun; Zeng, Xiaobing; Lv, Xiaohua; Cui, Liao; Yao, Weimin; Liu, Yuyu

    2017-09-01

    In Traditional Chinese Medicine, Polygonum multiflorum (PM) is known for its anti-aging properties. A previous study by our group showed that extracts of PM were able to prevent and treat bone loss in vivo, and the active components emodin and 2,3,5,4,-tetrahydroxystilbene-2-O-β-glucoside (TSG) promoted the osteogenic differentiation of mesenchymal stem cells in vitro. The aim of the present study was to investigate the preventive effects of PM on glucocorticoid-induced osteoporosis (GIO) in rats. A crude extract of PM was prepared with 75% ethanol, purified and enriched using a D-101 macroresin column and elution with 30% ethanol, and the material obtained was assessed by high-performance liquid chromatography. Male or female Sprague Dawley rats (n=180) were randomly divided into nine groups: Control, prednisone, prednisone plus calcitriol (CAL), prednisone plus 30% ethanolic eluate of PM [high (H), medium (M) and low (L) dose] and prednisone plus crude extract of PM (H, M and L dose). Prednisone was orally administered to the osteoporosis model rats for 21 weeks, alongside which they received PM extracts. The weight of the viscera, anterior tibial muscle and other tissues was recorded at the end of the experiment. The femur and lumbar vertebra were collected for the measurement of three-dimensional microarchitecture by micro-computed tomography scanning, assessment of biomechanical properties and determination of bone mineral density (BMD). In the 30% ethanolic eluate of the PM extract, the content of TSG and combined anthraquinone was 9.20 and 0.15%, respectively, and that in the crude extract of PM was 2.23 and 0.03%, respectively. Over 6 weeks, the weight of the rats the in prednisone group decreased (P<0.05), while the weight of rats treated with M and H doses of 30% ethanolic eluate was increased compared with that in the prednisone group (P<0.05). Rats exposed to prednisone exhibited a deteriorated bone microarchitecture, low BMD, decreased bone volume

  6. Bone Metabolism in Obesity and Weight Loss

    PubMed Central

    Shapses, Sue A.; Sukumar, Deeptha

    2014-01-01

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

  7. Countermeasures against space flight related bone loss

    NASA Technical Reports Server (NTRS)

    Leblanc, Adrian; Schneider, Victor

    1992-01-01

    A general review is presented of data on bone loss with references to countermeasures for use during spaceflight and bedrest. The two primary countermeasures against skeletal atrophy are skeletal loading such as centrifugation and exercise and/or the administration of drugs designed to alter the rate of bone remodeling. Bone loss is argued to be unavoidable in long-duration spaceflight in spite of countermeasures utilized, but a combination of exercise, biochemical treatments, and post-flight therapy is considered the optimal solution.

  8. Decreased bone mineral density and vertebral compression fractures in a young adult male with 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH): is CAH an unrecognized population at risk for glucocorticoid-induced osteoporosis?

    PubMed

    Loechner, Karen J; Patel, Shipra; Fordham, Lynne; McLaughlin, James T

    2010-01-01

    CAH, most often due to a molecular defect in the 21-OH enzyme, results in inadequate cortisol production and subsequent life-long GC replacement. To heighten awareness for risk of GIO in children with CAH including (1) ongoing assessment of GC dosing, (2) screening for bone health, and (3) prophylactic measures/early intervention once GIO is identified. 23 year-old male with 21OHD CAH referred for osteopenia. Chart review; radiological, serological and urine assessment. Patient has old vertebral compression fractures and diminished BMD, the onset of which likely corresponds to excessive GC dosing during adolescence. As with other GC-dependent conditions, children with CAH may represent a previously unrecognized population at risk for GIO. Physicians need to be cognizant of the consequences of excessive GC dosing on bone health, especially during infancy and adolescence, critical periods for both linear growth as well as bone accretion.

  9. Aromatase Activity and Bone Loss in Men

    PubMed Central

    Merlotti, Daniela; Gennari, Luigi; Stolakis, Konstantinos; Nuti, Ranuccio

    2011-01-01

    Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. This enzyme is encoded by the CYP19A1 gene located at chromosome 15q21.2, that is, expressed in ovary and testis, but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone. Importantly, extraglandular aromatization of circulating androgen precursors is the major source of estrogen in men. Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, the attainment of peak bone mass, pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men. PMID:21772971

  10. Arterial hypertension perpetuates alveolar bone loss.

    PubMed

    de Medeiros Vanderlei, Janine Montenegro Toscano Moura; Messora, Michel Reis; Fernandes, Patrícia Garani; Novaes, Arthur B; Palioto, Daniela Bazan; de Moraes Grisi, Marcio Fernando; Scombatti de Souza, Sergio Luis; Gerlach, Raquel Fernanda; Antoniali, Cristina; Taba, Mario

    2013-01-01

    Few studies have focused on the impact of hypertension on the progression of periodontitis (PD). The purpose of this study was to evaluate whether hypertension affects PD by enhancing bone loss even after the stimulus for PD induction is removed. Ligature-induced PD was created on the first mandibular molars of spontaneously hypertensive rats (SHR) and normotensive rats (Wistar Kyoto-WKY). The animals were assigned to non-ligated controls (C) and PD groups: WKY-C, WKY-PD, SHR-C, and SHR-PD. After 10 days, five animals of each group were killed and the ligatures of the other animals were removed. On the 21st day (11 days without PD induced), the remaining animals were killed. The jaws were defleshed and the amount of bone loss was measured. After 10 days, the PD groups showed more bone loss than its controls (P < .05); SHR-PD = 0.72 ± 0.05 mm, SHR-C = 0.39 ± 0.04 mm, WKY-PD = 0.75 ± 0.04 mm, and WKY-C = 0.56 ± 0.04 mm. The cumulative bone loss on day 21 (0.94 ± 0.13 mm) was significantly worse than on day 10 only in SHR-PD group (P < .05). The final bone loss differences between PD and C groups accounted for 102% (SHR) and 26% (WKY) increase in comparison with the initial control levels. Hypertension is associated with progressive alveolar bone loss even when the stimulus for PD induction is removed and it may be speculated that host condition perpetuates alveolar bone loss.

  11. Weightlessness and bone loss in man

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.

    1983-01-01

    A review is presented of data whicih has been accumulated on the calcium and skeletal changes occurring in humans subjected to various periods of weightlessness. These data reveal that spaceflight induces an overall loss of calcium which continues unabated for at least three months. Urinary calcium levels reach a constant level within approximately four weeks while fecal calcium losses continue to increase throughout the flight period. A decline in the mineral density of weight-bearing bones accompanies these changes. Available data support the contention that the demineralization affects primarily the weight bearing bones. The rates of loss and recovery of calcium and bone mineral density are approximately equal to those observed during and following bedrest of comparable duration. No measure to wholly prevent these losses has yet been devised.

  12. Mechanisms of age-related bone loss.

    PubMed

    Mosekilde, L

    2001-01-01

    The human skeleton is formed and modelled during childhood and youth through the influence of hormones and daily mechanical usage. Around the age of 20-25 years, the skeleton achieves its maximum mass and strength. Thereafter, and throughout adult life, bone is lost at an almost constant rate due to the dynamic bone turnover process: the remodelling process. During this process, small packets of bone are renewed by teams of bone cells coupled together in time and space. In an adult human skeleton there will be 1-2 million active remodelling sites at any time point. The vast number of turnover units combined with a slightly negative balance at the completion of each process leads to the age-related loss of bone mass mentioned above and, concomitantly, to loss of structural continuity and strength. The magnitude of this loss will be determined by hormonal factors, nutrition and mechanical usage. As a consequence of the remodelling process, the bone tissue of the skeleton will always be younger than the age of the individual. However, as a consequence of the remodelling process, osteopenia and osteoporotic fractures will also occur. In this article, the remodelling-induced changes in the human spine will be used as an example of ageing bone.

  13. Bone Loss in Adolescents After Bariatric Surgery

    PubMed Central

    Bean, Judy A.; Inge, Thomas H.; Dolan, Lawrence M.; Kalkwarf, Heidi J.

    2011-01-01

    OBJECTIVE: To evaluate bone loss in adolescents after Roux-en-Y gastric bypass surgery and to determine the extent to which bone loss was related to weight loss. We hypothesized that adolescents would lose bone mass after surgery and that it would be associated with weight loss. PATIENTS AND METHODS: We conducted a retrospective case review of 61 adolescents after bariatric surgery. Whole-body bone mineral content (BMC) and density (BMD) were measured by dual-energy radiograph absorptiometry, and age- and gender-specific BMD z scores were calculated. Measurements were obtained when possible before surgery and then every 3 to months after surgery for up to 2 years. Data were analyzed by using a mixed-models approach, and regression models were adjusted for age, gender, and height. RESULTS: Whole-body BMC, BMD z score, and weight decreased significantly over time after surgery (P < .0001 for all). In the first 2 years after surgery, predicted values on the basis of regression modeling for BMC decreased by 7.4%, and BMD z score decreased from 1.5 to 0.1. During the first 12 months after surgery, change in weight was correlated with change in BMC (r = 0.31; P = .02). Weight loss accounted for 14% of the decrease in BMC in the first year after surgery. CONCLUSION: Bariatric surgery is associated with significant bone loss in adolescents. Although the predicted bone density was appropriate for age 2 years after surgery, longer follow-up is warranted to determine whether bone mass continues to change or stabilizes. PMID:21444596

  14. Periprosthetic bone loss: diagnostic and therapeutic approaches

    PubMed Central

    Cavalli, Loredana; Brandi, Maria Luisa

    2014-01-01

    Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numerous particles of debris that cause a complex biological response. Dual-energy X-ray Absorptiometry (DXA) is regarded as an accurate method to evaluate Bone Mineral Density (BMD) around hip or knee prostheses. Further data may be provided by a new device, the Bone Microarchitecture Analysis (BMA), which combines bone microarchitecture quantification and ultra high resolution osteo-articular imaging. Pharmacological strategies have been developed to prevent bone mass loss and to extend implant survival. Numerous trials with bisphosphonates show a protective effect on periprosthetic bone mass, up to 72 months after arthroplasty. Strontium ranelate has been demonstrated to increase the osseointegration of titanium implants in treated animals with improvement of bone microarchitecture and bone biomaterial properties. PMID:25642325

  15. Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats.

    PubMed

    Hozayen, Walaa G; El-Desouky, Mohamed A; Soliman, Hanan A; Ahmed, Rasha R; Khaliefa, Amal K

    2016-06-02

    Glucocorticoid-induced osteoporosis (GIO) is one of the serious side effects which have become the most common secondary osteoporosis. The purpose of this study is to evaluate the effect of aqueous extract of parsley, basil and chicory on glucocorticoid-induced osteoporosis in rats. Fifty Female rats were divided into five groups and treated for 8 weeks as follow: group 1 served as control; group (2) subcutaneously injected with 0.1 mg/kg b. wt. dexamethasone dissolved in saline; group 3 received similar dose of dexamethasone together with aqueous parsley extract in a dose of 2 g/kg b. wt.; group 4 received similar dose of dexamethasone together with 400 mg/kg b. wt. aqueous basil extract and group 5 received similar dose of dexamethasone together with 100 mg/kg b. wt. aqueous chicory extract. The dexamethasone group showed a significant decrease in serum E2, Ca, P levels and significant decrease in total BMD, BMC and a significant increase in serum PTH, ALP and ACP. Bone TBARs was significantly increased while GSH, antioxidant enzymes were significantly decreased. These changes were attenuated by parsley, basil and chicory extracts in the group 3, 4 and 5 respectively. Aqueous extracts of parsley, basil and chicory showed bone protection against glucocorticoid-induced in rats. From our results, we concluded that chicory has a potent protective effect more than parsley and basil due to containing flavonoids and inulin.

  16. Tooth rotation and alveolar bone loss.

    PubMed

    Peretz, B; Machtei, E E

    1996-07-01

    Tooth rotation and periodontal breakdown has not been thoroughly studied due to lack of quantitative tools. The purpose of the present study was to examine this correlation, with respect to alveolar bone loss, from direct observation of 17 skulls. A photograph of the mandibular occlusal plane was taken from a fixed reference point, and the midcentral fossa and the extreme mesial and distal points of each tooth were marked on the photograph. A computer program established the arch form of each mandibular from the midtooth landmarks. The angle between individual teeth and the arch (at any given point) was calculated. Bone loss, indicated by the distance of the bone crest from the cementoenamel junction, was measured at six reference points around each tooth with a caliper. A positive correlation, through weak, was found between increased tooth rotation and greater bone loss. Mean bone loss of teeth with rotation of 20 degrees and greater was 4.03 mm, while that of teeth with less than 20 degrees of rotation was 3.49 mm.

  17. Vitamin C reverses hypogonadal bone loss

    USDA-ARS?s Scientific Manuscript database

    Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, ...

  18. Pathophysiology of bone loss in disuse osteoporosis.

    PubMed

    Alexandre, Christian; Vico, Laurence

    2011-12-01

    Osteoporosis, or rather the localised bone loss observed in patients with spinal cord injury, as well as during any type of immobilisation involves various processes and structures including the direct response of the musculoskeletal system to unloading, the central and peripheral nervous systems and their effects on bone cells and on the vascular system, the bone remodelling unit in its marrow compartment and a number of local factors controlling cell-cell cross-talk as well as calciotropic hormones. The authors present a detailed review of these different mechanisms which are all involved regardless of the type of immobilisation: pathological, environmental, or experimental. These factors are interconnected and put bone at the centre of the regulation of body homeostasis. A better knowledge of these mechanisms should promote the development of preventive therapies for the often neglected osteoporotic fractures that occur in patients with spinal cord injury.

  19. Glucocorticoid-induced apoptosis of healthy and malignant lymphocytes

    PubMed Central

    Smith, Lindsay K.; Cidlowski, John A.

    2016-01-01

    Glucocorticoids exert a wide range of physiological effects, including the induction of apoptosis in lymphocytes. The progression of glucocorticoid-induced apoptosis is a multi-component process requiring contributions from both genomic and cytoplasmic signaling events. There is significant evidence indicating that the transactivation activity of the glucocorticoid receptor is required for the initiation of glucocorticoid-induced apoptosis. However, the rapid cytoplasmic effects of glucocorticoids may also contribute to the glucocorticoid-induced apoptosis-signaling pathway. Endogenous glucocorticoids shape the T-cell repertoire through both the induction of apoptosis by neglect during thymocyte maturation and the antagonism of T-cell receptor (TCR)-induced apoptosis during positive selection. Owing to their ability to induce apoptosis in lymphocytes, synthetic glucocorticoids are widely used in the treatment of haematological malignancies. Glucocorticoid chemotherapy is limited, however, by the emergence of glucocorticoid resistance. The development of novel therapies designed to overcome glucocorticoid resistance will dramatically improve the efficacy of glucocorticoid therapy in the treatment of haematological malignancies. PMID:20541659

  20. GLUCOCORTICOID-INDUCED ALTERATION OF THE SURFACE MEMBRANE OF CULTURED HEPATOMA CELLS

    PubMed Central

    Ballard, Philip L.; Tomkins, Gordon M.

    1970-01-01

    Glucocorticoids induce an alteration of the surface of hepatoma tissue culture (HTC) cells as expressed by changes in cell electrophoretic, antigenic, and adhesive properties. The alteration is assayed by the increased adhesiveness of induced cells for a glass surface. The induction process has a lag period of about 3 hr and attains a plateau level after 24–30 hr when 50–80% of the steroid-treated cells are firmly adhered. Less than 10% of untreated cells adhere under the same conditions. Induction is inhibited by actinomycin D and cycloheximide, demonstrates both pH and temperature dependence, and responds to changes in steroid concentration and structure. By contrast, the attachment per se of preinduced cells is not affected by inhibitors of RNA and protein synthesis, fluctuations of temperature and pH, and the presence or absence of the hormone. When the induction process is reversed by removal of steroid or addition of actinomycin D, preinduced adhesiveness is lost with a half-life of 13–24 hr, but in the presence of cycloheximide the loss is accelerated (t1/2 3–5.5 hr). These results suggest that glucocorticoids induce the biosynthesis of a protein which either modifies the cell surface (an enzyme) or is incorporated into surface structures (structural protein). PMID:4327515

  1. Diagnostic systems for assessing alveolar bone loss.

    PubMed

    Ivanusa, T; Babic, A; Petelin, M

    1997-01-01

    Radiological diagnostics serves as a basic monitoring technique for alveolar bone loss which is a severe consequence of periodontal disease. To evaluate efficacy of Conventional Visual Radiography (CVR), and to assess a complete clinical status, we had used two more diagnostic systems. These are Digital Subtraction Radiography (DSR) and Probing Pocket Depth (PPD). Experimental Periodontitis was studied in 20 beagle dogs based on the measurements taken in the beginning (baseline), and before (11th month) and after the medical treatment (12th month). Data analyses pointed out the same clinical trend, i.e. a significant bone loss prior to medical treatment and its recovery to the initial state. Differences in metrics and measurement errors could be identified as causes for discrepancies between the systems, but a relationship between the CVR and PPD is worth of further research, as these systems do not appear to be entirely compatible, but rather complementary to each other.

  2. An Unusual Bone Loss Around Implants

    PubMed Central

    Rokn, Amir Reza; Sajedinejad, Neda; Yousefyfakhr, Hosnieh; Badri, Samare

    2013-01-01

    Pre-implant disease is an inflammatory process that affects the surrounding tissues of a functional osseointegrated implant. It is usually the result of a disequilibrium between the micro-flora and the defense system. This case reports a 57-year-old man with unusual bone loss around dental implants. This was an unusual case of peri-implantitis that occurred only in the implants on one side of the mouth although they were all unloaded implants. PMID:24396359

  3. Efficacy and safety of zoledronic acid in the treatment of glucocorticoid-induced osteoporosis

    PubMed Central

    Serefoglu, Ege Can; Tandogdu, Zafer

    2010-01-01

    Glucocorticoids are essential in treating many disorders and they are widely used in spite of their negative impact on the skeletal system. As bisphosphonates reduce bone resorption through their action on osteoclasts, they play an important role in management of glucocorticoid-induced osteoporosis. Unlike other bisphosphonates, zoledronic acid is given by intravenous infusion and it has a potential advantage of increasing the compliance and adherence of patients when it is given 5 mg once a year. However, this treatment modality seems to be associated with more adverse events than oral administrations, and further studies with longer follow-up periods must be conducted to determine the safety and cost-effectiveness of long-term treatment with zoledronic acid. PMID:20526439

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Evaluating Bone Loss in ISS Astronauts.

    PubMed

    Sibonga, Jean D; Spector, Elisabeth R; Johnston, Smith L; Tarver, William J

    2015-12-01

    The measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is the Medical Assessment Test used at the NASA Johnson Space Center to evaluate whether prolonged exposure to spaceflight increases the risk for premature osteoporosis in International Space Station (ISS) astronauts. The DXA scans of crewmembers' BMD during the first decade of the ISS existence showed precipitous declines in BMD for the hip and spine after the typical 6-mo missions. However, a concern exists that skeletal integrity cannot be sufficiently assessed solely by DXA measurement of BMD. Consequently, use of relatively new research technologies is being proposed to NASA for risk surveillance and to enhance long-term management of skeletal health in long-duration astronauts. Sibonga JD, Spector ER, Johnston SL, Tarver WJ. Evaluating bone loss in ISS astronauts.

  7. A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice.

    PubMed

    Plotkin, L I; Bivi, Nicoletta; Bellido, T

    2011-07-01

    Although a major effect of bisphosphonates on bone is inhibition of resorption resulting from their ability to interfere with osteoclast function, these agents also prevent osteoblast and osteocyte apoptosis in vitro and in vivo. However, the contribution of the latter property to the overall beneficial effects of the drugs on bone remains unknown. We compared herein the action on glucocorticoid-induced bone disease of the classical bisphosphonate alendronate with that of IG9402, a bisphosphonate analog that preserves osteoblast and osteocyte viability but does not induce osteoclast apoptosis in vitro. The bisphosphonates were injected daily (2.3 μmol/kg) to 5-month-old Swiss Webster mice (6-11 per group), starting 3 days before implantation of pellets releasing the glucocorticoid prednisolone (2.1 mg/kg/day). IG9402 did not affect levels of circulating C-telopeptide or osteocalcin, markers of resorption and formation, respectively, nor did it decrease mRNA levels of osteocalcin or collagen 1a1 in bone. On the other hand, alendronate decreased all these parameters. Moreover, IG9402 did not reduce cancellous mineralizing surface, mineral apposition rate, or bone formation rate, whereas alendronate induced a decrease in each of these bone formation measures. These findings demonstrate that, in contrast to alendronate, IG9402 does not inhibit bone turnover. Both alendronate and IG9402, on the other hand, activated survival kinase signaling in vivo, as evidenced by induction of ERK phosphorylation in bone. Furthermore, both bisphosphonates prevented the increase in osteoblast and osteocyte apoptosis as well as the decrease in vertebral bone mass and strength induced by glucocorticoids. We conclude that a bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice.

  8. The in vivo effects of a fraction from Dioscorea spongiosa on glucocorticoid-induced osteoporosis.

    PubMed

    Han, Na; Xu, Jinghua; Xu, Feng; Liu, Zhihui; Yin, Jun

    2016-06-05

    In traditional Chinese medicines, osteoporosis was considered to be induced by the deficiency of kidney's function. The Rhizoma of Dioscorea spongiosa was one of the kidney tonifying and bone strengthening agent in the traditional usage and previous study had shown that its 90% ethanol fraction was effective on anti-osteoporosis using the ovariectomized (OVX) rats. However, for the secondary osteoporosis, like glucocorticoid-induced osteoporosis (GIO), its effect was still unknown. The GIO model was established by injecting dexamethasone into the muscles of rats. The 90% ethanol extraction of Dioscorea spongiosa (DSE) were administrated to rats in three different dosages, 125, 250 and 500mg/Kg/d, respectively. After the administration, the rats were sacrificed to measure different kinds of indicators, including the biochemical indexes in urine and serum, the bone tissue metrology, BMC and BMD, biomechanical indicators and histological changes. DSE could significantly reduce the content of BGP, ALT, TRAcP, HOP/Cr and Ca/Cr, increase the content of P/Cr compared with the control group, suggesting that DSE is effective on controlling the excessive transition of bones and inhibiting the bone resorption. By the administration of DSE, the dry bone weight/volume, ash weight/volume, the content of Ca, BMD and BMC were also obviously increased, suggesting that DSE could increase the bone mass by increasing its Ca content. Besides, the flexure strength and maximum bending force could be improved by DSE, suggesting that it could strengthen the hardness and strength of bones. In the histological investigation, DSE could repair the broken of cancellous bones and bone trabecular with the similar activity with XLGB. The results showed that DSE is effective on inhibiting GIO in rats by improving the bone tissue metrology, BMC and BMD as well as biomechanical indicators, and also repairing the microscopic changes of cancellous bones and trabecular bones. The mechanism was related

  9. Interventions to prevent bone loss in astronauts during space flight.

    PubMed

    Iwamoto, Jun; Takeda, Tsuyoshi; Sato, Yoshihiro

    2005-06-01

    This paper reviews the interventions to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight. Weightlessness during space flight results in calcium, vitamin D, and vitamin K deficiency, increases urinary calcium excretion, decreases intestinal calcium absorption, and increases serum calcium level, with decreased levels of serum parathyroid hormone and calcitriol. Bone resorption is increased, whereas bone formation is decreased. The loss of bone mineral density (BMD) in the spine, femoral neck and trochanter, and pelvis is 1.0-1.6% per month. High calcium intake and vitamin D supplementation during space flight does not affect bone metabolism, but prevents an elevation of serum calcium level through increased calcitriol level, while vitamin K counteracts the reduction in bone formation. However, there are no data to show the efficacy of pharmaceutical agents for prevention of development of osteoporosis in astronauts during flight, although the preventative effect of bisphosphonates, testosterone, and vitamin K2 on cancellous bone loss in the tibia or BMD loss in the hindlimb was reported in tail-suspended mature rats. It still remains uncertain whether these agents can prevent cortical bone loss caused by weightlessness in tail-suspended rats. Therefore, in addition to calcium, vitamin D, and vitamin K supplementation, agents that have both potent anti-resorptive and anabolic effects on cancellous and cortical bone may be needed to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight.

  10. Homocysteine and bone loss in epilepsy.

    PubMed

    Elliott, John O; Jacobson, Mercedes P; Haneef, Zulfi

    2007-01-01

    Epidemiological studies reveal fracture incidence in epilepsy is twice that of the normal population. Much interest has been focused on Vitamin D, however, considering mixed results on non-enzyme inducing anti-epileptic drugs (AEDs) and bone mineral density (BMD) additional metabolic effects may be to blame. AEDs increase serum homocysteine (s-Hcy) by lowering blood folate levels. An association between elevated homocysteine, BMD and increased fracture incidence has been found in non-epilepsy populations. Additionally, folate and Vitamin B12 levels are independently related to bone mineral density in various non-epilepsy populations. This study supports previous research, which found elevated s-Hcy in subjects taking AEDs and that bone loss is related to the use of enzyme-inducing AEDs and changes in alkaline phosphatase. By one-way ANOVA, subjects on phenytoin monotherapy had significantly higher levels of s-Hcy than those on other AEDs (F=5.89, p=.016). Regression analyses revealed homocysteine, fracture history, length of years on AEDs, ethnicity were predictors of spine T scores. Weight and BMI were predictors of both BMD and DEXA T scores. Use of enzyme-inducing AEDs was a negative predictor of spine BMD and T scores, while phenytoin monotherapy was a positive predictor of spine BMD. Lamotrigine was found to be a negative predictor of spine T score. Ambulatory status, menopause and alcohol consumption were predictors of BMD but not T scores. In this study, persons with epilepsy who take nutritional supplementation have 25% lower s-Hcy levels than those who do not. Supplementation continues to be important in preventative epilepsy care.

  11. Prostaglandin E2 Prevents Disuse-Induced Cortical Bone Loss

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Akamine, T.; Ke, Hua Zhu; Li, Xiao Jian; Tang, L. Y.; Zeng, Q. Q.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloaded)-induced cortical bone loss as well as add extra bone to underloaded bones. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to simultaneous right hindlimb immobilization by bandaging and daily subcutaneous doses of 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). Disuse-induced cortical bone loss occurred by enlarging the marrow cavity and increasing intracortical porosity. PGE2 treatment of disuse shafts further increased intracortical porosity above that in disuse alone controls. This bone loss was counteracted by enhancement of periosteal and corticoendosteal bone formation. Stimulation of periosteal and corticoendosteal bone formation slightly enlarged the total tissue (cross-sectional) area and inhibited marrow cavity enlargement. These PGE2-induced activities netted the same percentage of cortical bone with a different distribution than the beginning and age related controls. These findings indicate the PGE2-induced increase in bone formation compensated for the disuse and PGE2-induced bone loss, and thus prevented immobilization induced bone loss.

  12. Subtle shake-up in bone-loss research.

    PubMed

    Flinn, Edward D

    2002-03-01

    Recent research in the prevention of bone loss during weightlessness is described. Scientists are studying the effects of vibration on bone loss in laboratory animals and humans. Research is focused on determining how bone formation is triggered, the effects of stimulation of the stress response in bones, and the mechanisms behind the effects. Clinton Rubin at the State University of New York at Stony Brook is experimenting with 90 Hz vibration frequencies in rats. Other researchers are studying the effects of vibration plates in the treatment of osteoporosis in postmenopausal women and in children with low bone density. Tests among astronauts have been proposed, but none are scheduled.

  13. Novel Radiomitigator for Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

    2016-01-01

    Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

  14. Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis.

    PubMed

    Ringe, J D; Dorst, A; Faber, H; Schacht, E; Rahlfs, V W

    2004-03-01

    Supplementation therapy with plain vitamin D plus calcium is in general regarded as effective prevention or first-step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to compare the therapeutic efficacy of the D-hormone analog alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid (GC) therapy were included as matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n=103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n=101). The two groups were well matched in terms of mean age, sex ratio, mean height and weight, daily dosage, and duration of GC therapy, and the percentages of the three underlying diseases included chronic obstructive pulmonary disease, rheumatoid arthritis, and polymyalgia rheumatica. The baseline mean bone mineral density (BMD) values at the lumbar spine for the two groups were -3.26 (alfacalcidol) and -3.25 (vitamin D(3)) and, at the femoral neck, -2.81 and -2.84, respectively (T scores). Rates of prevalent vertebral and nonvertebral fractures did not differ between groups. During the 3-year study, we observed a median percentage increase of BMD at the lumbar spine of 2.4% in group A and a loss of 0.8% in group B ( P<0.0001). There also was a larger median increase at the femoral neck in group A (1.2%) than in group B (0.8%) ( P<0.006). The 3-year rates of patients with at least one new vertebral fracture were 9.7% among those assigned to the alfacalcidol group and 24.8% in the vitamin D group (risk reduction 0.61, 95% CI 0.24-0.81, P=0.005). The 3-year rates of patients with at least one new nonvertebral fracture were 15% in the alfacalcidol group and 25% in the vitamin D group (risk reduction 0.41, 95% CI 0.06-0.68, P=0.081). The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D

  15. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

    PubMed

    Intini, G; Katsuragi, Y; Kirkwood, K L; Yang, S

    2014-05-01

    This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of

  16. Periarticular Bone Loss in Antigen-Induced Arthritis

    PubMed Central

    Engdahl, Cecilia; Lindholm, Catharina; Stubelius, Alexandra; Ohlsson, Claes; Carlsten, Hans; Lagerquist, Marie K

    2013-01-01

    Objective Bone loss in arthritis is a complex process characterized by bone erosions and periarticular and generalized bone loss. The antigen-induced arthritis (AIA) model is mainly used to study synovitis and joint destruction, including bone erosions; however, periarticular bone loss has been less extensively investigated. The objectives of this study were to characterize and establish AIA as a model for periarticular bone loss, and to determine the importance of NADPH oxidase 2 (NOX-2)–derived reactive oxygen species (ROS) in periarticular bone loss. Methods Arthritis was induced in mice by local injection of antigen in one knee; the other knee was used as a nonarthritis control. At study termination, the knees were collected for histologic assessment. Periarticular bone mineral density (BMD) was investigated by peripheral quantitative computed tomography. Flow cytometric analyses were performed using synovial and bone marrow cells. Results AIA resulted in decreased periarticular trabecular BMD and increased frequencies of preosteoclasts, neutrophils, and monocytes in the arthritic synovial tissue. Arthritis induction resulted in an increased capability to produce ROS. However, induction of arthritis in Ncf1*/* mice, which lack NOX-2–derived ROS, and control mice resulted in similar reductions in periarticular trabecular BMD. Conclusion The initiation of AIA resulted in periarticular bone loss associated with local effects on inflammatory cells and osteoclasts. Furthermore, based on our observations using this model, we conclude that NOX-2–derived ROS production is not essential for inflammation-mediated periarticular bone loss. Thus, AIA can be used as a model to investigate the pathogenesis of local inflammation–mediated bone loss. PMID:23918694

  17. Once-weekly teriparatide improves glucocorticoid-induced osteoporosis in patients with inadequate response to bisphosphonates.

    PubMed

    Seno, Takahiro; Yamamoto, Aihiro; Kukida, Yuji; Hirano, Aiko; Kida, Takashi; Nakabayashi, Amane; Fujioka, Kazuki; Nagahara, Hidetake; Fujii, Wataru; Murakami, Ken; Oda, Ryo; Fujiwara, Hiroyoshi; Kohno, Masataka; Kawahito, Yutaka

    2016-01-01

    Patients with glucocorticoid-induced osteoporosis (GIOP) are at very high risk of fracture, and patients with severe GIOP often experience fractures during treatment with bisphosphonates. Teriparatide (TPTD) is the only currently available anabolic agent expected to be effective for GIOP. Once-weekly TPTD decreased bone resorption marker with primary osteoporosis different from daily TPTD, but it has not yet been tested with GIOP. To evaluate the efficacy of once-weekly TPTD for patients with GIOP and inadequate response to bisphosphonates. Patients with GIOP and collagen diseases treated with prednisolone for at least 6 months with inadequate responses to bisphosphonates were administered once-weekly TPTD. Bone density of the lumbar spine and femoral neck, measured as percent young adult mean (YAM); serum concentrations of cross-linked N-terminal telopeptides of type I collagen (NTx), bone alkaline phosphatase (BAP), and calcium; and FRAX were measured at baseline and 6, 12 and 18 months after starting TPTD. Of the 12 GIOP patients with collagen diseases enrolled, nine (seven females, two males; mean age 57.4 ± 11.1 years) completed treatment, including six with systemic lupus erythematosus, two with rheumatoid arthritis, and one with adult onset still disease. Only one new fracture event, a lumbar compression fracture, occurred during the study period, although seven patients experienced eight fracture events within 18 months before starting TPTD (p = 0.04). Lumbar spine YAM significantly improved at 18 months (p = 0.04), whereas femoral neck YAM did not (p = 0.477). Serum NTx, BAP, Ca, and FRAX were not significantly affected by TPTD treatment. Once-weekly TPTD reduces fracture events and increases bone density of the lumbar spine of GIOP patients with inadequate response to bisphosphonates.

  18. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    NASA Technical Reports Server (NTRS)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  19. Norepinephrine Regulates Condylar Bone Loss via Comorbid Factors.

    PubMed

    Jiao, K; Niu, L; Xu, X; Liu, Y; Li, X; Tay, F R; Wang, M

    2015-06-01

    Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.

  20. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    SciTech Connect

    Aguilar, David; Strom, Joshua; Chen, Qin M.

    2014-04-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA.

  1. Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model.

    PubMed

    Liu, Chengcheng; Janke, Laura J; Kawedia, Jitesh D; Ramsey, Laura B; Cai, Xiangjun; Mattano, Leonard A; Boyd, Kelli L; Funk, Amy J; Relling, Mary V

    2016-01-01

    Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006). Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007). As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001). This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027) and asparaginase (P = 0.036). We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids.

  2. Augmentation of peri-implant bone improves implant stability: quantification using simulated bone loss.

    PubMed

    Wirth, Andreas J; Müller, Ralph; van Lenthe, G Harry

    2012-02-01

    Low bone quality, such as induced by osteoporosis, is considered a main factor leading to failure of fracture fixations. Peri-implant bone augmentation has been proposed as a means of reducing failure rates in osteoporotic bone by improving implant stability. The beneficial effects of pharmacological augmentation of bone in the immediate vicinity of the implant have been demonstrated. Yet, a quantitative understanding of the role of peri-implant bone in implant stability is lacking. Therefore, the aim of our study was to quantify the effects of bone loss and peri-implant bone augmentation on implant stability using image-based finite element analyses. Using a validated model, we simulated how osteoporotic bone loss would affect implant stability in human humeral heads. We also quantified how augmentation of peri-implant bone can enhance implant stability. Our simulations revealed that a 30% reduction in bone mass led to a 50% decrease in implant stability. We also found that peri-implant bone augmentation increased implant stability and that the efficiency of bone augmentation decreased with increasing peri-implant distance. These findings highlight the strong effect that bone loss has on implant fixation and the potential of peri-implant bone augmentation for improving implant anchorage in low quality bone. Copyright © 2011 Orthopaedic Research Society.

  3. Metastasis and bone loss: advancing treatment and prevention.

    PubMed

    Coleman, Robert E; Lipton, Allan; Roodman, G David; Guise, Theresa A; Boyce, Brendon F; Brufsky, Adam M; Clézardin, Philippe; Croucher, Peter I; Gralow, Julie R; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R; Smith, Matthew R; Suva, Larry J

    2010-12-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.

  4. [Therapy of glucocorticoid-induced osteoporosis with alfacalcidol/calcium and vitamin D/calcium].

    PubMed

    Ringe, J D; Cöster, A; Meng, T; Schacht, E; Umbach, R

    2000-06-01

    Calcium/vitamin D supplementation is generally used as a first step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of this trial was to compare the efficacy of the D-hormone alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid-therapy were treated either with 1 microgram alfacalcidol plus 5000 mg calcium (group A: n = 43) or with 1000 IU vitamin D plus 500 mg calcium (group B: n = 42). The two groups were not different in respect to initial characteristics such as age, sex distribution, concomittant diseases, bone mineral density (mean T-score values at lumbar spine and femoral neck: -3.29 and -3.25 resp.), and in the number of prevalent vertebral and non-vertebral fractures. During the 3 years of treatment we found a significant increase in lumbar spine density in group A (+2.0%, p < 0.0001), while no significant changes could be documented in group B at both measuring sites. After 3 years 12 new vertebral fractures had occurred in 10 patients of group A and 21 in 17 patients in group B (ns). Correspondingly we registered a significant decrease of back pain only in group A (p < 0.0001). We conclude that alfacalcidol treatment in superior to plain vitamin D in GIOP.

  5. [Bone loss in lactating women and post-pregnancy osteoporosis].

    PubMed

    Hirata, Go; Chaki, Osamu

    2011-09-01

    Measurement of the bone mineral density have shown that lactating women had 1 to 3% decrease in bone mineral density. Post pregnancy osteoporosis is rare condition that causes fragile fracture mostly in vertebrae. The bone loss in lactating women is caused by calcium loss, decrease in estrogen level, and increase in PTHrP (parathyroid hormone related protein) level. Some data have shown that extended lactation and amenorrhea had an association with the degree of bone loss. Mostly, the bone loss of the lactating women recovers to the baseline level, soon after the weaning, and there is no long term effect. Post pregnancy osteoporosis should be concerned, when we see a lactating woman with fragile fracture of the vertebrae.

  6. Modeling Calcium Loss from Bones During Space Flight

    NASA Technical Reports Server (NTRS)

    Wastney, Meryl E.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Nillen, Jeannie L.; Davis-Street, Janis E.; Lane, Helen W.; Smith, Scott M.; Paloski, W. H. (Technical Monitor)

    1999-01-01

    Calcium loss from bones during space flight creates a risk for astronauts who travel into space, and may prohibit space flights to other planets. The problem of calcium loss during space flight has been studied using animal models, bed rest (as a ground-based model), and humans in-flight. In-flight studies have typically documented bone loss by comparing bone mass before and after flight. To identify changes in metabolism leading to bone loss, we have performed kinetic studies using stable isotopes of calcium. Oral (Ca-43) and intravenous (Ca-46) tracers were administered to subjects (n=3), three-times before flight, once in-flight (after 110 days), and three times post-flight (on landing day, and 9 days and 3 months after flight). Samples of blood, saliva, urine, and feces were collected for up to 5 days after isotope administration, and were analyzed for tracer enrichment. Tracer data in tissues were analyzed using a compartmental model for calcium metabolism and the WinSAAM software. The model was used to: account for carryover of tracer between studies, fit data for all studies using the minimal number of changes between studies, and calculate calcium absorption, excretion, bone calcium deposition and bone calcium resorption. Results showed that fractional absorption decreased by 50% during flight and that bone resorption and urinary excretion increased by 50%. Results were supported by changes in biochemical markers of bone metabolism. Inflight bone loss of approximately 250 mg Ca/d resulted from decreased calcium absorption combined with increased bone resorption and excretion. Further studies will assess the time course of these changes during flight, and the effectiveness of countermeasures to mitigate flight-induced bone loss. The overall goal is to enable human travel beyond low-Earth orbit, and to allow for better understanding and treatment of bone diseases on Earth.

  7. Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.

    PubMed Central

    Kimble, R B; Vannice, J L; Bloedow, D C; Thompson, R C; Hopfer, W; Kung, V T; Brownfield, C; Pacifici, R

    1994-01-01

    Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and bone cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because of its potent stimulatory effects on bone resorption in vitro and in vivo. To investigate whether IL-1 plays a direct causal role in post ovariectomy bone loss, 6-mo-old ovariectomized rats were treated with subcutaneous infusions of IL-1 receptor antagonist (IL-1ra), a specific competitor of IL-1, for 4 wk, beginning either at the time of surgery or 4 wk after ovariectomy. The bone density of the distal femur was measured non invasively by dual-energy X-ray absorptiometry. Bone turnover was assessed by bone histomorphometry and by measuring serum osteocalcin, a marker of bone formation, and the urinary excretion of pyridinoline cross-links, a marker of bone resorption. Ovariectomy caused a rapid increase in bone turnover and a marked decrease in bone density which were blocked by treatment with 17 beta estradiol. Ovariectomy also increased the production of IL-1 from cultured bone marrow cells. Ovariectomy induced-bone loss was significantly decreased by IL-1ra treatment started at the time of ovariectomy and completely blocked by IL-1ra treatment begun 4 wk after ovariectomy. In both studies IL-1ra also decreased bone resorption in a manner similar to estrogen, while it had no effect on bone formation. In contrast, treatment with IL-1ra had no effect on the bone density and the bone turnover of sham-operated rats, indicating that IL-1ra specifically blocked estrogen-dependent bone loss. In conclusion, these data indicate that IL-1, or mediators induced by IL-1, play an important causal role in the mechanism by which ovariectomy induces bone loss in rats, especially following the immediate post ovariectomy period. Images PMID:8182127

  8. [Bone loss in women with malignant genital neoplasms].

    PubMed

    Magnowski, Piotr; Wolski, Hubert; Magnowska, Magdalena; Nowak-Markwitz, Ewa

    2014-12-01

    Nowadays, women with genital cancers live longer due to early diagnosis and better treatment schemes. Only few studies assessed bone mass in patients with genital cancer Osteoporosis is a condition characterized by progressive loss of bone mass, weakening of the spatial structure of the bone, and increased susceptibility to fractures. Osteopenia is a condition of reduced, but not yet reaching the pathological values, bone density in relation to norms for age and sex. Metastases are the primary cause of death in cancer patients. It is estimated that approximately half of people dying due to cancer have bone metastases. Osteoporosis in neoplastic disease may occur due to bone metastases or therapy-related adverse effects, i.e. reduced bone mineral density (BMD). Bone microenvironment provides a good medium for the growth of cancer cells. BMD of the femur and spine should be measured by DXA. Computed tomography (CT) and magnetic resonance imaging (MRI) are the techniques used to detect bone metastases. Lifestyle is the key to improving the quality of life and maximize any pharmacological treatment in cancer patients. It is proposed that treatment of cancer without bone metastases does not require therapy increasing bone mass. Further studies in women treated for gynecological malignancies undergoing oophorectomy and adjuvant treatment are needed to elucidate the mechanisms associated with bone loss.

  9. Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis in vivo and in vitro.

    PubMed

    Chen, Zhiguang; Xue, Jinqi; Shen, Tao; Ba, Gen; Yu, Dongdong; Fu, Qin

    2016-02-01

    Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti-inflammation and anti-cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid-induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)-induced osteoporosis in vivo and Dex-induced osteoblast apoptosis in vivo and in vitro. The GIO rat model was induced by subcutaneous injection of Dex for 60 days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X-ray absorptiometry. Subsequently, curcumin administration (100 mg/kg) for 60 days obviously increased BMD and bone-alkaline phosphatase, decreased carboxy-terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex-induced osteoporosis. Mechanically, curcumin remarkably reversed Dex-induced femoral osteoblast apoptosis in vivo. In cultured primary osteoblasts, pretreatment with curcumin concentration-dependently decreased the number of Dex-induced apoptotic osteoblasts by down-regulating the ratio of Bax/Bcl-2 as well as the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex-induced osteoblasts by up-regulating the expression level of p-ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.

  10. Role of Oxidative Damage in Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

  11. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    PubMed

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  12. Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss

    PubMed Central

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H.; Farman, Helen H.; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice. PMID:24637895

  13. A Novel Murine Model for Chronic Inflammatory Alveolar Bone loss

    PubMed Central

    Oz, Helieh S; Ebersole, Jeffrey L

    2009-01-01

    Objective Chronic inflammatory bowel disease (IBD) demonstrates some similarities of dysregulated chronic immunoinflammatory lesion of periodontitis. Trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulphate (DSS) administered to rodents have been shown to elicit inflammatory responses that undermine the integrity of the gut epithelium similar to IBD in humans. The objective of this study was to evaluate the ability of these chemicals to elicit periodontal inflammation as a novel model for alveolar bone loss. Methods Mice were treated by oral application of TNBS 2 times/week, or with DSS in the diet over a period of 18 weeks. Alveolar bone loss was assessed on defleshed skull using morphometric measures for area of bone resorption. Results TNBS-treated animals tolerated oral administration with no clinical symptoms and gained weight similar to normal controls. In contrast, DSS exerted a systemic response including shortening of colonic tissue and liver enzyme changes. Both TNBS and DSS caused a localized action on periodontal tissues with alveolar bone loss observed in both maxilla and mandibles with progression in a time dependent manner. Bone loss was detected as early as week 7, with more severe periodontitis increasing over the 18 weeks (p<0.001). Young (7 month) and old (12 month) SCID mice were treated with TNBS for a period of 7 weeks and did not develop significant bone loss. Conclusions These data show that oral administration of TNBS and DSS provoke alveolar bone loss in concert with the autochthonous oral microbiota. PMID:19602109

  14. Bone loss in chronic hemiplegia: a longitudinal cohort study.

    PubMed

    de Brito, Christina May Moran; Garcia, Ana Cristina Ferreira; Takayama, Liliam; Fregni, Felipe; Battistella, Linamara Rizzo; Pereira, Rosa Maria Rodrigues

    2013-01-01

    The purpose of this study was to evaluate hemiplegic stroke patients in terms of long-term changes in bone mineral density and related factors. We conducted a longitudinal cohort study, involving 57 first-stroke patients (40 males) with chronic hemiplegia (for more than 12mo), at a university rehabilitation center in the city of São Paulo, Brazil. Bone loss, body composition, lean mass, and fat mass were evaluated at 2 time points (mean interval, 16mo). Bone loss was significantly greater in paretic forearms than in nonparetic forearms (p=0.001) and in patients having suffered strokes more recently (p=0.015). We found no difference between paretic and nonparetic femurs. Femoral bone loss was significantly greater in patients using anticoagulants or anticonvulsants (p=0.025) and in those with greater spasticity (p=0.040), regardless of the time since stroke. Our results provide additional evidence that hemiplegic stroke patients have progressive bone loss and that such bone loss is more common in the arms than in the legs. Patients with poststroke hemiplegia should be densitometric monitored mainly in paretic arm and treated for bone loss, with attention to the determinants identified in this study. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  15. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    SciTech Connect

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-08-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.

  16. Expression of glucocorticoid-induced leucine zipper (GILZ) in cardiomyocytes.

    PubMed

    Aguilar, David C; Strom, Josh; Xu, Beibei; Kappeler, Kyle; Chen, Qin M

    2013-06-01

    Glucocorticoids (GCs) are frequently prescribed pharmacological agents most notably for their immunosuppressive effects. Endogenous GCs mediate biological processes such as energy metabolism and tissue development. At the cellular level, GCs bind to the glucocorticoid receptor (GR), a cytosolic protein that translocates to the nuclei and functions to alter transcription upon ligand binding. Among a long list of genes activated by GCs is the glucocorticoid-induced leucine zipper (GILZ). GC-induced GILZ expression has been well established in lymphocytes and mediates GC-induced apoptosis. Unlike lymphocytes, cardiomyocytes respond to GCs by gaining resistance against apoptosis. We determined GILZ expression in cardiomyocytes in vivo and in vitro. Expression of GILZ in mouse hearts as a result of GC administration was confirmed by Western blot analyses. GCs induced dose- and time-dependent elevation of GILZ expression in primary cultured rat cardiomyocytes, with dexamethasone (Dex) as low as 0.1 μM being effective. Time course analysis indicated that GILZ protein levels increased at 8 h and peaked at 48 h after exposure to 1 μM Dex. H9c2(2-1) cell line showed a similar response of GILZ induction by Dex as primary cultured rat cardiomyocytes, providing a convenient model for studying the biological significance of GILZ expression. With corticosterone (CT), an endogenous form of corticosteroids in rodents, 0.1-2.5 μM was found to induce GILZ in H9c2(2-1) cells. Time course analysis with 1 μM CT indicated induction of GILZ at 6 h with peak expression at 18 h. Inhibition of the GR by mifepristone led to blunting of GILZ induction by GCs. Our data demonstrate GILZ induction in cardiomyocytes both in vivo and in vitro by GCs, pointing to H9c2(2-1) cells as a valid model for studying the biological function of GILZ in cardiomyocytes.

  17. Expression of Glucocorticoid Induced Leucine Zipper (GILZ) in Cardiomyocytes

    PubMed Central

    Aguilar, David C.; Strom, Josh; Xu, Beibei; Kappeler, Kyle; Chen, Qin M.

    2014-01-01

    Glucocorticoids (GCs) are frequently prescribed pharmacological agents most notably for their immunosuppressive effects. Endogenous GCs mediate biological processes such as energy metabolism and tissue development. At the cellular level, GCs bind to the Glucocorticoid Receptor (GR), a cytosolic protein that translocates to the nuclei and functions to alter transcription upon ligand binding. Amongst a long list of genes activated by GCs is the Glucocorticoid Induced Leucine Zipper (GILZ). GC induced GILZ expression has been well established in lymphocytes and mediates GC induced apoptosis. Unlike lymphocytes, cardiomyocytes respond to GCs by gaining resistance against apoptosis. We determined GILZ expression in cardiomyocytes in vivo and in vitro. Expression of GILZ in mouse hearts as a result of GC administration was confirmed by Western blot analyses. GCs induced dose and time dependent elevation of GILZ expression in primary cultured rat cardiomyocytes, with dexamethasone (Dex) as low as 0.1 M being effective. Time course analysis indicated that GILZ protein levels increased at 8 hr and peaked at 48 hr after exposure to 1 M Dex. H9c2(2-1) cell line showed a similar response of GILZ induction by Dex as primary cultured rat cardiomyocytes, providing a convenient model for studying the biological significance of GILZ expression. With corticosterone (CT), an endogenous form of corticosteroids in rodents, 0.1–2.5 M was found to induce GILZ in H9c2(2-1) cells. Time course analysis with 1 M CT indicated induction of GILZ at 6 hr with peak expression at 18 hr. Inhibition of the GR by mifepristone led to blunting of GILZ induction by GCs. Our data demonstrate GILZ induction in cardiomyocytes both in vivo and in vitro by GCs, pointing to H9c2(2-1) cells as a valid model for studying the biological function of GILZ in cardiomyocytes. PMID:23090754

  18. Differential activities of glucocorticoid-induced leucine zipper protein isoforms.

    PubMed

    Soundararajan, Rama; Wang, Jian; Melters, Daniël; Pearce, David

    2007-12-14

    Glucocorticoid-induced leucine zipper protein (GILZ) is expressed in both epithelial and immune tissues and modulates a variety of cellular functions, including proliferation and epithelial sodium channel (ENaC) activity. A number of reports have described various GILZ activities, focusing on a single isoform with molecular mass of approximately 17 kDa, now termed GILZ1. In GILZ immunoblots using a newly developed antiserum, we detected multiple species in extracts from cultured kidney cells. Mass spectrometric analysis revealed that one of these represented a previously uncharacterized distinct isoform of GILZ, GILZ2. Rapid amplification of cDNA ends was used to clone cDNAs corresponding to four isoforms, which, in addition to GILZ1 and GILZ2, included new isoforms GILZ3 and GILZ4. Heterologous expression of these four GILZ isoforms in cultured cells revealed striking functional differences. Notably, GILZ1 was the only isoform that significantly stimulated ENaC-mediated Na+ current in a kidney collecting duct cell line, although GILZ2 and GILZ3 also stimulated ENaC surface expression in HEK 293 cells. GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation. Interestingly, GILZ4, which had no effect on either ENaC or ERK, potently suppressed cellular proliferation, as did GILZ1, but not GILZ2 or GILZ3. Finally, rat and mouse tissues all expressed multiple GILZ species but varied in the relative abundance of each. These data suggest that multiple GILZ isoforms are expressed in most cells and tissues and that these play distinct roles in regulating key cellular functions, including proliferation and ion transport. Furthermore, GILZ inhibition of ERK appears to play an essential role in stimulation of cell surface ENaC but not in inhibition of proliferation.

  19. 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.

  20. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

    PubMed Central

    Bonetto, Andrea; Kays, Joshua K.; Parker, Valorie A.; Matthews, Ryan R.; Barreto, Rafael; Puppa, Melissa J.; Kang, Kyung S.; Carson, James A.; Guise, Theresa A.; Mohammad, Khalid S.; Robling, Alexander G.; Couch, Marion E.; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2017-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia. PMID:28123369

  1. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia.

    PubMed

    Bonetto, Andrea; Kays, Joshua K; Parker, Valorie A; Matthews, Ryan R; Barreto, Rafael; Puppa, Melissa J; Kang, Kyung S; Carson, James A; Guise, Theresa A; Mohammad, Khalid S; Robling, Alexander G; Couch, Marion E; Koniaris, Leonidas G; Zimmers, Teresa A

    2016-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and Apc(Min/+). The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the Apc(Min/+) mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.

  2. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeff; Shapiro, Jay; Lang, Tom; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; hide

    2011-01-01

    Experiment Hypothesis -- The combined effect of anti-resorptive drugs plus in-flight exercise regimen will have a measurable effect in preventing space flight induced bone mass and strength loss and reducing renal stone risk.

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

    PubMed Central

    Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc

    2016-01-01

    ABSTRACT Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption. PMID:27956598

  4. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; hide

    2009-01-01

    Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.

  5. Pronounced enhancement of glucocorticoid-induced gene expression following severe heat shock of heat-conditioned cells hints to intricate cell survival tactics.

    PubMed

    Mitsiou, Dimitra J; Florentin, Ida; Baki, Lia; Georgakopoulos, Anastasios; Alexis, Michael N

    2005-02-01

    We have previously reported that severe heat shock of HeLa cells stably transfected with a chloramphenicol acetyltransferase (CAT) gene, transcription of which is controlled by two glucocorticoid-responsive elements and a minimal promoter, pronouncedly enhanced glucocorticoid-induced CAT expression compared to that of non-heated cells, in spite of the glucocorticoid-receptor-mediated transcription of the gene being temporarily compromised by the shock. We now report that prolonged severe heat shock of properly heat-conditioned cells resulted in far more pronounced enhancement of glucocorticoid-induced CAT mRNA and protein expressions, in spite of a similar heat-induced loss of receptor-mediated CAT gene transcription. During recovery from the shock the hormonal activation of transcription exceeded that of non-heated cells. While CAT mRNA translation was restored appreciably later than CAT gene transcription, mRNA and protein expressions were thermally enhanced to a comparable extent, consistent with the integrity of CAT mRNA being preserved during recovery. CAT mRNA turnover was fully impaired during early recovery, suggesting that stabilisation of CAT mRNA as well as stimulation of the hormonal activation of CAT gene transcription account for the thermal enhancement of glucocorticoid-induced CAT expression. This data hint to cell survival tactics designed to safeguard high expression of genes of stress-enduring function.

  6. Pathophysiology of bone loss in the female athlete.

    PubMed

    Lambrinoudaki, Irene; Papadimitriou, Dimitra

    2010-09-01

    Low bone mass is frequent among female athletes. The "female athlete triad" is a term that describes the interaction among energy availability, menstrual function, and bone metabolism that may lead to amenorrhea and osteopenia or osteoporosis. The main pathophysiologic mechanisms that lead to low bone mass in female athletes are low energy availability and functional hypothalamic amenorrhea. Increased energy expenditure and/or decreased energy intake, as well as the presence of eating disorders, are associated with low bone mass. In addition, menstrual dysfunction is quite common, especially among athletes competing in sports favoring leanness, and also associates with low bone mass. Screening for bone loss in female athletes should take place in the presence of amenorrhea or body mass index <18 kg/m(2) . Management of low bone mass aims to restore normal energy availability and nutritional habits. Hormone replacement therapy has no effect in abnormally underweight patients unless normal eating behaviors are restored.

  7. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, A.; Matsumoto, T.; Jones, J.; Shapiro, J.; Lang, T.; Shackelford, L.; Smith, S.; Evans, H.; Spector, E.; Ploutz-Snyder, R.; hide

    2011-01-01

    This poster reviews the possibility of using Bisphosphonates to counter the bone loss that is experienced during space flight. The Hypothesis that is tested in this experiment is that the combined effect of anti-resorptive drugs plus in-flight exercise regimen will attenuate space flight induced loss in bone mass and strength and reduce renal stone risk. The experiment design, the status and the results are described.

  8. The Correlation between Bone Loss and Tooth Malalignment.

    DTIC Science & Technology

    1982-01-22

    positive correlation among increasing scores of m ii Inment and increas- ing amounts of plaque , gingivitis , dent .I ,! (ulus, and marginal bone loss. In...the mandibular anterior Led the amounts of plaque , gingivitis , and bone loss were faOLr Jo increase respectively with increasing malalignm ,it (1, !iH...able nidus for periodontal disease. Plaque retention, food impaction, occlusal trauma, and root proximity may result from malaligned teeth which can

  9. Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy

    PubMed Central

    Andres-Mateos, Eva; Brinkmeier, Heinrich; Burks, Tyesha N; Mejias, Rebeca; Files, Daniel C; Steinberger, Martin; Soleimani, Arshia; Marx, Ruth; Simmers, Jessica L; Lin, Benjamin; Finanger Hedderick, Erika; Marr, Tom G; Lin, Brian M; Hourdé, Christophe; Leinwand, Leslie A; Kuhl, Dietmar; Föller, Michael; Vogelsang, Silke; Hernandez-Diaz, Ivan; Vaughan, Dana K; Alvarez de la Rosa, Diego; Lang, Florian; Cohn, Ronald D

    2013-01-01

    Maintaining skeletal muscle mass is essential for general health and prevention of disease progression in various neuromuscular conditions. Currently, no treatments are available to prevent progressive loss of muscle mass in any of these conditions. Hibernating mammals are protected from muscle atrophy despite prolonged periods of immobilization and starvation. Here, we describe a mechanism underlying muscle preservation and translate it to non-hibernating mammals. Although Akt has an established role in skeletal muscle homeostasis, we find that serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates muscle mass maintenance via downregulation of proteolysis and autophagy as well as increased protein synthesis during hibernation. We demonstrate that SGK1 is critical for the maintenance of skeletal muscle homeostasis and function in non-hibernating mammals in normal and atrophic conditions such as starvation and immobilization. Our results identify a novel therapeutic target to combat loss of skeletal muscle mass associated with muscle degeneration and atrophy. PMID:23161797

  10. Serum Bone Biomarkers and Oral/Systemic Bone Loss in Humans

    PubMed Central

    Payne, J.B.; Stoner, J.A.; Lee, H.-M.; Nummikoski, P.V.; Reinhardt, R.A.; Golub, L.M.

    2011-01-01

    We recently reported that subantimicrobial-dose doxycycline (SDD) significantly reduced serum bone-resorption biomarkers in subgroups of post-menopausal women. We hypothesize that changes in serum bone biomarkers are associated not only with systemic bone mineral density (BMD) changes, but also with alveolar bone changes over time. One hundred twenty-eight eligible post-menopausal women with periodontitis and systemic osteopenia were randomly assigned to receive SDD or placebo tablets twice daily for two years, adjunctive to periodontal maintenance. Sera were analyzed for bone biomarkers. As expected, two-year changes in a serum bone biomarker were significantly associated with systemic BMD loss at the lumbar spine (osteocalcin, bone-turnover biomarker, p = 0.0002) and femoral neck (osteocalcin p = 0.0025). Two-year changes in serum osteocalcin and serum pyridinoline-crosslink fragment of type I collagen (ICTP; bone-resorption biomarker) were also significantly associated with alveolar bone density loss (p < 0.0001) and alveolar bone height loss (p = 0.0008), respectively. Thus, we have shown that serum bone biomarkers are associated with not only systemic BMD loss, but with alveolar bone loss as well. Clinical Trial Registration Information: Protocol registered at ClinicalTrials.gov, NCT00066027. Abbreviations: bone mineral density (BMD), bone-specific alkaline phosphatase (BSAP), computer-assisted densitometric image analysis (CADIA), confidence interval (CI), deoxypyridinoline-containing degradation fragment of the C-terminal telopeptide region of type I collagen (CTX), coefficient of variation (CV), dual-energy x-ray absorptiometry (DXA), pyridinoline-crosslink-containing degradation fragment of the C-terminal telopeptide region of type I collagen (ICTP), and subantimicrobial-dose doxycycline (SDD). PMID:21422479

  11. Bariatric surgery, bone loss, obesity and possible mechanisms.

    PubMed

    Brzozowska, M M; Sainsbury, A; Eisman, J A; Baldock, P A; Center, J R

    2013-01-01

    Bariatric surgery remains the most effective treatment for severely obese patients. However, the potential long-term effects of bariatric surgical procedures on health, including bone health, are only partially understood. The goal of this review was to present data on the impact of bariatric surgery on bone metabolism and to analyse possible reasons for the loss of bone mass that frequently occurs after bariatric surgery. Such factors include nutritional deficiencies, rapid weight loss per se, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. However, the relative roles of these factors in skeletal regulation and the mechanisms by which they work are not yet fully defined. Our review was focussed on the complex relationship between body weight, fat mass and bone mass, as well as peripheral and central mediators potentially involved in the dual regulation of both energy and bone homeostasis. We also review the data on the inverse relationship between central obesity, bone marrow fat and osteoporosis. As the number of bariatric operations increases, it is imperative to recognize mechanisms responsible for bariatric surgery-induced bone loss, with careful monitoring of bone health including long-term fracture incidence in patients undergoing these procedures.

  12. Bone loss in HIV—a contemporary review

    PubMed Central

    Hileman, Corrilynn O; Eckard, Allison Ross; McComsey, Grace A

    2015-01-01

    Purpose of the review Because of antiretroviral therapy, people are living with HIV infection longer than ever before. As this patient group ages, it is expected that medical co-morbidities such as osteoporosis and fragility fractures will increase. The purpose of this review is to address the epidemiology and what is known regarding the pathogenesis of bone loss in people living with HIV infection with a focus on recently published literature. Recent findings HIV-infected individuals are at increased risk for low bone mineral density and bone fractures. The cause of bone loss in HIV is multifactorial including traditional risk factors some of which disproportionately affect HIV-infected individuals and alterations in bone metabolism due to antiretroviral therapy (ART), HIV viral proteins and chronic inflammation. Lifestyle modification, changing ART, calcium and vitamin D supplementation and pharmacologic treatment for osteoporosis may all be employed to abrogate bone loss in this patient group. Summary Clinicians should be aware of the contributors to bone loss in people living with HIV in order to recognize high risk individuals and to take appropriate steps to address modifiable risk factors to prevent future fracture. PMID:26414081

  13. Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss.

    PubMed

    Botolin, Sergiu; McCabe, Laura R

    2006-12-01

    Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin-deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A-diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes-associated hyperglycemia or weight loss, but did prevent diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro-computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype.

  14. Characterization of perimenopausal bone loss: a prospective study.

    PubMed

    Recker, R; Lappe, J; Davies, K; Heaney, R

    2000-10-01

    This study characterized the change in bone mass, bone markers, pituitary/gonadal hormones, vitamin D, parathyroid hormone, and anthropometric variables in a cohort of healthy women as they passed through normal menopause. We recruited 75 women > 46 years old who had premenopausal estradiol (E2) and gonadotropin levels and regular menses. During 9.5 years of observation, 54 experienced normal menopause (PM group) and 21 remained estrogen replete (ER group). Before the beginning of the menopausal drop and after its completion, the slope of bone mass on time in the PM group was 0% for the spine, -0.61% per year for the total body, and -0.45 % per year for the femoral neck. Designating these losses as "age related," there were 0, 4.88, and 3.40% losses for spine, total body bone mineral (TBBM), and femoral neck, respectively, in the 8-year period for which the data were analyzed. Across menopause, we found a sigmoid pattern of bone loss in the PM group beginning about 2-3 years before the last menses and ending about 3-4 years after the last menses. The total estrogen-deprivation bone losses were 10.50, 7.73, and 5.30% for the spine, TBBM, and femoral neck, respectively. In the ER group, we found a 0, 0.59, and 0.93% per year loss in spine, TBBM, and femoral neck, respectively. Serum osteocalcin rose 77%, serum total alkaline phosphatase rose 34%, and urinary hydroxyproline/creatinine (Hypro/Cr) ratio rose 44% in the PM group, while remaining stable in the ER group. We conclude that menopausal bone loss is a composite of loss caused by estrogen deprivation and age per se for the hip and total body, but is caused by estrogen deprivation alone for the spine.

  15. Associations among Endocrine, Inflammatory, and Bone Markers, Body Composition and Physical Activity to Weight Loss Induced Bone Loss

    PubMed Central

    Labouesse, Marie A.; Gertz, Erik R.; Piccolo, Brian D.; Souza, Elaine C.; Schuster, Gertrud U.; Witbracht, Megan G.; Woodhouse, Leslie R.; Adams, Sean H.; Keim, Nancy L.; Van Loan, Marta D.

    2015-01-01

    INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC METHODS Overweight/obese women (BMI: 28–37 kg/m2) were enrolled in an energy reduced (−500 kcal/d; −2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n=25, 32.2 ± 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 ± 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p= 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r= −0.28, p=0.04 to −0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = −0.29 (p=0.04) to r = −0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD

  16. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

    PubMed

    Govey, Peter M; Zhang, Yue; Donahue, Henry J

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

  17. Inflammation and Uncoupling as Mechanisms of Periodontal Bone Loss

    PubMed Central

    Graves, D.T.; Li, J.; Cochran, D.L.

    2011-01-01

    Periodontal disease is characterized by both inflammation and bone loss. Advances in research in both these areas have led to a new appreciation of not only each field but also the intimate relationship between inflammation and bone loss. This relationship has resulted in a new field of science called osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. In this review, we discuss several aspects of the immuno-inflammatory host response that ultimately results in loss of alveolar bone. A proposal is made that periodontal inflammation not only stimulates osteoclastogenesis but also interferes with the uncoupling of bone formation and bone resorption, consistent with a pathologic process. Furthermore, arguments based on experimental animal models suggest a critical role of the spatial and temporal aspects of inflammation in the periodontium. A review of these findings leads to a new paradigm to help explain more fully the impact of inflammation on alveolar bone in periodontal disease so that it includes the effects of inflammation on uncoupling of bone formation from resorption. PMID:21135192

  18. [Secondary osteoporosis UPDATE. Bone loss due to bed rest and human space flight study].

    PubMed

    Ohshima, Hiroshi

    2010-05-01

    Bone loss and renal stone are significant medical concerns for bed rest subjects and space flight astronauts. Bone mineral loss occurs as secondary osteoporosis due to the unloading of weight bearing bones during bed rest and space flight. Increased bone resorption and bone metabolic uncoupling promote bone loss through the release of calcium from unloaded weight bearing bones. The rate of bone mineral loss during bed rest and space flight is about 1-2 percent per month, and recovery requires a period three or four times longer. To prevent bone loss caused by bed rest and space flight, a prophylactic countermeasure program based on scientific evidence should be developed.

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

    USGS Publications Warehouse

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

    2003-01-01

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

  20. Prevalence and risk factors associated with glucocorticoid-induced osteoporosis in Chinese patients with rheumatoid arthritis.

    PubMed

    Ma, Can-Chen; Xu, Sheng-Qian; Gong, Xun; Wu, Ying; Qi, Shan; Liu, Wen; Xu, Jian-Hua

    2017-12-01

    Usage of glucocorticoid (GC) is a strong risk factor of osteoporosis (OP) and osteoporotic fracture (OPF) in Chinese patients with rheumatoid arthritis (RA). Controlling GC daily dosage and shortening GC course are helpful in preventing glucocorticoid-induced osteoporosis (GIOP) and OPF for Chinese patients with RA. This study aims to investigate the prevalence and risk factors of GIOP, and also identify influences of GC daily dosage and GC treatment course for GIOP in Chinese patients with RA. Seven hundred and ninety patients with RA and 158 normal subjects were enrolled in the study. Clinical and laboratory features and medications of GC were recorded in detail. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in all subjects. BMD at all measured sites in RA was significantly lower than that in control group. Prevalence of OP was obviously higher in RA with GC group (41.6%), compared with RA without GC group (29.4%). Prevalence of OPF in group of RA with GC (21.0%) was higher than that in group of RA without GC (13.3%). Usage of GC, female, and age were risk factors for the occurrence of OP and OPF in RA, while body mass index (BMI) was the protective factor of OP. Prevalence of GIOP and OPF had statistical significance among groups of different treatment courses with GC, whereas no statistical difference was found among groups with different daily dosages of GC. GIOP exists generally in Chinese patients with RA, which relates to treatment course not daily dosage of GC. Usage of GC is also the risk factor for the happening of OPF in Chinese patients with RA.

  1. Treatment of glucocorticoid-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium.

    PubMed

    Ringe, J D; Cöster, A; Meng, T; Schacht, E; Umbach, R

    1999-10-01

    Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1alpha) compared with the native vitamin D(3) in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D(3) plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score -3.28 and -3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1alpha (+2.0%, P < 0.0001) and no significant changes at the femoral neck. In the D(3) group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1alpha and 21 in 17 patients of the D(3) group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P < 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.

  2. Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

    PubMed

    Kittivanichkul, Donlaporn; Charoenphandhu, Narattaphol; Khemawoot, Phisit; Malaivijitnond, Suchinda

    2016-11-01

    Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry). © 2016 Society for Endocrinology.

  3. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

    PubMed Central

    Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

  4. Role of Corticosteroids in Bone Loss During Space Flight

    NASA Technical Reports Server (NTRS)

    Wronski, Thomas J.; Halloran, Bernard P.; Miller, Scott C.

    1998-01-01

    The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

  5. Management of severe femoral bone loss in revision total hip arthroplasty.

    PubMed

    Sheth, Neil P; Melnic, Christopher M; Rozell, Joshua C; Paprosky, Wayne G

    2015-07-01

    Femoral bone loss is a complex problem in revision total hip arthroplasty. The Paprosky classification is used when determining the degree and location of bone loss. Meticulous operative planning is essential where severe bone loss is a concern. One must correctly identify the bone loss pattern, safely remove the existing components, and proceed with the proper reconstruction technique based on the pattern of bone loss. This article discusses the etiology and classification of bone loss, clinical and radiographic evaluation, components of effective preoperative planning, and clinical results of various treatment options with a focus on more severe bone loss patterns. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Bone Loss During Spaceflight: Available Models and Counter-Measures

    NASA Technical Reports Server (NTRS)

    Morris, Jonathan; Bach, David; Geller, David

    2015-01-01

    There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground

  7. Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

    NASA Technical Reports Server (NTRS)

    Li, Wei; Duncan, Randall L.; Karin, Norman J.; Farach-Carson, Mary C.

    1997-01-01

    We demonstrated for the first time that vitamin D3 influences the effect of PTH on bone cell calcium ion levels. This is a rapid effect, taking place within seconds/minutes. This may prove to be a critical contribution to our understanding of bone physiology in that these two hormones are among the most potent regulators of bone calcium content and of systemic calcium homeostasis. Together with the data gathered from the study of astronauts exposed to microgravity for extended periods, these observations suggest the interaction of vitamin D3 and PTH as a possible therapeutic target in the treatment of bone loss disorders such as osteoporosis and disuse atrophy. Chronic exposure of cultured osteoblasts to vitamin D, altered the number of voltage-sensitive Ca(+2) channels expressed. Estrogen treatment yielded a similar result, suggesting that there is overlap in the mechanism by which these hormones elicit long-term effects on bone cell calcium homeostasis.

  8. Numerical analysis of an osseointegrated prosthesis fixation with reduced bone failure risk and periprosthetic bone loss.

    PubMed

    Tomaszewski, P K; van Diest, M; Bulstra, S K; Verdonschot, N; Verkerke, G J

    2012-07-26

    Currently available implants for direct attachment of prosthesis to the skeletal system after transfemoral amputation (OPRA system, Integrum AB, Sweden and ISP Endo/Exo prosthesis, ESKA Implants AG, Germany) show many advantages over the conventional socket fixation. However, restraining biomechanical issues such as considerable bone loss around the stem and peri-prosthetic bone fractures are present. To overcome these limiting issues a new concept of the direct intramedullary fixation was developed. We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling by restoring the natural load transfer in the femur. Generic CT-based finite element models of an intact femur and amputated bones implanted with 3 analyzed implants were created and loaded with a normal walking and a forward fall load. The strain adaptive bone remodeling theory was used to predict long-term bone changes around the implants and the periprosthetic bone failure risk was evaluated by the von Mises stress criterion. The results show that the new design provides close to physiological distribution of stresses in the bone and lower bone failure risk for the normal walking as compared to the OPRA and the ISP implants. The bone remodeling simulations did not reveal any overall bone loss around the new design, as opposed to the OPRA and the ISP implants, which induce considerable bone loss in the distal end of the femur. This positive outcome shows that the presented concept has a potential to considerably improve safety of the rehabilitation with the direct fixation implants.

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

    PubMed

    Ohshima, Hiroshi

    2006-01-01

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

  10. Fractal texture analysis of the healing process after bone loss.

    PubMed

    Borowska, Marta; Szarmach, Janusz; Oczeretko, Edward

    2015-12-01

    Radiological assessment of treatment effectiveness of guided bone regeneration (GBR) method in postresectal and postcystal bone loss cases, observed for one year. Group of 25 patients (17 females and 8 males) who underwent root resection with cystectomy were evaluated. The following combination therapy of intraosseous deficits was used, consisting of bone augmentation with xenogenic material together with covering regenerative membranes and tight wound closure. The bone regeneration process was estimated, comparing the images taken on the day of the surgery and 12 months later, by means of Kodak RVG 6100 digital radiography set. The interpretation of the radiovisiographic image depends on the evaluation ability of the eye looking at it, which leaves a large margin of uncertainty. So, several texture analysis techniques were developed and used sequentially on the radiographic image. For each method, the results were the mean from the 25 images. These methods compute the fractal dimension (D), each one having its own theoretic basis. We used five techniques for calculating fractal dimension: power spectral density method, triangular prism surface area method, blanket method, intensity difference scaling method and variogram analysis. Our study showed a decrease of fractal dimension during the healing process after bone loss. We also found evidence that various methods of calculating fractal dimension give different results. During the healing process after bone loss, the surfaces of radiographic images became smooth. The result obtained show that our findings may be of great importance for diagnostic purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Biologic therapies and bone loss in rheumatoid arthritis.

    PubMed

    Zerbini, C A F; Clark, P; Mendez-Sanchez, L; Pereira, R M R; Messina, O D; Uña, C R; Adachi, J D; Lems, W F; Cooper, C; Lane, N E

    2017-02-01

    Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures. Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the

  12. A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

    PubMed

    Beauchesne, Patrick; Agarwal, Sabrina C

    2017-09-01

    One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed. © 2017 Wiley Periodicals, Inc.

  13. Bone mineral loss in young women with amenorrhoea.

    PubMed Central

    Davies, M C; Hall, M L; Jacobs, H S

    1990-01-01

    OBJECTIVE--To examine the impact of amenorrhoea on bone mineral density in women of reproductive age. DESIGN--Cross sectional study of 200 amenorrhoeic women compared with normally menstruating controls. SETTING--Teaching hospital outpatient clinic specialising in reproductive medicine. SUBJECTS--200 Women aged 16-40 with a past or current history of amenorrhoea from various causes and of a median duration of three years, and a control group of 57 age matched normal volunteers with no history of menstrual disorder. MAIN OUTCOME MEASURE--Bone mineral density in the lumbar spine (L1-L4) as measured by dual energy x ray absorptiometry. RESULTS--The amenorrhoeic group showed a mean reduction in bone mineral density of 15% (95% confidence interval 12% to 18%) as compared with controls (mean bone mineral density 0.89 (SD 0.12) g/cm2 v 1.05 (0.09) g/cm2 in controls). Bone loss was related to the duration of amenorrhoea and the severity of oestrogen deficiency rather than to the underlying diagnosis. Patients with a history of fracture had significantly lower bone density than those without a history of fracture. Ten patients had suffered an apparently atraumatic fracture. CONCLUSIONS--Amenorrhoea in young women should be investigated and treated to prevent bone mineral loss. Menopausal women with a past history of amenorrhoea should be considered to be at high risk of osteoporosis. PMID:2224267

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. Microthreaded Implants and Crestal Bone Loss: A Systematic Review.

    PubMed

    Al-Thobity, Ahmad; Kutkut, Ahmad; Almas, Khalid

    2016-11-21

    This systematic literature review investigated the effect of microthreaded-neck dental implants on crestal bone loss. Using the participants, interventions, comparison groups, outcomes, and study design (PICOS) system, we addressed the following focused question: Do microthreaded-neck dental implants positively affect the crestal bone level around dental implants? We searched 3 electronic databases to find articles published between January 1995 and June 2016 that contained any combination of the following keywords: dental implant, microthread, microthreaded, crestal bone level, crestal bone loss, and alveolar bone level. We excluded case reports, review articles, letters to the editor, commentaries, and articles published in a language other than English. We found a total of 70 articles. After eliminating duplicates and applying PICOS eligibility criteria, we selected only articles that reported the results of randomized controlled trials, prospective or retrospective cohort studies, case-control studies, cross-sectional studies, or other types of clinical trials that compared the microthreaded implant design to other implant designs. We were left with 23 articles for review. The 23 articles reported crestal bone loss ranging from 0.05 mm to 0.9 mm, with a range of 12 to 96 months of follow-up. Less crestal bone was lost with dental implants that had a microthreaded neck design than with machined-surface or conventional rough-surface dental implants. Thus, microthreaded dental implants are a better choice than are implants with other designs. Future studies should use standardized imaging techniques to to evaluate the placement of these implants in bone-augmented sites.

  16. Artemisia capillaris Alleviates Bone Loss by Stimulating Osteoblast Mineralization and Suppressing Osteoclast Differentiation and Bone Resorption.

    PubMed

    Lee, Chung-Jo; Shim, Ki-Shuk; Ma, Jin Yeul

    2016-01-01

    Artemisia capillaris has been used to treat jaundice and relieve high liver-heat in traditional medicine. In this study, we found that the administration of a water extract from A. capillaris (WEAC) to the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model significantly prevents osteoporotic bone loss, increasing bone volume/trabecular volume by 22% and trabecular number by 24%, and decreasing trabecular separation by 29%. WEAC stimulated in vitro osteoblast mineralization from primary osteoblasts in association with increasing expression of osterix, nuclear factor of activated T cells cytoplasmic 1, and activator protein-1, as well as phosphorylation of extracellular signal-regulated kinase. In contrast to the anabolic effect of WEAC, WEAC significantly suppressed in vitro osteoclast formation from bone marrow macrophages by inhibiting the RANKL signaling pathways and bone resorption by downregulating the expression of resorption markers. Therefore, this study demonstrated that WEAC has a beneficial effect on bone loss through the regulation of osteoblast mineralization, as well as osteoclast formation and bone resorption. These results suggest that A. capillaris may be a promising herbal candidate for therapeutic agents to treat or prevent osteoporotic bone diseases.

  17. Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, Ira

    1987-01-01

    Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

  18. Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian D.; Driscol, Theda B.; Shackelford, Linda C.; Evans, Harlan J.; Rianon, Nahid J.; Smith, Scott M.; Lai, Dejian

    2002-01-01

    Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

  19. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss

    PubMed Central

    Harre, Ulrike; Lang, Stefanie C.; Pfeifle, René; Rombouts, Yoann; Frühbeißer, Sabine; Amara, Khaled; Bang, Holger; Lux, Anja; Koeleman, Carolien A.; Baum, Wolfgang; Dietel, Katharina; Gröhn, Franziska; Malmström, Vivianne; Klareskog, Lars; Krönke, Gerhard; Kocijan, Roland; Nimmerjahn, Falk; Toes, René E. M.; Herrmann, Martin; Scherer, Hans Ulrich; Schett, Georg

    2015-01-01

    Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss. PMID:25825024

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

    PubMed

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

    2013-01-01

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

  1. Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling

    PubMed Central

    Zheng, Xi; Lee, Sun-Kyeong

    2016-01-01

    Abstract Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

  2. Effect of bone loss in anterior shoulder instability

    PubMed Central

    Garcia, Grant H; Liu, Joseph N; Dines, David M; Dines, Joshua S

    2015-01-01

    Anterior shoulder instability with bone loss can be a difficult problem to treat. It usually involves a component of either glenoid deficiency or a Hill-Sachs lesion. Recent data shows that soft tissue procedures alone are typically not adequate to provide stability to the shoulder. As such, numerous surgical procedures have been described to directly address these bony deficits. For glenoid defects, coracoid transfer and iliac crest bone block procedures are popular and effective. For humeral head defects, both remplissage and osteochondral allografts have decreased the rates of recurrent instability. Our review provides an overview of current literature addressing these treatment options and others for addressing bone loss complicating anterior glenohumeral instability. PMID:26085984

  3. Raloxifene inhibits bone loss and improves bone strength through an Opg-independent mechanism.

    PubMed

    Yan, Mei-zhu; Xu, Yong; Gong, Yun-xia; Liu, Jian-min; Lu, Shun-yuan; Huang, Lei; Wang, Zhu-gang; Zhao, Yong-ju; Pang, Xiao-fen

    2010-02-01

    The osteoblast-derived paracrine factor osteoprotegerin (OPG) is considered to play a key role in inhibition of osteoclast formation and activity. Recently, raloxifene, a nonsteroidal benzothiophene, was found to exert anti-resorptive effects via modulating OPG expression in osteoblasts. To explore whether raloxifene regulates bone metabolism via an OPG-dependant pathway in vivo, we investigated the effects of raloxifene on bone loss in Opg-deficient mice. The results show that bone mineral density and bone strength are increased in mice deficient for Opg after treatment with raloxifene for 30 days. Histomorphometric analysis shows that raloxifene can increase bone trabecular area and decrease the number of osteoclasts in Opg (-/-) mice. Moreover, raloxifene reduces Rankl transcription and serum level of Rankl, which is dramatically increased in Opg knockout mice. These results suggest that raloxifene-induced inhibition of bone resorption may be independent of Opg pathway in mice.

  4. Rate of bone loss in postmenopausal and osteoporotic women

    SciTech Connect

    Aloia, J.F.; Ross, P.; Vaswani, A.; Zanzi, I.; Cohn, S.H.

    1982-02-01

    Regional and total bone mass were determined in three groups of women by photon absorptiometry of the distal radius (bone mineral content (BMC)) and total neutron activation analysis (total body calcium (TBCa)), respectively. There were three groups of patients: group A, osteoporotic women treated with a variety of pharmacologic agents; group B, osteoporotic women (controls) taking only calcium supplements; and group C, normal postmenopausal women. The mean TBCa and BMC were considerably higher in the postmenopausal women than in the osteoporotic women. The rate of change of bone mass in group C was -0.45%/yr and -0.9%/yr for the total skeleton and radius, respectively. Group B had no significant rate of loss, whereas group A demonstrated a significant increase in TBCa of 0.75%/yr with no change in the BMC of the radius. There were no significant between-subject correlations for the slopes (rates of change) of the two bone mineral measurements.

  5. Glucocorticoid-induced osteoporosis in children with 21-hydroxylase deficiency.

    PubMed

    Ventura, Annamaria; Brunetti, Giacomina; Colucci, Silvia; Oranger, Angela; Ladisa, Filomena; Cavallo, Luciano; Grano, Maria; Faienza, Maria Felicia

    2013-01-01

    21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.

  6. Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency

    PubMed Central

    Ventura, Annamaria; Brunetti, Giacomina; Colucci, Silvia; Oranger, Angela; Ladisa, Filomena; Cavallo, Luciano; Grano, Maria; Faienza, Maria Felicia

    2013-01-01

    21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD. PMID:23484098

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

    PubMed Central

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

    1988-01-01

    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 45Ca release from 45Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 45Ca-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, from 27 +/- 2% (mean +/- SEM) 45Ca release in cultures with no added cadmium to 68 +/- 6% release in cultures containing cadmium (n = 4). 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. Images PMID:3186759

  8. 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.

  9. Weight, muscle and bone loss during space flight: another perspective.

    PubMed

    Stein, T P

    2013-09-01

    Space flight is a new experience for humans. Humans adapt if not perfectly, rather well to life without gravity. There is a reductive remodeling of the musculo-skeletal system. Protein is lost from muscles and calcium from bones with anti-gravity functions. The observed biochemical and physiological changes reflect this accommodative process. The two major direct effects of the muscle loss are weakness post-flight and the increased incidence of low back ache pre- and post-flight. The muscle protein losses are compromised by the inability to maintain energy balance inflight. Voluntary dietary intake is reduced during space flight by ~20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity. Exercise, the obvious counter-measure has been repeatedly tried and since the muscle and bone losses persist it is not unreasonable to assume that success has been limited at best. Nevertheless, more than 500 people have now flown in space for up to 1 year and have done remarkably well. This review addresses the question of whether enough is now known about these three problems (negative energy balance, muscle loss and bone loss) for to the risks to be considered either acceptable or correctible enough to meet the requirements for a Mars mission.

  10. Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

    USDA-ARS?s Scientific Manuscript database

    The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

  11. Prosthesis misfit and marginal bone loss in edentulous implant patients.

    PubMed

    Jemt, T; Book, K

    1996-01-01

    The objective of this study was to statistically correlate in vivo measurements of prosthesis misfit and change of marginal bone level in implants placed in the edentulous maxilla. Two groups, each comprising seven patients, were followed up either prospectively for 1 year or retrospectively for the last 4 years of the 5-year period after second-stage surgery. Measurements of prosthesis misfit were performed by means of a three-dimensional photogrammetric technique, and marginal bone levels were measured from standard intraoral radiographs. Results showed that none of the prostheses presented a completely passive fit to the implants in vivo. Furthermore, similar distortions of the prostheses were found in the two groups, indicating that the implants seemed to be stable and did not move, even after several years in function. The maximal range of three-dimensional distortion of cylinder center points was about 275 microns for both groups. Mean center point misfit was 111 (SD 59) and 91 (SD 51) microns for the 1-year and 5-year groups, respectively. The corresponding mean marginal bone loss was 0.5 and 0.2 mm for the two follow-up groups. No statistical correlations (P > .05) between change of marginal bone levels and different parameters of prosthesis misfit were observed in the two groups. The study indicated that a certain biologic tolerance for misfit may be present. The degree of misfit reported in the study was clinically acceptable with regard to observed marginal bone loss.

  12. Segmental bone loss in pediatric lower extremity fractures: indications and results of bone transport.

    PubMed

    Arslan, Hüseyin; Özkul, Emin; Gem, Mehmet; Alemdar, Celil; Şahin, İlhami; Kişin, Bülent

    2015-03-01

    In this study, we evaluated the results of external bone transport, which was applied to 11 patients with traumatic bone loss who had not completed their bone development. The average age of the 9 male and 2 female patients was 10.6 (range, 8 to 16) years. Eight of the defects were located in the tibia, whereas the other 3 were in the femur. The average defect was 5.4 (range, 4.5 to 8.5) cm. External bone transport was applied in the early period in 7 patients, whereas in 4 patients it was performed due to nonunion. Bifocal osteosynthesis and single osteotomy were performed in 2 patients with type B2 nonunion. Compression to the nonunion region and lengthening in the osteotomy region were applied. In 2 patients with type B1 nonunion, and the other 9 patients who had external bone transport, the gap was eliminated by bifocal osteosynthesis, single osteotomy, and bone transport to the osteotomy line. The mean follow-up period was 21 (range, 13 to 48) months. Complete union was achieved in all patients without any bone operation or graft application. No refracture was observed after the removal of the external fixator, and the average hospitalization time was 16 (range, 7 to 65) days. The average external fixation time was 4.2 (range, 3.5 to 5.5) months, and the mean external fixator index was 0.8 months (23 d/cm). The mean bone healing time was 5.1 (range, 4.6 to 6) months. To initially consider the open fractures with true or in situ bone loss in children as "anticipated nonunion," and determine the treatment strategies regarding this fact, may prevent nonunion and shorten the healing period. Bone transport in the treatment of traumatic bone defects in children is an easy biological procedure, with lower complications but higher success ratios. Level IV-therapeutic.

  13. Cortical bone loss with age in three native American populations.

    PubMed

    Ericksen, M F

    1976-11-01

    Age-related thinning of cortical bone was investigated in archaeological populations of Eskimos, Pueblos, and Arikaras. Medial-lateral cortical thickness was measured on radiographs of humerus and femur, and thickness of the anterior femoral cortex was measured directly on samples taken for histologic study. Maximum length of the bones was used to calculate indices of relative cortical thickness, in order to minimize differences due to body size and build. Bone loss in the humerus begins before middle age in all three populations and, except for Eskimo males, the same is true of the anterior femoral cortex. In general, overall female loss of cortical bone amounts to two or three times that of the males, and in the case of the humerus and the anterior cortex of the femur, this difference is evident by middle age. The weight-bearing femoral medial-lateral cortex shows less sexual difference but has the greatest number of statistically significant differences between populations and the greatest contrast between populations in pattern of loss with age. It appears that of the cortical regions studied this is the area upon which environmental factors have the greatest effect, whereas areas more subject to tensile stress, the humerus and anterior femoral cortex, are less affected by these factors.

  14. Targeting mRNA Stability Arrests Inflammatory Bone Loss

    PubMed Central

    Patil, Chetan S; Liu, Min; Zhao, Wenpu; Coatney, Derek D; Li, Fei; VanTubergen, Elizabeth A; D’Silva, Nisha J; Kirkwood, Keith L

    2009-01-01

    Many proinflammatory cytokines contain adenylate-uridylate-rich elements (AREs) within the 3′-untranslated region (UTR) that confer rapid mRNA destabilization. During the inflammatory response, cytokine mRNA are stabilized via complex interactions with RNA-binding proteins controlled by phosphorylation via multiple signaling pathways including the mitogen-activated protein kinases (MAPKs). In the absence of inflammation, a key cytokine-regulating RNA-binding protein, tristetraprolin (TTP), shuttles mRNA transcripts to degradation machinery in order to maintain low levels of inflammatory cytokines. Using this general model of mRNA decay, over expression of TTP was evaluated in an experimental model of inflammatory bone loss to determine whether altering cytokine mRNA stability has an impact in pathological bone resorption. Using adenoviral-delivered TTP, significant reductions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin (PG)E2 were observed in vitro through a mechanism consistent with targeting mRNA stability. In vivo analysis indicates a significant protective effect from inflammation-induced bone loss and inflammatory infiltrate in animals overexpressing TTP compared with reporter controls. These findings provide experimental evidence that mRNA stability is a valid therapeutic target in inflammatory bone loss. PMID:18682699

  15. Hand osteoarthritis and bone loss: is there an inverse relationship?

    PubMed

    Weiss, Elizabeth

    2013-10-01

    An inverse relationship between osteoarthritis (OA) and bone loss has been supported in clinical research, but there has been little research on bioarchaeological skeletal remains. The current study examines 115 adults from a prehistoric hunter-gatherer population to aid in determining whether hand OA and bone loss are negatively correlated. OA lipping is scored on a four-point scale on left and right trapezia, MC1s, and MC2s and then analyzed with regard to their relationships with sex, age, right MC2 cortical index, and left and right MC1 robusticity, midshaft circumference, and midshaft diameter values. With sexes and ages combined, higher OA scores are found in individuals with greater midshaft diameters. However, lower cortical indices were found in individuals with higher right MC2 OA scores. The data presented tenuously support that bone loss is lower in individuals with more severe osteoarthritis, but age-related changes in bone deposition may make cortical index and other external shaft dimensions an unsuitable variable to examine this relationship.

  16. 3-year results of a member and physician intervention to reduce risk associated with glucocorticoid-induced osteoporosis in a health plan.

    PubMed

    Chitre, Mona M; Hayes, William

    2008-04-01

    Accelerated bone loss is a well-known outcome of chronic treatment with glucocorticoids, making glucocorticoid-induced osteoporosis a significant cause of morbidity and a burden on health care resources. Recommendations for prevention and treatment of glucocorticoid-induced osteoporosis include therapy with a bisphosphonate or calcitonin for patients taking a prednisone equivalent of 5 mg per day or more for 3 months or more. To evaluate the effects of a targeted member and physician educational intervention on the use of anti-osteoporotic drug therapy in patients using chronic oral glucocorticoid therapy. Pharmacy claims were analyzed for a 4-month period in each of 3 years, for claims with dates of service from April 1 through July 30, 2003, May 1 through August 31, 2004, and February 4 through May 5, 2005, to identify all adult members of a health plan of approximately 1.3 million members who received an oral glucocorticoid (e.g., prednisone, dexamethasone) for at least 90 of 120 days (chronic use) and did not receive a medication for osteoporosis prevention (e.g., risedronate, ibandronate, etidronate, raloxifene, alendronate, calcitonin) during the same 120-day time period. The intervention involved direct-to-patient mailing of a cover letter and a 2-page educational brochure, and a physician mailing that included the same 2-page educational brochure, a 1-page table of recommended drug therapies for prevention of osteroporosis, and an invitation for physicians to request by fax-back a list of at-risk patients. Follow-up claims analyses were conducted for 120 days after each of the 3 intervention periods to determine the number and percentage of target patients who were initiated and maintained on a medication to prevent osteoporosis. The prevalence of health plan members at risk of glucocorticoidinduced osteoporosis was 0.28% in 2003, 0.29% in 2004, 0.29% in 2005, and 0.29% during the 3 years combined. Approximately 47.5% of patients (n = 5,140) during the 3

  17. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    PubMed Central

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  18. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation.

    PubMed

    Fan, Ruoxun; Gong, He; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone.

  19. Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia

    bone tissue. The macrophages are incorporated into resorption lacunaes and utilize the organic matrix and cellular detritus. The products are secreted to remodeling zones and act as haemoattractants for recruiting and subsequent differentiation here of the osteogenic precursor cells. However, as shown by our results with 3H-glycine, in absence of mechanical stimulus the activization of osteoblastogenesis either doesn't occur, or takes place on a smaller scale. According to our electron-microscopic data a load deficit leads to an adaptive differentiation of fibroblasts and adipocytes in this remodeling zones. This sequence of events is considered as a mechanism of bone tissue loss which underlies the development of osteopenia and osteoporosis under space flight condition.

  20. Does bone loss begin after weight loss ends? Results 2 years after weight loss or regain in postmenopausal women.

    PubMed

    Von Thun, Nancy L; Sukumar, Deeptha; Heymsfield, Steven B; Shapses, Sue A

    2014-05-01

    Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact of weight loss on bone in reduced overweight/obese women compared with women who regained their weight was examined in this study using a case-control design. Postmenopausal women (N = 42; mean [SD] body mass index, 28.3 [2.8] kg/m; mean [SD] age, 60.7 [5.5] y) were recruited 2 years after the start of a 6-month weight loss trial; those who maintained their weight (weight loss maintainer [WL-M] group) were matched to a cohort of women who regained their weight (weight loss regainer [WL-R] group). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck, trochanter, spine, radius, and total body, and soft-tissue composition were taken at baseline, 0.5 years, and 2 years. During weight loss, both groups lost 9.3% (3.4%) of body weight, with no significant difference between the groups. After weight loss, weight change was -0.1% (2.7%) and 6.0% (3.3%) in the WL-M (n = 22) and WL-R (n = 20) groups, respectively. After 2 years, both groups lost BMD at the femoral neck and trochanter (P ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (P < 0.001). There was greater BMD loss at the trochanter (-6.8% [5.7%]) and 1/3 radius (-4.5% [3.3%]) in the WL-M group compared with the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (P < 0.05). After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for those who maintain weight and those who regain weight.

  1. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss

    PubMed Central

    Yuan, X; Cao, J; Liu, T; Li, Y-P; Scannapieco, F; He, X; Oursler, M J; Zhang, X; Vacher, J; Li, C; Olson, D; Yang, S

    2015-01-01

    Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre. Deletion of Rgs12 in hematopoietic cells or specifically in OC precursors resulted in increased bone mass with decreased OC numbers. Loss of Rgs12 impaired OC differentiation and function with impaired Ca2+ oscillations and reduced nuclear factor of activated T cells (NFAT) 2 expression. The introduction of wild-type osteoblasts did not rescue the defective osteoclastogenesis. Ectopic expression of NFAT2 rescued defective OC differentiation in CD11b;Rgs12fl/fl cells and promoted normal OC differentiation. Moreover, deletion of Rgs12 significantly inhibited pathological osteoclastogenesis and bone destruction in Rgs12-deficient mice that were subjected to ovariectomy and lipodysaccharide for bone loss. Thus our findings demonstrate that Rgs12 is an important regulator in OC differentiation and function and identify Rgs12 as a potential therapeutic target for osteoporosis and inflammation-induced bone loss. PMID:25909889

  2. Alendronate prevents glucocorticoid-induced osteoporosis in patients with rheumatic diseases: A meta-analysis.

    PubMed

    Kan, Shun-Li; Yuan, Zhi-Fang; Li, Yan; Ai, Jie; Xu, Hong; Sun, Jing-Cheng; Feng, Shi-Qing

    2016-06-01

    Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases.We retrieved randomized controlled trials from PubMed, EMBASE, and the Cochrane Library. Two reviewers extracted the data and evaluated the risk of bias and quality of the evidence. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes, and the mean difference (MD) with a 95% CI for continuous outcomes using Review Manager, version 5.3.A total of 339 studies were found, and 9 studies (1134 patients) were included. Alendronate was not able to reduce the incidence of vertebral fractures (RR = 0.63, 95% CI: 0.10-4.04, P = 0.62) and nonvertebral fractures (RR = 0.40, 95% CI: 0.15-1.12, P = 0.08). Alendronate significantly increased the percent change in bone mineral density (BMD) at the lumbar spine (MD = 3.66, 95% CI: 2.58-4.74, P < 0.05), total hip (MD = 2.08, 95% CI: 0.41-3.74, P < 0.05), and trochanter (MD = 1.68, 95% CI: 0.75-2.61, P < 0.05). Significant differences were not observed in the percent change in BMD at the femoral neck (MD = -0.33, 95% CI: -2.79 to 2.13, P = 0.79) and total body (MD = 0.64, 95% CI: -0.06 to 1.34, P = 0.07). No significant differences in the adverse events were observed in patients treated with alendronate versus the controls (RR = 1.00, 95% CI: 0.94-1.07, P = 0.89). The odds of gastrointestinal adverse events were significantly reduced (RR = 0.77, 95% CI: 0.62-0.97, P < 0.05).Our analysis suggests that alendronate can increase the percent change in BMD at the lumbar spine, total hip, and

  3. Diabetes Enhances Periodontal Bone Loss through Enhanced Resorption and Diminished Bone Formation

    PubMed Central

    Liu, R.; Bal, H.S.; Desta, T.; Krothapalli, N.; Alyassi, M.; Luan, Q.; Graves, D.T.

    2008-01-01

    Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9- fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells. PMID:16723646

  4. Irreversible bone loss in osteomalacia. Comparison of radial photon absorptiometry with iliac bone histomorphometry during treatment.

    PubMed Central

    Parfitt, A M; Rao, D S; Stanciu, J; Villanueva, A R; Kleerekoper, M; Frame, B

    1985-01-01

    We examined the relationships between the changes in bone mineral deficit in the radius, determined by single-energy photon absorptiometry at standard proximal and distal sites, and in the ilium, determined by bone histomorphometry, during the treatment of osteomalacia of diverse etiology in 28 patients. In the ilium, relative osteoid volume decreased by 75-80% in both cortical bone (from 6.0% to 1.5%) and trabecular bone (from 30.1% to 6.6%) during a mean treatment duration of 2 yr. There was also a significant fall in iliac cortical porosity from 10.3% to 7.8%. As a result, mineralized bone volume increased by 7.5% in cortical and by 40.1% in trabecular bone; the cortical and trabecular increments were correlated (r = 0.69, P less than 0.001). The properly weighted increase for the entire tissue sample was 18.6%. By contrast, there was no change in bone mineral at either radial site, although there was a 2% increase at both sites when allowance was made for age-related bone loss during treatment. The proximal and distal age-adjusted increments was correlated (r = 0.76, P less than 0.001), but there was no correlation between the changes in any photon absorptiometric and any histomorphometric index. In that iliac cortical bone turnover in normal subjects was 7.2%/yr, we estimated the rate of bone turnover to be less than 2%/yr at both proximal and distal radial sites, including any trabecular bone present at the distal site. Compared to appropriate control subjects, the bone mineral deficits fell during treatment from 19.2% to 17.1% at the proximal radius (greater than 95% cortical bone) and from 20.5% to 18.5% at the distal radius (greater than 75% cortical bone). In the ilium the deficits, assuming attainment of normal values for osteoid volume and cortical porosity, fell from 41.7% to 36.1% in cortical and from 31.5% to 6.3% in trabecular bone, the properly weighted combined deficit falling from 38.6% to 27.7%. The irreversible iliac cortical deficit was

  5. Massive Bone Loss Due to Orchidectomy and Localized Disuse: Preventive Effects of a Biosphonsphonate

    NASA Astrophysics Data System (ADS)

    Libouban, H.; Moreau, M. F.; Chappard, D.

    2008-06-01

    Orchidectomy (ORX) and hindlimb paralysis induced by botulinum neurotoxin (BTX) were combined to see if their effects were cumulative and if bone loss could be prevented by an antiresorptive agent (risedronate) or testosterone. Four groups of mature rats were studied for 1 month: SHAM operated; ORX and right hindlimb immobilization (BTX); ORX+BTX+risedronate or testosterone. Bone loss and microarchitecture deterioration were maximized on the immobilized bone. Risedronate but not testosterone prevented trabecular bone loss but was less effective on cortical bone loss. ORX and BTX had additive effects on bone loss which can be prevented by risedronate but not testosterone.

  6. Bone loss and human adaptation to lunar gravity

    NASA Technical Reports Server (NTRS)

    Keller, T. S.; Strauss, A. M.

    1992-01-01

    Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

  7. Simulating Bone Loss in Microgravity Using Mathematical Formulations of Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Pennline, James A.

    2009-01-01

    Most mathematical models of bone remodeling are used to simulate a specific bone disease, by disrupting the steady state or balance in the normal remodeling process, and to simulate a therapeutic strategy. In this work, the ability of a mathematical model of bone remodeling to simulate bone loss as a function of time under the conditions of microgravity is investigated. The model is formed by combining a previously developed set of biochemical, cellular dynamics, and mechanical stimulus equations in the literature with two newly proposed equations; one governing the rate of change of the area of cortical bone tissue in a cross section of a cylindrical section of bone and one governing the rate of change of calcium in the bone fluid. The mechanical stimulus comes from a simple model of stress due to a compressive force on a cylindrical section of bone which can be reduced to zero to mimic the effects of skeletal unloading in microgravity. The complete set of equations formed is a system of first order ordinary differential equations. The results of selected simulations are displayed and discussed. Limitations and deficiencies of the model are also discussed as well as suggestions for further research.

  8. Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia

    PubMed Central

    Tamma, Roberto; Sun, Li; Cuscito, Concetta; Lu, Ping; Corcelli, Michelangelo; Li, Jianhua; Colaianni, Graziana; Moonga, Surinder S.; Di Benedetto, Adriana; Grano, Maria; Colucci, Silvia; Yuen, Tony; New, Maria I.; Zallone, Alberta; Zaidi, Mone

    2013-01-01

    Although hyponatremia is known to be associated with osteoporosis and a high fracture risk, the mechanism through which bone loss ensues has remained unclear. As hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, we examined whether AVP can affect the skeleton directly as yet another component of the pituitary-bone axis. Here, we report that the two Avp receptors, Avpr1α and Avpr2, coupled to Erk activation, are expressed in osteoblasts and osteoclasts. AVP injected into wild-type mice enhanced and reduced, respectively, the formation of bone-resorbing osteoclasts and bone-forming osteoblasts. Conversely, the exposure of osteoblast precursors to Avpr1α or Avpr2 antagonists, namely SR49059 or ADAM, increased osteoblastogenesis, as did the genetic deletion of Avpr1α. In contrast, osteoclast formation and bone resorption were both reduced in Avpr1α−/− cultures. This process increased bone formation and reduced resorption resulted in a profound enhancement of bone mass in Avpr1α−/− mice and in wild-type mice injected with SR49059. Collectively, the data not only establish a primary role for Avp signaling in bone mass regulation, but also call for further studies on the skeletal actions of Avpr inhibitors used commonly in hyponatremic patients. PMID:24167258

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

    PubMed

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

    2017-07-01

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

  10. Chinese herbal medicine Yougui Pill reduces exogenous glucocorticoid-induced apoptosis in anterior pituitary cells

    PubMed Central

    Ji, Yong-zhi; Geng, Long; Zhou, Hong-bo; Wei, Hua-chen; Chen, Hong-duo

    2016-01-01

    Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill (YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated mRNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated mRNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway. PMID:28197193

  11. Loss of Rictor with aging in osteoblasts promotes age-related bone loss

    PubMed Central

    Lai, Pinling; Song, Qiancheng; Yang, Cheng; Li, Zhen; Liu, Sichi; Liu, Bin; Li, Mangmang; Deng, Hongwen; Cai, Daozhang; Jin, Dadi; Liu, Anling; Bai, Xiaochun

    2016-01-01

    Osteoblast dysfunction is a major cause of age-related bone loss, but the mechanisms underlying changes in osteoblast function with aging are poorly understood. This study demonstrates that osteoblasts in aged mice exhibit markedly impaired adhesion to the bone formation surface and reduced mineralization in vivo and in vitro. Rictor, a specific component of the mechanistic target of rapamycin complex 2 (mTORC2) that controls cytoskeletal organization and cell survival, is downregulated with aging in osteoblasts. Mechanistically, we found that an increased level of reactive oxygen species with aging stimulates the expression of miR-218, which directly targets Rictor and reduces osteoblast bone surface adhesion and survival, resulting in a decreased number of functional osteoblasts and accelerated bone loss in aged mice. Our findings reveal a novel functional pathway important for age-related bone loss and support for miR-218 and Rictor as potential targets for therapeutic intervention for age-related osteoporosis treatment. PMID:27735936

  12. Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

    DTIC Science & Technology

    2011-05-01

    first series, adult female mice were subjected to unilateral Botox -induced muscle paralysis of the lower limb via Botox (20 U/kg) injection into the...equal loss in muscle mass induced by Botox , Sost+/+ mice lost a significant percentage of their initial lower-limb aBMD and BMC over the experimental...trabecular thickness, and trabecular bone mineral content (Tb.BMC) in the distal femur. We also investigated the osteopenic effects of Botox

  13. The role of the macrophage in periprosthetic bone loss

    PubMed Central

    Santerre, J. Paul; Labow, Rosalind S.; Boynton, Erin L.

    2000-01-01

    Aseptic loosening after total joint replacement remains the most common reason for long-term implant failure. Macrophages activated by submicron wear particles of the polyethylene liner used in joint replacement have been shown to be the source of periprosthetic bone loss. Understanding the role of material chemistry in macrophage activation and the subsequent effects that macrophage-derived enzymes play in the degradation of implanted biomaterials is key to developing methods for prolonging the lifespan of implantable materials. PMID:10851410

  14. NELL-1 in the treatment of osteoporotic bone loss

    PubMed Central

    James, Aaron W.; Shen, Jia; Zhang, Xinli; Asatrian, Greg; Goyal, Raghav; Kwak, Jin H.; Jiang, Lin; Bengs, Benjamin; Culiat, Cymbeline T.; Turner, A. Simon; Seim III, Howard B.; Wu, Benjamin M.; Lyons, Karen; Adams, John S.; Ting, Kang; Soo, Chia

    2015-01-01

    NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss. PMID:26082355

  15. NELL-1 in the treatment of osteoporotic bone loss

    DOE PAGES

    James, Aaron W.; Shen, Jia; Zhang, Xinli; ...

    2015-06-17

    NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast: osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to amore » large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Furthermore, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.« less

  16. NELL-1 in the treatment of osteoporotic bone loss

    SciTech Connect

    James, Aaron W.; Shen, Jia; Zhang, Xinli; Asatrian, Greg; Goyal, Raghav; Kwak, Jin H.; Jiang, Lin; Bengs, Benjamin; Culiat, Cymbeline T.; Turner, A. Simon; Seim, III, Howard B.; Wu, Benjamin M.; Lyons, Karen; Adams, John S.; Ting, Kang; Soo, Chia

    2015-06-17

    NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast: osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Furthermore, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.

  17. NELL-1 in the treatment of osteoporotic bone loss.

    PubMed

    James, Aaron W; Shen, Jia; Zhang, Xinli; Asatrian, Greg; Goyal, Raghav; Kwak, Jin H; Jiang, Lin; Bengs, Benjamin; Culiat, Cymbeline T; Turner, A Simon; Seim Iii, Howard B; Wu, Benjamin M; Lyons, Karen; Adams, John S; Ting, Kang; Soo, Chia

    2015-06-17

    NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.

  18. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-12-1-0377 TITLE: The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation PRINCIPAL...Sep 2015 4. TITLE AND SUBTITLE The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in 5a. CONTRACT NUMBER PR110178 Bone...adapt to mechanical loading (exercise). Degeneration in peripheral nerve function with age may be one of these mechanisms, as neuropeptides affect

  19. 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

  20. Measurement of spinal or peripheral bone mass to estimate early postmenopausal bone loss

    SciTech Connect

    Riis, B.J.; Christiansen, C.

    1988-04-01

    This report presents data from 153 healthy, early postmenopausal women who were randomly allocated to two years of treatment with estrogen or placebo. Bone mineral content in the forearms was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine and total-body bone mineral by dual-photon absorptiometry, before and after one and two years of treatment. At the end of the two years, there were highly significant differences of 6 to 7 percent between the estrogen and the placebo groups at all sites measured. The range of the changes of the spine measurement was twice that of the forearm and total-body measurements. It is concluded that measurement of the forearm by single-photon absorptiometry is superior to measurement of the spine by dual-photon absorptiometry both in clinical studies and in the individual patient for detecting estrogen-dependent bone loss and its treatment by estrogen replacement.

  1. Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats.

    PubMed

    Kim, Jonggun; Kim, Hyung Kwan; Kim, Saehun; Imm, Ji-Young; Whang, Kwang-Youn

    2015-12-01

    Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats.

  2. Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats

    PubMed Central

    Kim, Jonggun; Kim, Hyung Kwan; Kim, Saehun; Imm, Ji-Young

    2015-01-01

    Abstract Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats. PMID:26367331

  3. Protection by Salidroside against Bone Loss via Inhibition of Oxidative Stress and Bone-Resorbing Mediators

    PubMed Central

    Yuan, Zhi; Fan, Jing; Li, Dan; Chen, Jian-Zong; Shi, Tian-Yao; Hu, Hui-Min; Wei, Bo-Yuan; Luo, Zhuo-Jing; Liu, Jian

    2013-01-01

    Oxidative stress is a pivotal pathogenic factor for bone loss in mouse model. Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L, exhibits potent antioxidative effects. In the present study, we used an in vitro oxidative stress model induced by hydrogen peroxide (H2O2) in MC3T3-E1 cells and a murine ovariectomized (OVX) osteoporosis model to investigate the protective effects of salidroside on bone loss and the related mechanisms. We demonstrated that salidroside caused a significant (P<0.05) elevation of cell survival, alkaline phosphatase (ALP) staining and activity, calcium deposition, and the transcriptional expression of Alp, Col1a1 and Osteocalcin (Ocn) in the presence of H2O2. Moreover, salidroside decreased the production of intracellular reactive oxygen species (ROS), and osteoclast differentiation inducing factors such as receptor activator of nuclear factor-kB ligand (RANKL) and IL-6 induced by H2O2. In vivo studies further demonstrated that salidroside supplementation for 3 months caused a decrease in malondialdehyde (MDA) and an increase in reduced glutathione (GSH) concentration in blood of ovariectomized mouse (P<0.05), it also improved trabecular bone microarchitecture and bone mineral density in the fourth lumbar vertebra and distal femur. Our study indicated that the protection provided by salidroside in alleviating bone loss was mediated, at least in part, via inhibition of the release of bone-resorbing mediators and oxidative damage to bone-forming cells, suggesting that salidroside can be used as an effective remedy in the treatment or prevention of osteoporosis. PMID:23437352

  4. Protection by salidroside against bone loss via inhibition of oxidative stress and bone-resorbing mediators.

    PubMed

    Zhang, Jin-Kang; Yang, Liu; Meng, Guo-Lin; Yuan, Zhi; Fan, Jing; Li, Dan; Chen, Jian-Zong; Shi, Tian-Yao; Hu, Hui-Min; Wei, Bo-Yuan; Luo, Zhuo-Jing; Liu, Jian

    2013-01-01

    Oxidative stress is a pivotal pathogenic factor for bone loss in mouse model. Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L, exhibits potent antioxidative effects. In the present study, we used an in vitro oxidative stress model induced by hydrogen peroxide (H(2)O(2)) in MC3T3-E1 cells and a murine ovariectomized (OVX) osteoporosis model to investigate the protective effects of salidroside on bone loss and the related mechanisms. We demonstrated that salidroside caused a significant (P<0.05) elevation of cell survival, alkaline phosphatase (ALP) staining and activity, calcium deposition, and the transcriptional expression of Alp, Col1a1 and Osteocalcin (Ocn) in the presence of H(2)O(2). Moreover, salidroside decreased the production of intracellular reactive oxygen species (ROS), and osteoclast differentiation inducing factors such as receptor activator of nuclear factor-kB ligand (RANKL) and IL-6 induced by H(2)O(2). In vivo studies further demonstrated that salidroside supplementation for 3 months caused a decrease in malondialdehyde (MDA) and an increase in reduced glutathione (GSH) concentration in blood of ovariectomized mouse (P<0.05), it also improved trabecular bone microarchitecture and bone mineral density in the fourth lumbar vertebra and distal femur. Our study indicated that the protection provided by salidroside in alleviating bone loss was mediated, at least in part, via inhibition of the release of bone-resorbing mediators and oxidative damage to bone-forming cells, suggesting that salidroside can be used as an effective remedy in the treatment or prevention of osteoporosis.

  5. Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone

    PubMed Central

    Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

    2011-01-01

    Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

  6. Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone

    PubMed Central

    Todd, Henry; Galea, Gabriel L.; Meakin, Lee B.; Delisser, Peter J.; Lanyon, Lance E.

    2015-01-01

    Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to

  7. Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass.

    PubMed

    Wang, Feng-Sheng; Lin, Chun-Liang; Chen, Yeung-Jen; Wang, Ching-Jen; Yang, Kuender D; Huang, Yu-Ting; Sun, Yi-Chih; Huang, Hui-Chen

    2005-05-01

    Prolonged glucocorticoid treatment is known to cause osteoporosis or aseptic necrosis. Secreted frizzled-related proteins 1 (SFRP1) and low-density lipoprotein-related protein 5 (LRP5), a Wnt protein antagonist and a coreceptor, have been found to regulate skeletogenesis. Whereas recent studies have reported that excess glucocorticoid promotes bone loss, the biological role of SFRP1 and LRP5 in regulating glucocorticoid attenuation of bone formation is not fully understood. We showed that a supraphysiological level of glucocorticoid enhanced SFRP1 but not LRP5 expression of primary mesenchymal cell cultures in vitro and osteoblasts at metaphyseal trabecular endosteum and chondrocytes at calcified cartilage in vivo. Glucocorticoid augmentation of SFRP1 expression was transcriptionally mediated. The inhibitory action of glucocorticoid on osteogenic differentiation appeared to be regulated by SFRP1 mediation of beta-catenin destabilization because knocking down SFRP1 by RNA interference abrogated the supraphysiological level of glucocorticoid attenuation of osteogenesis. Recombinant human SFRP1 reduced the promoting effect of physiological level of glucocorticoid on cytosolic beta-catenin accumulation, runt-related transcription factor-2 activation, and osteogenic activities. Glucocorticoid and recombinant human SFRP1 significantly increased osteochondral cell apoptosis associated with reduced mineral density, biomechanical properties, trabecular bone volume, and midshaft cortical bone areas in rat femurs. These findings suggest that SFRP1 modulates glucocorticoid-induced bone loss. Regulation of Wnt/SFRP signal transduction can be used in the future as an alternative strategy for the prevention of glucocorticoid-induced osteoporosis.

  8. Daily parathyroid hormone administration enhances bone turnover and preserves bone structure after severe immobilization-induced bone loss.

    PubMed

    Harlow, Lauren; Sahbani, Karim; Nyman, Jeffry S; Cardozo, Christopher P; Bauman, William A; Tawfeek, Hesham A

    2017-09-01

    Immobilization, as a result of motor-complete spinal cord injury (SCI), is associated with severe osteoporosis. Whether parathyroid hormone (PTH) administration would reduce bone loss after SCI remains unclear. Thus, female mice underwent sham or surgery to produce complete spinal cord transection. PTH (80 μg/kg) or vehicle was injected subcutaneously (SC) daily starting on the day of surgery and continued for 35 days. Isolated tibias and femurs were examined by microcomputed tomography scanning (micro-CT) and histology and serum markers of bone turnover were measured. Micro-CT analysis of tibial metaphysis revealed that the SCI-vehicle animals exhibited 49% reduction in fractional trabecular bone volume and 18% in trabecular thickness compared to sham-vehicle controls. SCI-vehicle animals also had 15% lower femoral cortical thickness and 16% higher cortical porosity than sham-vehicle counterparts. Interestingly, PTH administration to SCI animals restored 78% of bone volume, increased connectivity to 366%, and lowered structure model index by 10% compared to sham-vehicle animals. PTH further favorably attenuated femoral cortical bone loss to 5% and prevented the SCI-associated cortical porosity. Histomorphometry evaluation of femurs of SCI-vehicle animals demonstrated a marked 49% and 38% decline in osteoblast and osteoclast number, respectively, and 35% reduction in bone formation rate. In contrast, SCI-PTH animals showed preserved osteoblast and osteoclast numbers and enhanced bone formation rate. Furthermore, SCI-PTH animals had higher levels of bone formation and resorption markers than either SCI- or sham-vehicle groups. Collectively, these findings suggest that intermittent PTH receptor activation is an effective therapeutic strategy to preserve bone integrity after severe immobilization. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  9. Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; LeBlanc, A.; Shackelford, L. C.; Heer, M. A.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

  10. Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; LeBlanc, A.; Shackelford, L. C.; Heer, M. A.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

  11. Comparison of Bone Loss around Bone Platform Shift and Non-Bone Platform Shift Implants After 12 Months

    PubMed Central

    Rokn, Amir Reza; Badri, Samareh; Rasouli Ghahroudi, Amir Alireza; Manasheof, Rebeca; Kharazi Fard, Mohamad Javad; Barikani, Hamidreza

    2015-01-01

    Objectives: The aim of the present randomized clinical trial was to evaluate marginal bone loss around two types of implants modified at the neck area: Nobel Active and Nobel Replace Groovy, both manufactured by Nobel Biocare. Materials and Methods: A total of 25 Nobel Active and 21 Nobel Replace Groovy implants were included in the present study. The implants were placed based on the relevant protocol and patient inclusion and exclusion criteria. The amount of bone loss around implants was compared at 6 and 12-month intervals using digital periapical radiographs. Results: The mean bone loss values in the Nobel Active and Nobel Replace Groovy groups were 0.682 mm and 0.645 mm, respectively, with no statistically significant difference based on the results of independent t-test (P=0.802). Conclusion: Use of both implant types yielded favorable results, with high durability. The two implant types exhibited no superiority over each other in terms of bone loss. PMID:26622270

  12. Role of carbonic anhydrase in bone - Plasma acetazolamide concentrations associated with inhibition of bone loss

    NASA Technical Reports Server (NTRS)

    Kenny, A. D.

    1985-01-01

    The effects of acetazolamide and benzolamide on bone formation are examined. Solutions of acetazolamide and benzolamide with 1 M THAM/tris(hydromethyl)aminoethane/ or without 1 M THAM were injected subcutaneous with a minipump and into the food of Sprague-Dawley rats. The data reveal that for 8-day and 12-day infusions only acetazolamide combined with 1 M THAM caused any reduction in bone loss and there were no changes in body weights, food consumption and plasma calcium and phosphorus values. Following 8 days of infusion of acetazolamide with 1 M THAM at infusion rates of 0.5, 5.0, and 50 micrograms/hr, no reduction was detected at 0.5 microgram/hr, a 30 percent reduction occurred at 5.0 micrograms/hr and a 49 percent decrease at 50 micrograms/hr. In the benzolamide experiment it was observed that 0.5 percent of the solution in the food caused no reduction in bone loss; however, infusions with benzolamide plus 1 M THAM resulted in a bone loss reduction of 30 percent at 5.0 micrograms/hr, and a 49 percent decrease at 50 micrograms/hr. Acetazolamide levels in the plasma at 50 micrograms/hr doses are calculated as ranging from 99 ng/ml-223 ng/ml and as 46 ng/ml at 5 micrograms/hr doses.

  13. Zanthoxylum piperitum reversed alveolar bone loss of periodontitis via regulation of bone remodeling-related factors.

    PubMed

    Kim, Mi Hye; Lee, Hye Ji; Park, Jung-Chul; Hong, Jongki; Yang, Woong Mo

    2017-01-04

    Zanthoxylum piperitum (ZP) has been used to prevent toothache in East Asia. In this study, we investigated the effects of ZP on periodontitis along with alveolar bone loss. Twenty-eight male Sprague-Dawley rats were assigned into 4 groups; non-ligated (NOR), ligated and treated vehicle (CTR), ligated and treated 1mg/mL ZP (ZP1), and ligated and treated 100mg/mL ZP (ZP100). Sterilized 3-0 nylon ligature was placed into the subgingival sulcus around the both sides of mandibular first molar. After topical application of 1 and 100mg/mL ZP for 2 weeks, mandibles was removed for histology. In addition, SaOS-2 osteoblast cells were treated 1, 10 and 100μg/mL ZP for 24h to analyze the expressions of alveolar bone-related markers. Several alveolar bone resorption pits, which indicate cementum demineralization were decreased by ZP treatment. Topical ZP treatment inhibited periodontitis-induced alveolar bone loss. In addition, there were significant reduction of osteoclastic activities following topical ZP treatment in periodontium. The expression of RANKL was decreased in SaOS-2 osteoblast cells by treating ZP, while that of OPG was increased. ZP treatment increased the expressions of Runx2 and Osterix in SaOS-2 cells. In summary, ZP treatment inhibited alveolar bone loss as well as maintained the integrity of periodontal structures via regulation of bone remodeling. ZP may be a therapeutic target for treating periodontitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass.

    PubMed

    Kim, Tiffany Y; Schwartz, Ann V; Li, Xiaojuan; Xu, Kaipin; Black, Dennis M; Petrenko, Dimitry M; Stewart, Lygia; Rogers, Stanley J; Posselt, Andrew M; Carter, Jonathan T; Shoback, Dolores M; Schafer, Anne L

    2017-08-09

    Bone marrow fat is a unique fat depot that may regulate bone metabolism. Marrow fat is increased in states of low bone mass, severe underweight, and diabetes. However, longitudinal effects of weight loss and improved glucose homeostasis on marrow fat are unclear, as is the relationship between marrow fat and bone mineral density (BMD) changes. We hypothesized that after Roux-en-Y gastric bypass (RYGB) surgery, marrow fat changes are associated with BMD loss. We enrolled 30 obese women, stratified by diabetes status. Before and 6 months after RYGB, we measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and vertebral marrow fat content by magnetic resonance spectroscopy. At baseline, those with higher marrow fat had lower BMD. Postoperatively, total body fat declined dramatically in all participants. Effects of RYGB on marrow fat differed by diabetes status (p = 0.03). Nondiabetic women showed no significant mean change in marrow fat (+1.8%, 95% confidence interval [CI] -1.8% to +5.4%, p = 0.29), although those who lost more total body fat were more likely to have marrow fat increases (r = -0.70, p = 0.01). In contrast, diabetic women demonstrated a mean marrow fat change of -6.5% (95% CI -13.1% to 0%, p = 0.05). Overall, those with greater improvements in hemoglobin A1c had decreases in marrow fat (r = 0.50, p = 0.01). Increases in IGF-1, a potential mediator of the marrow fat-bone relationship, were associated with marrow fat declines (r = -0.40, p = 0.05). Spinal volumetric BMD decreased by 6.4% ± 5.9% (p < 0.01), and femoral neck areal BMD decreased by 4.3% ± 4.1% (p < 0.01). Marrow fat and BMD changes were negatively associated, such that those with marrow fat increases had more BMD loss at both spine (r = -0.58, p < 0.01) and femoral neck (r = -0.49, p = 0.01), independent of age and menopause. Our findings suggest that glucose metabolism and

  15. Glucocorticoid-induced laminitis with hepatopathy in a Thoroughbred filly.

    PubMed

    Ryu, Seung Ho; Kim, Byung Sun; Lee, Chang Woo; Yoon, Junghee; Lee, Yonghoon Lyon

    2004-09-01

    A 3-year-old Thoroughbred filly was referred to the Equine Hospital, Korea Racing Association for evaluation of hematuria, inappetite, weight loss and depression. From 25 days prior to admission, the horse was treated for right carpal lameness with 20 mg intramuscular administration of triamcinolone acetonide per day for consecutive 10 days by a local veterinarian. Clinical and laboratory findings included vaginal hyperemia, flare in bladder wall, neutrophilia, lymphopenia, polyuria, polydipsia and laminitis in the end. High activities of aspartate transaminase and gamma glutamyltransferase and high concentration of total bilirubin indicated hepatopathy. Further hematology, serum biochemistry and urinalysis did not reveal any abnormalities. Medical history, physical and clinicopathologic findings suggest that the laminitis and hepatopathy in this horse were most likely induced by repeated administration of exogenous corticosteroid. However, guarded prognosis of treating laminitis undermined the benefit of improvement of hematuria following electroacupuncture stimulation. The combined stimulation of kidney related acupoints (Shen Peng, Shen Shu), lumber related acupoints (Yao Qian, Yao Zhong) and associate acupoints (Guan Yuan Shu, Bai Hui) at 5Hz, 1-2V, for 40 minutes was of value in the treatment of hematuria. This case shows that horses under steroids may exhibit laminitis and steroid hepatopathy. Early recognition and good management of laminitis are important in the limitation of complications.

  16. Accelerated bone loss and increased post-fracture mortality in elderly women and men.

    PubMed

    Bliuc, D; Nguyen, N D; Alarkawi, D; Nguyen, T V; Eisman, J A; Center, J R

    2015-04-01

    Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We found accelerated bone loss (≥1.31 % bone loss/year for women and ≥1.35 % bone loss/year for men) associated with 44-77 % increased mortality. It remains unclear whether bone loss is a marker or plays a role in mortality. Osteoporotic fractures are associated with increased mortality although the cause is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated with increased mortality, but its role in mortality risk post-fracture is unclear. This study aimed to examine post-fracture mortality risk according to levels of bone loss. Community-dwelling participants aged 60+ from Dubbo Osteoporosis Epidemiology Study with incident fractures were followed from 1989 to 2011. Kaplan-Meier survival curves were constructed according to bone loss quartiles. Cox proportional hazard models were used to determine the effect of bone loss on mortality. There were 341 women and 106 men with ≥2 BMD measurements. The rate of bone loss was similar for women and men (women mean -0.79 %/year, highest bone loss quartile -1.31 %/year; men mean -0.74 %/year, highest quartile -1.35 %/year). Survival was lowest for the highest quartile of bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture type, the association of bone loss with mortality was observed for vertebral (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an additional role in mortality risk following hip fractures. Importantly, overall, rapid bone loss was associated with 44-77 % increased mortality risk after multiple variable adjustment. Rapid bone loss was an independent predictor of post-fracture mortality risk in both women and men. The association of bone loss and post-fracture mortality was predominantly observed following vertebral fracture in both women and men

  17. Prostaglandin E2 Prevents Bone Loss and Adds Extra Bone to Immobilized Distal Femoral Metaphysis in Female Rats

    NASA Technical Reports Server (NTRS)

    Akamine, T.; Jee, W. S. S.; Ke, H. Z.; Li, X. J.; Lin, B. Y.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented disuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

  18. Prostaglandin E2 Prevents Bone Loss and Adds Extra Bone to Immobilized Distal Femoral Metaphysis in Female Rats

    NASA Technical Reports Server (NTRS)

    Akamine, T.; Jee, W. S. S.; Ke, H. Z.; Li, X. J.; Lin, B. Y.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented disuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

  19. Bone turnover markers in peripheral blood and marrow plasma reflect trabecular bone loss but not endocortical expansion in aging mice.

    PubMed

    Shahnazari, Mohammad; Dwyer, Denise; Chu, Vivian; Asuncion, Frank; Stolina, Marina; Ominsky, Michael; Kostenuik, Paul; Halloran, Bernard

    2012-03-01

    We examined age-related changes in biochemical markers and regulators of osteoblast and osteoclast activity in C57BL/6 mice to assess their utility in explaining age-related changes in bone. Several recently discovered regulators of osteoclasts and osteoblasts were also measured to assess concordance between their systemic levels versus their levels in marrow plasma, to which bone cells are directly exposed. MicroCT of 6-, 12-, and 24-month-old mice indicated an early age-related loss of trabecular bone volume and surface, followed by endocortical bone loss and periosteal expansion. Trabecular bone loss temporally correlated with reductions in biomarkers of bone formation and resorption in both peripheral blood and bone marrow. Endocortical bone loss and periosteal bone gain were not reflected in these protein biomarkers, but were well correlated with increased expression of osteocalcin, rank, tracp5b, and cathepsinK in RNA extracted from cortical bone. While age-related changes in bone turnover markers remained concordant in blood versus marrow, aging led to divergent changes in blood versus marrow for the bone cell regulators RANKL, OPG, sclerostin, DKK1, and serotonin. Bone expression of runx2 and osterix increased progressively with aging and was associated with an increase in the number of osteoprogenitors and osteoclast precursors. In summary, levels of biochemical markers of bone turnover in blood and bone marrow plasma were predictive of an age-related loss of trabecular surfaces in adult C57BL/6 mice, but did not predict gains in cortical surfaces resulting from cortical expansion. Unlike these turnover markers, a panel of bone cell regulatory proteins exhibited divergent age-related changes in marrow versus peripheral blood, suggesting that their circulating levels may not reflect local levels to which osteoclasts and osteoblasts are directly exposed.

  20. Oral bone loss induced by mineral deficiency in a rat model: effect of a synthetic bone mineral (SBM) preparation.

    PubMed

    Mijares, Dindo; Kulkarni, Anupama; Lewis, Kanthi; Yao, Fang; Xi, Qing; Tannous, Samar; Dias, Renata; LeGeros, Racquel Z

    2012-09-01

    Osteoporosis affects the craniofacial and oral structures and has been associated with periodontal bone loss, tooth loss and reduced jaw bone mass. This study aimed to test the therapeutic efficacy of synthetic bone mineral (SBM) in minimizing alveolar bone loss induced by mineral deficiency in a rat model. SBM consists of a calcium carbonate apatite (similar to bone apatite) matrix incorporating magnesium, zinc, and fluoride ions. Thirty female Sprague Dawley rats (2 months old) were randomly distributed into 3 groups (10 rats per group): GA (control), on basic diet; GB, on mineral deficient (MD) diet; and GC, on MD+SBM. The rats were sacrificed after 3 months, the jawbones were isolated and the soft tissues removed. Bone density was determined using X-ray radiography (Faxitron); mandibular cortical width, panoramic mandibular index, and alveolar resorption degree (M/M ratio) using BioquantOsteo; and bone micro-architecture micro-computed tomography and scanning electron microscopy. Compared to control (GA), the rats on MD diet (GB) experienced significant mandibular bone loss while the rats on MD+SBM diet (GC) experienced significantly less bone loss compared to the GB group. SBM, administered orally, may have the potential as an osteoporosis therapeutic agent in minimizing or preventing alveolar bone loss induced by mineral deficiency. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. 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

  2. Bone Density Loss Is Associated With Blood Cell Counts.

    PubMed

    Valderrábano, Rodrigo J; Lui, Li-Yung; Lee, Jennifer; Cummings, Steven R; Orwoll, Eric S; Hoffman, Andrew R; Wu, Joy Y

    2017-02-01

    Hematopoiesis depends on a supportive microenvironment. Preclinical studies in mice have demonstrated that osteoblasts influence the development of blood cells, particularly erythrocytes, B lymphocytes, and neutrophils. However, it is unknown whether osteoblast numbers or function impact blood cell counts in humans. We tested the hypothesis that men with low BMD or greater BMD loss have decreased circulating erythrocytes and lymphocytes and increased myeloid cells. We performed a cross-sectional analysis and prospective analysis in the Osteoporotic Fractures in Men (MrOS) study, a multisite longitudinal cohort study. A total of 2571 community-dwelling men (≥65 years) who were able to walk without assistance, did not have a hip replacement or fracture, and had complete blood counts (CBCs) at the third study visit were analyzed. Multivariable (MV)-adjusted logistic regression estimated odds of white blood cell (WBC) subtypes (highest and lowest quintile versus middle), and anemia (clinically defined) associated with BMD by DXA scan (at visit 3), annualized percent BMD change (baseline to visit 3), and high BMD loss (>0.5%/year, from baseline to visit 3) at the femoral neck (FN) and total hip (TH). MV-adjusted models included age, BMI, cancer history, smoking status, alcohol intake, corticosteroid use, self-reported health, thiazide use, and physical activity. At visit 3 greater TH BMD loss (per 1 SD) was associated with increased odds of anemia, high neutrophils, and low lymphocytes. Annualized BMD loss of >0.5% was associated with increased odds of anemia, high neutrophils, and low lymphocytes. Similar results were observed for FN BMD regarding anemia and lymphocytes. We conclude that community-dwelling older men with declining hip BMD over about 7 years had increased risks of anemia, lower lymphocyte count, and higher neutrophil count, consistent with preclinical studies. Bone health and hematopoiesis may have greater interdependency than previously recognized.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  4. Spaceflight-induced bone loss: is there an osteoporosis risk?

    PubMed

    Sibonga, Jean D

    2013-06-01

    Currently, the measurement of areal bone mineral density (aBMD) is used at NASA to evaluate the effects of spaceflight on the skeletal health of astronauts. Notably, there are precipitous declines in aBMD with losses >10 % detected in the hip and spine in some astronauts following a typical 6-month mission in space. How those percentage changes in aBMD relate to fracture risk in the younger-aged astronaut is unknown. Given the unique set of risk factors that could be contributing to this bone loss (eg, adaptation to weightlessness, suboptimal diet, reduced physical activity, perturbed mineral metabolism), one might not expect skeletal changes due to spaceflight to be similar to skeletal changes due to aging. Consequently, dual-energy X-ray absorptiometry (DXA) measurement of aBMD may be too limiting to understand fracture probability in the astronaut during a long-duration mission and the risk for premature osteoporosis after return to Earth. Following a brief review of the current knowledge-base, this paper will discuss some innovative research projects being pursued at NASA to help understand skeletal health in astronauts.

  5. Estradiol antagonism of glucocorticoid-induced GILZ expression in human uterine epithelial cells and murine uterus.

    PubMed

    Whirledge, Shannon; Cidlowski, John A

    2013-01-01

    Sex hormone signaling regulates a variety of functions in the uterine endometrium essential for embryo implantation and immunity. Epithelial cells of the uterine endometrium are the target of the coordinated actions of estradiol (E(2)) and progesterone. However, little information exists regarding the interplay of estrogens with glucocorticoids in this tissue. Using the human uterine epithelial cell line ECC1, E(2) was found to antagonize induction of the glucocorticoid-induced leucine zipper (GILZ) gene expression, which is associated with several of the immune-related functions of glucocorticoids. Interestingly, E(2) antagonizes glucocorticoid regulated nascent RNA GILZ expression within 1 h of hormone treatment. Repression of glucocorticoid-induced GILZ expression requires the estrogen receptor (ER), because both treatment with the ER-antagonist ICI 182,780 and small interfering RNA knockdown of ERα block E(2)'s ability to repress GILZ gene expression. Antagonism of glucocorticoid-induced GILZ expression may not be unique to ERα, as the ERβ agonist Liquiritigenin is also able to antagonize glucocorticoid signaling. Transcriptional regulation appears to be at the level of promoter binding. Both the glucocorticoid receptor and ERα are recruited to regions of the GILZ promoter containing glucocorticoid response elements and the transcriptional start site. Glucocorticoid receptor binding to these regions in the presence of dexamethasone decreases with E(2) treatment. GILZ gene expression was also found to be repressed in the whole mouse uterus treated with a combination of dexamethasone and E(2). Regulation of the antiinflammatory gene GILZ by glucocorticoids and E(2) suggests cross talk between the immune modulating functions of glucocorticoids and the reproductive actions of estradiol signaling.

  6. Silencing miR-106b accelerates osteogenesis of mesenchymal stem cells and rescues against glucocorticoid-induced osteoporosis by targeting BMP2.

    PubMed

    Liu, Ke; Jing, Ying; Zhang, Wen; Fu, Xuejie; Zhao, Huan; Zhou, Xichao; Tao, Yunxia; Yang, Huilin; Zhang, Yan; Zen, Ke; Zhang, Chenyu; Li, Donghai; Shi, Qin

    2017-04-01

    Osteoporosis is a serious health problem worldwide. MicroRNA is a post-transcriptional regulator of gene expression by either promoting mRNA degradation or interfering with mRNA translation of specific target genes. It plays a significant role in the pathogenesis of osteoporosis. Here, we first demonstrated that miR-106b (miR-106b-5p) negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro. Then, we found that miR-106b expression increased in C57BL/6 mice with glucocorticoid-induced osteoporosis (GIOP), and that silencing of miR-106b signaling protected mice against GIOP through promoting bone formation and inhibiting bone resorption. At last, we showed that miR-106b inhibited osteoblastic differentiation and bone formation partly through directly targeting bone morphogenetic protein 2 (BMP2) both in vitro and in the GIOP model. Together, our findings have identified the role and mechanism of miR-106b in negatively regulating osteogenesis. Inhibition of miR-106b might be a potential new strategy for treating osteoporosis and bone defects.

  7. Treatment of excessive bone loss from both crus bones with internal bone transport using an intramedullary nail. Case report.

    PubMed

    Bereza, Przemysław; Wojciechowski, Piotr; Kusz, Damian

    2013-01-01

    We present a case report of a 16-year-old patient who suffered multisite and multiorgan injuries following a road accident. The most prominent musculoskeletal problem was a bilateral crush injury of the crus in combination with open fractures. The aim of this study is to present the possibilities and available methods of treatment of patients with extensive posttraumatic and postinflammatory bone loss of the lower limbs that make it possible to avoid amputation. We used intramedullary nailing and internal bone transport to reconstruct continuity and leg length of both crus bones. The treatment was complicated by poor vascularity and emerging complications. After several months and multi-stage treatment the patient was able to walk with full weight-bearing without crutches. Importantly, the patient is satisfied with the outcome of the treatment and does not consider herself disabled. The study presents our approach to the dilemma of choosing between prolonged reconstruction surgery and amputation as a final method.

  8. Three-Dimensional Micro-Computed Tomographic Imaging of Alveolar Bone in Experimental Bone Loss or Repair

    PubMed Central

    Park, Chan Ho; Abramson, Zachary R.; Taba, Mario; Jin, Qiming; Chang, Jia; Kreider, Jaclynn M.; Goldstein, Steven A.; Giannobile, William V.

    2008-01-01

    Background Micro-computed tomography (micro-CT) offers significant potential for identifying mineralized structures. However, three-dimensional (3-D) micro-CT of alveolar bone has not been adapted readily for quantification. Moreover, conventional methods are not highly sensitive for analyzing bone loss or bone gain following periodontal disease or reconstructive therapy. The objective of this investigation was to develop a micro-CT methodology for quantifying tooth-supporting alveolar bone in 3-D following experimental preclinical situations of periodontitis or reconstructive therapy. Methods Experimental in vivo bone loss or regeneration situations were developed to validate the micro-CT imaging techniques. Twenty mature Sprague-Dawley rats were divided into two groups: bone loss (Porphyromonas gingivalis lipopolysaccharide-mediated bone resorption) and regenerative therapy. Micro-CT and software digitized specimens were reconstructed three-dimensionally for linear and volumetric parameter assessment of alveolar bone (linear bone height, bone volume, bone volume fraction, bone mineral content, and bone mineral density). Intra- and interexaminer reproducibility and reliability were compared for methodology validation. Results The results demonstrated high examiner reproducibility for linear and volumetric parameters with high intraclass correlation coefficient (ICC) and coefficient of variation (CV). The ICC showed that the methodology was highly reliable and reproducible (ICC >0.99; 95% confidence interval, 0.937 to 1.000; CV <1.5%), suggesting that 3-D measurements may provide better alveolar bone analysis than conventional 2-D methods. Conclusions The developed methods allow for highly accurate and reproducible static measurements of tooth-supporting alveolar bone following preclinical situations of bone destruction or regeneration. Future investigations should focus on using in vivo micro-CT imaging for real-time assessments of alveolar bone changes. PMID

  9. Role of Osteoblast Gi Signaling in Age-Related Bone Loss in Female Mice.

    PubMed

    Millard, Susan M; Wang, Liping; Wattanachanya, Lalita; O'Carroll, Dylan; Fields, Aaron J; Pang, Joyce; Kazakia, Galateia; Lotz, Jeffrey C; Nissenson, Robert A

    2017-06-01

    Age-related bone loss is an important risk factor for fractures in the elderly; it results from an imbalance in bone remodeling mainly due to decreased bone formation. We have previously demonstrated that endogenous G protein-coupled receptor (GPCR)-driven Gi signaling in osteoblasts (Obs) restrains bone formation in mice during growth. Here, we launched a longitudinal study to test the hypothesis that Gi signaling in Obs restrains bone formation in aging mice, thereby promoting bone loss. Our approach was to block Gi signaling in maturing Obs by the induced expression of the catalytic subunit of pertussis toxin (PTX) after the achievement of peak bone mass. In contrast to the progressive cancellous bone loss seen in aging sex-matched littermate control mice, aging female Col1(2.3)+/PTX+ mice showed an age-related increase in bone volume. Increased bone volume was associated with increased bone formation at both trabecular and endocortical surfaces as well as increased bending strength of the femoral middiaphyses. In contrast, male Col1(2.3)+/PTX+ mice were not protected from age-related bone loss. Our results indicate that Gi signaling markedly restrains bone formation at cancellous and endosteal bone surfaces in female mice during aging. Blockade of the relevant Gi-coupled GPCRs represents an approach for the development of osteoporosis therapies-at least in the long bones of aging women.

  10. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    USDA-ARS?s Scientific Manuscript database

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  11. Curcumin analogue UBS109 prevents bone loss in breast cancer bone metastasis mouse model: involvement in osteoblastogenesis and osteoclastogenesis.

    PubMed

    Yamaguchi, Masayoshi; Zhu, Shijun; Zhang, Shumin; Wu, Daqing; Moore, Terry M; Snyder, James P; Shoji, Mamoru

    2014-07-01

    Bone metastasis of breast cancer typically leads to osteolysis, which causes severe pathological bone fractures and hypercalcemia. Bone homeostasis is skillfully regulated through osteoblasts and osteoclasts. Bone loss with bone metastasis of breast cancer may be due to both activation of osteoclastic bone resorption and suppression of osteoblastic bone formation. This study was undertaken to determine whether the novel curcumin analogue UBS109 has preventive effects on bone loss induced by breast cancer cell bone metastasis. Nude mice were inoculated with breast cancer MDA-MB-231 bone metastatic cells (10(6) cells/mouse) into the head of the right and left tibia. One week after inoculation, the mice were treated with control (vehicle), oral administration (p.o.) of UBS109 (50 or 150 mg/kg body weight), or intraperitoneal administration (i.p.) of UBS109 (10 or 20 mg/kg body weight) once daily for 5 days per week for 7 weeks. After UBS109 administration for 7 weeks, hind limbs were assessed using an X-ray diagnosis system and hematoxylin and eosion staining to determine osteolytic destruction. Bone marrow cells obtained from the femurs and tibias were cultured to estimate osteoblastic mineralization and osteoclastogenesis ex vivo and in vitro. Remarkable bone loss was demonstrated in the tibias of mice inoculated with breast cancer MDA-MB-231 bone metastatic cells. This bone loss was prevented by p.o. administration of UBS109 (50 and 150 mg/kg body weight) and i.p. treatment of UBS109 (10 and 20 mg/kg) in vivo. Culture of bone marrow cells obtained from the bone tissues of mice with breast cancer cell bone metastasis showed suppressed osteoblastic mineralization and stimulated osteoclastogenesis ex vivo. These changes were not seen after culture of the bone marrow cells obtained from mice treated with UBS109. Moreover, UBS109 was found to stimulate osteoblastic mineralization and suppress lipopolysaccharide (LPS)-induced osteoclastogenesis in bone marrow

  12. Comparison of single- and dual-photon absorptiometry in postmenopausal bone mineral loss

    SciTech Connect

    Nilas, L.; Borg, J.; Gotfredsen, A.; Christiansen, C.

    1985-11-01

    The authors describe a single photon absorptiometric (SPA) technique, which enables differential estimation of the rates of loss from trabecular and cortical bone. Ten scans are obtained in the forearm: six in an area with about 7% trabecular bone and four scans in the adjacent distal area with a trabecular bone content of 25%. By comparing bone masses of these two sites in 19 postmenopausal and 53 premenopausal women, the postmenopausal trabecular bone loss was estimated to be approximately seven times greater than cortical loss within the first years of cessation of regular vaginal bleeding. On a group basis the bone loss at the distal forearm scan site (by SPA) corresponded closely to the spinal bone loss (by dual-photon absorptiometry). The reproducibility of the two scan sites in the forearm was 1-1.5% (CV%), which makes the method suitable for longitudinal studies. Corrections for variations in fatty tissue covering can be made without deterioration of the reproducibility.

  13. B10 Cells Alleviate Periodontal Bone Loss in Experimental Periodontitis.

    PubMed

    Wang, Yuhua; Yu, Xiaoqian; Lin, Jiang; Hu, Yang; Zhao, Qian; Kawai, Toshihisa; Taubman, Martin A; Han, Xiaozhe

    2017-09-01

    B10 cells can regulate inflammatory responses in innate immunity. Toll-like receptors (TLRs) play an important role in B cell-mediated immune responses in periodontal disease. This study aimed to determine the effects of TLR-activated B10 cells on periodontal bone loss in experimental periodontitis. Spleen B cells isolated from C57BL/6J mice were cultured with Porphyromonas gingivalis lipopolysaccharide (LPS) and cytosine-phospho-guanine (CpG) oligodeoxynucleotides for 48 h. B10-enriched CD1d(hi) CD5(+) B cells were sorted by flow cytometry and were adoptively transferred to recipient mice through tail vein injection. At the same time, P. gingivalis-soaked ligatures were placed subgingivally around the maxillary second molars and remained there for 2 weeks before the mice were euthanized. Interleukin-10 (IL-10) production and the percentage of CD1d(hi) CD5(+) B cells were significantly increased with treatment with P. gingivalis LPS plus CpG compared to those in mice treated with P. gingivalis LPS or CpG alone. Mice with CD1d(hi) CD5(+) B cell transfer demonstrated reduced periodontal bone loss compared to the no-transfer group and the group with CD1d(lo) CD5(-) B cell transfer. Gingival IL-10 mRNA expression was significantly increased, whereas expressions of receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG), tumor necrosis factor alpha (TNF-α), and IL-1β were significantly inhibited in the CD1d(hi) CD5(+) B cell transfer group. The percentages of CD19(+) IL-10(+) cells, CD19(+) CD1d(hi) CD5(+) cells, and P. gingivalis-binding CD19(+) cells were significantly higher in recovered mononuclear cells from gingival tissues of the CD1d(hi) CD5(+) B cell transfer group than in tissues of the no-transfer group and the CD1d(lo) CD5(-) B cell transfer group. This study indicated that the adoptive transfer of B10 cells alleviated periodontal inflammation and bone loss in experimental periodontitis in mice. Copyright © 2017 American Society for Microbiology.

  14. Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow. Evidence for autonomy from factors released during bone resorption.

    PubMed Central

    Jilka, R L; Takahashi, K; Munshi, M; Williams, D C; Roberson, P K; Manolagas, S C

    1998-01-01

    Loss of sex steroids causes an increase in both the resorption and formation of bone, with the former exceeding the latter. Based on evidence that the increased bone resorption after estrogen loss is due to an increase in osteoclastogenesis, we hypothesized that estrogen loss also stimulates osteoblastogenesis. We report that the number of mesenchymal osteoblast progenitors in the murine bone marrow was increased two- to threefold between 2 and 8 wk after ovariectomy and returned to control levels by 16 wk. Circulating osteocalcin, as well as osteoclastogenesis and the rate of bone loss, followed a very similar temporal pattern. Inhibition of bone resorption by administration of the bisphosphonate alendronate led to a decrease of the absolute number of osteoblast progenitors; however, it did not influence the stimulating effect of ovariectomy on osteoblastogenesis or osteoclastogenesis. These observations indicate that the increased bone formation that follows loss of estrogen can be explained, at least in part, by an increase in osteoblastogenesis. Moreover, they strongly suggest that unlike normal bone remodeling, whereby osteoblast development is stimulated by factors released from the bone matrix during osteoclastic resorption, estrogen deficiency unleashes signals that can stimulate the differentiation of osteoblast progenitors in a fashion that is autonomous from the need created by bone resorption, and therefore, inappropriate. PMID:9576759

  15. The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors

    PubMed Central

    Lipton, Allan; Uzzo, Robert; Amato, Robert J.; Ellis, Georgiana K.; Hakimian, Behrooz; Roodman, G. David; Smith, Matthew R.

    2011-01-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  16. Diet-induced weight loss: the effect of dietary protein on bone.

    PubMed

    Tang, Minghua; O'Connor, Lauren E; Campbell, Wayne W

    2014-01-01

    High-protein (>30% of energy from protein or >1.2 g/kg/day) and moderately high-protein (22% to 29% of energy from protein or 1.0 to 1.2 g/kg/day) diets are popular for weight loss, but the effect of dietary protein on bone during weight loss is not well understood. Protein may help preserve bone mass during weight loss by stimulating insulin-like growth factor 1, a potent bone anabolism stimulator, and increasing intestinal calcium absorption. Protein-induced acidity is considered to have minimal effect on bone resorption in adults with normal kidney function. Both the quantity and predominant source of protein influence changes in bone with diet-induced weight loss. Higher-protein, high-dairy diets may help attenuate bone loss during weight loss.

  17. The osteogenic effects of swimming, jumping, and vibration on the protection of bone quality from disuse bone loss.

    PubMed

    Falcai, M J; Zamarioli, A; Okubo, R; de Paula, F J A; Volpon, J B

    2015-06-01

    We assessed and compared the effects of swimming, jumping, and vibration therapies on the prevention of bone loss because of unloading. Eighty Wistar rats were randomly divided into eight groups: S, permanent hind limb-suspended rats; CON, control rats; S + Swim, unloading interrupted by swimming exercise; S + C(Swim), suspension interrupted by regular weight-bearing with the same duration as in the S + Swim protocol; S + Jump, unloading interrupted by jumping exercise; S + C(Jump), suspension interrupted for regular weight-bearing as in the S + Jump group; S + Vibr, unloading interrupted by vibration; and S + C(Vibr), suspension with interruptions for regular weight-bearing with the same protocol as that used for the S + Vibr rats. At the end of the experiment, the bone mineral density, bone strength, histomorphometric parameters, and serum levels of the bone markers were analyzed. The hind limb-suspended rats exhibited bone quality loss. In contrast, the trained rats showed a significant increase in bone mass, bone strength, bone formation, and serum levels of bone markers compared with the respective controls. Although we did not find a significant difference among the three physical exercises, the osteogenic effect of vibration was slightly lower than that of swimming and jumping. Thus, all physical exercises were efficient in preventing bone loss because of unloading and preserving bone quality.

  18. A comparative study of bone shortening and bone loss with use of saw blades versus burr in hallux valgus surgery.

    PubMed

    Shahid, Muhammad Saleem; Lee, Paul; Evans, Sam; Thomas, Rhys

    2012-09-01

    The aim of this study was to assess bone loss and thickness of the cut with the use of a burr in percutaneous hallux valgus surgery. Twelve blocks of saw bone were used. Cuts of same depth were made in each block with two different saw blades and a burr. Each block was assessed for bone loss and thickness of the cut. There was statistically significant (p<0.05) increased bone loss and thickness of the cuts with the use of a burr as compared to use of two different saw blades. The use of a burr resulted in threefold increased loss of bone material and fourfold increase in the thickness of the cut as compare to use of two different saw blades. The metatarsal shortening is a risk factor in percutaneous hallux valgus surgery with the use of a burr. Copyright © 2011 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  19. Bone loss of vertebral bodies at the operative segment after cervical arthroplasty: a potential complication?

    PubMed

    Heo, Dong Hwa; Lee, Dong Chan; Oh, Jong Yang; Park, Choon Keun

    2017-02-01

    OBJECTIVE Bony overgrowth and spontaneous fusion are complications of cervical arthroplasty. In contrast, bone loss or bone remodeling of vertebral bodies at the operation segment after cervical arthroplasty has also been observed. The purpose of this study is to investigate a potential complication-bone loss of the anterior portion of the vertebral bodies at the surgically treated segment after cervical total disc replacement (TDR)-and discuss the clinical significance. METHODS All enrolled patients underwent follow-up for more than 24 months after cervical arthroplasty using the Baguera C disc. Clinical evaluations included recording demographic data and measuring the visual analog scale and Neck Disability Index scores. Radiographic evaluations included measurements of the functional spinal unit's range of motion and changes such as bone loss and bone remodeling. The grading of the bone loss of the operative segment was classified as follows: Grade 1, disappearance of the anterior osteophyte or small minor bone loss; Grade 2, bone loss of the anterior portion of the vertebral bodies at the operation segment without exposure of the artificial disc; or Grade 3, significant bone loss with exposure of the anterior portion of the artificial disc. RESULTS Forty-eight patients were enrolled in this study. Among them, bone loss developed in 29 patients (Grade 1 in 15 patients, Grade 2 in 6 patients, and Grade 3 in 8 patients). Grade 3 bone loss was significantly associated with postoperative neck pain (p < 0.05). Bone loss was related to the motion preservation effect of the operative segment after cervical arthroplasty in contrast to heterotopic ossification. CONCLUSIONS Bone loss may be a potential complication of cervical TDR and affect early postoperative neck pain. However, it did not affect mid- to long-term clinical outcomes or prosthetic failure at the last follow-up. Also, this phenomenon may result in the motion preservation effect in the operative segment

  20. Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

    PubMed Central

    Amarasekara, Dulshara Sachini; Yu, Jiyeon; Rho, Jaerang

    2015-01-01

    Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases. PMID:26065006

  1. Bone loss and avascular necrosis of bone after hematopoietic cell transplantation.

    PubMed

    McClune, Brian; Majhail, Navneet S; Flowers, Mary E D

    2012-01-01

    Advances in transplantation technology and supportive care measures have resulted in significant decrease in early mortality resulting in continued growth in the number of long-term hematopoietic cell transplantation (HCT) survivors. The intensity of chemotherapy and total body irradiation regimen used pretransplantation to eradicate the primary disease can lead to organ toxicities, including significant bone complications after HCT. Bone loss is frequent in HCT recipients and results from impaired bone mineralization through disturbances of calcium and vitamin D homeostasis, osteoblast and osteoclast dysfunction, and deficiencies in growth or gonadal hormone secretion. Exposure to glucocorticoids and calcineurin inhibitors for prevention and treatment of graft-versus-host disease (GVHD) represents one of the major causes for the increased risk of osteoporosis and avascular necrosis of bone (AVN) in recipients of allogeneic HCT. In this article we review the incidence, pathogenesis, and risk factors for osteoporosis and AVN after allogeneic HCT and discuss general guidelines for their treatment and monitoring based on the limited available reports. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Inefficacy of the cementation of femoral head collapse in glucocorticoid-induced osteonecrosis

    PubMed Central

    Gangji, Valérie; Rooze, Marcel; De Maertelaer, Viviane

    2008-01-01

    The objective of this paper was to assess the efficacy of cementation of the femoral head in stage III glucocorticoid-induced osteonecrosis. Ten hips (nine patients) were treated by the injection of low-viscosity cement to reduce the collapse. The follow up included clinical and radiological assessments preoperatively and at 3, 6 and 12 months after surgery. The visual analogue scale (VAS) score, the Lequesne index and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score did not show any significant improvement. Eight of the ten hips showed a worsening of the collapse and required total hip arthroplasty during follow up. The mean time before total hip replacement was 8.6 ± 7 months. The other two hips did not show any relapse of collapse nor functional worsening at the maximum follow up of 5 years. Our results suggest that cement injection is not a treatment that should be proposed for glucocorticoid-induced osteonecrosis. PMID:18297285

  3. Periodontal Disease: Linking the Primary Inflammation to Bone Loss

    PubMed Central

    Di Benedetto, Adriana; Gigante, Isabella; Colucci, Silvia; Grano, Maria

    2013-01-01

    Periodontal disease (PD), or periodontitis, is defined as a bacterially induced disease of the tooth-supporting (periodontal) tissues. It is characterized by inflammation and bone loss; therefore understanding how they are linked would help to address the most efficacious therapeutic approach. Bacterial infection is the primary etiology but is not sufficient to induce the disease initiation or progression. Indeed, bacteria-derived factors stimulate a local inflammatory reaction and activation of the innate immune system. The innate response involves the recognition of microbial components by host cells, and this event is mediated by toll-like receptors (TLRs) expressed by resident cells and leukocytes. Activation of these cells leads to the release of proinflammatory cytokines and recruitment of phagocytes and lymphocytes. Activation of T and B cells initiates the adaptive immunity with Th1 Th2 Th17 Treg response and antibodies production respectively. In this inflammatory scenario, cytokines involved in bone regulation and maintenance have considerable relevance because tissue destruction is believed to be the consequence of host inflammatory response to the bacterial challenge. In the present review, we summarize host factors including cell populations, cytokines, and mechanisms involved in the destruction of the supporting tissues of the tooth and discuss treatment perspectives based on this knowledge. PMID:23762091

  4. Alfacalcidol versus plain vitamin D in inflammation induced bone loss.

    PubMed

    Scharla, Stephan H; Schacht, Erich; Lempert, Uta G

    2005-09-01

    Inflammatory diseases lead to systemic osteoporosis. Causal factors include increased circulating concentrations of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), glucocorticoid medication, and reduced physical activity. In addition, disturbances of vitamin D metabolism play an important role for the development of inflammation induced osteoporosis. Therefore, D-hormone analogs offer an important treatment option. 1,25-dihydroxyvitamin D (D-hormone) prevented bone loss in the rat model of inflammation mediated osteopenia and in an arthritis model. One explanation is that animals and humans with inflammatory diseases exhibit markedly reduced circulating concentrations of D-hormone, partly the result of inhibition of renal 1-alpha-hydroxylase by TNF-alpha. In addition, the number of vitamin D receptors is reduced by glucocorticoids. Moreover, D-hormone has pleiotropic effects not only on calcium homoeostasis but also on muscle (improving power), the nervous system, and the immune system. D-hormone inhibits the release of cytokines (IL-1, IL-6, TNF-alpha) from macrophages and stimulates osteoprotegerin secretion in vitro and improves arthritis in animal models. This article reviews the interaction between inflammatory disease and vitamin D metabolism, summarizes the rationale for the therapeutic use of alfacalcidol, and provides recent data from controlled clinical trials comparing the effect of alfacalcidol versus plain vitamin D in secondary osteoporosis. Alfacalcidol, but not plain vitamin D, has pleiotropic effects improving bone and muscle metabolism and clinical symptoms in patients with rheumatoid arthritis.

  5. 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

  6. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

    PubMed

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael J; Puzas, Edward J; Boyce, Brendan F; Mooney, Robert A; Xing, Lianping

    2015-04-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children.

  7. Extent and location of bone loss at dental implants in patients with peri-implantitis.

    PubMed

    Serino, Giovanni; Turri, Alberto

    2011-01-11

    Peri-implantitis is an infectious disease, which leads to loss of supporting bone around dental implants. To evaluate the extent and location of bone loss, 43 patients with peri-implantitis were examined. The bone loss was clinically measured at the time of dental surgery. Data revealed that 25% of subjects had bone loss associated with all their implants although the majority of the subjects had fewer than 50% of their implants affected by bone loss. A total number of 264 implants were examined and 131 of those had peri-implantitis associated bone loss. The pattern of bone loss at implants varied between and within subjects and location in the jaws. The highest proportion of implants with peri-implantitis was found in the upper jaw and within this group, at implants located in the incisor area of the upper jaw; the lowest was the canine area of the lower jaw. The highest proportion of implants that lost ≥ 2/3 of their bone support was found in the incisor area of the maxilla. We concluded that in the presence of peri-implant inflammation, bone quantity and characteristics may influence the progression of peri-implantitis bone loss at dental implants. We hypothesize that the ability of the bone to withstand occlusal forces will be altered as consequence of the loss of bone at the neck of the implants. To achieve an understanding of the local degradation of bone due to peri-implantitis, we need to analyze the microstructure of the bone as well the cellular biology of the peri-implant inflammation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. THE EFFECT OF GLUCOCORTICOIDS ON BONE AND MUSCLE

    PubMed Central

    Klein, Gordon L

    2015-01-01

    This article examines the current knowledge of the effects of both exogenous and endogenous glucocorticoids on bone and muscle. It demonstrates the similarity of effects of supraphysiologic loads of glucocorticoids regardless of whether they enter the body in the form of medication or are manufactured by the body in response to stimuli such as inflammation. The effects of endogenous glucocorticoids and the systemic inflammatory response resulting from pediatric burn injury are compared and the difficulty in sorting out which of the two factors is responsible for the ultimate effects on bone and muscle is pointed out. The focus then switches to the body’s response to the influence of both glucocorticoids and inflammatory cytokines and evidence supporting a common pathway of response to oxidative damage caused by both is discussed. Current recommended medical management of glucocorticoid-induced bone and muscle loss is discussed and the failure to reconcile current management with known mechanisms is highlighted. PMID:26557727

  9. Effect of anti-osteoporotic agents on the prevention of bone loss in unloaded bone.

    PubMed

    Siu, Wing Sum; Ko, Chun Hay; Hung, Leung Kim; Lau, Ching Po; Lau, Clara Bik San; Fung, Kwok Pui; Leung, Ping Chung

    2013-10-01

    Pharmaceutical countermeasures to treat disuse osteoporosis are rarely studied. Pharmaceutical studies for the treatment and prevention of osteoporosis depend on the ovariectomized rat model, which is a suitable model for the disease in women. Disuse osteoporosis affects men and women, but there is lack of awareness and relevant pharmaceutical studies for this condition. The objectives of this study were to verify the validity of an unusual tail-suspension rat model in the induction of disuse osteoporosis and subsequent pharmaceutical treatments. This model was created by unloading the hind limbs of the rats in order to create a state of weightlessness in their hindlimb bones. Validation of the model was performed with non-suspended rats. This study included five groups of suspended rats fed with different agents, such as distilled water (control), high-, medium- and low-dose raloxifene and a bisphosphonate (alendronate). The experiment lasted for 28 days. Comparisons were made between the suspended control and treatment groups. Ovariectomized and sham‑operated rats were also included as a reference for bone changes during osteoporosis. Changes in bone mineral density (BMD) at the distal femur and proximal tibia, microarchitecture at the distal femur and biomechanical strength at the diaphyseal femur were studied. Reduction of BMD and deterioration of trabeculae were similar between the suspended control and ovariectomized rats. Loss of BMD induced by tail suspension was reduced most effectively by medium-dose raloxifene. Deterioration of trabecular microarchitecture was also prevented by raloxifene. The tail-suspension rat model is suitable for the study of disuse osteoporosis under the effects of various therapeutic agents. The preventive effects of raloxifene against bone loss under disuse conditions have been demonstrated using this model.

  10. Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

    PubMed Central

    Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified

  11. Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein.

    PubMed

    Foster, B L; Ao, M; Willoughby, C; Soenjaya, Y; Holm, E; Lukashova, L; Tran, A B; Wimer, H F; Zerfas, P M; Nociti, F H; Kantovitz, K R; Quan, B D; Sone, E D; Goldberg, H A; Somerman, M J

    2015-09-01

    Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp(-/-) mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp(-/-) mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp(-/-) mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp(-/-) mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in

  12. Depression induces bone loss through stimulation of the sympathetic nervous system

    PubMed Central

    Yirmiya, Raz; Goshen, Inbal; Bajayo, Alon; Kreisel, Tirzah; Feldman, Sharon; Tam, Joseph; Trembovler, Victoria; Csernus, Valér; Shohami, Esther; Bab, Itai

    2006-01-01

    Major depression is associated with low bone mass and increased incidence of osteoporotic fractures. However, causality between depression and bone loss has not been established. Here, we show that mice subjected to chronic mild stress (CMS), an established model of depression in rodents, display behavioral depression accompanied by impaired bone mass and structure, as portrayed by decreases in trabecular bone volume density, trabecular number, and trabecular connectivity density assessed in the distal femoral metaphysis and L3 vertebral body. Bone remodeling analysis revealed that the CMS-induced skeletal deficiency is accompanied by restrained bone formation resulting from reduced osteoblast number. Antidepressant therapy, which prevents the behavioral responses to CMS, completely inhibits the decrease in bone formation and markedly attenuates the CMS-induced bone loss. The depression-triggered bone loss is associated with a substantial increase in bone norepinephrine levels and can be blocked by the β-adrenergic antagonist propranolol, suggesting that the sympathetic nervous system mediates the skeletal effects of stress-induced depression. These results define a linkage among depression, excessive adrenergic activity, and reduced bone formation, thus demonstrating an interaction among behavioral responses, the brain, and the skeleton, which leads to impaired bone structure. Together with the common occurrence of depression and bone loss in the aging population, the present data implicate depression as a potential major risk factor for osteoporosis and the associated increase in fracture incidence. PMID:17075068

  13. Radiographic analyses of "advanced" marginal bone loss around Brånemark dental implants.

    PubMed

    Pikner, Solweig Sundén; Gröndahl, Kerstin

    2009-06-01

    Dental implant failures have a multifactorial background; dependency within patient/jaw exists. Failures caused by bone loss are rare. Lately, advanced bone loss around implants has been discussed. Our aim was to study advanced bone level changes (>or=2 mm) regarding "clustering effect," prediction, and dependency. Further, we also aimed to study if the number of radiographs/radiographic examinations could be reduced. Six hundred and forty patients (3,462 Brånemark implants) with radiographic follow-ups >or=5 years were included, whereas patients with overdentures and augmentation procedures were excluded. Progression rate for implants with advanced bone loss was largest during the first year; thereafter, slow. A cluster effect was found with more advanced bone loss in few patients. Position was important for lower jaw implants with larger bone loss for implants placed close to midline. Age, jaw type, and implant placement were identified as predictors. The longer the follow-ups, the more bone loss around a randomly selected and examined implant, and the more implants per patient, the higher the risk for bone loss >or=2 mm around any other implant. Still, it seems safe to exclude radiographic follow-ups during the first 5 years. Dependency within the patient was found, hence the "one-implant-per-patient technique" can be applied. The number of intraoral radiographs per examination and, more importantly, radiographic examinations can be reduced without jeopardizing good clinical management, a statement valid even for Brånemark implants with advanced bone loss.

  14. Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

    PubMed

    Alves, C Henrique; Farrell, Eric; Vis, Marijn; Colin, Edgar M; Lubberts, Erik

    2016-08-01

    Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.

  15. Loss of endogenous bone morphogenetic protein-6 aggravates renal fibrosis.

    PubMed

    Dendooven, Amélie; van Oostrom, Olivia; van der Giezen, Dionne M; Leeuwis, Jan Willem; Snijckers, Cristel; Joles, Jaap A; Robertson, Elizabeth J; Verhaar, Marianne C; Nguyen, Tri Q; Goldschmeding, Roel

    2011-03-01

    Bone morphogenetic protein-6 (BMP-6) suppresses inflammatory genes in renal proximal tubular cells and regulates iron metabolism by inducing hepcidin. In diabetic patients, an increase of myofibroblast progenitor cells (MFPCs), also known as fibrocytes, was found to be associated with decreased BMP-6 expression. We hypothesized that loss of endogenous BMP-6 would aggravate renal injury and fibrosis. Wild type (WT) and BMP-6 null mice underwent unilateral ureteral obstruction. In WT mice, ureteral obstruction down-regulated BMP-6. Obstructed kidneys of BMP-6 null mice showed more casts (1.5-fold), epithelial necrosis (1.4-fold), and brush border loss (1.3-fold). This was associated with more inflammation (1.8-fold more CD45(+) cells) and more pronounced overexpression of profibrotic genes for αSMA (2.0-fold), collagen I (6.8-fold), fibronectin (4.3-fold), CTGF (1.8-fold), and PAI-1 (3.8-fold), despite similar BMP-7 expression. Also, 1.3-fold more MFPCs were obtained from BMP-6 null than from WT mononuclear cell cultures, but in vivo only very few MFPCs were observed in obstructed kidneys, irrespective of BMP-6 genotype. The obstructed kidneys of BMP-6 null mice showed 2.2-fold more iron deposition, in association with 3.3-fold higher expression of the oxidative stress marker HO-1. Thus, ureteral obstruction leads to down-regulation of BMP-6 expression, and BMP-6 deficiency aggravates tubulointerstitial damage and fibrosis independent of BMP-7. This process appears to involve loss of both direct anti-inflammatory and antifibrotic action and indirect suppressive effects on renal iron deposition, oxidative stress, and MFPCs.

  16. Loss of Endogenous Bone Morphogenetic Protein-6 Aggravates Renal Fibrosis

    PubMed Central

    Dendooven, Amélie; van Oostrom, Olivia; van der Giezen, Dionne M.; Willem Leeuwis, Jan; Snijckers, Cristel; Joles, Jaap A.; Robertson, Elizabeth J.; Verhaar, Marianne C.; Nguyen, Tri Q.; Goldschmeding, Roel

    2011-01-01

    Bone morphogenetic protein-6 (BMP-6) suppresses inflammatory genes in renal proximal tubular cells and regulates iron metabolism by inducing hepcidin. In diabetic patients, an increase of myofibroblast progenitor cells (MFPCs), also known as fibrocytes, was found to be associated with decreased BMP-6 expression. We hypothesized that loss of endogenous BMP-6 would aggravate renal injury and fibrosis. Wild type (WT) and BMP-6 null mice underwent unilateral ureteral obstruction. In WT mice, ureteral obstruction down-regulated BMP-6. Obstructed kidneys of BMP-6 null mice showed more casts (1.5-fold), epithelial necrosis (1.4-fold), and brush border loss (1.3-fold). This was associated with more inflammation (1.8-fold more CD45+ cells) and more pronounced overexpression of profibrotic genes for αSMA (2.0-fold), collagen I (6.8-fold), fibronectin (4.3-fold), CTGF (1.8-fold), and PAI-1 (3.8-fold), despite similar BMP-7 expression. Also, 1.3-fold more MFPCs were obtained from BMP-6 null than from WT mononuclear cell cultures, but in vivo only very few MFPCs were observed in obstructed kidneys, irrespective of BMP-6 genotype. The obstructed kidneys of BMP-6 null mice showed 2.2-fold more iron deposition, in association with 3.3-fold higher expression of the oxidative stress marker HO-1. Thus, ureteral obstruction leads to down-regulation of BMP-6 expression, and BMP-6 deficiency aggravates tubulointerstitial damage and fibrosis independent of BMP-7. This process appears to involve loss of both direct anti-inflammatory and antifibrotic action and indirect suppressive effects on renal iron deposition, oxidative stress, and MFPCs. PMID:21356359

  17. Quantitative assessment and characterization of glenoid bone loss in a spectrum of patients with glenohumeral osteoarthritis.

    PubMed

    Lombardo, D J; Khan, J; Prey, B; Zhang, L; Petersen-Fitts, G R; Sabesan, V J

    2016-12-01

    Eccentric posterior bone loss and associated glenoid retroversion represent challenges to glenoid placement during total shoulder arthroplasty. This bone loss can lead to poor stability and perforation of the glenoid during arthroplasty. The purpose of this study was to evaluate the morphology of glenoid bone loss for a spectrum of osteoarthritis patients using 3D computed tomography imaging and simulation software. This study included 29 patients with glenohumeral osteoarthritis treated with shoulder arthroplasty. Three-dimensional reconstruction of preoperative CT images was performed. Glenoid bone loss was measured at ten, vertically equidistant axial planes along the glenoid surface at four distinct anterior-posterior points on each plane. The images were fitted with modeled pegged glenoid implants to predict glenoid perforation. The 3D maps demonstrated greatest average bone loss posteriorly in the AP plane at the central axis of the glenoid in the SI plane. The average amount of bone loss was 3.85 mm. Walch A2 and B1 shoulders showed more central bone loss, while Walch B2 shoulders displayed more posterior and inferior bone loss. Patients with predicted peg perforation displayed significantly greater bone loss than those without predicted peg perforation (p = 0.037). Peg perforation was most common in Walch B2 shoulders occurring in the posterior direction involving the central and posterior-inferior peg. These data demonstrate an anatomic pattern of glenoid bone loss for different classes of glenohumeral arthritis. These findings can be used to develop various models of glenoid bone loss to guide surgeons, predict failures, and develop better glenoid implants. This study has been approved by the Cleveland Clinic IRB: Number 6235.

  18. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2013-10-01

    CONTRACTING ORGANIZATION: University of California, Davis Davis, CA 95818 REPORT DATE: October 2013 TYPE OF REPORT: Annual PREPARED FOR...Nerve Function in Age-Related Bone Loss and Changes in 5a. CONTRACT NUMBER Bone Adaptation 5b. GRANT NUMBER W81XWH- 12-1-0377 5c...metabolism, and neuropeptide concentrations in bone compared to vehicle-injected mice (months 1-12): 1a. Institutional approval of animal use protocols

  19. A crucial role for thiol antioxidants in estrogen-deficiency bone loss

    PubMed Central

    Lean, Jenny M.; Davies, Julie T.; Fuller, Karen; Jagger, Christopher J.; Kirstein, Barrie; Partington, Geoffrey A.; Urry, Zoë L.; Chambers, Timothy J.

    2003-01-01

    The mechanisms through which estrogen prevents bone loss are uncertain. Elsewhere, estrogen exerts beneficial actions by suppression of reactive oxygen species (ROS). ROS stimulate osteoclasts, the cells that resorb bone. Thus, estrogen might prevent bone loss by enhancing oxidant defenses in bone. We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-β estradiol. Moreover, administration of N-acetyl cysteine (NAC) or ascorbate, antioxidants that increase tissue glutathione levels, abolished ovariectomy-induced bone loss, while L-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis, caused substantial bone loss. The 17-β estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro. Furthermore, in vitro NAC prevented osteoclast formation and NF-κB activation. BSO and hydrogen peroxide did the opposite. Expression of TNF-α, a target for NF-κB and a cytokine strongly implicated in estrogen-deficiency bone loss, was suppressed in osteoclasts by 17-β estradiol and NAC. These observations strongly suggest that estrogen deficiency causes bone loss by lowering thiol antioxidants in osteoclasts. This directly sensitizes osteoclasts to osteoclastogenic signals and entrains ROS-enhanced expression of cytokines that promote osteoclastic bone resorption. PMID:12975476

  20. Periprosthetic femoral bone loss in total hip arthroplasty: systematic analysis of the effect of stem design.

    PubMed

    Knutsen, Ashleen R; Lau, Nicole; Longjohn, Donald B; Ebramzadeh, Edward; Sangiorgio, Sophia N

    2017-02-21

    Periprosthetic bone loss may lead to major complications in total hip arthroplasty (THA), including loosening, migration, and even fracture. This study analysed the influence of femoral implant designs on periprosthetic bone mineral density (BMD) after THA. The results of all previous published studies reporting periprosthetic femoral BMD following THA were compiled. Using these results, we compared percent changes in bone loss as a function of: femoral stem fixation, material, and geometry. The greatest bone loss was in the calcar region (Gruen Zone 7). Overall, cemented stems had more bone loss distally than noncemented stems, while noncemented stems had more proximal bone loss than cemented stems. Within noncemented stems, cobalt-chromium (CoCr) stems had nearly double the proximal bone loss compared to titanium (Ti) alloy stems. Finally, within noncemented titanium alloy group, straight stems had less bone loss than anatomical, tapered, and press-fit designs. The findings from the present study quantified percent changes in periprosthetic BMD as a function of fixation method, alloy, and stem design. While no one stem type was identified as ideal, we now have a clearer understanding of the influence of stem design on load transfer to the surrounding bone.

  1. The correlation between postmenopausal osteoporosis and inflammatory periodontitis regarding bone loss in experimental models.

    PubMed

    Kobayashi, Megumi; Matsumoto, Chiho; Hirata, Michiko; Tominari, Tsukasa; Inada, Masaki; Miyaura, Chisato

    2012-01-01

    We have invented a mouse model of periodontitis associated with alveolar bone loss induced by lipopolysaccharide. Ovariectomized (OVX) animals are widely used as a model for osteoporosis due to estrogen deficiency. To define the relationship between periodontitis and osteoporosis, we examined the influence of estrogen deficiency on the mouse alveolar bone mass. In OVX mice, bone loss was detected not only in the femur, but also in the alveolar bone, indicating that estrogen deficiency could induce resorption in alveolar bone. In experiments using a combination of osteoporosis and periodontitis models, OVX significantly enhanced the alveolar bone loss in the model of periodontitis. Therefore, postmenopausal osteoporosis may enhance the risk of periodontitis associated with inflammatory alveolar bone resorption.

  2. The combined effects of X-ray radiation and hindlimb suspension on bone loss.

    PubMed

    Xu, Dan; Zhao, Xin; Li, Yi; Ji, Yinli; Zhang, Jiangyan; Wang, Jufang; Xie, Xiaodong; Zhou, Guangming

    2014-07-01

    Outer space is a complex environment with various phenomena that negatively affect bone metabolism, including microgravity and highly energized ionizing radiation. In the present study, we used four groups of male Wistar rats treated with or without four-week hindlimb suspension after 4 Gy of X-rays to test whether there is a combined effect for hindlimb suspension and X-ray radiation. We tested trabecular parameters and some cytokines of the bone as leading indicators of bone metabolism. The results showed that hindlimb suspension and X-ray radiation could cause a significant increase in bone loss. Hindlimb suspension caused a 56.6% bone loss (P = 0.036), while X-ray radiation caused a 30.7% (P = 0.041) bone loss when compared with the control group. The combined factors of hindlimb suspension and X-rays exerted a combined effect on bone mass, with a reduction of 64.8% (P = 0.003).

  3. Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

    PubMed

    Iwaniec, U T; Philbrick, K A; Wong, C P; Gordon, J L; Kahler-Quesada, A M; Olson, D A; Branscum, A J; Sargent, J L; DeMambro, V E; Rosen, C J; Turner, R T

    2016-10-01

    Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies

  4. Glucocorticoids suppress bone formation via the osteoclast.

    PubMed

    Kim, Hyun-Ju; Zhao, Haibo; Kitaura, Hideki; Bhattacharyya, Sandip; Brewer, Judson A; Muglia, Louis J; Ross, F Patrick; Teitelbaum, Steven L

    2006-08-01

    The pathogenesis of glucocorticoid-induced (GC-induced) bone loss is unclear. For example, osteoblast apoptosis is enhanced by GCs in vivo, but they stimulate bone formation in vitro. This conundrum suggests that an intermediary cell transmits a component of the bone-suppressive effects of GCs to osteoblasts in the intact animal. Bone remodeling is characterized by tethering of the activities of osteoclasts and osteoblasts. Hence, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To define the direct impact of GCs on bone-resorptive cells, we compared the effects of dexamethasone (DEX) on WT osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells (GRoc-/- mice). While the steroid prolonged longevity of osteoclasts, their bone-degrading capacity was suppressed. The inhibitory effect of DEX on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. DEX specifically arrested M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances GRoc-/- mice were spared the impact of DEX on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of DEX, GRoc-/- mice are protected from the steroid's inhibition of bone formation.

  5. Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients.

    PubMed

    Yee, Andrew J; Raje, Noopur S

    2012-01-01

    Bone loss is a common side effect of cancer treatments, especially antihormonal treatments used in the treatment of breast and prostate cancer. Denosumab is a monoclonal antibody given subcutaneously that inhibits osteoclast activity by targeting the RANK ligand. It is effective in settings ranging from preventing skeletal-related complications in cancer patients with metastatic disease to increasing bone mineral density in patients with osteoporosis. In cancer patients with early stage disease, denosumab can attenuate bone loss from antihormonal treatments, and in prostate cancer, may reduce disease progression. Here, we will discuss the important role denosumab may play in the management of bone loss in patients with cancer.

  6. AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure.

    PubMed

    Bolam, K A; Galvão, D A; Spry, N; Newton, R U; Taaffe, D R

    2012-12-01

    Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

  7. Alcohol-induced bone loss is blocked in p47phox -/- mice lacking functional nadph oxidases

    USDA-ARS?s Scientific Manuscript database

    Chronic ethanol (EtOH) consumption produces bone loss. Previous data suggest a role for NADPH oxidase enzymes (Nox) since the pan-Nox inhibitor diphenylene iodonium (DPI) blocks EtOH-induced bone loss in rats. The current study utilized mice in which Nox enzymes 1,2,3 and 5 are inactivated as a resu...

  8. Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

    USDA-ARS?s Scientific Manuscript database

    Despite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7(MK-7) on the rate of bone loss in o...

  9. S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

    NASA Technical Reports Server (NTRS)

    Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

    1993-01-01

    The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S

  10. Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model.

    PubMed

    Courbon, Guillaume; Cleret, Damien; Linossier, Marie-Thérèse; Vico, Laurence; Marotte, Hubert

    2017-06-01

    Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R(2)  = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength.

    PubMed

    McGee-Lawrence, Meghan E; Stoll, Danielle M; Mantila, Emily R; Fahrner, Bryna K; Carey, Hannah V; Donahue, Seth W

    2011-04-15

    Lack of activity causes bone loss In most animals. Hibernating bears have physiological processes to prevent cortical and trabecular bone loss associated with reduced physical activity, but different mechanisms of torpor among hibernating species may lead to differences in skeletal responses to hibernation. There are conflicting reports regarding whether small mammals experience bone loss during hibernation. To investigate this phenomenon, we measured cortical and trabecular bone properties in physically active and hibernating juvenile and adult 13-lined ground squirrels (Ictidomys tridecemlineatus, previous genus name Spermophilus). Cortical bone geometry, strength and mineral content were similar in hibernating compared with active squirrels, suggesting that hibernation did not cause macrostructural cortical bone loss. Osteocyte lacunar size increased (linear regression, P=0.001) over the course of hibernation in juvenile squirrels, which may indicate an osteocytic role in mineral homeostasis during hibernation. Osteocyte lacunar density and porosity were greater (+44 and +59%, respectively; P<0.0001) in hibernating compared with active squirrels, which may reflect a decrease in osteoblastic activity (per cell) during hibernation. Trabecular bone volume fraction in the proximal tibia was decreased (-20%; P=0.028) in hibernating compared with physically active adult squirrels, but was not different between hibernating and active juvenile squirrels. Taken together, these data suggest that 13-lined ground squirrels may be unable to prevent microstructural losses of cortical and trabecular bone during hibernation, but importantly may possess a biological mechanism to preserve cortical bone macrostructure and strength during hibernation, thus preventing an increased risk of bone fracture during remobilization in the spring.

  12. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength

    PubMed Central

    McGee-Lawrence, Meghan E.; Stoll, Danielle M.; Mantila, Emily R.; Fahrner, Bryna K.; Carey, Hannah V.; Donahue, Seth W.

    2011-01-01

    SUMMARY Lack of activity causes bone loss In most animals. Hibernating bears have physiological processes to prevent cortical and trabecular bone loss associated with reduced physical activity, but different mechanisms of torpor among hibernating species may lead to differences in skeletal responses to hibernation. There are conflicting reports regarding whether small mammals experience bone loss during hibernation. To investigate this phenomenon, we measured cortical and trabecular bone properties in physically active and hibernating juvenile and adult 13-lined ground squirrels (Ictidomys tridecemlineatus, previous genus name Spermophilus). Cortical bone geometry, strength and mineral content were similar in hibernating compared with active squirrels, suggesting that hibernation did not cause macrostructural cortical bone loss. Osteocyte lacunar size increased (linear regression, P=0.001) over the course of hibernation in juvenile squirrels, which may indicate an osteocytic role in mineral homeostasis during hibernation. Osteocyte lacunar density and porosity were greater (+44 and +59%, respectively; P<0.0001) in hibernating compared with active squirrels, which may reflect a decrease in osteoblastic activity (per cell) during hibernation. Trabecular bone volume fraction in the proximal tibia was decreased (–20%; P=0.028) in hibernating compared with physically active adult squirrels, but was not different between hibernating and active juvenile squirrels. Taken together, these data suggest that 13-lined ground squirrels may be unable to prevent microstructural losses of cortical and trabecular bone during hibernation, but importantly may possess a biological mechanism to preserve cortical bone macrostructure and strength during hibernation, thus preventing an increased risk of bone fracture during remobilization in the spring. PMID:21430199

  13. Multiple projection DEXA scanner for precision bone and muscle loss measurements and analysis during prolonged spaceflight

    NASA Astrophysics Data System (ADS)

    Charles, H. K.; Beck, T. J.; Feldmesser, H. S.; Magee, T. C.; Spisz, T. S.; Pisacane, V. L.

    2000-01-01

    Bone structural information derived from DEXA data is shown to be relevant in explaining BMD loss versus strength-related observations in both aging populations and individuals exposed to microgravity for prolonged periods. Commercial DEXA instruments are limited (and not optimized) to make these critical structural measurements. Progress on the development of a multiple projection DEXA scanner system for making precision bone and muscle loss measurements and their resultant implications on bone strength and fracture risk is described. .

  14. Emerging and future therapies for the treatment of bone loss associated with chronic inflammation.

    PubMed

    Haynes, D R

    2006-12-01

    Currently there are many emerging therapies for the treatment of chronic osteoporosis. This is a major problem world wide and particularly of concern in post-menopausal women. This has offered a large expanding market for the pharmaceutical industry and consequently large amounts of money and resources have been used to develop new treatments. These new and emerging treatments have largely targeted the mechanisms of bone loss associated with post-menopausal osteoporosis. However, there are many other important bone loss disorders and it is possible that some of these new therapies may be useful in treating bone loss associated with other diseases. This review identifies several of these pharmacologic treatments of osteoporosis and discusses the possibility of using these drugs for the treatment of bone loss associated with inflammatory diseases. In addition, other approaches, such as regulating apoptosis and intracellular signalling, may be developed in the future and may better target bone loss associated with chronic inflammation are identified.

  15. Identification of new biomarker candidates for glucocorticoid induced insulin resistance using literature mining

    PubMed Central

    2013-01-01

    Background Glucocorticoids are potent anti-inflammatory agents used for the treatment of diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis. Unfortunately, usage is limited because of metabolic side-effects, e.g. insulin resistance, glucose intolerance and diabetes. To gain more insight into the mechanisms behind glucocorticoid induced insulin resistance, it is important to understand which genes play a role in the development of insulin resistance and which genes are affected by glucocorticoids. Medline abstracts contain many studies about insulin resistance and the molecular effects of glucocorticoids and thus are a good resource to study these effects. Results We developed CoPubGene a method to automatically identify gene-disease associations in Medline abstracts. We used this method to create a literature network of genes related to insulin resistance and to evaluate the importance of the genes in this network for glucocorticoid induced metabolic side effects and anti-inflammatory processes. With this approach we found several genes that already are considered markers of GC induced IR, such as phosphoenolpyruvate carboxykinase (PCK) and glucose-6-phosphatase, catalytic subunit (G6PC). In addition, we found genes involved in steroid synthesis that have not yet been recognized as mediators of GC induced IR. Conclusions With this approach we are able to construct a robust informative literature network of insulin resistance related genes that gave new insights to better understand the mechanisms behind GC induced IR. The method has been set up in a generic way so it can be applied to a wide variety of disease networks. PMID:23379763

  16. Cost-effectiveness of multifaceted evidence implementation programs for the prevention of glucocorticoid-induced osteoporosis

    PubMed Central

    Saag, K. G.; Curtis, J. R.; Kilgore, M. L.; Pisu, M.

    2013-01-01

    Summary Using a computer simulation model, we determined that an intervention aimed at improving the management of glucocorticoid-induced osteoporosis is likely to be cost-effective to third-party health insurers only if it focuses on individuals with very high fracture risk and the proportion of prescriptions for generic bisphosphonates increases substantially. Introduction The purpose of this study is to determine whether an evidence implementation program (intervention) focused on increasing appropriate management of glucocorticoid-induced osteoporosis (GIOP) might be cost-effective compared with current practice (no intervention) from the perspective of a third-party health insurer. Methods We developed a Markov microsimulation model to determine the cost-effectiveness of the intervention. The hypothetical patient cohort was of current chronic glucocorticoid users 50–65 years old and 70% female. Model parameters were derived from published literature, and sensitivity analyses were performed. Results The intervention resulted in incremental cost-effectiveness ratios (ICERs) of $298,000 per quality adjusted life year (QALY) and $206,000 per hip fracture averted. If the cohort’s baseline risk of fracture was increased by 50% (10-year cumulative incidence of hip fracture of 14%), the ICERs improved significantly: $105,000 per QALY and $137,000 per hip fracture averted. The ICERs improved significantly if the proportion of prescriptions for generic bisphosphonates was increased to 75%, with $113,000 per QALY and $77,900 per hip fracture averted. Conclusions Evidence implementation programs for the management of GIOP are likely to be cost-effective to third-party health insurers only if they are targeted at individuals with a very high risk of fracture and the proportion of prescriptions for less expensive generic bisphosphonates increases substantially. PMID:19937227

  17. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model

    PubMed Central

    Britton, Robert A.; Irwin, Regina; Quach, Darin; Schaefer, Laura; Zhang, Jing; Lee, Taehyung; Parameswaran, Narayanan; McCabe, Laura R.

    2014-01-01

    Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this candidate probiotic could reduce bone loss associated with estrogen deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L. reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast bone resorption markers and activators (Trap5 and RANKL) as well as osteoclastogenesis are significantly decreased in L. reuteri treated mice. Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed osteoclastogenesis in vitro. We also identif ied that L. reuteri treatment modifies microbial communities in the Ovx mouse gut. Together, our studies demonstrate that L. reuteri treatment suppresses bone resorption and loss associated with estrogen deficiency. Thus, L. reuteri treatment may be a straightforward and cost-effective approach to reduce post-menopausal bone loss. PMID:24677054

  18. GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women.

    PubMed

    Iepsen, Eva W; Lundgren, Julie R; Hartmann, Bolette; Pedersen, Oluf; Hansen, Torben; Jørgensen, Niklas R; Jensen, Jens-Erik B; Holst, Jens J; Madsbad, Sten; Torekov, Signe S

    2015-08-01

    Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction. Randomized control study. Outpatient research hospital clinic. Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2) and age 46 ± 2 years. After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss. Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment. Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P < .0001), but not significantly in the liraglutide group. Thus, total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group (estimated difference, 27 g; 95% confidence interval, 5-48; P = .01), although the 12% weight loss was maintained in both groups. In the liraglutide group, the bone formation marker P1NP increased by 16% (7 ± 3 μg/L) vs a 2% (-1 ± 4 μg/L) decrease in the control group (P < .05). The bone resorption marker CTX-1 collagen did not change during the weight loss maintenance phase. Treatment with a long-acting GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.

  19. 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

  20. Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.

    PubMed

    Arai, Yuki; Aoki, Kazuhiro; Shimizu, Yasuhiro; Tabata, Yasuhiko; Ono, Takashi; Murali, Ramachandran; Mise-Omata, Setsuko; Wakabayashi, Noriyuki

    2016-07-05

    Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone.

  1. Tooth loss early in life accelerates age-related bone deterioration in mice.

    PubMed

    Kurahashi, Minori; Kondo, Hiroko; Iinuma, Mitsuo; Tamura, Yasuo; Chen, Huayue; Kubo, Kin-ya

    2015-01-01

    Both osteoporosis and tooth loss are health concerns that affect many older people. Osteoporosis is a common skeletal disease of the elderly, characterized by low bone mass and microstructural deterioration of bone tissue. Chronic mild stress is a risk factor for osteoporosis. Many studies showed that tooth loss induced neurological alterations through activation of a stress hormone, corticosterone, in mice. In this study, we tested the hypothesis that tooth loss early in life may accelerate age-related bone deterioration using a mouse model. Male senescence-accelerated mouse strain P8 (SAMP8) mice were randomly divided into control and toothless groups. Removal of the upper molar teeth was performed at one month of age. Bone response was evaluated at 2, 5 and 9 months of age. Tooth loss early in life caused a significant increase in circulating corticosterone level with age. Osteoblast bone formation was suppressed and osteoclast bone resorption was activated in the toothless mice. Trabecular bone volume fraction of the vertebra and femur was decreased in the toothless mice with age. The bone quality was reduced in the toothless mice at 5 and 9 months of age, compared with the age-matched control mice. These findings indicate that tooth loss early in life impairs the dynamic homeostasis of the bone formation and bone resorption, leading to reduced bone strength with age. Long-term tooth loss may have a cumulative detrimental effect on bone health. It is important to take appropriate measures to treat tooth loss in older people for preventing and/or treating senile osteoporosis.

  2. [Hormones and osteoporosis update. Glucocorticoids and bone].

    PubMed

    Ikeda, Kyoji

    2009-07-01

    Glucocorticoids are a class of vital steroid hormone which exhibit permissive effects on transactivation in a variety of cells, including those in bone. Glucocorticoid-induced osteoporosis, on the other hand, predisposes to fragility fracture by compromising bone strength and can be understood as a disease primarily characterized by a deficiency in bone quality. It is a major challenge in bone biology to understand these two contrasting sides of glucocorticoid activity in bone.

  3. Dried Plum’s Unique Capacity to Reverse Bone Loss and Alter Bone Metabolism in Postmenopausal Osteoporosis Model

    PubMed Central

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

    2013-01-01

    Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum’s unique effects on bone. PMID:23555991

  4. Minimum Abutment Height to Eliminate Bone Loss: Influence of Implant Neck Design and Platform Switching.

    PubMed

    Spinato, Sergio; Galindo-Moreno, Pablo; Bernardello, Fabio; Zaffe, Davide

    2017-08-17

    This retrospective study quantitatively analyzed the minimum prosthetic abutment height to eliminate bone loss after 4.7-mm-diameter implant placement in maxillary bone and how grafting techniques can affect the marginal bone loss in implants placed in maxillary areas. Two different implant types with a similar neck design were singularly placed in two groups of patients: the test group, with platform-switched implants, and the control group, with conventional (non-platform-switched) implants. Patients requiring bone augmentation underwent unilateral sinus augmentation using a transcrestal technique with mineralized xenograft. Radiographs were taken immediately after implant placement, after delivery of the prosthetic restoration, and after 12 months of loading. The average mesial and distal marginal bone loss of the control group (25 patients) was significantly more than twice that of the test group (26 patients), while their average abutment height was similar. Linear regression analysis highlighted a statistically significant inverse relationship between marginal bone loss and abutment height in both groups; however, the intercept of the regression line, both mesially and distally, was 50% lower for the test group than for the control group. The marginal bone loss was annulled with an abutment height of 2.5 mm for the test group and 3.0 mm for the control group. No statistically significant differences were found regarding marginal bone loss of implants placed in native maxillary bone compared with those placed in the grafted areas. The results suggest that the shorter the abutment height, the greater the marginal bone loss in cement-retained prostheses. Abutment height showed a greater influence in platform-switched than in non-platform-switched implants on the limitation of marginal bone loss.

  5. Connexin 43 deficiency attenuates loss of trabecular bone and prevents suppression of cortical bone formation during unloading.

    PubMed

    Lloyd, Shane A; Lewis, Gregory S; Zhang, Yue; Paul, Emmanuel M; Donahue, Henry J

    2012-11-01

    Connexin 43 (Cx43) is the most abundant gap junction protein in bone and has been demonstrated as an integral component of skeletal homeostasis. In the present study, we sought to further refine the role of Cx43 in the response to mechanical unloading by subjecting skeletally mature mice with a bone-specific deletion of Cx43 (cKO) to 3 weeks of mechanical unloading via hindlimb suspension (HLS). The HLS model was selected to recapitulate the effects of skeletal unloading due to prolonged bed rest, reduced activity associated with aging, and spaceflight microgravity. At baseline, the cortical bone of cKO mice displayed an osteopenic phenotype, with expanded cortices, decreased cortical thickness, decreased bone mineral density, and increased porosity. There was no baseline trabecular phenotype. After 3 weeks of HLS, wild-type (WT) mice experienced a substantial decline in trabecular bone volume fraction, connectivity density, trabecular thickness, and trabecular tissue mineral density. These deleterious effects were attenuated in cKO mice. Conversely, there was a similar and significant amount of cortical bone loss in both WT and cKO. Interestingly, mechanical testing revealed a greater loss of strength and rigidity for cKO during HLS. Analysis of double-label quantitative histomorphometry data demonstrated a substantial decrease in bone formation rate, mineralizing surface, and mineral apposition rate at both the periosteal and endocortical surfaces of the femur after unloading of WT mice. This suppression of bone formation was not observed in cKO mice, in which parameters were maintained at baseline levels. Taken together, the results of the present study indicate that Cx43 deficiency desensitizes bone to the effects of mechanical unloading, and that this may be due to an inability of mechanosensing osteocytes to effectively communicate the unloading state to osteoblasts to suppress bone formation. Cx43 may represent a novel therapeutic target for investigation as

  6. Prevention and Treatment of Bone Loss after a Spinal Cord Injury: A Systematic Review

    PubMed Central

    Ashe, Maureen C.; Craven, Cathy; Eng, Janice J.; Krassioukov, Andrei

    2012-01-01

    Preserving and maintaining bone mass after a spinal cord injury (SCI) is crucial to decrease the risk of fragility or low trauma fractures— significant health events that occur as a result of minimal trauma such as falling during transfers or from a standing height or less. There is an increased risk for low trauma fractures after a SCI especially in the lower extremity. Therefore, purpose of this systematic review was to appraise the literature to provide clinical guidance for the optimization of bone health after SCI. The key research questions focused on prevention of acute bone loss and effective treatment of established low bone mass with long-standing SCI (≥ 1year). We report moderate evidence for the treatment of bone loss using pharmacology; however, non-pharmacological evidence for preventing and treating bone loss is limited. PMID:22767990

  7. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

    PubMed

    Rivas, Daniel; Li, Wei; Akter, Rahima; Henderson, Janet E; Duque, Gustavo

    2009-10-01

    Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.

  8. The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans

    PubMed Central

    2013-01-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized. PMID:23689830

  9. The relevance of mouse models for investigating age-related bone loss in humans.

    PubMed

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  10. Prevention and Treatment of Bone Loss after a Spinal Cord Injury: A Systematic Review.

    PubMed

    Ashe, Maureen C; Craven, Cathy; Eng, Janice J; Krassioukov, Andrei

    2007-01-01

    Preserving and maintaining bone mass after a spinal cord injury (SCI) is crucial to decrease the risk of fragility or low trauma fractures- significant health events that occur as a result of minimal trauma such as falling during transfers or from a standing height or less. There is an increased risk for low trauma fractures after a SCI especially in the lower extremity. Therefore, purpose of this systematic review was to appraise the literature to provide clinical guidance for the optimization of bone health after SCI. The key research questions focused on prevention of acute bone loss and effective treatment of established low bone mass with long-standing SCI (≥ 1year). We report moderate evidence for the treatment of bone loss using pharmacology; however, non-pharmacological evidence for preventing and treating bone loss is limited.

  11. Prostaglandin E2 Prevents Ovariectomy-Induced Cancellous Bone Loss in Rats

    NASA Technical Reports Server (NTRS)

    Ke, Hua Zhu; Li, Mei; Jee, Webster S. S.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2, (PGE2) can prevent ovariectomy induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0,1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE, at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2, administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher

  12. Deficiency of ATP6V1H Causes Bone Loss by Inhibiting Bone Resorption and Bone Formation through the TGF-β1 Pathway

    PubMed Central

    Duan, Xiaohong; Liu, Jin; Zheng, Xueni; Wang, Zhe; Zhang, Yanli; Hao, Ying; Yang, Tielin; Deng, Hongwen

    2016-01-01

    Vacuolar-type H +-ATPase (V-ATPase) is a highly conserved, ancient enzyme that couples the energy of ATP hydrolysis to proton transport across vesicular and plasma membranes of eukaryotic cells. Previously reported mutations of various V-ATPase subunits are associated with increased bone density. We now show that haploinsufficiency for the H subunit of the V1 domain (ATP6V1H) is associated with osteoporosis in humans and mice. A genome-wide SNP array analysis of 1625 Han Chinese found that 4 of 15 tag SNPs (26.7%) within ATP6V1H were significantly associated with low spine bone mineral density. Atp6v1h+/- knockout mice generated by the CRISPR/Cas9 technique had decreased bone remodeling and a net bone matrix loss. Atp6v1h+/- osteoclasts showed impaired bone formation and increased bone resorption. The increased intracellular pH of Atp6v1h+/- osteoclasts downregulated TGF-β1 activation, thereby reducing induction of osteoblast formation but the bone mineralization was not altered. However, bone formation was reduced more than bone resorption. Our data provide evidence that partial loss of ATP6V1H function results in osteoporosis/osteopenia. We propose that defective osteoclast formation triggers impaired bone formation by altering bone remodeling. In the future, ATP6V1H might, therefore, serve as a target for the therapy of osteoporosis. PMID:27924156

  13. Does vitamin D deficiency contribute to post-burn bone loss?

    PubMed

    Klein, Gordon L

    2012-01-01

    Burn injury results in the acute loss of bone as well as the development of progressive vitamin D deficiency. Bone loss occurs acutely due to resorption, which is then followed by apoptosis of osteoblasts preventing repair of the bone loss. The acute resorption is due to a combination of the inflammatory response and the stress response to the burn injury. The resultant production of inflammatory cytokines and endogenous glucocorticoids initially stimulate the osteoblasts to produce RANK ligand, which stimulates marrow stem cell differentiation into osteoclasts. As the stress response persists for approximately one year post-burn the glucocorticoids produced by the body will cause osteoblast apoptosis and adynamic bone, impairing the ability of bone to recover its resorptive losses. The vitamin D deficiency is due to the failure to supplement the diet of burn patients with vitamin D on discharge from hospital and to failure of the skin to make normal quantities of vitamin D on sunlight exposure. Because the bone resorption can be prevented by the acute administration of bisphosphonates it is unlikely that vitamin D deficiency is responsible for the early-onset bone loss following burns. However, because a deficit in trabecular bone remains for at least two years post-burn, it is possible that vitamin D deficiency prevents the recovery of trabecular bone density over the long term.

  14. Delay of natural bone loss by higher intakes of specific minerals and vitamins.

    PubMed

    Schaafsma, A; de Vries, P J; Saris, W H

    2001-05-01

    For early prevention or inhibition of postmenopausal and age-related bone loss, nutritional interventions might be a first choice. For some vitamins and minerals an important role in bone metabolism is known or suggested. Calcium and vitamin D support bone mineral density and are basic components in most preventive strategies. Magnesium is involved in a number of activities supporting bone strength, preservation, and remodeling. Fluorine and strontium have bone-forming effects. However, high amounts of both elements may reduce bone strength. Boron is especially effective in case of vitamin D, magnesium, and potassium deficiency. Vitamin K is essential for the activation of osteocalcin. Vitamin C is an important stimulus for osteoblast-derived proteins. Increasing the recommended amounts (US RDA 1989), adequate intakes (US DRI 1997), or assumed normal intakes of mentioned food components may lead to a considerable reduction or even prevention of bone loss, especially in late postmenopausal women and the elderly.

  15. Regulation of osteoclast homeostasis and inflammatory bone loss by MFG-E81

    PubMed Central

    Abe, Toshiharu; Shin, Jieun; Hosur, Kavita; Udey, Mark C.; Chavakis, Triantafyllos; Hajishengallis, George

    2014-01-01

    The glycoprotein milk fat globule-EGF factor 8 (MFG-E8) is expressed in several tissues and mediates diverse homeostatic functions. However, whether MFG-E8 plays a role in bone homeostasis has not been established. Here we show for the first time that osteoclasts express and are regulated by MFG-E8. Bone marrow-derived osteoclast precursors (OCPs) from MFG-E8–deficient (Mfge8−/−) mice underwent increased RANKL-induced osteoclastogenesis leading to enhanced resorption pit formation as compared with wild-type controls. Consistently, exogenously added MFG-E8 inhibited RANKL-induced osteoclastogenesis from mouse or human OCPs. Upon induction of experimental periodontitis, an oral inflammatory disease characterized by loss of bone support of the dentition, Mfge8−/− mice exhibited higher numbers of osteoclasts and more bone loss than wild-type controls. Accordingly, local microinjection of anti-MFG-E8 mAb exacerbated periodontal bone loss in wild-type mice. Conversely, microinjection of MFG-E8 inhibited bone loss in experimental mouse periodontitis. In comparison to wild-type controls, Mfge8−/− mice also experienced >60% more naturally occurring chronic periodontal bone loss. In conclusion, MFG-E8 is a novel homeostatic regulator of osteoclasts and could be exploited therapeutically to treat periodontitis and perhaps other immunological disorders associated with inflammatory bone loss. PMID:24958900

  16. AQP9: a novel target for bone loss induced by microgravity.

    PubMed

    Bu, Guoyun; Shuang, Feng; Wu, Ye; Ren, Dongfeng; Hou, Shuxun

    2012-03-23

    The aim of current study was to elucidate whether aquaporin-9 (AQP9) expression was involved in the progression of bone loss induced by microgravity. We used the hind-limb suspension (HLS) mice model to simulate microgravity and induce bone loss. It was found that HLS exposure decreased femur bone mineral density (BMD), and enhanced femur AQP9 mRNA and protein levels. Then, the relationship between AQP9 mRNA expression and BMD was studied and it was showed that femur AQP9 mRNA level was negatively related to femur BMD in mice exposed to HLS. We sought to exam the function of AQP9 in the femur using the AQP9-null mice. It was found that AQP9 knockout attenuated bone loss and inhibited osteoclastogenesis under the condition of HLS exposure, but had no similar effect on bone under normal physiological conditions. In addition, it was found that exposure to simulated hypergravity or exercise training, main countermeasures against microgravity, reduced AQP9 mRNA and protein levels in femur of mice. Moreover, it was found that both aging and estrogen deprivation, another two risk factors of bone loss, had no significant effect on femur AQP9 expression. In conclusion, AQP9 plays an important role in the development of microgravity-induced bone loss, and may be a potential target for the prevention or management of microgravity-induced bone loss.

  17. TLR2 signaling and Th2 responses drive Tannerella forsythia-induced periodontal bone loss.

    PubMed

    Myneni, Srinivas R; Settem, Rajendra P; Connell, Terry D; Keegan, Achsah D; Gaffen, Sarah L; Sharma, Ashu

    2011-07-01

    Periodontal disease (PD) is a chronic inflammation of the tooth-supporting soft tissue and alveolar bone due to infection by a select group of gram-negative microbes, which leads to tooth loss if untreated. Because mice deficient in CD4(+) cells are resistant to infection-induced alveolar bone loss, Th cells have been implicated in bone-destructive processes during PD. However, the extent to which different Th cell subtypes play roles in pathogenesis or host protection remains to be defined and is likely to vary depending on the dominant microorganism involved. By far, Porphyromonas gingivalis is the best-studied periodontal microbe in PD. Although the gram-negative anaerobe Tannerella forsythia is also a vital contributor to periodontal bone loss, almost nothing is known about immune responses to this organism. Previous studies from our laboratory revealed that T. forsythia induces periodontal bone loss in mice and that this bone loss depends on the bacterially expressed BspA protein. In this study, we showed that T. forsythia activates murine APCs primarily through TLR2-dependent signaling via BspA. Furthermore, T. forsythia infection causes a pronounced Th2 bias, evidenced by T cell expression of IL-5, but not IFN-γ or IL-17, in draining lymph nodes. Consistently, deficiencies in TLR2 or STAT6 result in resistance to T. forsythia-induced alveolar bone loss. Thus, TLR2 signaling and Th2 cells play pathogenic roles in T. forsythia-induced alveolar bone destruction.

  18. Cyclical behavior of bone remodeling and bone loss in healthy women after menopause: results of a prospective study.

    PubMed

    Mazzuoli, G; Marinucci, D; D'erasmo, E; Acca, M; Pisani, D; Rinaldi, M G; Bianchi, G; Diacinti, D; Minisola, S

    2002-12-01

    Annual changes in lumbar bone mineral density (LBMD) and bone remodeling markers were measured in 238 healthy pre- and postmenopausal women, aged 45-74 years. The subjects were divided into groups according to their menstrual status and years since menopause. The results obtained indicate that bone loss is not a constant process over time but rather exhibits cyclical damping oscillations. When the log-linear trend of LBMD decrement was transformed into a constant by considering annual percentage changes, the presence of a cyclical component of 7 years was evident. By employing a harmonic regression model, the cyclical component was also statistically significant on baseline data. The cyclical behavior of LBMD decrement corresponded to an analogous behavior of the bone remodeling markers. These results suggest that a lack of estrogen acts as a synchronizer on bone remodeling by triggering a latent cyclical rhythm of bone loss that persists throughout life after menopause. The existence of a chronobiological rhythm of bone loss starting after menopause, if confirmed, could have important clinical implications.

  19. Obesity and Hyperlipidemia Modulate Alveolar Bone Loss in Wistar Rats.

    PubMed

    Cavagni, Juliano; de Macedo, Isabel Cristina; Gaio, Eduardo José; Souza, Andressa; de Molon, Rafael Scaf; Cirelli, Joni Augusto; Hoefel, Ana Lúcia; Kucharski, Luiz Carlos; Torres, Iraci Lucena da Silva; Rösing, Cassiano Kuchenbecker

    2016-02-01

    A positive association between obesity-associated metabolic disorders (e.g., hyperlipidemia and diabetes) and periodontitis has been demonstrated in the literature. This study evaluates the role of cafeteria diet-induced obesity/hyperlipidemia (CAF) on alveolar bone loss (ABL) in rats. Sixty male Wistar rats were randomly divided in four groups: control, periodontitis (PERIO), obesity/hyperlipidemia (CAF), and obesity/hyperlipidemia plus periodontitis (CAF+PERIO). Groups CAF and CAF+PERIO were exposed to a high-fat, hypercaloric diet. At week 12, periodontal disease was induced in groups PERIO and CAF+PERIO by ligatures in the upper second molar. The contralateral tooth was considered the intragroup control. Body weight and Lee index were evaluated weekly during the experiment. Serum glucose and cholesterol/triglycerides in the liver were evaluated, and percentage of ABL was measured by microcomputed tomography. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β were evaluated by enzyme-linked immunosorbent assay at week 17. Body weight, Lee index, and cholesterol/triglycerides in the liver increased in groups exposed to the cafeteria diet. Groups PERIO and CAF+PERIO exhibited a significantly higher ABL compared to control and CAF groups. The presence of obesity and hyperlipidemia significantly increased ABL in the CAF+PERIO group compared to the PERIO group (53.60 ± 3.44 versus 42.78 ± 7.27, respectively) in the sides with ligature. Groups exposed to CAF exhibited higher ABL in the sides without ligature. No differences were observed among groups for IL-1β and TNF-α. Obesity and hyperlipidemia modulate the host response to challenges in the periodontium, increasing the expression of periodontal breakdown.

  20. Coadministration of puerarin (low dose) and zinc attenuates bone loss and suppresses bone marrow adiposity in ovariectomized rats.

    PubMed

    Liu, Hao; Li, Wei; Ge, Xiyuan; Jia, Shengnan; Li, Binbin

    2016-12-01

    Puerarin is a phytoestrogen that shows osteogenic effects. Meanwhile, zinc stimulates bone formation and inhibits bone resorption. The study aims to investigate the effects of coadministration of puerarin (low dose) and zinc on bone formation in ovariectomized rats. Co-administration or use alone of puerarin (low dose) and/or zinc were gavaged in OVX rats. The estrogen-like effects were detected by the uterus weight, the histologic observation and the IGF-1 protein expression. The osteogenic effects were determined by bone histomorphometric and mechanical parameters, osteogenic and adipogenic blood markers, and so on. The results showed that oral administration of puerarin (low dose) plus zinc didn't significantly increase uterus weight. The glandular epithelial of endometrium had no proliferation and no protein expression of IGF-1. Moreover, co-administration attenuated bone loss and biomechanical decrease more than single use of puerarin or zinc (p<0.05). Next, combined administration of puerarin and zinc promoted the serological level of osteocalcin, bone marrow stromal cell (BMSC) proliferation, and the expression of alkaline phosphatase (ALP), and suppressed the serological level of adiponectin and adiposity in bone marrow (BM). In conclusion, co-administrated puerarin (low dose) and zinc can partially reverse OVX-induced bone loss and suppress the adiposity of BM in rats, which shed light on the potential use of puerarin and zinc in the treatment of osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  2. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  3. Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice.

    PubMed

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2015-02-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2(KI/KI)) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2(KI/KI) mice. Bone marrow (BM) cells from wild-type (Sh3bp2(+/+)) mice were transplanted to 6-week-old Sh3bp2(KI/KI) mice with developing inflammation and to 10-week-old Sh3bp2(KI/KI) mice with established inflammation. Six-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10weeks after BMT compared to Sh3bp2(KI/KI) mice transplanted with Sh3bp2(KI/KI) BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20weeks in 6-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2(KI/KI) mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients. Copyright © 2013. Published by Elsevier Inc.

  4. Bone Marrow Transplantation Improves Autoinflammation and Inflammatory Bone Loss in SH3BP2 Knock-In Cherubism Mice

    PubMed Central

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2014-01-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2KI/KI) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2KI/KI mice. Bone marrow (BM) cells from wild-type (Sh3bp2+/+) mice were transplanted to 6-week-old Sh3bp2KI/KI mice with developing inflammation and to 10-week-old Sh3bp2KI/KI mice with established inflammation. Six-week-old Sh3bp2KI/KI mice transplanted with Sh3bp2+/+ BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10 weeks after BMT compared to Sh3bp2KI/KI mice transplanted with Sh3bp2KI/KI BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20 weeks in 6-week-old Sh3bp2KI/KI mice transplanted with Sh3bp2+/+ BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2KI/KI mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients. PMID:25445458

  5. Reveromycin A Administration Prevents Alveolar Bone Loss in Osteoprotegerin Knockout Mice with Periodontal Disease.

    PubMed

    Mizuno, Manami; Miyazawa, Ken; Tabuchi, Masako; Tanaka, Miyuki; Yoshizako, Mamoru; Minamoto, Chisato; Torii, Yasuyoshi; Tamaoka, Yusuke; Kawatani, Makoto; Osada, Hiroyuki; Maeda, Hatsuhiko; Goto, Shigemi

    2015-11-12

    Chronic periodontal disease is characterized by alveolar bone loss and inflammatory changes. Reveromycin A (RMA) was recently developed and is a unique agent for inhibiting osteoclast activity. This study analysed the effects of RMA in an experimental mouse model of periodontitis involving osteoprotegerin (OPG)-knockout mice, specifically, whether it could control osteoclasts and reduce inflammation in periodontal tissue. We examined wild-type (WT) and OPG knockout mice (OPG KO) ligated with wire around contact points on the left first and second molars. RMA was administered twice a day to half of the mice. Using micro-computed tomography, we measured the volume of alveolar bone loss between the first and second molars, and also performed histological analysis. The OPG KO RMA+ group had significantly decreased osteoclast counts, alveolar bone loss, attachment loss, and inflammatory cytokine expression 8 weeks after ligation. Thus, RMA may reduce alveolar bone loss and inflamed periodontal tissues in patients with periodontitis.

  6. Reveromycin A Administration Prevents Alveolar Bone Loss in Osteoprotegerin Knockout Mice with Periodontal Disease

    PubMed Central

    Mizuno, Manami; Miyazawa, Ken; Tabuchi, Masako; Tanaka, Miyuki; Yoshizako, Mamoru; Minamoto, Chisato; Torii, Yasuyoshi; Tamaoka, Yusuke; Kawatani, Makoto; Osada, Hiroyuki; Maeda, Hatsuhiko; Goto, Shigemi

    2015-01-01

    Chronic periodontal disease is characterized by alveolar bone loss and inflammatory changes. Reveromycin A (RMA) was recently developed and is a unique agent for inhibiting osteoclast activity. This study analysed the effects of RMA in an experimental mouse model of periodontitis involving osteoprotegerin (OPG)-knockout mice, specifically, whether it could control osteoclasts and reduce inflammation in periodontal tissue. We examined wild-type (WT) and OPG knockout mice (OPG KO) ligated with wire around contact points on the left first and second molars. RMA was administered twice a day to half of the mice. Using micro-computed tomography, we measured the volume of alveolar bone loss between the first and second molars, and also performed histological analysis. The OPG KO RMA+ group had significantly decreased osteoclast counts, alveolar bone loss, attachment loss, and inflammatory cytokine expression 8 weeks after ligation. Thus, RMA may reduce alveolar bone loss and inflamed periodontal tissues in patients with periodontitis. PMID:26561427

  7. Does the presence of glenoid bone loss influence coracoid bone graft osteolysis after the Latarjet procedure? A computed tomography scan study in 2 groups of patients with and without glenoid bone loss.

    PubMed

    Di Giacomo, Giovanni; de Gasperis, Nicola; Costantini, Alberto; De Vita, Andrea; Beccaglia, Mario A Rojas; Pouliart, Nicole

    2014-04-01

    Coracoid bone graft osteolysis and fibrous union are the principal causes of failure in patients treated with the Latarjet procedure. This study aims to investigate the hypothesis that coracoid bone graft osteolysis is more pronounced in cases without glenoid bone loss, which may be due to a diminished mechanotransduction effect at the bone healing site. We prospectively followed up 34 patients, treated with a mini-plate Latarjet procedure, divided into 2 groups (group A patients had glenoid bone loss >15% and group B patients had no glenoid bone loss). A computed tomography scan evaluation with 3-dimensional reconstruction was then performed on all patients to evaluate coracoid bone graft osteolysis according to our coracoid bone graft osteolysis classification. The computed tomography scan analysis showed a different distribution of osteolysis between group A and group B. The statistical analysis showed a significant difference (P < .01, Bonferroni test) between groups A and B for the following sections: proximal/lateral/superficial, proximal/medial/deep, distal/lateral/superficial, and distal/lateral/deep. On average, the coracoid grafts in group A patients showed less osteolysis than the coracoid grafts in group B patients (39.6% vs 65.1%). The coracoid bone graft underwent much less osteolysis in patients with significant glenoid bone loss (>15%) than in those without it. Because factors of blood supply, compression, and surgical technique were the same for both groups, we believe that the mechanotransduction effect from the humeral head on the graft influences its remodeling. The results of this study suggest that the bone graft part of the Latarjet procedure plays a role in patients with significant coracoid bone loss but much less so when there is no bone loss. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  8. Male Astronauts Have Greater Bone Loss and Risk of Hip Fracture Following Long Duration Spaceflights than Females

    NASA Technical Reports Server (NTRS)

    Ellman, Rachel; Sibonga, Jean; Bouxsein, Mary

    2010-01-01

    This slide presentation reviews bone loss in males and compares it to female bone loss during long duration spaceflight. The study indicates that males suffer greater bone loss than females and have a greater risk of hip fracture. Two possible reason for the greater male bone loss are that the pre-menopausal females have the estrogen protection and the greater strength of men max out the exercise equipment that provide a limited resistance to 135 kg.

  9. Hand bone loss as an outcome measure in established rheumatoid arthritis: 2-year observational study comparing cortical and total bone loss

    PubMed Central

    Hoff, Mari; Haugeberg, Glenn; Kvien, Tore K

    2007-01-01

    The aim of this 2-year longitudinal observational study was to explore hand bone loss as a disease outcome measure in established rheumatoid arthritis (RA). A cohort of 215 patients with RA (170 women and 45 men, aged 20–70 years) were recruited from the Oslo RA registry and studied for changes in hand bone mass during a 2-year follow-up. Digital X-ray radiogrammetry (DXR) was used to measure cortical hand bone mineral density (BMD) and metacarpal cortical index, whereas dual-energy X-ray absorptiometry (DXA) was used to assess whole hand BMD, which measures total cortical and trabecular bone. DXA-BMD total hip and spine and informative data for disease and therapy were also collected. Hand bone loss could be revealed over a 2-year follow-up measured by DXR-BMD (-0.90%, P < 0.01), but not by DXA-BMD (0.00%, P = 0.87). DXA-BMD hand bone loss was only observed in patients with disease duration ≤3 years and not in patients with longer disease duration (-0.96% versus 0.24%, P < 0.01), whereas loss of DXR-BMD was independent of disease duration. Disease activity (measured by the disease activity score including 28 joints) independently predicted loss of DXR-BMD but not changes in the DXA-BMD hand in the multivariate analysis. The change in DXR metacarpal cortical index was highly correlated to DXR-BMD (r = 0.94, P < 0.001). These data suggest that DXR-BMD may be a more appropriate technique to identify RA-related bone involvement in hands compared with DXA-BMD measurement, but further studies are needed to explore this hypothesis. PMID:17705865

  10. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    NASA Technical Reports Server (NTRS)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  11. Possible methods for the prevention of bone loss in persons with epilepsy.

    PubMed

    Elliott, John O

    2009-06-01

    Various antiepileptic drugs are known to cause bone mineral density (BMD) loss in persons with epilepsy. In general population studies, physical activity has a profound effect on bone health. Vitamin D deficiency, common in persons with epilepsy, is also associated with various chronic health conditions and osteoporosis in the general population. People with epilepsy would benefit from interventional research focused on the prevention of BMD loss. Exercise, healthy dietary habits and nutritional supplementation are important for the development and maintenance of bone health as well as for the prevention of comorbid conditions that are common in epilepsy. Consensus guidelines are needed for the prevention, screening and treatment of BMD loss in epilepsy.

  12. Monoaxial distraction of ulna to second metacarpal followed by single bone forearm in massive post infective radial bone loss

    PubMed Central

    Pal, Jitendra N; Banik, Rajeeb

    2012-01-01

    Introduction: Radial bone loss associated with gross manus valgus deformity can be managed by open reduction internal fixation using intervening strut bone graft, callus distraction using ring or monoaxial fixator, and achieving union by distraction histogenesis. These methods are particularly suitable when bone loss is small. Single or staged procedure is described for congenital as well as in acquired extensive bone loss of radius. Distraction through radial proximal to distal segments, to achieve reduction of distal radio-ulnar joint (DRUJ), is also described in acquired cases. In the present series, functional results of distraction through ulna to 2nd metacarpal is studied alongwith, functional status of hand, stability of wrist, level of patient's satisfaction are also studied. Materials and Methods: 7 unilateral cases of radial loss (M = 5, F = 2) affecting 4 right hands of mean age 17 years (range 9 to 24 years) were included in this study. They were treated by distracting through ulna to 2nd metacarpal to achieve DRUJ alignment in first stage. Subsequently ulna was osteotomised and translated to distal stump of radius. It was then fixed to the distal radial remnant in 30° pronation in dominant and 30° supination non dominant hands. Results: Union was achieved in all cases associated with beneficial cross union of distal ulna. Hand functions improved near to normal, with fully corrected stable wrist joint, hypertrophied ulna and without recurrence. All of them had practically complete loss of forearm rotations, however patients were fully satisfied. Conclusion: This method is particularly suitable when associated with 6 cm or more radial bone loss. But when loss is small, sacrifice of one bone may not be justifiable. PMID:23325973

  13. Pueraria mirifica, a phytoestrogen-rich herb, prevents bone loss in orchidectomized rats.

    PubMed

    Urasopon, Nontakorn; Hamada, Yuzuru; Asaoka, Kazuo; Cherdshewasart, Wichai; Malaivijitnond, Suchinda

    2007-03-20

    Estrogens and estrogen-like substances have been reported to play an important role in male bone homeostasis and to prevent bone loss. Pueraria mirifica (Leguminosae), a Thai herbal plant, containing a high amount of phytoestrogens was a choice of interest for this study. We examined the effects of crude P. mirifica on bone loss and influences on reproductive organs in male rats. Using fully mature and orchidectomized (ORX) rats, the effects of 0, 10, 100 and 1000 mg/kgB.W./day of P. mirifica and 0.1mg/kg B.W./day of 17 alpha-ethinylestradiol (a positive control) were evaluated on bone mineral density (BMD) and bone mineral content (BMC) measured with a peripheral Quantitative Computerized Tomography (pQCT) densitometry. Bone loss in trabecular and cortical bones of the various sites of axial bone (fourth lumbar vertebral body) and long bones (tibia and femur) after ORX was dose-dependently prevented by P. mirifica. The effects were specific on bone types and sites. The weights of the accessory sex organs, seminal vesicle and ventral prostrate gland, which significantly decreased after 3-month of ORX, were not altered by P. mirifica. The results suggest that P. mirifica treatment may be useful to prevent an osteoporosis in elderly hypogonadism subjects without influences on reproductive organs.

  14. Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse

    PubMed Central

    Kondo, Hisataka; Yumoto, Kenji; Alwood, Joshua S.; Mojarrab, Rose; Wang, Angela; Almeida, Eduardo A. C.; Searby, Nancy D.; Limoli, Charles L.

    2010-01-01

    Exposure of astronauts in space to radiation during weightlessness may contribute to subsequent bone loss. Gamma irradiation of postpubertal mice rapidly increases the number of bone-resorbing osteoclasts and causes bone loss in cancellous tissue; similar changes occur in skeletal diseases associated with oxidative stress. Therefore, we hypothesized that increased oxidative stress mediates radiation-induced bone loss and that musculoskeletal disuse changes the sensitivity of cancellous tissue to radiation exposure. Musculoskeletal disuse by hindlimb unloading (1 or 2 wk) or total body gamma irradiation (1 or 2 Gy of 137Cs) of 4-mo-old, male C57BL/6 mice each decreased cancellous bone volume fraction in the proximal tibiae and lumbar vertebrae. The extent of radiation-induced acute cancellous bone loss in tibiae and lumbar vertebrae was similar in normally loaded and hindlimb-unloaded mice. Similarly, osteoclast surface in the tibiae increased 46% as a result of irradiation, 47% as a result of hindlimb unloading, and 64% as a result of irradiation + hindlimb unloading compared with normally loaded mice. Irradiation, but not hindlimb unloading, reduced viability and increased apoptosis of marrow cells and caused oxidative damage to lipids within mineralized tissue. Irradiation also stimulated generation of reactive oxygen species in marrow cells. Furthermore, injection of α-lipoic acid, an antioxidant, mitigated the acute bone loss caused by irradiation. Together, these results showed that disuse and gamma irradiation, alone or in combination, caused a similar degree of acute cancellous bone loss and shared a common cellular mechanism of increased bone resorption. Furthermore, irradiation, but not disuse, may increase the number of osteoclasts and the extent of acute bone loss via increased reactive oxygen species production and ensuing oxidative damage, implying different molecular mechanisms. The finding that α-lipoic acid protected cancellous tissue from the

  15. Bone-immune cell crosstalk: bone diseases.

    PubMed

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

    2015-01-01

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

  16. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    PubMed

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S S; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10(-6) mol/L to 10(-7) mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  17. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    PubMed Central

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  18. Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

    PubMed Central

    Gao, Liang; Orth, Patrick; Müller-Brandt, Kathrin; Goebel, Lars K. H.; Cucchiarini, Magali; Madry, Henning

    2017-01-01

    Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques. PMID:28345610

  19. Modern analysis of bone loss mechanisms in microgravity.

    PubMed

    Oganov, V S

    2004-07-01

    A summary of results of investigations by the author and a brief review of some literature data on human bone tissue deprived of mechanical loading (spaceflight, hypokinesia) is given. The direction and markedness of changes in bone mass--the bone mineral density and the bone mineral content--in different skeletal segments depend on their position relative to the gravity vector. A theoretically expected bone mass reduction was revealed in the trabecular structures of the bones of the lower part of the skeleton (local osteopenia). In the upper part of the skeleton, an increase in the bone mineral content is observed, which is considered as a secondary response and is due to redistribution of body fluids cephalad. The main cause of osteopenia is mechanical unloading. Arguments are presented that osteocyte osteolysis, delayed osteoblast histogenesis, and osteoclast resorption provoked by rearrangement in the hierarchy of the systems of fluid volume and ion regulation, and the endocrine control of calcium homeostasis are the main mechanisms of osteopenia.

  20. Bone loss during the acute stage following burn injury.

    PubMed

    Leblebici, Berrin; Sezgin, Nurzen; Ulusan, Serife Nur; Tarim, Akin M; Akman, M Nafiz; Haberal, Mehmet A

    2008-01-01

    The aim of this study was to investigate the effect of burn injury on bone metabolism and bone densitometry in the early period. Twenty-one patients with >25% total body surface area (TBSA) burns and 20 healthy controls participated. TBSA burned, ambulation, and functional status were recorded. After 30 days, we measured bone mineral densities of the L1-L4 vertebrae, the left distal forearm, and the left proximal femur in the patients. At 1 and 4 weeks after the burn, changes in bone turnover were assessed in patients by changes in deoxypyridinoline levels in the urine and osteocalcin in the serum and compared with the values of control group. In patients, Z-scores < -1 were found in 71.42% of left distal forearm, 23.80% of left proximal femur, and in 42.85% of L1-L4 vertebrae measurements. No significant correlations existed between Z-scores and TBSA, Functional Ambulation Scale, or Functional Independent Measure. When compared with controls, there was no statistically significant decrease of osteocalcin (a marker of bone formation) levels in patients 1 and 4 weeks after burn injury. However, when compared with controls, a statistically significant difference was found regarding deoxypyridinoline (a marker for bone resorption) in patients 1 and 4 weeks after burn injury (P < .001 and P < .001, respectively). Decreases in bone mineral density occurred during the first month following burn injury, which seemed to be linked with increases in bone resorption during this period. No correlation existed between reduction in bone mineral density and functional status.

  1. Effect of stochastic resonance on bone loss in osteopenic conditions.

    PubMed

    Rusconi, Marco; Zaikin, Alexey; Marwan, Norbert; Kurths, Jürgen

    2008-03-28

    We investigate the effect of noise on the remodelling process of the inner spongy part of the trabecular bone. Recently, a new noise-induced phenomenon in bone formation has been reported experimentally. We propose the first conceptual model for this finding, explained by the stochastic resonance effect, and provide a theoretical basis for the development of new countermeasures for bone degeneration in long space flights, which currently has dramatic consequences on return to standard gravity. These results may also be applicable on Earth for patients under osteopenic conditions.

  2. Effect of Stochastic Resonance on Bone Loss in Osteopenic Conditions

    NASA Astrophysics Data System (ADS)

    Rusconi, Marco; Zaikin, Alexey; Marwan, Norbert; Kurths, Jürgen

    2008-03-01

    We investigate the effect of noise on the remodelling process of the inner spongy part of the trabecular bone. Recently, a new noise-induced phenomenon in bone formation has been reported experimentally. We propose the first conceptual model for this finding, explained by the stochastic resonance effect, and provide a theoretical basis for the development of new countermeasures for bone degeneration in long space flights, which currently has dramatic consequences on return to standard gravity. These results may also be applicable on Earth for patients under osteopenic conditions.

  3. Correlation between interimplant distance and crestal bone loss in internal connection implants with platform switching.

    PubMed

    Jo, Deuk-Won; Yi, Yang-Jin; Kwon, Min-Jung; Kim, Young-Kyun

    2014-01-01

    The aim of this study was to investigate the influence of interimplant distance of internal connection implants with platform switching on crestal bone loss using radiographic evaluation. The present study included patients missing two consecutive teeth in the posterior quadrant and receiving internal connection implants. Digital periapical radiographs were taken at the time of superstructure connection and at the time of more than 1 year of loading. Bone level change was measured on the modified image using a digital subtraction program. The crestal bone loss between implants and the horizontal and vertical loss of peri-implant marginal bone were evaluated, and the influence of interimplant distance on crestal bone loss was analyzed at α = .05. A total of 10 pairs of implants having ≤ 3 mm of interimplant distance was included in this study (group 1). The other 15 pairs of implants having > 3 mm of interimplant distance were selected as a control group (group 2). After the mean 19.3 months of observation, the mean crestal bone loss between implants was -0.26 ± 0.14 mm in group 1 and -0.23 ± 0.29 mm in group 2 (P > .05). There was no significant difference between the interimplant distance and the crestal bone loss according to the regression analysis (P = .765). The mean horizontal and vertical marginal bone loss was -0.18 ± 0.25 mm and -0.15 ± 0.18 mm, respectively, in group 1 and -0.17 ± 0.31 mm and -0.11 ± 0.33 mm, respectively, in group 2. There were no significant differences between outside and inside bone loss of implants in horizontal and vertical change (P > .05). Within the limitations of the short-term study, the interimplant distance did not affect the crestal bone loss with internal connection implants with platform switching. The horizontal and vertical marginal bone loss was found to be too small to result in overlapping loss of the interimplant crestal bone.

  4. The effect of whey acidic protein fractions on bone loss in the ovariectomised rat.

    PubMed

    Kruger, Marlena C; Plimmer, Gabrielle G; Schollum, Linda M; Haggarty, Neill; Ram, Satyendra; Palmano, Kate

    2005-08-01

    Bovine milk has been shown to contain bioactive components with bone-protective properties. Earlier studies on bovine milk whey protein showed that it suppressed bone resorption in the female ovariectomised rat. A new osteotropic component was subsequently identified in the whey basic protein fraction, but bone bioactivity may also be associated with other whey fractions. In the present study, we investigated whether acidic protein fractions isolated from bovine milk whey could prevent bone loss in mature ovariectomised female rats. Six-month-old female rats were ovariectomised (OVX) or left intact (sham). The OVX rats were randomised into four groups. One group remained the control (OVX), whereas three groups were fed various whey acidic protein fractions from milk whey as 3 g/kg diet for 4 months. Outcomes were bone mineral density, bone biomechanics and markers of bone turnover. Bone mineral density of the femurs indicated that one of the whey AF over time caused a recovery of bone lost from OVX. Plasma C-telopeptide of type I collagen decreased significantly in all groups except OVX control over time, indicating an anti-resorptive effect of whey acidic protein. Biomechanical data showed that the AF may affect bone architecture as elasticity was increased by one of the whey AF. The femurs of AF-supplemented rats all showed an increase in organic matter. This is the first report of an acidic whey protein fraction isolated from milk whey that may support the recovery of bone loss in vivo.

  5. Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

    PubMed Central

    Jeney, Viktória

    2017-01-01

    Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

  6. Glucocorticoids induce glutamine synthetase in folliculostellate cells of rat pituitary glands in vivo and in vitro

    PubMed Central

    SHIRASAWA, NOBUYUKI; YAMANOUCHI, HIROSHI

    1999-01-01

    Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamate metabolism in the central and peripheral nervous system. In this study GS activity was measured and the amount of immunoreactive GS (ir-GS) cells in the rat anterior pituitary gland was quantified as a function of age. In addition, the effects of GS inhibitors, glucocorticoid administration, and adrenalectomy on GS activity were examined. Some of the ir-GS cells were also immunoreactive for S100 protein (ir-S100) which is a known marker for folliculostellate cells (FS) in the anterior pituitary. FS cells expressing GS were first detected in 3-d-old rats, and this cell population, expressed as the immunostained cell area divided by a standard unit area, increased as a function of age. The percentages of FS cells also expressing GS were 0.2, 6.4, 25 and 74% at 3 d, 30 d, 60 d and 2 y of age, respectively. GS enzyme activity also increased in parallel with the increase of ir-GS cell population maturation. The subcutaneous injection of methionine sulphoximine, a GS and γ-glutamylcysteine synthetase inhibitor, reduced pituitary GS activity by 83%, but increased the population of ir-GS cells 3.5-fold in 30-d-old rats. Buthionine sulphoximine, a specific inhibitor of γ-glutamylcysteine synthetase, had little effect on GS activity or the ir-GS cell population. Neither methionine sulphoximine nor buthionine sulphoximine changed the population of ir-S100 protein cells (FS cells). Dexamethasone and hydrocortisone increased the population of ir-GS cells by 3.1 and 4.2-fold, respectively, within 12 h after administration. A significant increase of GS activity due to the injection of glucocorticoids was observed in the anterior pituitary, but not in the brain, retina or liver of immature rats. Adrenalectomy did not cause decrease of pituitary GS activity, and dexamethasone administration increased GS activity in both adrenalectomised and intact rats. In the monolayer culture of

  7. Genetic risk factors for glucocorticoid-induced osteonecrosis: a meta-analysis.

    PubMed

    Gong, Li-Li; Fang, Lian-Hua; Wang, He-Yao; Peng, Jian-Hao; Si, Kun; Zhu, Jin; Han, Fei-Fei; Wang, Yue-Hua; Du, Guan-Hua; Pei, Li-Xia; Liu, Li-Hong

    2013-04-01

    Glucocorticoid-induced osteonecrosis is a common and severe adverse event. We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis. Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1). The meta-analysis revealed that the PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR=1.932, 95% CI=1.145-3.261). The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3.217 (95% CI 1.667-6.209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2.304 (95% CI=1.235-4.299) and 2.307 (95% CI=1.527-3.485) in combined studies, respectively. The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1.668, 95% CI=1.214-2.293) and TT genotype (OR 2.946, 95% CI=1.422-6.101). There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis. Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis.

  8. Increase in prophylaxis of glucocorticoid-induced osteoporosis by pharmacist feedback: a randomised controlled trial.

    PubMed

    Klop, C; de Vries, F; Vinks, T; Kooij, M J; van Staa, T P; Bijlsma, J W J; Egberts, A C G; Bouvy, M L

    2014-01-01

    The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis. The intervention did not significantly increase the prescribing of bisphosphonates in the total study population, but a significant increase was seen in men and in the elderly. However, the proportion of bisphosphonate-treated patients remained low. The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis (GIOP) would stimulate the implementation of the Dutch GIOP guideline. This randomised controlled trial included 695 patients who were dispensed ≥675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline. Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis. The primary endpoint was a bisphosphonate prescription. Secondary endpoints were a prescription of calcium supplements, vitamin D or any prophylactic osteoporosis drug (bisphosphonate, calcium supplements, vitamin D). The group assigned to the intervention was slightly younger than the control group (68.7 ± 15.4 vs. 65.9 ± 16.9 years, p = 0.02) and used hydrocortisone more often (7.0% vs. 3.1%, p = 0.02). Within 6 months, the intervention did not significantly increase the prescribing of bisphosphonates (11.4% after intervention vs. 8.0% for controls; hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.91-2.39). However, subgroup analyses showed a significant increase for the primary endpoint in men (12.8% vs. 5.1%, HR 2.53, 95% CI 1.11-5.74) and patients ≥70 years (13.4% vs. 4.9%, HR 2.88, 95% CI 1.33-6.23). The prescribing of calcium and vitamin D was not significantly altered. This study showed that active identification of patients eligible for

  9. Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

    PubMed

    Laaksonen, Marika M L; Impivaara, Olli; Sievänen, Harri; Viikari, Jorma S A; Lehtimäki, Terho J; Lamberg-Allardt, Christel J E; Kärkkäinen, Merja U M; Välimäki, Matti; Heikkinen, Jorma; Kröger, Liisa M; Kröger, Heikki P J; Jurvelin, Jukka S; Kähönen, Mika A P; Raitakari, Olli T

    2009-05-01

    Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young

  10. Inflammation, bone loss and fracture risk in spondyloarthritis

    PubMed Central

    Briot, Karine; Roux, Christian

    2015-01-01

    Osteoporosis (ie, low bone mineral density) is common in ankylosing spondylitis, related to both systemic inflammation and decreased mobility. Vertebral fracture risk is increased; acute back pain in these patients is not always a flare-up of the disease, as it can be related to bone complications. Intervertebral disc fractures in the ankylosed spine are associated with severe neurological complications. As expected from pathophysiology, treatments effective against inflammation have a positive effect on bone, and prospective open studies have shown that tumour-necrosis-factor blockers can improve bone mineral density at the spine and the hip. There is so far no evidence of a decreased risk of fractures with such treatment. PMID:26509065

  11. Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

    DTIC Science & Technology

    2014-07-01

    10 4  INTRODUCTION  Osteoporosis  (porous bone disease) is a disease characterized by low bone mass and structural...deteriora on of  bone  ssue, leading to bone fragility and an increased suscep bility to fractures. Disuse  osteoporosis  occurs  when the normal loading... osteoporosis .  Once that compound makes it to market,  there is significant precedent to try that compound in veterans returning from the ba lefield that are

  12. Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice.

    PubMed

    Motyl, Katherine J; DeMambro, Victoria E; Barlow, Deborah; Olshan, David; Nagano, Kenichi; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

    2015-07-01

    Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and clinical data are emerging that demonstrate increased fracture risk and bone loss after treatment with the AA, risperidone (RIS). The pharmacology underlying the adverse effects on bone is unknown. However, RIS action in the central nervous system could be responsible because the sympathetic nervous system (SNS) is known to uncouple bone remodeling. RIS treatment in mice significantly lowered trabecular bone volume fraction (bone volume/total volume), owing to increased osteoclast-mediated erosion and reduced osteoblast-mediated bone formation. Daytime energy expenditure was also increased and was temporally associated with the plasma concentration of RIS. Even a single dose of RIS transiently elevated expression of brown adipose tissue markers of SNS activity and thermogenesis, Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was also increased 1 hour after a single dose of RIS. Thus, we inferred that bone loss from RIS was regulated, at least in part, by the SNS. To test this, we administered RIS or vehicle to mice that were also receiving the nonselective β-blocker propranolol. Strikingly, RIS did not cause any changes in trabecular bone volume/total volume, erosion, or formation while propranolol was present. Furthermore, β2-adrenergic receptor null (Adrb2(-/-)) mice were also protected from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated bone loss from any AA. Because AA medications are widely prescribed, especially to young adults, clinical studies are needed to assess whether β-blockers will prevent bone loss in this vulnerable population.

  13. Prevention of alveolar bone loss in an osteoporotic animal model via interference of semaphorin 4d.

    PubMed

    Zhang, Y; Wei, L; Miron, R J; Zhang, Q; Bian, Z

    2014-11-01

    Semaphorin 4d (Sema4d) has been proposed as a novel target gene for the treatment of osteoporosis. Recently, we fabricated a site-specific bone-targeting system from polymeric nanoparticles that demonstrates an ability to prevent bone loss in an osteoporotic model by interfering with Sema4d gene expression using small interference RNA (siRNA) molecules. The aim of the present investigation was to determine the effects of this targeting system on the periodontium, an area of high bone turnover. We demonstrated, by single photon emission computed tomography, that intravenous injection of this molecule in ovariectomized Balb/C mice is able to target alveolar bone peaking 4 hr post-injection. We then compared, by histological analysis, the bone volume/total volume (BV/TV), alveolar bone height loss, immunohistochemical expression of Sema4d, and total number of osteoclasts in mandibular alveolar bone. Four treatment modalities were compared as follows: (1) sham-operated, (2) OVX-operated, (3) OVX+estrogen replacement therapy, and (4) OVX+siRNA-Sema4d animals. The results from the present study demonstrate that an osteoporotic condition significantly increases alveolar bone height loss, and that the therapeutic effects via bone-targeting systems featuring interference of Sema4d are able to partly counteract alveolar bone loss caused by osteoporosis. While the future therapeutic demand for the large number of patients suffering from osteoporosis faces many challenges, we demonstrate within the present study an effective drug-delivery moiety with anabolic effects on the bone remodeling cycle able to locate and target alveolar bone regeneration.

  14. Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse.

    PubMed

    Zhang, Dongye; Hu, Minyi; Chu, Timothy; Lin, Liangjun; Wang, Jingyu; Li, Xiaodong; Ke, Hua Zhu; Qin, Yi-Xian

    2016-06-01

    Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25mg/kg were made twice per week for 5weeks from the time of HLS. μCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS+OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin-neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading.

  15. Disruption of PTH Receptor 1 in T Cells Protects against PTH-Induced Bone Loss

    PubMed Central

    Tawfeek, Hesham; Bedi, Brahmchetna; Li, Jau-Yi; Adams, Jonathan; Kobayashi, Tatsuya; Weitzmann, M. Neale; Kronenberg, Henry M.; Pacifici, Roberto

    2010-01-01

    Background Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH) treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs. Methodology/Principal Findings Here we show that silencing of PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor α (TNF). Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio. Conclusions/Significance These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism. PMID:20808842

  16. Effectiveness of local delivery of alendronate in reducing alveolar bone loss following periodontal surgery in rats.

    PubMed

    Binderman, I; Adut, M; Yaffe, A

    2000-08-01

    Mucoperiosteal flaps are used to access bone and root surfaces for debridement, pocket elimination, management of periodontal defects, and in regenerative procedures, as well as in implant surgery. Many reports show that periodontal surgery stimulates osteoclast activity with varying amounts of alveolar bone loss. Alendronate given intravenously significantly reduced alveolar bone loss in mucoperiosteal flap procedures. In the present study, we explored the effectiveness of different concentrations of alendronate, delivered at the surgical site at the time of surgery, in distant delivery in reducing alveolar bone loss. Following elevation of a mucoperiosteal flap next to molars of the rat mandible, a gelatin sponge soaked with different concentrations of alendronate (0, 1, 5, 20, or 40 mg/ml; experiment A) was applied to exposed bone on the experimental side. In the second group (experiment B), alendronate (0, 50, 200, or 400 microg) was topically delivered in the cheek submucosa on the left side (distant to the surgical site) in a small cut into which the gelatin sponge soaked with the drug was placed. Topical application of 200 microg and 400 microg doses of alendronate at the time of surgery was significantly effective (P <0.001) in reducing bone loss. Generally, the percentage of sections with mild bone loss (V1, V2) increased with an increase in the dose of alendronate, while the percentage of sections with severe bone loss (H1, H2) decreased with an increase in alendronate dose. Topical application of 400 microg of alendronate had a systemic effect. This study implies that topical delivery of alendronate at the time of surgery reduces bone loss in periodontal procedures involving mucoperiosteal flap surgery. The most effective dose is 200 microg for topical delivery at the surgical site and 400 microg for distant sites.

  17. NADPH oxidases are critical targets for prevention of ethanol-induced bone loss

    USDA-ARS?s Scientific Manuscript database

    The molecular mechanisms through which chronic alcohol consumption induce bone loss and osteoporosis are largely unknown. Ethanol increases expression and activates NADPH (nicotinamide adenine dinucleotide phosphate) oxidase enzymes (Nox) in osteoblasts leading to accumulation of reactive oxygen spe...

  18. Efficacy of bisphosphonates for the control of alveolar bone loss in periodontitis.

    PubMed

    Jeffcoat, Marjorie K; Cizza, Giovanni; Shih, W Joe; Genco, Robert; Lombardi, Antonio

    2007-07-01

    Periodontal disease is characterized by periodontal bone loss. For this reason, we conducted a study to test the effect of alendronate (ALN), an inhibitor of bone resorption, on alveolar bone mass. A total of 335 patients with periodontal disease (men = 162, women = 173), aged 30 to 79, were randomized to either placebo or ALN 70 mg once weekly. All patients received prophylaxis at baseline, and at 6, 12, and 18 months. Smokers accounted for 62% of patients, and 71% of the patients had severe periodontal disease. The primary efficacy endpoint was the change in alveolar bone loss (ABL). When all subjects were analyzed, 2 years of treatment with alendronate 70 mg once weekly did not significantly change either ABL or alveolar bone density (ABD) relative to placebo. However, in the subgroup of patients with low mandibular bone mineral density (BMD) at baseline, alendronate significantly reduced bone loss relative to placebo (p < 0.01). No such effect was seen in patients with normal baseline mandibular BMD. The overall and upper gastrointestinal safety and tolerability profile of alendronate after 2 years of treatment was very favorable compared to placebo. No cases of osteonecrosis of the jaw were observed. In summary, in patients with periodontal disease receiving prophylaxis, alendronate 70 mg once weekly was well tolerated, but did not have a detectable effect on alveolar bone loss, except in those patients with low mandibular BMD at baseline.

  19. Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

    PubMed Central

    Conley, Melissa N.; Roberts, Cooper; Sharpton, Thomas J.; Iwaniec, Urszula T.

    2017-01-01

    Scope Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age‐related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. Methods and results Six‐month‐old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham‐operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low‐dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high‐dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose‐dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome. Conclusion These data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX. PMID:28087899

  20. Bone graft

    MedlinePlus

    Autograft - bone; Allograft - bone; Fracture - bone graft; Surgery - bone graft; Autologous bone graft ... Fuse joints to prevent movement Repair broken bones (fractures) that have bone loss Repair injured bone that ...

  1. Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss

    PubMed Central

    Calabrese, Gina; Mesner, Larry D.; Foley, Patricia L.; Rosen, Clifford J.; Farber, Charles R.

    2016-01-01

    The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected “hub” genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID:27378017

  2. Antiresorptive therapy in the management of cancer treatment-induced bone loss.

    PubMed

    Garg, Ashwani; Leitzel, Kim; Ali, Suhail; Lipton, Allan

    2015-04-01

    Cancer treatment-induced bone loss treatment has an important role to prevent bone loss-related events like fracture, significant morbidity, mortality, disfigurement and loss of self-esteem, and health-care expenditure. Numerous factors, including treatment regimens and bone metastasis, increase the risk of osteoporosis or local bone destruction in most breast and prostate cancer patients. Cytotoxic chemotherapies, radiation, and hormonal therapies can lead to premature menopause and decrease bone mineral density. Over 60 % of breast cancer patients within 1 year of beginning postoperative adjuvant chemotherapy experience ovarian failure. Also, ovarian ablation and aromatase inhibitors used to treat breast cancer and orchiectomy and androgen deprivation therapy (ADT; to treat prostate cancer) cause substantial bone loss. In this article, we will focus mainly on antiresorptive therapy in the management of cancer treatment-induced bone loss (CTIBL). An understanding of CTIBL is critical for determining how to assess the risk and identify which patients may benefit from preventive therapy.

  3. Correlation of the interdental and the interradicular bone loss: A radiovisuographic analysis.

    PubMed

    Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Mankotia, Chahat Singh; Bither, Rupika

    2014-07-01

    Presence of furcation involvement indicates advanced periodontitis, and a potentially less-favorable prognosis, for the affected tooth and its diagnosis has always been an enigma. The present study was carried out to measure and correlate the interdental and interradicular bone loss in patients suffering from periodontitis using radiovisuography (RVG) for the purpose of early furcation diagnosis. A total of 50 patients suffering from chronic generalized periodontitis and with furcation involvement in mandibular molars were selected. Under standardized conditions, RVGs were taken and the morphologic measurements defining the furcation areas were recorded and analyzed. Interradicular bone loss of about 0.8 mm or more, was observed in the study subjects only when the bone loss at the interdental area was minimal of 3.7 mm. The correlation between the interradicular and the interdental bone loss was statistically highly significant (T-test, P < 0.001). A stronger correlation was observed in subjects above 40 years of age as compared with the younger subjects. There was not much difference in the degree of correlation between the interradicular and the interdental bone loss when compared in the context of gender. The very first millimeter of interradicular bone loss was seen when the interdental bone loss was around 4 mm. Therefore, to detect the earliest lesions of furcations, the interdental bone loss can be kept as an approximate guide for the comprehensive diagnosis and management of such sites/patients. The current investigation paves the path for future longitudinal studies with larger samples to ascertain these findings.

  4. Managing cancer treatment-induced bone loss and osteoporosis in patients with breast or prostate cancer.

    PubMed

    Michaud, Laura Boehnke

    2010-04-01

    To discuss trends in breast and prostate cancer prevalence and survival; risk factors for bone loss, osteoporosis, and fractures and the approach to risk assessment in patients with these malignancies; established and investigational drug therapies for managing cancer treatment-induced bone loss and osteoporosis; and the role of health-system pharmacists in promoting bone health in patients with breast or prostate cancer. Breast cancer and prostate cancer are common, deadly diseases, but many survivors are alive today because of improvements in early detection and treatment over the past 10-15 years. Cancer chemotherapy, corticosteroids, hormone-ablation therapy, and other common risk factors place patients with breast or prostate cancer at high risk for bone loss, osteoporosis, and fractures. Most patients with breast or prostate cancer should undergo assessment of risk for bone loss and osteoporosis that involves a bone-related history and physical examination, dual-energy X-ray absorptiometry scanning, and the FRAX fracture risk assessment tool from the World Health Organization. A recent National Comprehensive Cancer Network task force report on bone health in cancer care provides recommendations for considering the use of pharmacologic therapy on the basis of the results of this assessment. Bisphosphonates are useful for slowing or preventing bone loss associated with hormone-ablation therapy in women with breast cancer and men with prostate cancer, although fracture data are limited in women and not available in men. The usefulness of other therapies (selective estrogen receptor modulators, teriparatide, calcitonin salmon, and estrogens) is limited by adverse effects, a lack of experience with the drugs in these patient populations, or both. Various drug therapies are in development for managing cancer treatment-induced bone loss and osteoporosis. The agent closest to approval by the Food and Drug Administration, denosumab, has been shown to improve bone

  5. A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis

    PubMed Central

    2009-01-01

    Introduction Osteoclasts play a key role in the pathogenesis of bone erosion and systemic bone mass loss during rheumatoid arthritis (RA). In this study, we aimed to determine the effect of methotrexate (MTX) and zoledronic acid (ZA), used alone or in combination, on osteoclast-mediated bone erosions and systemic bone mass loss in a rat model of collagen induced arthritis (CIA). We hypothesized that MTX and ZA could have an additive effect to prevent both bone erosion and systemic bone loss. Methods Arthritis was induced in 64 female Sprague-Dawley rats. After the clinical onset of CIA, rats were assigned to treatment with MTX (1 mg/kg/week), ZA (100 μg/kg twice weekly), both treatments at the same regimens, or vehicle. Arthritis score and paw thickness were recorded twice weekly. The rats were sacrificed on D28 and hind paws were removed for radiographic, histological and immunohistochemical analysis. The effects of treatments on osteoclastogenesis were determined by Tartrate resistant acid phosphatase (TRAP) staining. Micro-CT of the tibia was carried out for histomorphometric analysis. Bone mass density was evaluated by densitometry. Results MTX significantly decreased the severity of CIA, whereas ZA slightly exacerbated it. When these two drugs were used in combination, MTX prevented the pro-inflammatory effect of ZA. The combination of ZA with MTX was more effective than MTX alone for reducing structural joint damage with a dramatic decrease of osteoclasts' number in the eroded joints. However, MTX alone also significantly reduced the number of osteoclasts and the number of CD68+ mononuclear cells. ZA alone, or ZA with MTX, significantly increased the systemic bone mass density measured by densitometry and bone volume on histomorphometric analysis. Conclusions A combination of MTX and ZA prevented both bone erosion and systemic bone loss in a rat model of arthritis. Both treatments independently decreased the number of osteoclasts in the eroded joint. However

  6. Characterization of glucocorticoid receptor on lymphocytes in Chinese patients with glucocorticoid-induced glaucoma.

    PubMed

    Zhuo, Y; Ge, J; Guo, Y

    1998-09-01

    We studied the pathogenesis of glucocorticoid-induced glucoma (GIG) through characterization of glucocorticoid receptor (GR) on lymphocytes in Chinese patients with GIG. By radioligand receptor binding followed by Scatchard analysis, the specific binding sites were characterized and quantitated for glucocorticoid receptors on peripheral blood lymphocytes obtained from patients with GIG and the control group. The binding sites we detected were as follows: 12.7 +/- 1.47 x 10(3) receptors per cell with a KD of 3.02 +/- 0.62 nmol/L in patients with GIG, 7.26 +/- 0.45 x 10(3) receptors per cell with a KD of 3.03 +/- 0.56 nmol/L in the control group. The statistical difference of receptors per cell is significant between two groups (p < 0.05), patients with GIG having more GR binding sites, while the difference of Kd is not significant (p > 0.05). The preliminary findings suggest that patients with GIG are more sensitive to glucocorticoid and the increase of binding sites of GR may be the receptor and molecular basis of the pathogenesis of GIG.

  7. Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1992-01-01

    Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth.

  8. Expression and regulation of glucocorticoid-induced leucine zipper in the developing anterior pituitary gland.

    PubMed

    Ellestad, Laura E; Malkiewicz, Stefanie A; Guthrie, H David; Welch, Glenn R; Porter, Tom E

    2009-02-01

    The expression profile of glucocorticoid-induced leucine zipper (GILZ) in the anterior pituitary during the second half of embryonic development in the chick is consistent with in vivo regulation by circulating corticosteroids. However, nothing else has been reported about the presence of GILZ in the neuroendocrine system. We sought to characterize expression and regulation of GILZ in the chicken embryonic pituitary gland and determine the effect of GILZ overexpression on anterior pituitary hormone levels. Pituitary GILZ mRNA levels increased during embryogenesis to a maximum on the day of hatch, and decreased through the first week after hatch. GILZ expression was rapidly upregulated by corticosterone in embryonic pituitary cells. To determine whether GILZ regulates hormone gene expression in the developing anterior pituitary, we overexpressed GILZ in embryonic pituitary cells and measured mRNA for the major pituitary hormones. Exogenous GILZ increased prolactin mRNA above basal levels, but not as high as that in corticosterone-treated cells, indicating that GILZ may play a small role in lactotroph differentiation. The largest effect we observed was a twofold increase in FSH beta subunit in cells transfected with GILZ but not treated with corticosterone, suggesting that GILZ may positively regulate gonadotroph development in a manner not involving glucocorticoids. In conclusion, this is the first report to characterize avian GILZ and examine its regulation in the developing neuroendocrine system. We have shown that GILZ is upregulated by glucocorticoids in the embryonic pituitary gland and may regulate expression of several pituitary hormones.

  9. Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport.

    PubMed

    Lang, Florian; Vallon, Volker

    2012-02-01

    Serum- and glucocorticoid inducible-kinase 1 (SGK1) is an early gene transcriptionally upregulated by cell stress such as cell shrinkage and hypoxia and several hormones including gluco- and mineralocorticoids. It is activated by insulin and growth factors. SGK1 is a powerful regulator of a wide variety of channels and transporters. The present review describes the role of SGK1 in the regulation of potassium (K(+)) channels, K(+) transporters and K(+) homeostasis. SGK1-regulated K(+) channels include renal outer medullary K+ channel, Kv1.3, Kv1.5, KCNE1/KCNQ1, KCNQ4 and, via regulation of calcium (Ca(2+)) entry, Ca(2+)-sensitive K(+) channels. SGK1-sensitive transporters include sodium-potassium-chloride cotransporter 2 and sodium/potassium-adenosine triphosphatase. SGK1-dependent regulation of K(+) channels and K(+) transport contributes to the stimulation of renal K(+) excretion following high K(+) intake, to insulin-induced cellular K(+) uptake and hypokalemia, to inhibition of insulin release by glucocorticoids, to stimulation of mast cell degranulation and gastric acid secretion, and to cardiac repolarization. Thus, SGK1 has a profound effect on K(+) homeostasis and on a multitude of K(+)-sensitive cellular functions.

  10. Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1992-01-01

    Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth.

  11. Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.

    PubMed

    Calmette, Joseph; Bertrand, Matthieu; Vétillard, Mathias; Ellouze, Mehdi; Flint, Shaun; Nicolas, Valérie; Biola-Vidamment, Armelle; Pallardy, Marc; Morand, Eric; Bachelerie, Françoise; Godot, Véronique; Schlecht-Louf, Géraldine

    2016-12-01

    Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.

  12. The Glucocorticoid-induced leucine zipper (GILZ) Is essential for spermatogonial survival and spermatogenesis.

    PubMed

    Romero, Y; Vuandaba, M; Suarez, P; Grey, C; Calvel, P; Conne, B; Pearce, D; de Massy, B; Hummler, E; Nef, S

    2012-01-01

    Spermatogenesis relies on the precise regulation of the self-renewal and differentiation of spermatogonia to provide a continuous supply of differentiating germ cells. The understanding of the cellular pathways regulating this equilibrium remains unfortunately incomplete. This investigation aimed to elucidate the testicular and ovarian functions of the glucocorticoid-induced leucine zipper protein (GILZ) encoded by the X-linked Tsc22d3 (Gilz) gene. We found that GILZ is specifically expressed in the cytoplasm of proliferating spermatogonia and preleptotene spermatocytes. While Gilz mutant female mice were fully fertile, constitutive or male germ cell-specific ablation of Gilz led to sterility due to a complete absence of post-meiotic germ cells and mature spermatozoa. Alterations were observed as early as postnatal day 5 during the first spermatogenic wave and included extensive apoptosis at the spermatogonial level and meiotic arrest in the mid-late zygotene stage. Overall, these data emphasize the essential role played by GILZ in mediating spermatogonial survival and spermatogenesis.

  13. Glucocorticoid-induced leucine zipper protein regulates sodium and potassium balance in the distal nephron.

    PubMed

    Rashmi, Priyanka; Colussi, GianLuca; Ng, Michael; Wu, Xinhao; Kidwai, Atif; Pearce, David

    2017-05-01

    Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice. Furthermore, knockout mice are more sensitive to NCC inhibition by thiazides than are the wild type mice, and their phosphorylated NCC expression is higher. Despite increased NCC activity, knockout mice do not have higher blood pressure than wild type mice. However, during sodium deprivation, knockout mice come into sodium balance more quickly, than do the wild type, without a significant increase in plasma renin activity. Upon prolonged sodium restriction, knockout mice develop frank hyperkalemia. Finally, in HEK293T cells, exogenous GILZ inhibits NCC activity at least in part by inhibiting SPAK phosphorylation. Thus, GILZ promotes potassium secretion by inhibiting NCC and enhancing distal sodium delivery to the epithelial sodium channel. Additionally, Gilz(-/-) mice have features resembling familial hyperkalemic hypertension, a human disorder that manifests with hyperkalemia associated variably with hypertension. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Human glucocorticoid-induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states

    PubMed Central

    Zhou, Zhaocai; Song, Xiaomin; Berezov, Alan; Zhang, Geng; Li, Yanjing; Zhang, Hongtao; Murali, Ramachandran; Li, Bin; Greene, Mark I.

    2008-01-01

    Ligation between glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand (GITRL) provides an undefined signal that renders CD4+CD25− effector T cells resistant to the inhibitory effects of CD4+CD25+ regulatory T cells. To understand the structural basis of GITRL function, we have expressed and purified the extracellular domain of human GITR ligand in Escherichia coli. Chromotography and cross-linking studies indicate that human GITRL (hGITRL) exists as dimers and trimers in solution and also can form a supercluster. To gain insight into the nature of GITRL oligomerization, we determined the crystallographic structures of hGITRL, which revealed a loosely associated open trimer with a deep cavity at the molecular center and a flexible C-terminal tail bent for trimerization. Moreover, a tetramer of trimers (i.e., supercluster) has also been observed in the crystal, consistent with the cross-linking analysis. Deletion of the C-terminal distal three residues disrupts the loosely assembled trimer and favors the formation of a dimer that has compromised receptor binding and signaling activity. Collectively, our studies identify multiple oligomeric species of hGITRL that possess distinct kinetics of ERK activation. The studies address the functional implications and structural models for a process by which hGITRL utilizes multiple oligomerization states to regulate GITR-mediated signaling during T cell costimulation. PMID:18378892

  15. Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report.

    PubMed

    Banu, Jameela; Varela, Erika; Bahadur, Ali N; Soomro, Raheela; Kazi, Nishu; Fernandes, Gabriel

    2012-01-01

    Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.

  16. Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report

    PubMed Central

    Banu, Jameela; Varela, Erika; Bahadur, Ali N.; Soomro, Raheela; Kazi, Nishu; Fernandes, Gabriel

    2012-01-01

    Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice. PMID:22779034

  17. Nobiletin, a polymethoxy flavonoid, suppresses bone resorption by inhibiting NFκB-dependent prostaglandin E synthesis in osteoblasts and prevents bone loss due to estrogen deficiency.

    PubMed

    Harada, Suguru; Tominari, Tsukasa; Matsumoto, Chiho; Hirata, Michiko; Takita, Morichika; Inada, Masaki; Miyaura, Chisato

    2011-01-01

    Nobiletin, a polymethoxy flavonoid, prevents cancer and inflammation, but the roles of nobiletin in bone are unclear. We examined the effects of nobiletin on bone resorption in vitro and on bone mass in ovariectomized (OVX) mice in vivo. In vitro, nobiletin suppressed osteoclast formation and bone resorption induced by interleukin (IL)-1. Nobiletin suppressed the expression of cyclooxygenase-2, NFκB-dependent transcription, and prostaglandin E (PGE) production induced by IL-1 in osteoblasts. OVX mice showed severe bone loss in the femur by increased bone resorption due to estrogen deficiency, and nobiletin significantly restored the bone mass. Nobiletin could be beneficial to bone health in postmenopausal women.

  18. Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis

    PubMed Central

    Garimella, Manasa G.; Kour, Supinder; Piprode, Vikrant; Mittal, Monika; Kumar, Anil; Rani, Lekha; Pote, Satish T.; Mishra, Gyan C.; Chattopadhyay, Naibedya

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)–induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance. PMID:26538398

  19. Association between fat mass, lean mass, and bone loss: the Dubbo Osteoporosis Epidemiology Study.

    PubMed

    Yang, S; Center, J R; Eisman, J A; Nguyen, T V

    2015-04-01

    Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender. Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year). The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older were studied. Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P < 0.01). In bivariable regression analysis, each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower bone loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women. Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

  20. 32k Da protein improve ovariectomy-induced bone loss in rats

    PubMed Central

    Zhou, Yingtang; Jiang, Shenhua; Chen, Jing; Wang, Tao; Jiang, DengZhao; Chen, Hui; Yu, Huan

    2013-01-01

    The objective of the present study was to systematically explore the effects of 32K Da protein (32KP) on postmenopausal osteoporosis. Eighty 3-mo-old female Sprague-Dawley rats were employed and randomly divided into one sham-operated group (SHAM) and five ovariectomy (OVX) subgroups as OVX (control), OVX with 17-ethinylestradiol (E2, 25 g/kg/day), OVX with 32KP of graded doses (50, 50, or 150 mg/kg/day). 32KP or E2 diet was fed on week 4 after operation, for 16 weeks. Bone mass, bone turnover and strength were evaluated by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test, respectively. Femur marrow cavity was observed by light microscopy via hematoxylin-eosin staining. It is observed that different dosage treatment of 32KP increased the body weight and prevented the loss of bone mass induced by OVX. The prevention effect against bone loss was presumably due to the altering of the rate of bone remodeling. The bone mineral density and bone calcium content in OVX rats were lower than that in the control group, suggesting that 32KP was able to prevent significant bone loss. In addition, the data from three point bending test and femur sections showed that 32KP treatment enhanced bone strength and reduced the marrow cavity of the femur in OVX rats. In the serum and urine assay, 32KP decreased urinary deoxypyridinoline and calcium concentrations; however, serum alkaline phosphatase activities were not inhibited. It suggested that amelioration of bone loss was changed via inhibition of bone reabsorption. Our findings indicated that 32KP might be a potential alternative drug for the prevention and treatment of postmenopausal osteoporosis. PMID:23924638

  1. Preventive effects of Pueraria mirifica on bone loss in ovariectomized rats.

    PubMed

    Urasopon, Nontakorn; Hamada, Yuzuru; Cherdshewasart, Wichai; Malaivijitnond, Suchinda

    2008-02-20

    Effects of Pueraria mirifica on bone loss in fully mature ovariectomized rats are examined. Two series of experiments were performed. In the first series, rats were kept with their ovaries intact and divided into two groups; initial control (IC) and sham control (SH). The IC rats were sacrificed on day 1 and their data were kept as baseline control. The SH rats were subjected to sham operation on day 0 and gavaged daily with distilled water for 90 days. In the second series, rats were subjected to ovariectomy, divided into five groups and gavaged daily with 0.1mg/kg B.W./day of 17-alpha-ethinylestradiol (EE), 0, 10, 100 and 1000mg/kg B.W./day of P. mirifica (P0, P10, P100 and P1000, respectively) for 90 days. Changes of bone mineral density and bone mineral content were measured using peripheral Quantitative Computerized Tomography. Bone loss was significantly induced by ovariectomy and it was dose-dependently prevented by P. mirifica treatment for 90 days. The preventive effects of P. mirifica on bone loss depended on bone types (axial or long bone), bone sites (metaphysis or diaphysis), and bone compartments (trabecular and cortical). At P100 and P1000, bone loss was completely prevented both in trabecular bone mineral density and content. The effects of P. mirifica were, as expected, comparable to that in the EE group. These results suggest that P. mirifica may be applicable to treat the osteoporosis in menopausal women; however, an undesirable side effect on stimulating reproductive organs should be concerned.

  2. Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice

    USDA-ARS?s Scientific Manuscript database

    Cancer progression is accompanied by wasting that eventually results in cachexia characterized by significant weight loss and multi-organ functional failures. Limited clinical trials indicate that bone is adversely affected by cancer-associated wasting. To determine the effects of breast cancer on...

  3. Influence of bone osteocalcin levels on bone loss induced by ovariectomy in rats.

    PubMed

    Hara, Kuniko; Kobayashi, Masatoshi; Akiyama, Yasuhiro

    2007-01-01

    To investigate the role of osteocalcin (OC) in bones, bone parameters in warfarin (WF)-treated rats after ovariectomy (OVX) were compared with those in intact rats. Rats were divided into an intact group and WF-treated group. Warfarin was orally given to rats for 16 weeks, and then OVX was performed and rats in the WF-treated groups continued receiving WF. Twelve weeks after OVX, bone properties were observed. The diaphysial bone OC level in the WF group was 10%-14% of the normal level at the preoperative point and 12 weeks after surgery. On comparison of the intact and WF groups before surgery, no significant differences were noted in bone mass parameters or mechanical properties, but 12 weeks after surgery, the diaphysial bone mineral content (BMC), bone area, and cortical thickness (Cth) were significantly higher in the WF-sham group than in the intact-sham group. Ovariectomy significantly decreased the diaphysial BMC, bone mineral density (BMD), Cth, and maximum load, and increased the endosteal perimeter in the WF group. In the intact group, no such OVX-induced changes were noted, and the metaphysial bone area and the endosteal and periosteal perimeters were increased by OVX. The CO(3)/PO(4) ratio in the femur measured by Fourier-transform infrared imaging using reflection preparations was higher in the WF-sham group than the intact-sham group, and higher in the intact-OVX group than the intact-sham group, but no significant difference was noted between the WF-sham and WF-OVX groups. It has been reported that CO(3)(-) is contained in new bone and decreases with mineral maturation. These data suggest that long-term reduction in bone OC levels may induce the formation of immature bone, which is easily resorbed with changes in bone metabolism such as OVX, and that OC may be one of the factors affecting bone turnover.

  4. Wnt therapy for bone loss: golden goose or Trojan horse?

    PubMed

    Enders, Greg H

    2009-04-01

    The Wnt pathway has been found to play a role in the development of many tissues and to spur growth and differentiation of adult osteoblasts, sparking interest in its potential clinical application for bone growth. However, when deregulated, this pathway can be oncogenic in some tissues. In this issue of the JCI, Kansara and colleagues reveal that Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcomas and that its absence augments osteosarcoma formation in mice (see the related article beginning on page 837). These observations suggest the need for caution in stimulating the Wnt pathway for therapeutic bone growth.

  5. Wnt therapy for bone loss: golden goose or Trojan horse?

    PubMed Central

    Enders, Greg H.

    2009-01-01

    The Wnt pathway has been found to play a role in the development of many tissues and to spur growth and differentiation of adult osteoblasts, sparking interest in its potential clinical application for bone growth. However, when deregulated, this pathway can be oncogenic in some tissues. In this issue of the JCI, Kansara and colleagues reveal that Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcomas and that its absence augments osteosarcoma formation in mice (see the related article beginning on page 837). These observations suggest the need for caution in stimulating the Wnt pathway for therapeutic bone growth. PMID:19348043

  6. Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications

    NASA Technical Reports Server (NTRS)

    Charles, H. K. Jr; Beck, T. J.; Feldmesser, H. S.; Magee, T. C.; Spisz, T. S.; Pisacane, V. L.

    2001-01-01

    An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

  7. Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications

    NASA Technical Reports Server (NTRS)

    Charles, H. K. Jr; Beck, T. J.; Feldmesser, H. S.; Magee, T. C.; Spisz, T. S.; Pisacane, V. L.

    2001-01-01

    An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

  8. Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications.

    PubMed

    Charles, H K; Beck, T J; Feldmesser, H S; Magee, T C; Spisz, T S; Pisacane, V L

    2001-01-01

    An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

  9. Bone loss in revision total knee arthroplasty: graft options and adjuncts.

    PubMed

    Stulberg, S David

    2003-04-01

    The treatment of small bone defects in revision total knee arthroplasty should make immediate full weight bearing and full therapy possible, provide long-term stability for the implants, and restore bone stock. These objectives are achieved with bone grafts if the defects are cavitary or small (involving less than one fourth of the cortical rim) segmental defects. These objectives are achieved with porous metal augments if the defects are segmental and involve more than one fourth of the cortical rim. The treatment of bone loss on the femur must allow the re-establishment of the distal and posterior joint lines as well as provide a firm fixation base for the implants.

  10. Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss.

    PubMed

    Cheng, Tsung-Lin; Lai, Chao-Han; Shieh, Shyh-Jou; Jou, Yin-Bo; Yeh, Jwu-Lai; Yang, Ai-Lun; Wang, Yan-Hsiung; Wang, Chau-Zen; Chen, Chung-Hwan; Shi, Guey-Yueh; Ho, Mei-Ling; Wu, Hua-Lin

    2016-06-17

    Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-like domain. This study aimed to identify the role of myeloid TM (i.e., endogenous TM expression on the myeloid lineage) in osteoclastogenesis and inflammatory bone loss. Using human peripheral blood mononuclear cells and mouse bone marrow-derived macrophages, we observed that the protein levels of TM were dramatically reduced as these cells differentiated into osteoclasts. In addition, osteoclastogenesis and extracellular HMGB1 accumulation were enhanced in primary cultured monocytes from myeloid-specific TM-deficient mice (LysMcre/TM(flox/flox)) and from TM lectin-like domain deleted mice (TM(LeD/LeD)) compared with their respective controls. Micro-computerized tomography scans showed that ovariectomy-induced bone loss was more pronounced in TM(LeD/LeD) mice compared with controls. Finally, the inhibiting effects of recombinant TM lectin-like domain (rTMD1) on bone resorption in vitro, and bone loss in both the ovariectomized model and collagen antibody-induced arthritis model has been detected. These findings suggested that the myeloid TM lectin-like domain may inhibit osteoclastogenesis by reducing HMGB1 signaling, and rTMD1 may hold therapeutic potential for inflammatory bone loss.

  11. Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

    PubMed Central

    2012-01-01

    Background Despite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) on the rate of bone loss in ovariectomized (OVX) Norway rats. A secondary aim was to compare the effects of vitamin K with those of bisphosphonates (BP) on bone loss. Methods Rats (n = 96) were randomized to 6 dosing groups [n = 16/group; Sham; OVX; OVX + BP (100 μg/kg/100 μg/mL saline sc); OVX + PK; OVX + MK-4; and OVX + MK-7] for 6 wk. Equimolar daily doses of 107 mg PK/kg, 147 mg MK-4/kg, and 201 mg MK-7/kg diet were provided. Results BP significantly increased bone strength and bone mineral density (BMD) vs. OVX (P < 0.05). However, PK, MK-4 or MK-7 did not change bone strength or BMD compared to the OVX group. Whereas supplementation of PK, MK-4 and MK-7 increased serum and tibia concentrations of each respective form, PK concentrations were consistently higher despite equimolar intakes. Conclusion PK, MK-4, and MK-7 do not appear to prevent bone loss in OVX rats when administered concurrent with adequate intake of other nutrients. PMID:22348311

  12. The cellular basis of bone turnover and bone loss: a rebuttal of the osteocytic resorption--bone flow theory.

    PubMed

    Parfitt, A M

    1977-01-01

    There is now sufficient evidence to conclude that the osteocytic resorption--bone flow theory of bone turnove is untenable. According to this theory bone is resorbed not from the surface by osteoclasts but from within by osteocytes, towards which bone flows through tissue space away from bone forming surfaces. The need to invoke resorption by osteocytes stems from the belief that too few osteoclasts are present to account for normal bone resoption, a belief which reflects unawareness of the enormous capacity of the osteoclast and the rapidity of its advance. The belief that osteocytes resorb substantial amounts of bone rests on invalid conclusions from indirect techniques, various artifacts of specimen processing and unawareness of the microscopic characteristics of woven bone. Osteocytes enlarge their lacunae by resorbing bone only as a prelude to resorption from the surface, the osteocyte and osteoclast working together as a resorbing unit. The belief that bone can flow is incompatible both with the physical properties of bone and with a substantial body of evidence relating to Haversian remodelling; the experimental data purporting to demonstrate such flow can all be explained by conventional concepts of bone turnover.

  13. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

    PubMed Central

    Mendonça, Maira L.; Batista, Sérgio L.; Nogueira-Barbosa, Marcello H.; Salmon, Carlos E.G.; de Paula, Francisco J.A.

    2016-01-01

    OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity. PMID:27626477

  14. 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.

  15. Assessing bone loss in micro-gravity: a fuzzy approach.

    PubMed

    Zobel, Bruno Beomonte; Del Vescovo, Riccardo; Oliva, Gabriele; Russo, Valentina; Setola, Roberto

    2012-12-01

    A prolonged stay in microgravity has various negative effects on the human body; one of these problems is a noticeable demineralization of bone tissues. Such effects are quite similar to those experienced by subjects on earth affected by osteoporosis; therefore it seems quite straightforward to adopt a similar pharmacological therapy during the stay in the space. In this paper a first step in the identification of a monitoring procedure for the bone demineralization in microgravity, as well as some guidelines for the choice of adequate therapies are given. Such a procedure is based on a mathematical model of the interaction of the most relevant blood and urine indicators of bone demineralization. Specifically, some bone metabolites have been identified, which are relevant to the phenomena and are feasible to be evaluated in the space. Moreover, a model to foresee the evolution of these parameters in the space, depending on the therapy chosen, is provided. The model is derived from the experience of doctors and experts, hence it is based mainly on linguistic information; such an information is codified by means of fuzzy numbers, in order to take into account their uncertainty.

  16. Twelve-Minute Daily Yoga Regimen Reverses Osteoporotic Bone Loss

    PubMed Central

    Lu, Yi-Hsueh; Rosner, Bernard; Chang, Gregory

    2016-01-01

    Objective: Assess the effectiveness of selected yoga postures in raising bone mineral density (BMD). Methods: Ten-year study of 741 Internet-recruited volunteers comparing preyoga BMD changes with postyoga BMD changes. Outcome Measures: Dual-energy x-ray absorptiometric scans. Optional radiographs of hips and spine and bone quality study (7 Tesla). Results: Bone mineral density improved in spine, hips, and femur of the 227 moderately and fully compliant patients. Monthly gain in BMD was significant in spine (0.0029 g/cm2, P = .005) and femur (0.00022 g/cm2, P = .053), but in 1 cohort, although mean gain in hip BMD was 50%, large individual differences raised the confidence interval and the gain was not significant for total hip (0.000357 g/cm2). No yoga-related serious injuries were imaged or reported. Bone quality appeared qualitatively improved in yoga practitioners. Conclusion: Yoga appears to raise BMD in the spine and the femur safely. PMID:27226695

  17. Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study.

    PubMed

    Bauer, Douglas C; Garnero, Patrick; Harrison, Stephanie L; Cauley, Jane A; Eastell, Richard; Ensrud, Kris E; Orwoll, Eric

    2009-12-01

    We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of bone turnover would have accelerated bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow-up of 4.6 yr. Nonspine fractures were documented during a mean follow-up of 5.0 yr. Using fasting serum collected at baseline and stored at -190 degrees C, bone turnover measurements (type I collagen N-propeptide [PINP]; beta C-terminal cross-linked telopeptide of type I collagen [betaCTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or betaCTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between bone turnover and fracture. We conclude that higher levels of bone turnover are associated with greater hip bone loss in older men, but increased turnover is not independently associated with the risk of hip or nonspine fracture.

  18. Low Magnitude, High Frequency Signals Could Reduce Bone Loss During Spaceflight

    NASA Astrophysics Data System (ADS)

    Hawkey, A.

    The removal of gravitational loading results in a loss of homeostasis of the skeleton. This leads to significant losses of bone mass during long-duration missions in space. Conventional exercise countermeasures, such as running and resistance training, have only limited effectiveness in reducing the rate at which bone is demineralised in microgravity. Bone loss, therefore, remains a major concern and if not annulled could be so severe as to jeopardise an extended human presence in space. In addition, current exercise regimes occupy valuable crew time, and astronauts often find the equipment cumbersome and uncomfortable to use. Recent studies suggest that exposing the body to short periods (<20mins) of low magnitude (<1g), high frequency (15-35Hz) signals (vibration) everyday could reduce, even prevent, bone loss during conditions such as osteoporo- sis on earth. The new vibration therapy treatment could also have several advantages over existing exercise countermeasures used in spaceflight due to it being very simple to operate, relatively inexpensive, and requiring only short periods of time `training', unlike the complicated, expensive and time-consuming devices currently used. This review highlights the detrimen- tal effects that microgravity has on the strength and integrity of bone, how current countermeasures are ineffective at stemming this level of deterioration, and how new vibration techniques could significantly reduce space-induced bone loss.

  19. Influence of enhancement filters in apical bone loss measurement: A cone-beam computed tomography study.

    PubMed

    de Sousa, Emerson-Tavares; Pinheiro, Mayara-Abreu; Maciel, Patrícia-Pereira; Sales, Marcelo-Augusto-Oliveira

    2017-04-01

    The use of cone-beam computed tomography images (CBCT) providing a better assessment of bone injuries, although the sensibility of lesions measurement might be improved by the use of enhancement filters. Objective: This study aimed to analyze the influence of enhancement filters in apical bone loss measurement. Eighteen CBCT cases randomly selected of apical bone loss were evaluated. The analyses were carried out following the evaluation in axial, coronal and sagittal protocols, using enhancement filters as Hard, Normal, and Very Sharp. The variables were statistically analyzed by Friedman and Wilcoxon test, Spearman's rho, and intraclass correlation coefficient. The differences between filters in axial and sagittal protocols were significant (p<0.05); however, this was not observed in the coronal slice. The use of Hard filter demonstrates better results than Very Sharp and Normal filter, improving significantly the bone loss measurement. A strong, significant and positive correlation was noted for all filters (with p< 0.001), such as a strong agreement between the variables, when the Normal filter was used as a reference. The use of enhancement filters increases the sensitivity of alveolar bone loss measurement, with relative advantage for Hard filter. Key words:Cone-Beam computed tomography. endodontics. periapical periodontitis. image enhancement. alveolar bone loss.

  20. Aspirin prevents bone loss with little mechanical improvement in high-fat-fed ovariectomized rats.

    PubMed

    Lin, Sien; Lee, Wayne Y W; Huang, Meiling; Fu, Ziwei; Liang, Yanlong; Wu, Haiyou; Xu, Liangliang; Suen, Chun Wai; Huang, Jianping; Wu, Tie; Cui, Liao; Li, Gang

    2016-11-15

    Obesity and osteoporosis are often concurrently happened in the menopausal women. Obesity in menopausal women is not only related to a high risk of cardiovascular disease, but also results in a detrimental effect on bone health. This study aimed to investigate the effects of aspirin, a popular anti-thrombosis drug, on bone quantity and quality in the high-fat-fed animal model. Adult female rats were subjected to either sham operations or ovariectomized operations. The ovariectomized rats were orally administered with deionized water or standardized high fat emulsion with or without aspirin. All rats were injected with calcein before killed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, micro-computed tomography analysis, mechanical test, and component analysis were performed after 12 weeks. In vitro cell culture was also performed to observe the effect of aspirin in osteogenesis. We found that high fat remarkably impaired bone formation and bone biomechanics. Aspirin treatment significantly prevented bone loss by increasing bone formation. In vitro studies also validated the enhancement of osteogenic differentiation. However, aspirin presented no significant improvement in bone mechanical properties. Component analysis shown aspirin could significantly increase the content of mineral, but had limited effect on the content of collagen. In conclusion, aspirin is beneficial for the prevention of bone loss; meanwhile, it may cause an imbalance in the components of bone which may weaken the mechanical properties. The current study provided further evidence that aspirin might not be powerful for the prevention of fracture in osteoporotic patients.

  1. Protective effect of Pycnogenol® on ovariectomy-induced bone loss in rats.

    PubMed

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2012-01-01

    Pycnogenol® (PYC) is a natural plant extract from the bark of Pinus pinaster and has potent antioxidant activities. The protective effect of PYC on bone loss was studied in multiparous ovariectomized (OVX) female rats. Pycnogenol® (30 or 15 mg/kg body weight/day) was administered orally to 8-month-old OVX rats for 3 months. At the end of the experiment, bone strength was measured by a three-point bending test and bone mineral density was estimated by peripheral quantitative computed tomography. Ovariectomy significantly decreased femur bone strength and bone density. Supplementation with PYC suppressed the bone loss induced by OVX. The OVX treatment significantly increased serum osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTx). Supplementation with PYC reduced the serum OC and CTx in OVX rats to a level similar to that of the sham-operated group. The results indicated that orally administered PYC can decrease the bone turnover rate in OVX rats, resulting in positive effects on the biomechanical strength of bone and bone mineral density.

  2. Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet?

    PubMed

    Hanley, David A; Whiting, Susan J

    2013-01-01

    A popular concept in nutrition and lay literature is that of the role of a diet high in acid or protein in the pathogenesis of osteoporosis. A diet rich in fruit and vegetable intake is thought to enhance bone health as the result of its greater potassium and lower "acidic" content than a diet rich in animal protein and sodium. Consequently, there have been a number of studies of diet manipulation to enhance potassium and "alkaline" content of the diet to improve bone density or other parameters of bone health. Although acid loading or an acidic diet featuring a high protein intake may be associated with an increase in calciuria, the evidence supporting a role of these variables in the development of osteoporosis is not consistent. Similarly, intervention studies with a more alkaline diet or use of supplements of potassium citrate or bicarbonate have not consistently shown a bone health benefit. In the elderly, inadequate protein intake is a greater problem for bone health than protein excess. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  3. Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

    PubMed Central

    Cooper, Cyrus; Roux, Christian; Díez-Pérez, Adolfo; Guillemin, Francis; Jonsson, Bengt; Ortolani, Sergio; Pfeilschifter, Johannes; Horne, Rob; Kakad, Shilpa; Shepherd, Susan; Möller, Gerd; Marciniak, Anne; Martinez, Luc

    2010-01-01

    Summary Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries. Purpose The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications. Methods Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year. Results Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was −2.7 (SD 0.89; median −2.7 [interquartile range, −3.2, −2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study. Conclusions POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care. PMID:21258637

  4. An open, crossover trial of calcium-fortified milk in prevention of early postmenopausal bone loss.

    PubMed

    Cleghorn, D B; O'Loughlin, P D; Schroeder, B J; Nordin, B E

    2001-09-03

    To establish whether calcium-enriched milk reduces bone loss in women who are within five years of the menopause and have a basal calcium intake < or = 1,250 mg. Two-year open, crossover study. A community-based study carried out in Adelaide, South Australia, between September 1997 and June 2000. 115 women recruited by newspaper advertisement, who were less than five years postmenopausal, were not taking hormone or other therapy that could affect bone and had a usual calcium intake < or = 1,250 mg daily. Participants were randomly allocated to Group 1 (who received a supplement of 3 L of calcium-fortified milk weekly in the first year) or Group 2 (who followed their usual diets in the first year). In the second year, Group 1 reverted to their usual diets, and Group 2 received the milk supplement. Difference in loss of bone mineral density (BMD) at the spine and forearm in the same individuals on and off the milk supplement; urinary excretion of bone resorption markers in a subset of 72 participants in the first year. With each woman serving as her own control, the rate of bone loss from the spine was 1.76 percentage points less when the women were taking the milk supplement than when they were on their usual diet (95% CI, 0.54%-2.98%; P=0.006). However, there was no significant difference in bone loss in the forearm. Fasting urine levels of two markers of bone resorption (hydroxyproline and deoxypyridinoline) were significantly lower in 36 women in the milk group than in 36 women in the usual-diet group (P=0.03 for both markers). Supplementing the diet with calcium-fortified milk early in the postmenopausal period delays bone loss at the spine but not at the forearm, and reduces the excretion of bone resorption markers.

  5. Mechanisms of Radiation-Induced Bone Loss and Effects on Prostate Cancer Bone Metastases

    DTIC Science & Technology

    2013-06-01

    and in vivo bone imaging [months 6-10]. b. Determine apoptosis of bone cells (OT, OB & OC) by quantifying TUNEL staining [months 6-10]. Animal...Zoledronic acid will be used as positive control for inhibition of apoptosis and also inhibition of resorption [month 10]. c. Perform in vivo bone imaging ...described and presented in Task 3. Task 5: Image calvarial osteocytes in real-time after single dose exposure of 2 Gy [months 6-12] A single dose of

  6. Tail-suspended mice lacking calponin H1 experience decreased bone loss.

    PubMed

    Yotsumoto, Naoki; Takeoka, Michiko; Yokoyama, Minesuke

    2010-07-01

    Calponin h1 (CNh1) is an actin-binding protein originally isolated from vascular smooth muscle and has been reported to suppress bone formation. We are therefore curious how CNh1 is involved in bone loss that is caused by space flight in microgravity. We assessed the effects of tail suspension (TS) in C57BL/6J wild (CN+/+) and CNh1-deleted (CN-/-) mice to elucidate the role of CNh1 in bone loss under weightless conditions. Bone mineral density (BMD) of tibiae was measured by single energy X-ray absorptiometry, and bone volume fraction (BV/TV), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured by bone histomorphometry. BMD, BV/TV, MAR, and BFR/BS were lower in CN+/+ mice with TS than in those without. In the CN-/- group, however, the decrease in each of these parameters by TS was ameliorated. Decreases in serum osteocalcin levels by TS in CN+/+ mice were attenuated in CN-/- mice. Furthermore, urinary deoxypyridinolin (DPD), an indicator of bone resorption, was increased in CN+/+ mice following TS, but not in CN-/- mice. In transfection experiments, the degree of induction of bone formation markers, alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)-4 mRNA expression, under stimulation with BMP-2, was lower in MC3T3-E1 mouse osteoblast-like cells expressing CNh1 than that in mock transfected cells. Notably, the BMP-2-induced ALP activity was decreased by CNh1 expression, which was partially rescued by treatment with the Rho kinase inhibitor Y27632. Taken together, these results indicate that CNh1 is responsible for weightlessness-induced bone loss in part through Rho signaling pathway.

  7. Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced alveolar bone loss in rats.

    PubMed

    Li, Xianxian; Wu, Xiangnan; Ma, Yuanyuan; Hao, Zhichao; Chen, Shenyuan; Fu, Taozi; Chen, Helin; Wang, Hang

    2015-05-01

    5-Hydroxytryptophan (5-HTP) is the precursor of serotonin and 5-HTP has been widely used as a dietary supplement to raise serotonin level. Serotonin has recently been discovered to be a novel and important player in bone metabolism. As peripheral serotonin negatively regulates bone, the regular take of 5-HTP may affect the alveolar bone metabolism and therefore influence the alveolar bone loss induced by periodontitis. The aim of this study was to investigate the effect of 5-HTP on alveolar bone destruction in periodontitis. Male Sprague-Dawley rats were randomly divided into the following four groups: (1) the control group (without ligature); (2) the 5-HTP group (5-HTP at 25 mg/kg/day without ligature); (3) the L group (ligature+saline placebo); and (4) the L+5-HTP group (ligature+5-HTP at 25 mg/kg/day). Serum serotonin levels were determined by ELISA. The alveolar bones were evaluated with micro-computed tomography and histology. Tartrate-resistant acid phosphatase staining was used to assess osteoclastogenesis. The receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) expression in the periodontium as well as the interleukin-6 positive osteocytes were analysed immunohistochemically. 5-HTP significantly increased serum serotonin levels. In rats with experimental periodontitis, 5-HTP increased alveolar bone resorption and worsened the micro-structural destruction of the alveolar bone. 5-HTP also stimulated osteoclastogenesis and increased RANKL/OPG ratio and the number of IL-6 positive osteocytes. However, 5-HTP treatment alone did not cause alveolar bone loss in healthy rats. The present study showed that 5-HTP aggravated alveolar bone loss, deteriorated alveolar bone micro-structure in the presence of periodontitis, which suggests 5-HTP administration may increase the severity of periodontitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.

    PubMed

    Lennox, Alanda R; Goodship, Allen E

    2008-02-01

    Some hibernating animals are known to reduce muscle and bone loss associated with mechanical unloading during prolonged immobilisation,compared to humans. However, here we show that wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid significant bone loss altogether, despite six months of continuous hibernation. Using serum biochemical markers of bone turnover, we showed that concentrations for bone resorption are not significantly increased as a consequence of hibernation in wild polar bears. This is in sharp contrast to previous studies on other hibernating species, where for example, black bears (Ursus americanus), show a 3-4 fold increase in serum bone resorption concentrations posthibernation,and must compensate for this loss through rapid bone recovery on remobilisation, to avoid the risk of fracture. In further contrast to black bears, serum concentrations of bone formation markers were highly significantly increased in pregnant female polar bears compared to non-pregnant,thus non-hibernating females both prior to and after hibernation. However, bone formation concentrations in new mothers were significantly reduced compared to pre-hibernation concentrations. The de-coupling of bone turnover in favour of bone formation prior to hibernation, suggests that wild polar bears may posses a unique physiological mechanism for building bone in protective preparation against expected osteopenia associated with disuse,starvation, and hormonal drives to mobilise calcium for reproduction, during hibernation. Understanding this physiological mechanism could have profound implications for a natural solution for the prevention of osteoporosis in animals subjected to captivity with inadequate space for exercise,humans subjected to prolonged bed rest while recovering from illness, or astronauts exposed to antigravity during spaceflight.© 2008 Elsevier Inc. All rights reserved.

  9. Comparative study between two techniques for alveolar bone loss assessment: A pilot study

    PubMed Central

    Lira-Júnior, Ronaldo; Freires, Irlan de Almeida; de Oliveira, Isabelle LinsMacêdo; da Silva, Ennyo Sobral Crispim; da Silva, SeverinoCelestino; de Brito, Roberto Lira

    2013-01-01

    Objective: To conduct a comparative study between two techniques for assessment of alveolar bone loss. Materials and Methods: Absolute and relative techniques were evaluated. The sample consisted of 16 radiographs supposed to meet a single criterion: The reference points applied (Cementum-enamel junction (CEJ) alveolar bone crest and root apex) should be visible. Bone height was measured in the selected radiographs as the percentage of root length through both techniques. Data were submitted to the Statistical Package for Social Science software. Results obtained by both methods were converted into bone loss index values and then categorized. Sensitivity and specificity of the relative technique, compared to the absolute technique, were calculated. Wilcoxon test and the Bland and Altman's method were employed for comparisons. Significance level was set at 5%. Results: For the absolute and relative techniques, means of bone loss index were respectively of 4.81 (±2.25) and 4.75 (±1.80). Bone loss index ≥6 (alveolar bone loss ≥50%) was found in 5 (31.2%) teeth, in the absolute technique, and in 4 (25%) teeth, according to the relative technique. There was no statistically significant difference between both methods (P>0.05). According to the Bland and Altman's method, it was verified a bias of 0.06, and limits of upper and lower agreement of, respectively, 1.58 and –1.45. Sensitivity of 0.8 and specificity of 1 were found for the relative technique compared to the absolute one. Conclusion: There was no significant difference between the techniques evaluated, and the relative technique was found to be reliable for measuring alveolar bone loss. PMID:23633780

  10. Diabetes mellitus may increase bone loss after occlusal trauma and experimental periodontitis.

    PubMed

    de Oliveira Diniz, Claudia K; Corrêa, Mônica G; Casati, Marcio Z; Nociti, Francisco H; Ruiz, Karina G; Bovi Ambrosano, Gláucia Maria; Sallum, Enilson A

    2012-10-01

    Diabetes mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues, resulting in more prevalent and severe periodontitis and impaired bone formation. Occlusal trauma (OT) is an injury of the supportive periodontium that results in bone loss. It can be hypothesized that DM would increase bone loss after OT, mainly when associated with periodontitis. Thus, the aim of the present study is to evaluate the influence of DM on bone response in the furcation area of teeth subjected to OT in the presence, or absence, of experimental periodontitis (EP) in the rat model. Thirty-two male Wistar rats were assigned to four groups: 1) group 1 (G1): DM+OT+EP (n = 8); 2) group 2 (G2): DM+OT (n = 8); 3) group 3 (G3): OT+EP (n = 8); and 4) group 4 (G4): OT (n = 8). G1 and G2 received a single intraperitoneal injection of streptozotocin (STZ). After 10 days, G1 and G3 were subjected to EP by ligature placement. Fifteen days after the start of EP, OT was induced by the creation of a premature contact. The animals were euthanized 35 days after DM induction. DM enhanced bone loss in the presence of OT combined with EP, but did not increase bone loss in teeth subjected to OT alone. EP caused greater bone loss when associated with OT. Within the limits of this animal study, it can be concluded that DM enhances bone loss in the presence of occlusal trauma associated with EP.

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

    PubMed Central

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

    2015-01-01

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

  12. A Losing Battle: Weight Regain Does Not Restore Weight Loss-Induced Bone Loss in Postmenopausal Women

    PubMed Central

    Villalon, Karen L.; Gozansky, Wendolyn S.; Van Pelt, Rachael E.; Wolfe, Pam; Jankowski, Catherine M.; Schwartz, Robert S.; Kohrt, Wendy M.

    2013-01-01

    Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m2. They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow-up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (−1.7 ± 3.5%; P = 0.002) and hip (−0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C-terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (−0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: −3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss. PMID:21852813

  13. A statistical method (cross-validation) for bone loss region detection after spaceflight

    PubMed Central

    Zhao, Qian; Li, Wenjun; Li, Caixia; Chu, Philip W.; Kornak, John; Lang, Thomas F.

    2010-01-01

    Astronauts experience bone loss after the long spaceflight missions. Identifying specific regions that undergo the greatest losses (e.g. the proximal femur) could reveal information about the processes of bone loss in disuse and disease. Methods for detecting such regions, however, remains an open problem. This paper focuses on statistical methods to detect such regions. We perform statistical parametric mapping to get t-maps of changes in images, and propose a new cross-validation method to select an optimum suprathreshold for forming clusters of pixels. Once these candidate clusters are formed, we use permutation testing of longitudinal labels to derive significant changes. PMID:20632144

  14. A statistical method (cross-validation) for bone loss region detection after spaceflight.

    PubMed

    Zhao, Qian; Li, Wenjun; Li, Caixia; Chu, Philip W; Kornak, John; Lang, Thomas F; Fang, Jiqian; Lu, Ying

    2010-06-01

    Astronauts experience bone loss after the long spaceflight missions. Identifying specific regions that undergo the greatest losses (e.g. the proximal femur) could reveal information about the processes of bone loss in disuse and disease. Methods for detecting such regions, however, remains an open problem. This paper focuses on statistical methods to detect such regions. We perform statistical parametric mapping to get t-maps of changes in images, and propose a new cross-validation method to select an optimum suprathreshold for forming clusters of pixels. Once these candidate clusters are formed, we use permutation testing of longitudinal labels to derive significant changes.

  15. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

    PubMed

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2009-12-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

  16. Composite Bone and Soft Tissue Loss Treated with Distraction Histiogenesis

    DTIC Science & Technology

    2010-01-01

    Mahuluxmivala, J., Nadarajah, R., Allen, P. W., et al. Ilizarov external fixator: acute shortening and lengthening versus bone transport in the management of...Presented at the Limb Lengthening and Reconstruction Society Annual Meeting 2006,William Beaumont Army Medical Center, Texas Tech University Health... lengthening by the Ilizarov technique. Clin. Orthop. Relat. Res. 250:81– 104, 1990. 28 JOURNAL OF SURGICAL ORTHOPAEDIC ADVANCES

  17. Moderate zinc supplementation during prolonged steroid therapy exacerbates bone loss in rats.

    PubMed

    Kamal, Rozy; Bansal, S C; Khandelwal, N; Rai, D V; Dhawan, D K

    2014-09-01

    The present study was conducted to understand the influence of zinc on bone mineral metabolism in prednisolone-treated rats. Disturbance in bone mineral metabolism was induced in rats by subjecting them to prednisolone treatment for a period of 8 weeks. Female rats aged 6-8 weeks weighing 150 to 200 g were divided into four treatment groups, viz., normal control, prednisolone-treated (40 mg/kg body weight orally, thrice a week), zinc-treated (227 mg/L in drinking water, daily), and combined prednisolone + zinc-treated groups. Parameters such as changes in mineral levels in the bone and serum, bone mineral density (BMD), bone mineral content (BMC), and bone 99m-technetium-labeled methylene diphosphonate ((99m)Tc-MDP) uptake were studied in various treatment groups. Prednisolone treatment caused an appreciable decrease in calcium levels both in the bone and serum and also in bone dry weight, BMC, and BMD in rats. Prednisolone-treated rats when supplemented with zinc showed further reduction in calcium levels, bone dry weight, BMD, and BMC. The study therefore revealed that moderate intake of zinc as a nutritional supplement during steroid therapy could enhance calcium deficiency in the body and accelerate bone loss.

  18. Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

    PubMed Central

    Spirlandeli, Adriano L.; Dick-de-Paula, Ingrid; Zamarioli, Ariane; Jorgetti, Vanda; Ramalho, Leandra N.Z.; Nogueira-Barbosa, Marcello H.; Volpon, Jose B.; Jordão, Alceu A.; Cunha, Fernando Q.; Fukada, Sandra Y.; de Paula, Francisco J.A.

    2017-01-01

    OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice. PMID:28492723

  19. Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment.

    PubMed

    Spirlandeli, Adriano L; Dick-de-Paula, Ingrid; Zamarioli, Ariane; Jorgetti, Vanda; Ramalho, Leandra N Z; Nogueira-Barbosa, Marcello H; Volpon, Jose B; Jordão, Alceu A; Cunha, Fernando Q; Fukada, Sandra Y; de Paula, Francisco J A

    2017-04-01

    The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

  20. Effects of Resveratrol Supplementation on Methotrexate Chemotherapy-Induced Bone Loss

    PubMed Central

    Lee, Alice M. C.; Shandala, Tetyana; Soo, Pei Pei; Su, Yu-Wen; King, Tristan J.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

    2017-01-01

    Intensive cancer chemotherapy is known to cause bone defects, which currently lack treatments. This study investigated the effects of polyphenol resveratrol (RES) in preventing bone defects in rats caused by methotrexate (MTX), a commonly used antimetabolite in childhood oncology. Young rats received five daily MTX injections at 0.75 mg/kg/day. RES was orally gavaged daily for seven days prior to, and during, five-day MTX administration. MTX reduced growth plate thickness, primary spongiosa height, trabecular bone volume, increased marrow adipocyte density, and increased mRNA expression of the osteogenic, adipogenic, and osteoclastogenic factors in the tibial bone. RES at 10 mg/kg was found not to affect bone health in normal rats, but to aggravate the bone damage in MTX-treated rats. However, RES supplementation at 1 mg/kg preserved the growth plate, primary spongiosa, bone volume, and lowered the adipocyte density. It maintained expression of genes involved in osteogenesis and decreased expression of adipogenic and osteoclastogenic factors. RES suppressed osteoclast formation ex vivo of bone marrow cells from the treated rats. These data suggest that MTX can enhance osteoclast and adipocyte formation and cause bone loss, and that RES supplementation at 1 mg/kg may potentially prevent these bone defects. PMID:28282956

  1. Chromatin organization as an indicator of glucocorticoid induced natural killer cell dysfunction.

    PubMed

    Misale, Michael S; Witek Janusek, Linda; Tell, Dina; Mathews, Herbert L

    2017-09-12

    It is well-established that psychological distress reduces natural killer cell immune function and that this reduction can be due to the stress-induced release of glucocorticoids. Glucocorticoids are known to alter epigenetic marks associated with immune effector loci, and are also known to influence chromatin organization. The purpose of this investigation was to assess the effect of glucocorticoids on natural killer cell chromatin organization and to determine the relationship of chromatin organization to natural killer cell effector function, e.g. interferon gamma production. Interferon gamma production is the prototypic cytokine produced by natural killer cells and is known to modulate both innate and adaptive immunity. Glucocorticoid treatment of human peripheral blood mononuclear cells resulted in a significant reduction in interferon gamma production. Glucocorticoid treatment also resulted in a demonstrable natural killer cell nuclear phenotype. This phenotype was localization of the histone, post-translational epigenetic mark, H3K27me3, to the nuclear periphery. Peripheral nuclear localization of H3K27me3 was directly related to cellular levels of interferon gamma. This nuclear phenotype was determined by direct visual inspection and by use of an automated, high through-put technology, the Amnis ImageStream. This technology combines the per-cell information content provided by standard microscopy with the statistical significance afforded by large sample sizes common to standard flow cytometry. Most importantly, this technology provides for a direct assessment of the localization of signal intensity within individual cells. The results demonstrate glucocorticoids to dysregulate natural killer cell function at least in part through altered H3K27me3 nuclear organization and demonstrate H3K27me3 chromatin organization to be a predictive indicator of glucocorticoid induced immune dysregulation of natural killer cells. Copyright © 2017 Elsevier Inc. All rights

  2. Regulation of transport across cell membranes by the serum- and glucocorticoid-inducible kinase SGK1.

    PubMed

    Lang, Florian; Stournaras, Christos; Alesutan, Ioana

    2014-02-01

    The serum- and glucocorticoid-inducible kinase 1 (SGK1) is genomically upregulated by cell stress including energy depletion and hyperosmotic shock as well as a variety of hormones including glucocorticoids, mineralocorticoids and TGFβ. SGK1 is activated by insulin, growth factors and oxidative stress via phosphatidylinositide-3-kinase, 3-phosphoinositide-dependent kinase PDK1 and mTOR. SGK1 is a powerful stimulator of Na(+)/K(+)-ATPase, carriers (e.g., NCC, NKCC, NHE1, NHE3, SGLT1, several amino acid transporters) and ion channels (e.g., ENaC, SCN5A, TRPV4-6, ORAI1/STIM1, ROMK, KCNE1/KCNQ1, GluR6, CFTR). Mechanisms employed by SGK1 in transport regulation include direct phosphorylation of target transport proteins, phosphorylation and thus activation of other transport regulating kinases, stabilization of membrane proteins by phosphorylation and thus inactivation of the ubiquitin ligase NEDD4-2, as well as stimulation of transport protein expression by upregulation transcription factors (e.g., nuclear factor kappa-B [NFκB]) and by fostering of protein translation. SGK1 sensitivity of pump, carrier and channel activities participate in the regulation of epithelial transport, cardiac and neuronal excitability, degranulation, platelet function, migration, cell proliferation and apoptosis. SGK1-sensitive functions do not require the presence of SGK1 but are markedly upregulated by SGK1. Accordingly, the phenotype of SGK1 knockout mice is mild. The mice are, however, less sensitive to excessive activation of transport by glucocorticoids, mineralocorticoids, insulin and inflammation. Moreover, excessive SGK1 activity contributes to the pathophysiology of hypertension, obesity, diabetes, thrombosis, stroke, inflammation, autoimmune disease, fibrosis and tumor growth.

  3. Glucocorticoid-induced suppression of β-cell proliferation is mediated by Mig6.

    PubMed

    Colvin, E Scott; Ma, Hong-Yun; Chen, Yi-Chun; Hernandez, Angelina M; Fueger, Patrick T

    2013-03-01

    Glucocorticoids can cause steroid-induced diabetes or accelerate the progression to diabetes by creating systemic insulin resistance and decreasing functional β-cell mass, which is influenced by changes in β-cell function, growth, and death. The synthetic glucocorticoid agonist dexamethasone (Dex) is deleterious to functional β-cell mass by decreasing β-cell function, survival, and proliferation. However, the mechanism by which Dex decreases β-cell proliferation is unknown. Interestingly, Dex induces the transcription of an antiproliferative factor and negative regulator of epidermal growth factor receptor signaling, Mig6 (also known as gene 33, RALT, and Errfi1). We, therefore, hypothesized that Dex impairs β-cell proliferation by increasing the expression of Mig6 and thereby decreasing downstream signaling of epidermal growth factor receptor. We found that Dex induced Mig6 and decreased [(3)H]thymidine incorporation, an index of cellular replication, in mouse, rat, and human islets. Using adenovirally delivered small interfering RNA targeted to Mig6 in rat islets, we were able to limit the induction of Mig6 upon exposure to Dex, compared with islets treated with a control virus, and completely rescued the Dex-mediated impairment in replication. We demonstrated that both Dex and overexpression of Mig6 attenuated the phosphorylation of ERK1/2 and blocked the G(1)/S transition of the cell cycle. In conclusion, Mig6 functions as a molecular brake for β-cell proliferation during glucocorticoid treatment in β-cells, and thus, Mig6 may be a novel target for preventing glucocorticoid-induced impairments in functional β-cell mass.

  4. Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells.

    PubMed

    Wilson, Sylvia M; Shen, Pamela; Rider, Christopher F; Traves, Suzanne L; Proud, David; Newton, Robert; Giembycz, Mark A

    2009-11-15

    Prostacyclin receptor (IP-receptor) agonists display anti-inflammatory and antiviral activity in cell-based assays and in preclinical models of asthma and chronic obstructive pulmonary disease. In this study, we have extended these observations by demonstrating that IP-receptor activation also can enhance the ability of glucocorticoids to induce genes with anti-inflammatory activity. BEAS-2B bronchial epithelial cells stably transfected with a glucocorticoid response element (GRE) luciferase reporter were activated in a concentration-dependent manner by the glucocorticoid dexamethasone. An IP-receptor agonist, taprostene, increased cAMP in these cells and augmented luciferase expression at all concentrations of dexamethasone examined. Analysis of the concentration-response relationship that described this effect showed that taprostene increased the magnitude of transcription without affecting the potency of dexamethasone and was, thus, steroid-sparing in this simple system. RO3244794, an IP-receptor antagonist, and oligonucleotides that selectively silenced the IP-receptor gene, PTGIR, abolished these effects of taprostene. Infection of BEAS-2B GRE reporter cells with an adenovirus vector encoding a highly selective inhibitor of cAMP-dependent protein kinase (PKA) also prevented taprostene from enhancing GRE-dependent transcription. In BEAS-2B cells and primary cultures of human airway epithelial cells, taprostene and dexamethasone interacted either additively or cooperatively in the expression of three glucocorticoid-inducible genes (GILZ, MKP-1, and p57(kip2)) that have anti-inflammatory potential. Collectively, these data show that IP-receptor agonists can augment the ability of glucocorticoids to induce anti-inflammatory genes in human airway epithelial cells by activating a cAMP/PKA-dependent mechanism. This observation may have clinical relevance in the treatment of airway inflammatory diseases that are either refractory or respond suboptimally to

  5. Glucocorticoid-induced leucine zipper overexpression inhibits lipopolysaccharide-induced retinal inflammation in rats.

    PubMed

    Gu, Ruiping; Lei, Boya; Shu, Qinmeng; Li, Gang; Xu, Gezhi

    2017-02-24

    Glucocorticoid-induced leucine zipper (GILZ) mediates several effects of glucocorticoids and has important anti-inflammatory properties. Here, we explored the role of GILZ in inhibiting retinal inflammation. Endotoxin-induced uveitis (EIU) was established in rats by intravitreal injection of lipopolysaccharide (LPS). GILZ levels decreased in the EIU retina at 4 h after LPS injection and slowly recovered within 24 h. Retinal GILZ was downregulated by recombinant lentivirus-delivered short-hairpin RNA targeting GILZ (shRNA-GILZ-rLV) and upregulated by recombinant lentivirus-mediated GILZ overexpression (Oe-GILZ-rLV). GILZ silencing attenuated the anti-inflammatory effects of intravitreal injection of triamcinolone acetonide (TA) in the EIU retina, as demonstrated by increased retinal interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1and intercellular cell adhesion molecule-1 expression at 18 h after TA injection. A Bio-Plex cytokine assay and western blotting demonstrated that GILZ overexpression inhibited the effects of LPS, downregulating retinal IL-1β, MCP-1, MIP-1α, and IL-17 and inhibiting LPS-induced activation of the retinal toll-like receptor 4-myeloid differentiation factor 88 signaling pathway. At 48 and 72 h after LPS injection, the clinical score of inflammation was significantly lower in Oe-GILZ-rLV-transfected eyes than in blank-rLV-transfected eyes. Histological examination showed a 67.85% reduction of infiltrating inflammatory cells in the anterior chamber and a 58.97% reduction in vitreous cavity of Oe-GILZ-rLV transfected eyes at 48 h after LPS injection. Taken together, our results suggest that GILZ is a novel therapeutic target for the treatment of retinal inflammatory diseases.

  6. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

    PubMed

    Buckley, Lenore; Guyatt, Gordon; Fink, Howard A; Cannon, Michael; Grossman, Jennifer; Hansen, Karen E; Humphrey, Mary Beth; Lane, Nancy E; Magrey, Marina; Miller, Marc; Morrison, Lake; Rao, Madhumathi; Robinson, Angela Byun; Saha, Sumona; Wolver, Susan; Bannuru, Raveendhara R; Vaysbrot, Elizaveta; Osani, Mikala; Turgunbaev, Marat; Miller, Amy S; McAlindon, Timothy

    2017-08-01

    To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users. Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made. This guideline provides direction for clinicians and patients making treatment decisions. Clinicians

  7. Osteoporosis, a unitary hypothesis of collagen loss in skin and bone.

    PubMed

    Shuster, Sam

    2005-01-01

    Progress in osteoporosis has been stultified by repetitive, statistic-driven studies and catechistic reviews; in the absence of concept and hypothesis research is aimless, and the trivial associations it continually reveals, has led to the cul-de-sac of multifactorialism. A return to hypothesis-led research which seeks major causal defects and the conclusive therapies that arise from them is essential. The hypothesis proposed evolved from research into the mechanism of senile purpura. This predicted a causal loss of skin collagen that was contrary to contemporary opinion, but was confirmed when collagen was expressed absolutely, instead as a percentage or ratio: women have less collagen than men and it decreases by 1% a year in exposed and unexposed skin. Corticosteroids (which also produce shear purpura) reduce skin collagen and androgen and virilism increase it; growth hormone produces the greatest increase, and there is a decrease in hypopituitarism. All these changes in skin collagen correspond to changes in bone density, and the circumstances are too various for coincidence. This led to the hypothesis that the changes found in skin collagen also occur in bone collagen, leading to the associated changes in bone density; thus a loss of collagen in skin and bones with aging is the causal counterpart to loss of bone density in senile osteoporosis. If this is correct then, as with aging, androgen and virilisation, corticosteroids, growth hormone and hypopituitarism, changes in bone density should correspond to systemic changes in skin collagen. This correspondence is found to occur in osteogenesis imperfecta and Ehlers-Danlos syndrome, two genetically discrete families of disordered collagen production, and other situations, e.g., scurvy and homocystinuria. A primary loss of collagen in osteoporotic bones is an essential prediction of the hypothesis; in fact this loss is well established but, inexplicably, it has been assumed to be secondary to the bone loss

  8. Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats

    PubMed Central

    Sun, Yuxin; Lin, Sien; Gu, Weidong; Liu, Yamei; Zhang, Jinfang; Chen, Lin; Li, Gang

    2016-01-01

    Mesenchymal stem cells (MSCs) have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1) Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2) Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX) rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX) and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91). Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn’t show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study

  9. Two Different Isomers of Vitamin E Prevent Bone Loss in Postmenopausal Osteoporosis Rat Model

    PubMed Central

    Muhammad, Norliza; Luke, Douglas Alwyn; Shuid, Ahmad Nazrun; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV) and trabecular number (Tb.N) and an increase in trabecular separation (Tb.S). The increase in osteoclast surface (Oc.S) and osteoblast surface (Ob.S) in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model. PMID:23118785

  10. Effects of food groups and dietary nutrients on bone loss in elderly Chinese population.

    PubMed

    Chan, R; Woo, J; Leung, J

    2011-04-01

    To examine the effects of food groups and dietary nutrients on bone loss in elderly Chinese population. Prospective cohort study. A longitudinal study started at 2001 in Hong Kong. 1225 Chinese men and 992 women aged 65 years and over in the community. Daily intake of food groups and dietary nutrients at baseline was assessed by a food frequency questionnaire. Nutrient intake was adjusted for energy intake by residual method. Linear regression was used to examine the association of BMD change and food group or energy-adjusted nutrient intake with adjustment for demographic, anthropometric, lifestyle factors, and daily energy intake (for food group only). Higher fish intake was associated with smaller bone loss in hip (B=-0.611, p=0.004) and femoral neck (B=-0.724, p=0.040) in men. None of the food groups were associated with bone loss in both measured sites in women. For men, lower intake of protein (B=-0.012, p=0.003), phosphorus (B=-0.0008, p=0.001), sodium (B=-0.0002, p=0.023) and isoflavone (B=-1.084, p=0.030) was associated with greater BMD loss in hip, whereas lower intake of protein (B=-0.018, p=0.006) and sodium (B=-0.0004, p=0.018) was associated with greater BMD loss in femoral neck. However, these significant associations disappeared after further adjustment for energy-adjusted calcium and vitamin D intakes. None of the nutrients were associated with BMD loss in both measured sites in women. Greater fish intake may help to reduce bone loss in this sample of elderly Chinese men. The significant association between various nutrients and bone loss in elderly Chinese men was likely due to the influence of dietary calcium and vitamin D intakes. The role of food groups and dietary nutrients on bone health in this sample of elderly Chinese women seems to be minimal.

  11. Targeting cellular senescence prevents age-related bone loss in mice.

    PubMed

    Farr, Joshua N; Xu, Ming; Weivoda, Megan M; Monroe, David G; Fraser, Daniel G; Onken, Jennifer L; Negley, Brittany A; Sfeir, Jad G; Ogrodnik, Mikolaj B; Hachfeld, Christine M; LeBrasseur, Nathan K; Drake, Matthew T; Pignolo, Robert J; Pirtskhalava, Tamar; Tchkonia, Tamara; Oursler, Merry Jo; Kirkland, James L; Khosla, Sundeep

    2017-09-01

    Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi). In aged (20- to 22-month-old) mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAKi for 2-4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice. The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

  12. Androgen receptors and experimental bone loss - an in vivo and in vitro study.

    PubMed

    Steffens, Joao Paulo; Coimbra, Leila Santana; Rossa, Carlos; Kantarci, Alpdogan; Van Dyke, Thomas E; Spolidorio, Luis Carlos

    2015-12-01

    Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor. Copyright © 2015 Elsevier Inc. All rights

  13. Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

    NASA Astrophysics Data System (ADS)

    Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

    2017-08-01

    Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the

  14. Androgen receptors and experimental bone loss – An in vivo and in vitro study

    PubMed Central

    Steffens, Joao Paulo; Coimbra, Leila Santana; Rossa, Carlos; Kantarci, Alpdogan; Van Dyke, Thomas E.; Spolidorio, Luis Carlos

    2015-01-01

    Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1- orchiectomy (OCX); 2- OCX sham-surgery; or 3- OCX sham-surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor. PMID:26450018

  15. Ladder-Climbing Training Prevents Bone Loss and Microarchitecture Deterioration in Diet-Induced Obese Rats.

    PubMed

    Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Liu, Chentao; Wang, Xudan; Han, Yanqi; Zhao, Xinjuan; Chi, Aiping; Sun, Lijun

    2016-01-01

    Resistance exercise has been proved to be effective in improving bone quality in both animal and human studies. However, the issue about whether resistance exercise can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of ladder-climbing training, one of the resistance exercises, on bone mechanical properties and microarchitecture in high-fat (HF) diet-induced obese rats. Twenty-four rats were randomly assigned to the Control, HF + sedentary (HF-S) and HF + ladder-climbing training (HF-LCT) groups. Rats in the HF-LCT group performed ladder-climbing training for 8 weeks. The results showed that ladder-climbing training significantly reduced body and fat weight, and increased muscle mass along with a trend toward enhanced muscle strength in diet-induced obese rats. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by ladder-climbing training, as evidenced by increased trabecular bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor ladder-climbing training had an impact on femoral biomechanical properties. Moreover, ladder-climbing training significantly increased serum adiponectin, decreased serum leptin, TNF-α, IL-6 levels, and downregulated myostatin (MSTN) expression in diet-induced obese rats. Taken together, ladder-climbing training prevents bone loss and microarchitecture deterioration in diet-induced obese rats through multiple mechanisms including increasing mechanical loading on bone due to improved skeletal muscle mass and strength, regulating the levels of myokines and adipokines, and suppressing the release of pro-inflammatory cytokines. It indicates that resistance exercise may be a promising therapy for treating obesity-induced bone loss.

  16. Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Nillen, Jeannie L.; Davis-Street, Janis E.; DeKerlegand, Diane E.; LeBlanc, Adrian; Shackelford, Linda C.

    2001-01-01

    Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

  17. Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss

    PubMed Central

    Crotti, Tania N.; Dharmapatni, Anak A. S. S. K.; Alias, Ekram; Haynes, David R.

    2015-01-01

    The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA). Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR). PMID:26064999

  18. A murine model for bone loss from therapeutic and space-relevant sources of radiation.

    PubMed

    Hamilton, S A; Pecaut, M J; Gridley, D S; Travis, N D; Bandstra, E R; Willey, J S; Nelson, G A; Bateman, T A

    2006-09-01

    Cancer patients receiving radiation therapy are exposed to photon (gamma/X-ray), electron, and less commonly proton radiation. Similarly, astronauts on exploratory missions will be exposed to extended periods of lower-dose radiation from multiple sources and of multiple types, including heavy ions. Therapeutic doses of radiation have been shown to have deleterious consequences on bone health, occasionally causing osteoradionecrosis and spontaneous fractures. However, no animal model exists to study the cause of radiation-induced osteoporosis. Additionally, the effect of lower doses of ionizing radiation, including heavy ions, on general bone quality has not been investigated. This study presents data developing a murine model for radiation-induced bone loss. Female C57BL/6 mice were exposed to gamma, proton, carbon, or iron radiation at 2-Gray doses, representing both a clinical treatment fraction and spaceflight exposure for an exploratory mission. Mice were euthanized 110 days after irradiation. The proximal tibiae and femur diaphyses were analyzed using microcomputed tomography. Results demonstrate profound changes in trabecular architecture. Significant losses in trabecular bone volume fraction were observed for all radiation species: gamma, (-29%), proton (-35%), carbon (-39%), and iron (-34%). Trabecular connectivity density, thickness, spacing, and number were also affected. These data have clear implications for clinical radiotherapy in that bone loss in an animal model has been demonstrated at low doses. Additionally, these data suggest that space radiation has the potential to exacerbate the bone loss caused by microgravity, although lower doses and dose rates need to be studied.

  19. Bone Wax Is Effective in Reducing Blood Loss After Total Knee Arthroplasty.

    PubMed

    Moo, Ing H; Chen, Jerry Y Q; Pagkaliwaga, Eric H; Tan, See W; Poon, Kein B

    2017-05-01

    Total knee arthroplasty (TKA) is associated with major blood loss and blood transfusion is often required. This study aimed to evaluate the efficacy of bone wax in reducing blood loss and transfusion rates after TKA. A prospective randomized controlled study that included 100 patients undergoing primary unilateral TKA with cement was conducted in a tertiary center between March 2014 and June 2014. The bone wax group received 2.5 g of bone wax, applied onto the uncovered bone around the prostheses and the nail holes before the tourniquet was released, whereas the control group had hemostasis achieved using electrocautery only. Total blood loss was calculated using the hemoglobin balance method. There were no demographic differences between the 2 groups. The preoperative serum hemoglobin levels were comparable between the 2 groups. The drop in serum hemoglobin levels at 24 h post-TKA was 1.6 ± 0.9 and 2.1 ± 1.1 g/dL in the bone wax and control groups respectively (P = .021), while the drop in serum hemoglobin levels at 72 h post-TKA was 2.7 ± 1.1 and 3.6 ± 1.2 g/dL respectively (P = .013). Total blood loss at 72 h post-TKA was 987.9 and 1183.5 mL for the bone wax and control groups respectively (P = .017). There was no adverse event associated with the use of bone wax at the 3-month follow-up. The application of bone wax in TKA was safe and effective for reducing total blood loss and maintaining higher hemoglobin levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Preventing bone loss and weight gain with combinations of vitamin D and phytochemicals.

    PubMed

    Lai, Ching-Yi; Yang, Jeong-Yeh; Rayalam, Srujana; Della-Fera, Mary Anne; Ambati, Suresh; Lewis, Richard D; Hamrick, Mark W; Hartzell, Diane L; Baile, Clifton A

    2011-11-01

    Vitamin D and certain natural compounds have been shown to regulate both lipid metabolism and bone formation. Treatments that prevent or reverse age-related increase in bone marrow adiposity could both increase new bone formation and inhibit bone destruction. We tested the hypothesis that dietary supplementation with combinations of vitamin D and phytochemicals inhibits bone loss and decreases adiposity to a greater extent than control or vitamin D-alone diets. Aged ovariectomized female rats (12 months old, n=50, initial body weight=240 g) were given control (AIN-93M diet), vitamin D (2,400 IU/kg), or vitamin D plus resveratrol (16, 80, or 400 mg/kg of diet [low, medium, and high dose, respectively]), quercetin (80, 400, or 2,000 mg/kg of diet), and genistein (64, 256, or 1,040 mg/kg of diet) for 8 weeks. The high-dose treatment (vitamin D+400 mg/kg resveratrol+2,000 mg/kg quercetin+1,040 mg/kg genistein) reduced body weight gain (P<.05) and the fat pad weights (P<.05). This treatment also increased the serum concentration of insulin-like growth factor-1 (P<.05) and the bone mineral content of the femur. Micro-computed tomography and histomorphometric analyses indicated that the high-dose treatment prevented loss of trabecular bone (P<.05) and reduced marrow adipocytes (P<.001) and osteoclasts (P<.05) compared with the control and vitamin D alone (P<.05). We conclude that aged ovariectomized female rats supplemented with vitamin D combined with genistein, quercetin, and resveratrol had improved bone mineral density and reduced body weight gain and a significant decrease in bone marrow adipocytes. The synergistic effects of a combination of phytochemicals with vitamin D may be effective in reducing bone loss and weight gain after menopause.

  1. Bone loss in ovariectomized rats: dominant role for estrogen but apparently not for FSH.

    PubMed

    Rouach, V; Katzburg, S; Koch, Y; Stern, N; Somjen, D

    2011-01-01

    Estrogen deficiency as the sole factor underlying post-menopausal osteoporosis was challenged, in light of reports that both follicular stimulation hormone (FSH) receptor and FSHβ knockout mice were resistant to bone loss, suggesting a detrimental role for FSH. We assessed whether lowering FSH levels by gonadotropin realizing (GnRH) analog decapeptyl in ovariectomized female rats (OVX) affects bone. Wistar-derived 25 days old OVX female rats were injected for 10 weeks with estradiol-17β (E(2)), with GnRH analog (decapeptyl) or with both. FSH and luteinizing hormone (LH) serum levels were markedly increased in OVX rats, with smaller growth plates with disrupted architecture; heavy infiltration of bone marrow with numerous adipocytes and reduced thickness of cortical bone. In OVX rats treated with E(2), FSH, and LH levels were intermediate, the tibia was similar to that of intact rats, but there was reduced thickness of cortical bone. In decapeptyl treated OVX rats, FSH and LH levels were suppressed, the organization of growth plate and the trabecular bone were disrupted, and there were fewer proliferative and chondroblastic cells and a large adipocytes population in bone marrow, but an increased trabecular bone volume (TBV). In the E(2) + decapeptyl treatment, FSH and LH levels were suppressed, with partially restored growth plate architecture and improved TBV. In conclusion, E(2) deficiency is the dominant factor impairing bone loss in OVX and concomitant changes in FSH/LH levels achieved by decapeptyl have some modulating, though complex role in this setting. The role of high FSH levels in post-menopausal bone loss requires further investigation using combined sub-optimal doses of the different hormones.

  2. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

    PubMed Central

    Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

    2016-01-01

    Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

  3. 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.

  4. Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss.

    PubMed

    Wang, Xin; Zheng, Ting; Kang, Ju-Hee; Li, Hua; Cho, Hyewon; Jeon, Raok; Ryu, Jae-Ha; Yim, Mijung

    2016-03-05

    Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption.

  5. Trunk muscle strength is a strong predictor of bone loss in postmenopausal women.

    PubMed

    Iki, Masayuki; Saito, Yukie; Kajita, Etsuko; Nishino, Harumi; Kusaka, Yukinori

    2006-02-01

    To clarify whether trunk muscle strength and self-reported exercise habits predict subsequent bone loss in healthy post- menopausal women, we examined 143 community-dwelling ambulatory postmenopausal Japanese women (age: 59.9 +/- 6.5 years) without any diseases affecting bone metabolism at baseline, and followed 109 of the 143 subjects for 4 years. Bone mineral density at baseline and at followup was measured at the spine by DEXA to determine the annual change in bone mineral density during the followup. Subjects who lost bone mineral density at an annual rate exceeding -1.78% (1 standard deviation below the mean rate) were defined as rapid bone losers. The isokinetic concentric and eccentric peak torques of the trunk flexors and extensors were measured at baseline. The exercise habits of the subjects were evaluated through detailed interviews. The eccentric trunk flexor and extensor torques were found to correlate with a positive dose-dependent effect on change in bone mineral density while exercise habits showed no correlation. The lower tertile group for the extensor torque showed a ten-fold greater risk for rapid bone loss compared with the upper tertile group. Postmenopausal women with decreased trunk muscle torque may be at increased risk for osteoporosis and should be a target group for preventive measures. Prognostic study, level II (prospective study). See the Guidelines for Authors for a complete description of the levels of evidence.

  6. Age-related bone loss in the LOU/c rat model of healthy ageing.

    PubMed

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  7. Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading.

    PubMed

    Wang, Hong; Ji, Baohua; Liu, X Sherry; van Oers, René F M; Guo, X Edward; Huang, Yonggang; Hwang, Keh-Chih

    2014-01-01

    Osteocyte apoptosis is known to trigger targeted bone resorption. In the present study, we developed an osteocyte-viability-based trabecular bone remodeling (OVBR) model. This novel remodeling model, combined with recent advanced simulation methods and analysis techniques, such as the element-by-element 3D finite element method and the ITS technique, was used to quantitatively study the dynamic evolution of bone mass and trabecular microstructure in response to various loading and unloading conditions. Different levels of unloading simulated the disuse condition of bed rest or microgravity in space. The amount of bone loss and microstructural deterioration correlated with the magnitude of unloading. The restoration of bone mass upon the reloading condition was achieved by thickening the remaining trabecular architecture, while the lost trabecular plates and rods could not be recovered by reloading. Compared to previous models, the predictions of bone resorption of the OVBR model are more consistent with physiological values reported from previous experiments. Whereas osteocytes suffer a lack of loading during disuse, they may suffer overloading during the reloading phase, which hampers recovery. The OVBR model is promising for quantitative studies of trabecular bone loss and microstructural deterioration of patients or astronauts during long-term bed rest or space flight and thereafter bone recovery.

  8. Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest.

    PubMed

    Watanabe, Yukiko; Ohshima, Hiroshi; Mizuno, Koh; Sekiguchi, Chiharu; Fukunaga, Masao; Kohri, Kenjiro; Rittweger, Jörn; Felsenberg, Dieter; Matsumoto, Toshio; Nakamura, Toshitaka

    2004-11-01

    Long-term bed rest has potential risks of bone loss and renal stone formation. We examined the effects of resistive exercise and intravenous pamidronate on BMD, bone turnover, urinary calcium, and renal stone formation in 25 healthy males during 90-day bed rest. Pamidronate prevented femoral bone loss and renal stone formation, but resistive exercise showed little effects. Long-term bed rest increases the risks of bone loss and urinary stone formation. Resistive exercise increases bone formation, and bisphosphonates reduce bone resorption. However, the effects of muscle exercise and bisphosphonates have not been examined side-by-side. The objectives of this study are to compare the effects of pamidronate with resistiv